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Sample records for adipokines

  1. Adipokines in human reproduction.

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    Dupont, Joëlle; Pollet-Villard, Xavier; Reverchon, Maxime; Mellouk, Namya; Levy, Rachel

    2015-10-01

    Adipose tissue communicates with other central and peripheral organs by the synthesis and release of substances called adipokines. The most studied adipokine is leptin but others have been recently identified including resistin, adiponectin, chemerin, omentin and visfatin. These adipokines have a critical role in the development of obesity-related complications and inflammatory conditions. However, they are also involved in other functions in the organism including reproductive functions. Indeed, many groups have demonstrated that adipokine receptors, such as adiponectin and chemerin, but also adipokines themselves (adiponectin, chemerin, resistin, visfatin and omentin) are expressed in human peripheral reproductive tissues and that these adipokines are likely to exert direct effects on these tissues. After a brief description of these new adipokines, an overview of their actions in different human reproductive organs (hypothalamus, pituitary, ovary, testis, uterus and placenta) will be presented. Finally, comments will be made on the eventual alterations of these adipokines in reproductive disorders, with special attention to polycystic ovary syndrome, a disease characterized by dysfunction of gonadal axis and systemic nerve endocrine metabolic network with a prevalence of up to 10% in women of reproductive age.

  2. Epigenetic Regulation of Adipokines

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    Tho X. Pham

    2017-08-01

    Full Text Available Adipose tissue expansion in obesity leads to changes in the expression of adipokines, adipocyte-specific hormones that can regulate whole body energy metabolism. Epigenetic regulation of gene expression is a mechanism by which cells can alter gene expression through the modifications of DNA and histones. Epigenetic mechanisms, such as DNA methylation and histone modifications, are intimately tied to energy metabolism due to their dependence on metabolic intermediates such as S-adenosylmethionine and acetyl-CoA. Altered expression of adipokines in obesity may be due to epigenetic changes. The goal of this review is to highlight current knowledge of epigenetic regulation of adipokines.

  3. Clinical Relevance of Adipokines

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    Matthias Blüher

    2012-10-01

    Full Text Available The incidence of obesity has increased dramatically during recent decades. Obesity increases the risk for metabolic and cardiovascular diseases and may therefore contribute to premature death. With increasing fat mass, secretion of adipose tissue derived bioactive molecules (adipokines changes towards a pro-inflammatory, diabetogenic and atherogenic pattern. Adipokines are involved in the regulation of appetite and satiety, energy expenditure, activity, endothelial function, hemostasis, blood pressure, insulin sensitivity, energy metabolism in insulin sensitive tissues, adipogenesis, fat distribution and insulin secretion in pancreatic β-cells. Therefore, adipokines are clinically relevant as biomarkers for fat distribution, adipose tissue function, liver fat content, insulin sensitivity, chronic inflammation and have the potential for future pharmacological treatment strategies for obesity and its related diseases. This review focuses on the clinical relevance of selected adipokines as markers or predictors of obesity related diseases and as potential therapeutic tools or targets in metabolic and cardiovascular diseases.

  4. Adipokines in connective tissue diseases.

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    Sawicka, Karolina; Krasowska, Dorota

    2016-01-01

    Adipokines, pleiotropic molecules produced by white adipose tissue (WAT) have attracted the attention of scientists since 1994. The role of adipokines in metabolic syndrome is known and fixed. Adipokines exerting a variety of metabolic activities have contributed to the ethiopathogenesis and the consequences of metabolic syndrome. Furthermore, adipokines are involved in the regulation of inflammatory processes and autoimmunity in the light of pathogenesis of connective tissue diseases. Given some evidence for the influence of adipokines in metabolic syndrome, there may be a link between CVDs and rheumatic diseases. This review provides an overview of the literature focusing on the role of adipokines in rheumatic diseases by putting special emphasis on the potential role of leptin, resistin, adiponectin, chemerin, visfatin and novel adipokines in connective tissue diseases.

  5. Novel Adipokines and Bone Metabolism

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    Yuan Liu

    2013-01-01

    Full Text Available Osteoporosis is a serious social issue nowadays. Both the high morbidity and its common complication osteoporotic fracture load a heavy burden on the whole society. The adipose tissue is the biggest endocrinology organ that has a different function on the bone. The adipocytes are differentiated from the same cell lineage with osteoblast, and they can secrete multiple adipokines with various functions on bone remolding. Recently, several novel adipokines have been identified and investigated thoroughly. In this paper, we would like to highlight the complicated relation between the bone metabolism and the novel adipokines, and it may provide us with a new target for prediction and treatment of osteoporosis.

  6. Relationship between adipokines and periodontitis

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    Reiko Furugen

    2010-08-01

    Full Text Available Obesity is associated with an increased risk for developing characteristic features of metabolic syndrome, including hypertension, type 2 diabetes, and dyslipidemia. Interestingly, chronic exposure to periodontal pathogens’ endotoxin and increased cytokine production have been proposed to enhance the risk for causing type 2 diabetes and cardiovascular complications. Obesity has also recently been reported to be associated with periodontitis. Obesity induces macrophage accumulation in adipose tissue, promotes chronic low-grade inflammation, and increases adipokines derived from adipocytes. In this review, we summarize recent advances in understanding the roles of adipokines in chronic inflammatory states such as periodontitis and focus primarily on adiponectin, leptin, and resistin. Understanding the role of adipokines may help elucidate relationships among periodontitis, obesity, type 2 diabetes, and cardiovascular diseases.

  7. Fetal epigenetic programming of adipokines.

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    Houde, Andrée-Anne; Hivert, Marie-France; Bouchard, Luigi

    2013-01-01

    Epigenetics generates a considerable interest in the field of research on complex traits, including obesity and diabetes. Recently, we reported a number of epipolymorphisms in the placental leptin and adiponectin genes associated with maternal hyperglycemia during pregnancy. Our results suggest that DNA methylation could partly explain the link between early exposure to a detrimental fetal environment and an increased risk to develop obesity and diabetes later in life. This brief report discusses the potential importance of adipokine epigenetic changes in fetal metabolic programming. Additionally, preliminary data showing similarities between methylation variations of different tissues and cell types will be presented along with the challenges and future perspectives of this emerging field of research.

  8. The Intricate Network of Adipokines and Stroke

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    Ema Kantorová

    2015-01-01

    Full Text Available Cerebrovascular disorders, particularly ischemic stroke, are one of the most common neurological disorders. High rates of overweight and obesity support an interest in the role of adipose tissue and adipose tissue releasing cytokines in inducing associated comorbidities. Adipokines can serve as a key messenger to central energy homeostasis and metabolic homeostasis. They can contribute to the crosstalk between adipose tissue and brain. However recent research has offered ambiguous data on the network of adipose tissue, adipokines, and vascular disorders. In our paper we provide a critical insight into the role of adipokines in evolution of ischemic stroke.

  9. CARDIOVASCULAR DISORDERS WITH HYPOTHYROIDISM AND ADIPOKINES

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    S. Ye. Myasoyedova

    2015-01-01

    Full Text Available The article describes the mechanisms of development of cardiovascular disorders and dyslipidemia with hypothyroidism. Reference data are presented that are devoted to the study of adipokines content with hypothyroidism and their effect on echocardiographic indicators.

  10. Adipokines and cardiovascular disease: A comprehensive review.

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    Smekal, Ales; Vaclavik, Jan

    2017-03-01

    Adipokines are peptides that signal the functional status of adipose tissue to the brain and other target organs. In adipose tissue dysfunction, adipokine secretion is altered, and this can contribute to a spectrum of obesity-associated conditions including cardiovascular disease. Some adipokines have anti-inflammatory and cardioprotective effects (omentin, apelin, adiponectin). Others are pro-inflammatory with negative impact on cardiovascular function (leptin, visfatin, resistin, adipocyte fatty-acid-binding protein). In the first part, this article reviews the endocrine functions of adipose tissue in general, effects of the distribution and composition of fat tissue, and the roles of cortisol and the renin-angiotensin-aldosterone system in the development of the inflammatory state of addipose tissue. In the second part, the known cardiovascular effects of different adipokines and their clinical potential are discussed in detail.

  11. Adipokines mediate inflammation and insulin resistance

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    Jeffrey E. Pessin

    2013-06-01

    Full Text Available For many years, adipose tissue was considered as an inert energy storage organ that accumulates and stores triacylglycerols during energy excess and releases fatty acids in times of systemic energy need. However, over the last two decades adipose tissue depots have been established as highly active endocrine and metabolically important organs that modulate energy expenditure and glucose homeostasis. In rodents, brown adipose tissue plays an essential role in non-shivering thermogenesis and in energy dissipation that can serve to protect against diet-induced obesity. White adipose tissue collectively referred too as either subcutaneous or visceral adipose tissue is responsible for the secretion of an array of signaling molecules, termed adipokines. These adipokines function as classic circulating hormones to communicate with other organs including brain, liver, muscle, the immune system and adipose tissue itself. The dysregulation of adipokines has been implicated in obesity, type 2 diabetes and cardiovascular disease. Recently, inflammatory responses in adipose tissue have been shown as a major mechanism to induce peripheral tissue insulin resistance. Although leptin and adiponectin regulate feeding behavior and energy expenditure, these adipokines are also involved in the regulation of inflammatory responses. Adipose tissue secrete various pro- and anti-inflammatory adipokines to modulate inflammation and insulin resistance. In obese humans and rodent models, the expression of pro-inflammatory adipokines is enhanced to induce insulin resistance. Collectively, these findings have suggested that obesity-induced insulin resistance may result, at least in part, from an imbalance in the expression of pro- and anti-inflammatory adipokines. Thus we will review the recent progress regarding the physiological and molecular functions of adipokines in the obesity-induced inflammation and insulin resistance with perspectives on future directions.

  12. The role of adipokines in chronic inflammation.

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    Mancuso, Peter

    2016-01-01

    Adipose tissue has traditionally been defined as connective tissue that stores excess calories in the form of triacylglycerol. However, the physiologic functions attributed to adipose tissue are expanding, and it is now well established that adipose tissue is an endocrine gland. Among the endocrine factors elaborated by adipose tissue are the adipokines; hormones, similar in structure to cytokines, produced by adipose tissue in response to changes in adipocyte triacylglycerol storage and local and systemic inflammation. They inform the host regarding long-term energy storage and have a profound influence on reproductive function, blood pressure regulation, energy homeostasis, the immune response, and many other physiologic processes. The adipokines possess pro- and anti-inflammatory properties and play a critical role in integrating systemic metabolism with immune function. In calorie restriction and starvation, proinflammatory adipokines decline and anti-inflammatory adipokines increase, which informs the host of energy deficits and contributes to the suppression of immune function. In individuals with normal metabolic status, there is a balance of pro- and anti-inflammatory adipokines. This balance shifts to favor proinflammatory mediators as adipose tissue expands during the development of obesity. As a consequence, the proinflammatory status of adipose tissue contributes to a chronic low-grade state of inflammation and metabolic disorders associated with obesity. These disturbances are associated with an increased risk of metabolic disease, type 2 diabetes, cardiovascular disease, and many other pathological conditions. This review focuses on the impact of energy homeostasis on the adipokines in immune function.

  13. Adipokines and the Female Reproductive Tract

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    Maxime Reverchon

    2014-01-01

    Full Text Available It is well known that adipose tissue can influence puberty, sexual maturation, and fertility in different species. Adipose tissue secretes molecules called adipokines which most likely have an endocrine effect on reproductive function. It has been revealed over the last few years that adipokines are functionally implicated at all levels of the reproductive axis including the gonad and hypothalamic-pituitary axis. Many studies have shown the presence and the role of the adipokines and their receptors in the female reproductive tract of different species. These adipokines regulate ovarian steroidogenesis, oocyte maturation, and embryo development. They are also present in the uterus and placenta where they could create a favorable environment for embryonic implantation and play a key role in maternal-fetal metabolism communication and gestation. Reproductive functions are strongly dependent on energy balance, and thereby metabolic abnormalities can lead to the development of some pathophysiologies such as polycystic ovary syndrome (PCOS. Adipokines could be a link between reproduction and energy metabolism and could partly explain some infertility related to obesity or PCOS.

  14. Adipokine profile in patients with anorexia nervosa.

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    Baranowska-Bik, Agnieszka; Baranowska, Bogusława; Martyńska, Lidia; Litwiniuk, Anna; Kalisz, Małgorzata; Kochanowski, Jan; Bik, Wojciech

    2017-01-01

    Anorexia nervosa (AN) is an eating disorder characterised with extremely low weight. Adipokines are adipose tissue-derived substances that show a wide spectrum of biological activities. We aimed to assess selected adipokine levels in women with AN before and after nutritional intervention. We also sought to examine whether BMI is the only confounding factor influencing adipokine assessment in AN. Sixty-five women participated in the study: 20 individuals with AN before any treatment, 18 AN patients after nutritional intervention lasting for at least six months, and 27 women as controls. In all participants blood collection and anthropometric measurements were performed. ELISA was used for evaluation of leptin receptor, adiponectin and its isoforms, and resistin. Leptin was assessed with RIA, and visfatin was measured with EIA assay. Leptin and free leptin index (FLI) were lowest in treatment-naïve AN women. HMW-adiponectin and visfatin were enhanced in AN. Other adipokine levels showed no significant differences. When two subsets of anorexia nervosa were compared, only leptin, leptin receptor, and FLI were markedly different. When data were adjusted to BMI, leptin and FLI remained significantly different in the pre-treated AN subgroup when compared with the control group. Our results suggest that leptin is the most important adipokine in AN. It is also important that in our AN population leptin and FLI are the only factors that are influenced not only by the fat content.

  15. Adipokines as Potential Biomarkers in Rheumatoid Arthritis

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    Annalisa Del Prete

    2014-01-01

    Full Text Available Rheumatoid arthritis (RA is a chronic systemic inflammatory autoimmune disease characterized by severe joint injury. Recently, research has been focusing on the possible identification of predictor markers of disease onset and/or progression, of joint damage, and of therapeutic response. Recent findings have uncovered the role of white adipose tissue as a pleiotropic organ not only specialized in endocrine functions but also able to control multiple physiopathological processes, including inflammation. Adipokines are a family of soluble mediators secreted by white adipose tissue endowed with a wide spectrum of actions. This review will focus on the recent advances on the role of the adipokine network in the pathogenesis of RA. A particular attention will be devoted to the action of these proteins on RA effector cells, and on the possibility to use circulating levels of adipokines as potential biomarkers of disease activity and therapeutic response.

  16. The Importance of Adipokines in Alzheimer's Disease

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    Seyid Ahmet Ay

    2015-06-01

    Full Text Available Dementia and Alzheimers disease are characterized by disturbances in brain function and structure. Similarly, body mass index and obesity are associated with certain brain pathologies, including Alzheimers disease and dementia. In fact, there is mounting evidence linking metabolic dysfunction with dementia and Alzheimers disease. Major endocrine axes constitute links between brain and peripheral tissues, especially adipose tissue. Adipose tissue is metabolically very active and produces a variety of adipokines known to affect both peripheral and central nervous system processes. Experimental studies suggest that changes in adipokine function may contribute to the pathogenesis of Alzheimers disease. Herein, we review the adipokines leptin and adiponectin which are associated with morbidities related to obesity as well as dementia and Alzheimers disease. [Dis Mol Med 2015; 3(2.000: 22-28

  17. The role of adipokines in chronic inflammation

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    Mancuso P

    2016-05-01

    Full Text Available Peter Mancuso Department of Nutritional Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA Abstract: Adipose tissue has traditionally been defined as connective tissue that stores excess calories in the form of triacylglycerol. However, the physiologic functions attributed to adipose tissue are expanding, and it is now well established that adipose tissue is an endocrine gland. Among the endocrine factors elaborated by adipose tissue are the adipokines; hormones, similar in structure to cytokines, produced by adipose tissue in response to changes in adipocyte triacylglycerol storage and local and systemic inflammation. They inform the host regarding long-term energy storage and have a profound influence on reproductive function, blood pressure regulation, energy homeostasis, the immune response, and many other physiologic processes. The adipokines possess pro- and anti-inflammatory properties and play a critical role in integrating systemic metabolism with immune function. In calorie restriction and starvation, proinflammatory adipokines decline and anti-inflammatory adipokines increase, which informs the host of energy deficits and contributes to the suppression of immune function. In individuals with normal metabolic status, there is a balance of pro- and anti-inflammatory adipokines. This balance shifts to favor proinflammatory mediators as adipose tissue expands during the development of obesity. As a consequence, the proinflammatory status of adipose tissue contributes to a chronic low-grade state of inflammation and metabolic disorders associated with obesity. These disturbances are associated with an increased risk of metabolic disease, type 2 diabetes, cardiovascular disease, and many other pathological conditions. This review focuses on the impact of energy homeostasis on the adipokines in immune function. Keywords: calorie restriction, obesity, adipose tissue, type 2 diabetes, macrophage, infection, chronic

  18. Serum adipokine profiles in Kawasaki disease.

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    Kemmotsu, Yasushi; Saji, Tsutomu; Kusunoki, Natsuko; Tanaka, Nahoko; Nishimura, Chiaki; Ishiguro, Akira; Kawai, Shinichi

    2012-02-01

    Adipokines are cytokines derived from adipose tissue. Recently it has been established that adipokines are closely linked to the pathophysiology of not only metabolic diseases, such as diabetes mellitus, obesity, and atherosclerosis, but also to inflammation and immune diseases. In this study we measured serum levels of adipokines in patients with acute Kawasaki disease to investigate the role of adipokines in the pathophysiology of Kawasaki disease. Serum resistin, high-molecular-weight (HMW) adiponectin, leptin, and visfatin levels were measured by enzyme-linked immunosorbent assay in a total of 117 subjects: 56 patients with acute Kawasaki disease, 30 healthy children, and 31 patients with acute infectious diseases. Serum resistin levels in patients with Kawasaki disease were significantly higher than those of healthy children and patients with acute infectious diseases. In contrast, mean serum HMW adiponectin, leptin, and visfatin levels in patients with Kawasaki disease exhibited no statistically significant differences compared with those in healthy children and patients with infectious diseases. Serum resistin levels decreased significantly after administration of intravenous immune globulin. Serum resistin levels on admission were significantly higher in nonresponders compared with responders to intravenous immune globulin therapy. A multivariate model revealed that C-reactive protein was a factor that was significantly related to elevated serum resistin level in patients with Kawasaki disease. In patients with Kawasaki disease, serum resistin levels were elevated, but decreased to nearly normal after intravenous administration of immune globulin. In contrast, serum HMW adiponectin, leptin, and visfatin levels showed no statistically significant changes. These findings suggest that resistin plays an important role, while other adipokines do not play a major role, in the pathogenesis of Kawasaki disease.

  19. Sputum as a source of adipokines in bronchial asthma

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    V. N. Mineev

    2014-01-01

    Full Text Available Forty-four patients with allergic (ABA and non-allergic (NABA variants of bronchial asthma (BA were examined to evaluate levels of key adipokines (leptin, resistin, adiponectin in sputum in different variants of BA. Adipokines in sputum and blood plasma were measured by Enzyme-Linked Immunosorbent Assay (ELISA. The indices that reflect the percentage of adipokines in sputum regarding adipokines in plasma of the same patients were worked out to evaluate the ratio of levels of corresponding adipokines in plasma and sputum in patients with BA. Two regularities are clearly seen in the study: the first - levels of proinflammatory adipokines (leptin, resistin in sputum in ABA correlate directly with indicators of respiratory function but levels of anti-inflammatory adipokines (adiponectin in sputum correlate inversely with indicators of respiratory function; the second -correlation of levels of the studied adipokines with indicators of respiratory function are almost not revealed in NABA. The first regularity reflects the important fact that the content of adipokines in bronchial secretion is to a certain extent one of regulating local mechanisms in target organ controlled system levels of corresponding adipokines in exacerbation of BA.

  20. Basic Science for the Clinician 52: adipokines.

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    Sigal, Leonard H

    2011-04-01

    Adipocytes, the cells that maintain fat stores and influence energy metabolism, produce a variety of messengers, called adipokines (or adipocytokines). These proteins have broad reaching effects on glucose and fat metabolism, but also influence inflammation, by modulating the production of inflammatory cytokines and modifying how established cytokines such as interleukin 6 and tumor necrosis factor α themselves induce or modulate inflammation; some of these proteins are produced by synovial tissue adipocytes, suggesting a very direct effect on the modification of local inflammation. Adipokines provide mechanisms that might explain accelerated atherosclerosis and impaired glucose metabolism in some of our chronic inflammatory diseases and offer potential unique therapeutic approaches to control these and other manifestations of inflammation.

  1. Adipokines, metabolic syndrome and rheumatic diseases.

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    Abella, Vanessa; Scotece, Morena; Conde, Javier; López, Verónica; Lazzaro, Verónica; Pino, Jesús; Gómez-Reino, Juan J; Gualillo, Oreste

    2014-01-01

    The metabolic syndrome (MetS) is a cluster of cardiometabolic disorders that result from the increasing prevalence of obesity. The major components of MetS include insulin resistance, central obesity, dyslipidemia, and hypertension. MetS identifies the central obesity with increased risk for cardiovascular diseases (CVDs) and type-2 diabetes mellitus (T2DM). Patients with rheumatic diseases, such as rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, and ankylosing spondylitis, have increased prevalence of CVDs. Moreover, CVD risk is increased when obesity is present in these patients. However, traditional cardiovascular risk factors do not completely explain the enhanced cardiovascular risk in this population. Thus, MetS and the altered secretion patterns of proinflammatory adipokines present in obesity could be the link between CVDs and rheumatic diseases. Furthermore, adipokines have been linked to the pathogenesis of MetS and its comorbidities through their effects on vascular function and inflammation. In the present paper, we review recent evidence of the role played by adipokines in the modulation of MetS in the general population, and in patients with rheumatic diseases.

  2. Adipokines, Metabolic Syndrome and Rheumatic Diseases

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    Vanessa Abella

    2014-01-01

    Full Text Available The metabolic syndrome (MetS is a cluster of cardiometabolic disorders that result from the increasing prevalence of obesity. The major components of MetS include insulin resistance, central obesity, dyslipidemia, and hypertension. MetS identifies the central obesity with increased risk for cardiovascular diseases (CVDs and type-2 diabetes mellitus (T2DM. Patients with rheumatic diseases, such as rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, and ankylosing spondylitis, have increased prevalence of CVDs. Moreover, CVD risk is increased when obesity is present in these patients. However, traditional cardiovascular risk factors do not completely explain the enhanced cardiovascular risk in this population. Thus, MetS and the altered secretion patterns of proinflammatory adipokines present in obesity could be the link between CVDs and rheumatic diseases. Furthermore, adipokines have been linked to the pathogenesis of MetS and its comorbidities through their effects on vascular function and inflammation. In the present paper, we review recent evidence of the role played by adipokines in the modulation of MetS in the general population, and in patients with rheumatic diseases.

  3. Correlation between obesity, adipokines and the immune system

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    Marcos Regini Silveira

    2009-09-01

    Full Text Available Obesity is a worldwide health problem and the increase in its incidence, risks and consequences are a matter of growing concern. Obesity is characterized by the accumulation of fat in the body. Many studies are currently investigating obesity and associated comorbidities in an attempt to clarify the mechanisms involved. Fat tissue is a dynamic organ that secretes several factors, including adipokines. Adipokines are bioactive peptides secreted by fat cells, which are important for energy regulation and inflammatory and immune responses. Leptin, adiponectin and resistin are the most studied adipokines. The aim of this review was to gather information about these adipokines (leptin, adiponectin and resistin and their relationship with the immune response in obese individuals, as well as the susceptibility of these patients to infections. The results of the literature review permit some observations. The circulating levels of these adipokines are directly involved in the degree of obesity of the patient. High or low circulating concentrations of these adipokines may have beneficial or negative effects on immune competence, with obese patients being more susceptible to infection and inflammation than eutrophic individuals.Key words: Obesity; Adipokines; Leptin; Adiponectin; Resistin; Immune system.

  4. Adipokines as drug targets in diabetes and underlying disturbances.

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    Andrade-Oliveira, Vinícius; Câmara, Niels O S; Moraes-Vieira, Pedro M

    2015-01-01

    Diabetes and obesity are worldwide health problems. White fat dynamically participates in hormonal and inflammatory regulation. White adipose tissue is recognized as a multifactorial organ that secretes several adipose-derived factors that have been collectively termed "adipokines." Adipokines are pleiotropic molecules that gather factors such as leptin, adiponectin, visfatin, apelin, vaspin, hepcidin, RBP4, and inflammatory cytokines, including TNF and IL-1β, among others. Multiple roles in metabolic and inflammatory responses have been assigned to these molecules. Several adipokines contribute to the self-styled "low-grade inflammatory state" of obese and insulin-resistant subjects, inducing the accumulation of metabolic anomalies within these individuals, including autoimmune and inflammatory diseases. Thus, adipokines are an interesting drug target to treat autoimmune diseases, obesity, insulin resistance, and adipose tissue inflammation. The aim of this review is to present an overview of the roles of adipokines in different immune and nonimmune cells, which will contribute to diabetes as well as to adipose tissue inflammation and insulin resistance development. We describe how adipokines regulate inflammation in these diseases and their therapeutic implications. We also survey current attempts to exploit adipokines for clinical applications, which hold potential as novel approaches to drug development in several immune-mediated diseases.

  5. Fatty acid-gene interactions, adipokines and obesity.

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    Stryjecki, C; Mutch, D M

    2011-03-01

    It is now recognized that the low-grade inflammation observed with obesity is associated with the development of a wide range of downstream complications. As such, there is considerable interest in elucidating the regulatory mechanisms underlying the production of inflammatory molecules to improve the prevention and treatment of obesity and its co-morbidities. White adipose tissue is no longer considered a passive reservoir for storing lipids, but rather an important organ influencing energy metabolism, insulin sensitivity and inflammation by the secretion of proteins, commonly referred to as adipokines. Dysregulation of several adipokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and adiponectin, contributes to the low-grade inflammation that is a hallmark of obesity. Evidence now suggests that fatty acids represent a class of molecules that can modulate adipokine production, thereby influencing inflammatory status. Although the precise molecular mechanisms by which dietary fats regulate adipokine production remain unclear, recent findings indicate that diet-gene interactions may have an important role in the transcriptional and secretory regulation of adipokines. Single-nucleotide polymorphisms in the genes encoding TNF-α, IL-6 and adiponectin can modify circulating levels of these adipokines and, subsequently, obesity-related phenotypes. This genetic variation can also alter the influence of dietary fatty acids on adipokine production. Therefore, the current review will show that it is paramount to consider both genetic information and dietary fat intake to unravel the inter-individual variability in inflammatory response observed in intervention protocols targeting obesity.

  6. Adipokines linking obesity with colorectal cancer risk in postmenopausal women

    National Research Council Canada - National Science Library

    Ho, Gloria Y F; Wang, Tao; Gunter, Marc J; Strickler, Howard D; Cushman, Mary; Kaplan, Robert C; Wassertheil-Smoller, Sylvia; Xue, Xiaonan; Rajpathak, Swapnil N; Chlebowski, Rowan T; Vitolins, Mara Z; Scherer, Philipp E; Rohan, Thomas E

    2012-01-01

    Mechanistic associations between obesity and colorectal cancer remain unclear. In this study, we investigated whether adipokines are risk factors for colorectal cancer and whether they may mediate its association with obesity...

  7. Exercise Induced Adipokine Changes and the Metabolic Syndrome

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    Saeid Golbidi

    2014-01-01

    Full Text Available The lack of adequate physical activity and obesity created a worldwide pandemic. Obesity is characterized by the deposition of adipose tissue in various parts of the body; it is now evident that adipose tissue also acts as an endocrine organ capable of secreting many cytokines that are though to be involved in the pathophysiology of obesity, insulin resistance, and metabolic syndrome. Adipokines, or adipose tissue-derived proteins, play a pivotal role in this scenario. Increased secretion of proinflammatory adipokines leads to a chronic inflammatory state that is accompanied by insulin resistance and glucose intolerance. Lifestyle change in terms of increased physical activity and exercise is the best nonpharmacological treatment for obesity since these can reduce insulin resistance, counteract the inflammatory state, and improve the lipid profile. There is growing evidence that exercise exerts its beneficial effects partly through alterations in the adipokine profile; that is, exercise increases secretion of anti-inflammatory adipokines and reduces proinflammatory cytokines. In this paper we briefly describe the pathophysiologic role of four important adipokines (adiponectin, leptin, TNF-α, and IL-6 in the metabolic syndrome and review some of the clinical trials that monitored these adipokines as a clinical outcome before and after exercise.

  8. The Adipokine Chemerin Induces Apoptosis in Cardiomyocytes

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    Diego Rodríguez-Penas

    2015-08-01

    Full Text Available Background: The adipokine chemerin has been associated with cardiovascular disease. We investigated the effects of chemerin on viability and intracellular signalling in murine cardiomyocytes, and the effects of insulin and TNF-α on cardiomyocyte chemerin production. Methods: Hoechst dye vital staining and cell cycle analysis were used to analyse the viability of murine cardiac cells in culture. Western blot was used to explore the phosphorylation of AKT and caspase-9 activity in neonatal rat cardiomyocytes and HL-1 cells. Finally, RT-qPCR, ELISA and western blot were performed to examine chemerin and CMKLR1 expression after insulin and TNF-α treatment in cardiac cells. Results: Chemerin treatment increased apoptosis, reduced phosphorylation of AKT at Thr308 and increased caspase-9 activity in murine cardiomyocytes. Insulin treatment lowered chemerin and CMKLR1 mRNA and protein levels, and the amount of chemerin in the cell media, while TNF-α treatment increased chemerin mRNA and protein levels but decreased expression of the CMKLR1 gene. Conclusion: Chemerin induces apoptosis, reduces AKT phosphorylation and increases the cleavage of caspase-9 in murine cardiomyocytes. The expression of chemerin is regulated by important metabolic (insulin and inflammatory (TNF-α mediators at cardiac level. Our results suggest that chemerin could play a role in the physiopathology of cardiac diseases.

  9. Visfatin/Nampt: An Adipokine with Cardiovascular Impact

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    Tania Romacho

    2013-01-01

    Full Text Available Adipose tissue is acknowledged as an endocrine organ that releases bioactive factors termed adipokines. Visfatin was initially identified as a novel adipokine with insulin-mimetic properties in mice. This adipokine was identical to two previously described molecules, namely, pre-B cell colony-enhancing factor (PBEF and the enzyme nicotinamide phosphoribosyltransferase (Nampt. Enhanced circulating visfatin/Nampt levels have been reported in metabolic diseases, such as obesity and type 2 diabetes. Moreover, visfatin/Nampt circulating levels correlate with markers of systemic inflammation. In cardiovascular diseases, visfatin/Nampt was initially proposed as a clinical marker of atherosclerosis, endothelial dysfunction, and vascular damage, with a potential prognostic value. Nevertheless, beyond being a surrogate clinical marker, visfatin/Nampt is an active player promoting vascular inflammation, and atherosclerosis. Visfatin/Nampt effects on cytokine and chemokine secretion, macrophage survival, leukocyte recruitment by endothelial cells, vascular smooth muscle inflammation and plaque destabilization make of this adipokine an active factor in the development and progression of atherosclerosis. Further research is required to fully understand the mechanisms mediating the cellular actions of this adipokine and to better characterize the factors regulating visfatin/Nampt expression and release in all these pathologic scenarios. Only then, we will be able to conclude whether visfatin/Nampt is a therapeutical target in cardiometabolic diseases.

  10. Obesity, adipokines and metabolic syndrome in polycystic ovary syndrome.

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    Carmina, Enrico

    2013-01-01

    The complex mechanisms linking fat excess to metabolic syndrome are not well understood, but several experimental studies have shown that altered production of adipokines plays a main role in development and progression of this disorder. In particular, reduced secretion of adiponectin has a crucial role in inducing insulin resistance but also in determining the clustering of elevated triglycerides and small, dense LDL particles. Increased leptin secretion may be responsible for sympathetic nervous system overactivity and hypertension, while reduced omentin may have an important permissive role in the development of atherogenic processes. Finally, cytokines and other adipokines (resistin, visfatin) determine and modulate the inflammatory process that is an essential component of this condition of cardiovascular risk. Because obesity is prevalent in polycystic ovary syndrome (PCOS), it is not surprising that patients with PCOS present altered adipokine levels and increased prevalence of metabolic syndrome. However, because of the presence of other CV risk factors (androgen excess), in PCOS adipokine dysfunction is particularly severe. Understanding and treating adipokine dysfunction in young women with PCOS is an essential component of any politics of prevention of CV diseases in the general population. Copyright © 2013 S. Karger AG, Basel.

  11. A link between sleep loss, glucose metabolism and adipokines

    Directory of Open Access Journals (Sweden)

    H.G. Padilha

    2011-10-01

    Full Text Available The present review evaluates the role of sleep and its alteration in triggering problems of glucose metabolism and the possible involvement of adipokines in this process. A reduction in the amount of time spent sleeping has become an endemic condition in modern society, and a search of the current literature has found important associations between sleep loss and alterations of nutritional and metabolic contexts. Studies suggest that sleep loss is associated with problems in glucose metabolism and a higher risk for the development of insulin resistance and type 2 diabetes mellitus. The mechanism involved may be associated with the decreased efficacy of regulation of the hypothalamus-pituitary-adrenal axis by negative feedback mechanisms in sleep-deprivation conditions. In addition, changes in the circadian pattern of growth hormone (GH secretion might also contribute to the alterations in glucose regulation observed during sleep loss. On the other hand, sleep deprivation stress affects adipokines - increasing tumor necrosis factor-α (TNF-α and interleukin-6 (IL-6 and decreasing leptin and adiponectin -, thus establishing a possible association between sleep-debt, adipokines and glucose metabolism. Thus, a modified release of adipokines resulting from sleep deprivation could lead to a chronic sub-inflammatory state that could play a central role in the development of insulin resistance and type 2 diabetes mellitus. Further studies are necessary to investigate the role of sleep loss in adipokine release and its relationship with glucose metabolism.

  12. From Placenta to Polycystic Ovarian Syndrome: The Role of Adipokines

    Directory of Open Access Journals (Sweden)

    Chiara Sartori

    2016-01-01

    Full Text Available Adipokines are cytokines produced mainly by adipose tissue, besides many other tissues such as placenta, ovaries, peripheral-blood mononuclear cells, liver, muscle, kidney, heart, and bone marrow. Adipokines play a significant role in the metabolic syndrome and in cardiovascular diseases, have implications in regulating insulin sensitivity and inflammation, and have significant effects on growth and reproductive function. The objective of this review was to analyze the functions known today of adiponectin, leptin, resistin, and visfatin from placenta throughout childhood and adolescence. It is well known now that their serum concentrations during pregnancy and lactation have long-term effects beyond the fetus and newborn. With regard to puberty, adipokines are involved in the regulation of the relationship between nutritional status and normal physiology or disorders of puberty and altered gonadal function, as, for example, premature pubarche and polycystic ovarian syndrome (PCOS. Cytokines are involved in the maturation of oocytes and in the regular progression of puberty and pregnancy.

  13. Adipokines and Non-Alcoholic Fatty Liver Disease: Multiple Interactions

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    Timon E. Adolph

    2017-07-01

    Full Text Available Accumulating evidence links obesity with low-grade inflammation which may originate from adipose tissue that secretes a plethora of pro- and anti-inflammatory cytokines termed adipokines. Adiponectin and leptin have evolved as crucial signals in many obesity-related pathologies including non-alcoholic fatty liver disease (NAFLD. Whereas adiponectin deficiency might be critically involved in the pro-inflammatory state associated with obesity and related disorders, overproduction of leptin, a rather pro-inflammatory mediator, is considered of equal relevance. An imbalanced adipokine profile in obesity consecutively contributes to metabolic inflammation in NAFLD, which is associated with a substantial risk for developing hepatocellular carcinoma (HCC also in the non-cirrhotic stage of disease. Both adiponectin and leptin have been related to liver tumorigenesis especially in preclinical models. This review covers recent advances in our understanding of some adipokines in NAFLD and associated HCC.

  14. Adipokines and the Endocrine Role of Adipose Tissues.

    Science.gov (United States)

    Giralt, Marta; Cereijo, Rubén; Villarroya, Francesc

    2016-01-01

    The last two decades have witnessed a shift in the consideration of white adipose tissue as a mere repository of fat to be used when food becomes scarce to a true endocrine tissue releasing regulatory signals, the so-called adipokines, to the whole body. The control of eating behavior, the peripheral insulin sensitivity, and even the development of the female reproductive system are among the physiological events controlled by adipokines. Recently, the role of brown adipose tissue in human physiology has been recognized. The metabolic role of brown adipose tissue is opposite to white fat; instead of storing fat, brown adipose tissue is a site of energy expenditure via adaptive thermogenesis. There is growing evidence that brown adipose tissue may have its own pattern of secreted hormonal factors, the so-called brown adipokines, having distinctive biological actions on the overall physiological adaptations to enhance energy expenditure.

  15. From Placenta to Polycystic Ovarian Syndrome: The Role of Adipokines

    Science.gov (United States)

    Sartori, Chiara; Lazzeroni, Pietro; Merli, Silvia; Patianna, Viviana Dora; Viaroli, Francesca; Cirillo, Francesca; Amarri, Sergio

    2016-01-01

    Adipokines are cytokines produced mainly by adipose tissue, besides many other tissues such as placenta, ovaries, peripheral-blood mononuclear cells, liver, muscle, kidney, heart, and bone marrow. Adipokines play a significant role in the metabolic syndrome and in cardiovascular diseases, have implications in regulating insulin sensitivity and inflammation, and have significant effects on growth and reproductive function. The objective of this review was to analyze the functions known today of adiponectin, leptin, resistin, and visfatin from placenta throughout childhood and adolescence. It is well known now that their serum concentrations during pregnancy and lactation have long-term effects beyond the fetus and newborn. With regard to puberty, adipokines are involved in the regulation of the relationship between nutritional status and normal physiology or disorders of puberty and altered gonadal function, as, for example, premature pubarche and polycystic ovarian syndrome (PCOS). Cytokines are involved in the maturation of oocytes and in the regular progression of puberty and pregnancy.

  16. Effect of periodontal treatment on adipokines in type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    Hiroshi; Ogawa; Teerasak; Damrongrungruang; Sayaka; Hori; Kaname; Nouno; Kumiko; Minagawa; Misuzu; Sato; Hideo; Miyazaki

    2014-01-01

    The association between adipokines and inflammatory periodontal diseases has been studied over the last two decades. This review was intended to explore the observation that periodontal therapy may lead to an improvement of adipokines in diabetic patients. In summary, substantial evidence suggests that diabetes is associated with increased prevalence, extent and severity of periodontitis. Numerous mechanisms have been elucidated to explain the impact of diabetes on the periodontium. However, current knowledge concerning the role of major adipokines indicates only some of their associations with the pathogenesis of periodontitis in type 2 diabetes. Conversely, treatment of periodontal disease and reduction of oral inflammation may have positive effects on the diabetic condition, although evidence for this remains somewhat equivocal.

  17. Adipokines, vascular wall, and cardiovascular disease: a focused overview of the role of adipokines in the pathophysiology of cardiovascular disease.

    Science.gov (United States)

    Maresca, Fabio; Di Palma, Vito; Bevilacqua, Michele; Uccello, Giuseppe; Taglialatela, Vittorio; Giaquinto, Alessandro; Esposito, Giovanni; Trimarco, Bruno; Cirillo, Plinio

    2015-01-01

    Epidemiological evidence has shown that abdominal obesity is closely associated with the development of cardiovascular (CV) disease, suggesting that it might be considered as an independent CV risk factor. However, the pathophysiological mechanisms responsible for the association between these 2 clinical entities remain largely unknown. Adipocytes are considered able to produce and secrete chemical mediators known as "adipokines" that may exert several biological actions, including those on heart and vessels. Of interest, a different adipokine profile can be observed in the plasma of patients with obesity or metabolic syndrome compared with healthy controls. We consider the main adipokines, focusing on their effects on the vascular wall and analyzing their role in CV pathophysiology. © The Author(s) 2014.

  18. Obesity-Related Adipokines Predict Patient-Reported Shoulder Pain

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    Rajiv Gandhi

    2013-12-01

    Full Text Available Background/Aims: Increasingly, an inflammatory modulating effect of adipokines within synovial joints is being recognized. To date, there has been no work examining a potential association between the presence of adipokines in the shoulder and patient-reported outcomes. This study undertakes an investigation assessing these potential links. Methods: 50 osteoarthritis patients scheduled for shoulder surgery completed a pre-surgery questionnaire capturing demographic information including validated, patient-reported function (Disabilities of the Arm, Shoulder, and Hand questionnaire and pain (Short Form McGill Pain Questionnaire measures. Synovial fluid (SF samples were analyzed for leptin, adiponectin, and resistin levels using Milliplex MAP assays. Linear regression modeling was used to assess the association between adipokine levels and patient-reported outcomes, adjusted for age, sex, BMI, and disease severity. Results: 54% of the cohort was female (n = 27. The mean age (SD of the sample was 62.9 (9.9 years and the mean BMI (SD was 28.1 (5.4 kg/m2. From regression analyses, greater SF leptin and adiponectin levels, but not regarding resistin, were found to be associated with greater pain (p Conclusions: The identified association between shoulder-derived SF leptin and adiponectin and shoulder pain is likely explained by the pro-inflammatory characteristics of the adipokines and represents potentially important therapeutic targets.

  19. Altered Systemic Adipokines in Patients with Chronic Urticaria.

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    Trinh, Hoang Kim Tu; Pham, Duy Le; Ban, Ga-Young; Lee, Hyun-Young; Park, Hae-Sim; Ye, Young-Min

    2016-01-01

    Increasing evidence suggests that adipokines affect immune responses and chronic urticaria (CU) is associated with an altered immune response related to chronic systemic inflammation. Our objectives were to investigate whether adipokines are involved in CU pathogenesis and to outline relationships between adipokines and urticaria severity and quality of life. Serum adiponectin, leptin, lipocalin-2 (LCN2), interleukin (IL)-10, IL-6, and tumor necrosis factor (TNF)-α concentrations were measured by enzyme-linked immunosorbent assays in 191 CU patients and 89 healthy controls. The effect of LCN2 on N-formyl-methionine-leucine-phenylalanine (fMLP)-induced neutrophil chemotaxis was assessed using migration assays. CU severity was assessed based on the urticaria activity score (UAS). To explore relationships between adipokines and UAS and the chronic urticaria-specific quality of life (CU-QoL) questionnaire, a structural equation model was used. Mean levels of serum LCN2, TNF-α, IL-6, and IL-10 were significantly higher in CU patients than in controls. Adiponectin levels were significantly lower in patients with CU than in controls. While serum IL-6 levels were significantly higher in refractory CU patients, compared to responsive CU individuals, LCN2 levels were significantly lower. LCN2 inhibited fMLP-induced neutrophil migration. LCN2 showed a direct relationship with UAS (β = -0.274, p < 0.001), and UAS was found to contribute to CU-QoL (β = 0.417, p < 0.001). Our results highlighted an imbalance in pro- and anti-inflammatory adipokines in CU patients. We suggest that LCN2 could be a differential marker for disease activity and the clinical responses to antihistamine treatment in CU patients. Modulation of systemic inflammation may be a therapeutic strategy for treating severe, refractory CU. © 2016 S. Karger AG, Basel.

  20. Omentin - a new adipokine with many roles to play

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    Halabis Magdalena

    2015-09-01

    Full Text Available Adipose tissue is at a point of high interest in medical research, not only as an energy depot, but also because it secretes nearly more than 600 cytokines. These are termed‚ adipokines’. Human adipokines are involved in numerous metabolic processes, including the regulation of appetite, energy expenditure, insulin sensitivity, inflammation and cardiovascular activity. Thus, these could be clinically important as a markers of adipose tissue function and increased metabolic risk. The search for novel adipokines linking obesity to related co-morbidities has become a major topic in obesity research. In such work, there is an increasing need to define their function, their molecular targets and their potential clinical relevance as biomarkers or in the treatment of obesity and other metabolic diseases.

  1. [Adipokines: adiponectin, leptin, resistin and coronary heart disease risk].

    Science.gov (United States)

    Kopff, Barbara; Jegier, Anna

    2005-01-01

    Visceral obesity is among the known risk factors of atherosclerotic cardiovascular diseases. As long as adipose tissue was considered only an inert store of excess energy, accumulated in triglycerides, explanation of the mechanisms causing increased cardiovascular risk in obesity was difficult. Finding that the adipose tissue is an active endocrine organ and that the adipokines secreted in it influence several metabolic processes, allowed better understanding of this correlation. Several disturbances in secretion, function and balance of adipokines occur in the course of obesity. Changes of adiponectin, leptin and resistin concentrations are among the reasons of accelerated atherosclerosis occurring in the visceral adiposity. Adiponectin concentrations are decreased in visceral adiposity. Adiponectin is adipokine possessing antiatherogenic properties. It's effects exerted though the specific receptors in skeletal muscles and liver include decreased insulin resistance and improved plasma lipid profile. Acting directly in the vessel wall adiponectin prevents development of atheromatic lesions by inhibiting production of adhesive molecules and formation of foam cells. It has been found that decreased adiponectin concentrations are connected not only with increased coronary risk but also with progression of atherosclerosis in coronary vessels. Moreover it was found that adiponectin plasma concentration is significantly decreased in acute coronary incidences. Leptin regulates energy metabolism and balance. The concentrations of this adipokine are increased in obesity and correlate with insulin resistance. Hiperleptinemia has been also recognized as cardiovascular diseases risk factor. Resistin is considered to be a substance increasing insulin resistance, however the exact mechanisms are not known. Resistin plasma concentrations are increased in obese subjects and correlate with the inflammatory state that underlies the initiation and progression of atherosclerotic

  2. Adipokine hormones and hand osteoarthritis: radiographic severity and pain.

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    Mei Massengale

    Full Text Available INTRODUCTION: Obesity's association with hand osteoarthritis cannot be fully explained by mechanical loading. We examined the relationship between adipokines and radiographic hand osteoarthritis severity and pain. METHODS: In a pilot study of 44 hand osteoarthritis patients (39 women and 5 men, serum adipokine concentrations and hand x-ray Kallman-scores were analyzed using linear regression models. Secondary analyses examined correlates of hand pain. RESULTS: The cohort had a mean age of 63.5 years for women and 72.6 for men; mean (standard deviation Kallman-scores were 43.3(17.4 for women and 46.2(10.8 for men. Mean body-mass-index was 30 kg/m(2 for women and men. Mean leptin concentration was 32.2 ng/ml (women and 18.5 ng/ml (men; mean adiponectin-total was 7.9 ng/ml (women and 5.3 ng/ml (men; mean resistin was 7.3 ng/ml (women and 9.4 ng/ml (men. No association was found between Kallman-scores and adipokine concentrations (R(2 = 0.00-0.04 unadjusted analysis, all p-values>0.22. Secondary analyses showed mean visual-analog-scale pain of 4.8(2.4 for women and 6.6(0.9 for men. Leptin, BMI, and history of coronary artery disease were found to be associated with visual-analog-scale scores for chronic hand pain (R(2 = 0.36 unadjusted analysis, p-values≤0.04. CONCLUSION: In this pilot study, we found that adipokine serum concentrations were not associated with hand osteoarthritis radiographic severity; the most important correlates of joint damage were age and disease duration. Leptin serum concentration, BMI, and coronary artery disease were associated with the intensity of chronic hand OA pain.

  3. [Occupational semicircular lipoatrophy associated with serum adipokine abnormalities].

    Science.gov (United States)

    Reinoso-Barbero, Luis; Díaz-Garrido, Ramón; González-Gómez, María-Fernanda; Olarrea, José; Gómez-Gallego, Félix; Bandrés, Fernando

    2015-10-21

    The aim of this study was to examine the relationship between semicircular lipoatrophy (SL), inflammation marker (high sensibility C-reactive protein [hs-CRP]), adipokines (leptine, chemerine and vaspine) and autoimmune markers (rheumatoid factor [RF], C3 and C4 complement fractions, antinuclear antibodies [ANA], HLA DR3, and DR4). Chemerine is an adipokine, but also is an immunity marker. A case-control study was performed in May 2013; 21 cases were included. The closest healthy coworker to each case was used as a control. We calculated Kruskal-Wallis nonparametric test. We found statistical significance (P<.05) between SL and raised hs-CRP, raised leptine and low chemerine. i) There seems to be an underlying inflammatory component (raised hs-CRP) in SL; ii) adipokine alteration (raised leptine and low chemerine) supports the idea that adipocytic differentiation is affected in SL, and iii) we have not found any immune marker associated with SL, except chemerine itself, which could explain a possible association between SL and immunity. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  4. Adipose tissue, obesity and adipokines: role in cancer promotion.

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    Booth, Andrea; Magnuson, Aaron; Fouts, Josephine; Foster, Michelle

    2015-01-01

    Adipose tissue is a complex organ with endocrine, metabolic and immune regulatory roles. Adipose depots have been characterized to release several adipocytokines that work locally in an autocrine and paracrine fashion or peripherally in an endocrine fashion. Adipocyte hypertrophy and excessive adipose tissue accumulation, as occurs during obesity, dysregulates the microenvironment within adipose depots and systemically alters peripheral tissue metabolism. The term "adiposopathy" is used to describe this promotion of pathogenic adipocytes and associated adipose - elated disorders. Numerous epidemiological studies confirm an association between obesity and various cancer forms. Proposed mechanisms that link obesity/adiposity to high cancer risk and mortality include, but are not limited to, obesity-related insulin resistance, hyperinsulinemia, sustained hyperglycemia, glucose intolerance, oxidative stress, inflammation and/or adipocktokine production. Several epidemiological studies have demonstrated a relationship between specific circulating adipocytokines and cancer risk. The aim of this review is to define the function, in normal weight and obesity states, of well-characterized and novel adipokines including leptin, adiponectin, apelin, visfatin, resistin, chemerin, omentin, nesfatin and vaspin and summarize the data that relates their dysfunction, whether associated or direct effects, to specific cancer outcomes. Overall research suggests most adipokines promote cancer cell progression via enhancement of cell proliferation and migration, inflammation and anti-apoptosis pathways, which subsequently can prompt cancer metastasis. Further research and longitudinal studies are needed to define the specific independent and additive roles of adipokines in cancer progression and reoccurrence.

  5. Adipokines as metabolic modulators of ovarian functions in livestock: A mini-review

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    Smruti Ranjan Mishra

    2016-09-01

    Full Text Available Adipose tissue is the principal fat storing tissue which secretes various molecules known as adipokines. The major adipokines secreted from adipose tissue are leptin, adiponectin, visfatin, resistin, chemerin and apelin. Adipokines are regarded as the and ldquo;marker of body metabolic status'' which maintains the body energy homeostasis. An adequate energy level is essential for the onset of puberty and ovarian functions. Adipokines act as energy sensor and signal the body energy level to hypothalamic neurons to regulate many physiological activities including ovarian functions such as onset of puberty, estrus behavior, follicular development and ovulation followed by corpus luteum (CL formation and function in livestock. However, adipose tissue dysfunctions limit adipokines secretion leading to an imbalance in body energy level which ultimately affects the reproduction in livestock. This mini-review highlights the modulatory roles of various adipokines in ovarian functions of livestock. [J Adv Vet Anim Res 2016; 3(3.000: 206-213

  6. Identification of adipokine clusters related to parameters of fat mass, insulin sensitivity and inflammation.

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    Gesine Flehmig

    Full Text Available In obesity, elevated fat mass and ectopic fat accumulation are associated with changes in adipokine secretion, which may link obesity to inflammation and the development of insulin resistance. However, relationships among individual adipokines and between adipokines and parameters of obesity, glucose metabolism or inflammation are largely unknown. Serum concentrations of 20 adipokines were measured in 141 Caucasian obese men (n = 67 and women (n = 74 with a wide range of body weight, glycemia and insulin sensitivity. Unbiased, distance-based hierarchical cluster analyses were performed to recognize patterns among adipokines and their relationship with parameters of obesity, glucose metabolism, insulin sensitivity and inflammation. We identified two major adipokine clusters related to either (1 body fat mass and inflammation (leptin, ANGPTL3, DLL1, chemerin, Nampt, resistin or insulin sensitivity/hyperglycemia, and lipid metabolism (vaspin, clusterin, glypican 4, progranulin, ANGPTL6, GPX3, RBP4, DLK1, SFRP5, BMP7, adiponectin, CTRP3 and 5, omentin. In addition, we found distinct adipokine clusters in subgroups of patients with or without type 2 diabetes (T2D. Logistic regression analyses revealed ANGPTL6, DLK1, Nampt and progranulin as strongest adipokine correlates of T2D in obese individuals. The panel of 20 adipokines predicted T2D compared to a combination of HbA1c, HOMA-IR and fasting plasma glucose with lower sensitivity (78% versus 91% and specificity (76% versus 94%. Therefore, adipokine patterns may currently not be clinically useful for the diagnosis of metabolic diseases. Whether adipokine patterns are relevant for the predictive assessment of intervention outcomes needs to be further investigated.

  7. Adipokines (adiponectin and plasminogen activator inhhibitor-1 in metabolic syndrome

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    M K Garg

    2012-01-01

    Full Text Available Background: The clustering of cardiovascular risk factors is termed the metabolic syndrome (MS, which strongly predicts the risk of diabetes and cardiovascular disease (CVD. Adipokines may contribute to the development of obesity and insulin resistance and may be a causal link between MS, diabetes and CVD. Hence, we studied the adipokines - adiponectin and plasminogen activator inhibitor-1 (PAI-1 - in subjects with MS. Materials and Methods: We studied 50 subjects with MS diagnosed by International Diabetes Federation (IDF criteria and 24 healthy age- and sex-matched controls. Clinical evaluation included anthropometry, body fat analysis by bioimpedance, highly sensitive C-reactive protein, insulin, adiponectin, and PAI-1 measurement. Results: Subjects with MS had lower adiponectin (4.01 ± 2.24 vs. 8.7 ± 1.77 μg/ml; P < 0.0001 and higher PAI-1 (53.85 ± 16.45 vs. 17.35 ± 4.45 ng/ml; P < 0.0001 levels than controls. Both were related with the number of metabolic abnormalities. Adiponectin was negatively and PAI-1 was positively associated with body mass index, waist hip ratio (WHR, body fat mass, percent body fat, and all the parameters of MS, except HDL where the pattern reversed. WHR and triglycerides were independent predictors of adipokines in multiple regression analysis. Receiver operating characteristic curve analysis showed that adiponectin (6.7 μg/ml and PAI-1 (25.0 ng/ml levels predicted the MS with high sensitivity, specificity and accuracy in Indian population. Conclusions: Subjects with MS have lower adiponectin and higher PAI-1 levels compared to healthy controls. Lifestyle measures have been shown to improve the various components of MS, and hence there is an urgent need for public health measures to prevent the ongoing epidemic of diabetes and CVD.

  8. Circulating Adipokines and Inflammatory Markers and Postmenopausal Breast Cancer Risk

    Science.gov (United States)

    Wang, Tao; Cushman, Mary; Xue, Xiaonan; Wassertheil-Smoller, Sylvia; Strickler, Howard D.; Rohan, Thomas E.; Manson, JoAnn E.; McTiernan, Anne; Kaplan, Robert C.; Scherer, Philipp E.; Chlebowski, Rowan T.; Snetselaar, Linda; Wang, Dan; Ho, Gloria Y. F.

    2015-01-01

    Background: Adipokines and inflammation may provide a mechanistic link between obesity and postmenopausal breast cancer, yet epidemiologic data on their associations with breast cancer risk are limited. Methods: In a case-cohort analysis nested within the Women’s Health Initiative Observational Study, a prospective cohort of postmenopausal women, baseline plasma samples from 875 incident breast cancer case patients and 839 subcohort participants were tested for levels of seven adipokines, namely leptin, adiponectin, resistin, interleukin-6, tumor necrosis factor-α, hepatocyte growth factor, and plasminogen activator inhibitor-1, and for C-reactive protein (CRP), an inflammatory marker. Data were analyzed by multivariable Cox modeling that included established breast cancer risk factors and previously measured estradiol and insulin levels. All statistical tests were two-sided. Results: The association between plasma CRP levels and breast cancer risk was dependent on hormone therapy (HT) use at baseline (P interaction = .003). In a model that controlled for multiple breast cancer risk factors including body mass index (BMI), estradiol, and insulin, CRP level was positively associated with breast cancer risk among HT nonusers (hazard ratio for high vs low CRP levels = 1.67, 95% confidence interval = 1.04 to 2.68, P trend = .029). None of the other adipokines were statistically significantly associated with breast cancer risk. Following inclusion of CRP, insulin, and estradiol in a multivariable model, the association of BMI with breast cancer was attenuated by 115%. Conclusion: These data indicate that CRP is a risk factor for postmenopausal breast cancer among HT nonusers. Inflammatory mediators, together with insulin and estrogen, may play a role in the obesity–breast cancer relation. PMID:26185195

  9. Adiponectin--a key adipokine in the metabolic syndrome.

    Science.gov (United States)

    Whitehead, J P; Richards, A A; Hickman, I J; Macdonald, G A; Prins, J B

    2006-05-01

    Adiponectin is a recently described adipokine that has been recognized as a key regulator of insulin sensitivity and tissue inflammation. It is produced by adipose tissue (white and brown) and circulates in the blood at very high concentrations. It has direct actions in liver, skeletal muscle and the vasculature, with prominent roles to improve hepatic insulin sensitivity, increase fuel oxidation [via up-regulation of adenosine monophosphate-activated protein kinase (AMPK) activity] and decrease vascular inflammation. Adiponectin exists in the circulation as varying molecular weight forms, produced by multimerization. Recent data indicate that the high-molecular weight (HMW) complexes have the predominant action in the liver. In contrast to other adipokines, adiponectin secretion and circulating levels are inversely proportional to body fat content. Levels are further reduced in subjects with diabetes and coronary artery disease. Adiponectin antagonizes many effects of tumour necrosis factor-alpha(TNF-alpha) and this, in turn, suppresses adiponectin production. Furthermore, adiponectin secretion from adipocytes is enhanced by thiazolidinediones (which also act to antagonize TNF-alpha effects). Thus, adiponectin may be the common mechanism by which TNF-alpha promotes, and the thiazolidinediones suppress, insulin resistance and inflammation. Two adiponectin receptors, termed AdipoR1 and AdipoR2, have been identified and these are ubiquitously expressed. AdipoR1 is most highly expressed in skeletal muscle and has a prominent action to activate AMPK, and hence promote lipid oxidation. AdipoR2 is most highly expressed in liver, where it enhances insulin sensitivity and reduces steatosis via activation of AMPK and increased peroxisome-proliferator-activated receptor alpha ligand activity. T-cadherin, which is expressed in endothelium and smooth muscle, has been identified as an adiponectin-binding protein with preference for HMW adiponectin multimers. Given the low

  10. Adipokines in metabolic processes regulating during obesity treatment

    Directory of Open Access Journals (Sweden)

    Larisa Sergeevna Litvinova

    2014-06-01

    Full Text Available Bariatric surgery serves as a model for the assessment of the relationship between body mass index (BMI reduction and changes in adipokine production and for exploring the endocrine function of the pancreas in patients who do not have the proximal part of the small intestine.Aim of the study was to assess the biochemical parameters and plasma levels of adipokines [adiponectin, adipsin, leptin, plasminogen activator inhibitor (PAI-1, resistin and visfatin], insulin, C-peptide, ghrelin and incretins [glucose insulinotropic polypeptide (GIP and glucagon-like peptide-1 (GLP-1] in patients with morbid obesity after surgery (gastric bypass and therapeutic correction.Materials and methodsA total of 75 patients (34 men and 41 women; age range: 24–67 years diagnosed as obese were divided into two groups according to the treatment they received. Biochemical analysis was performed to estimate carbohydrate and lipid metabolism rates and plasma levels of adipokines (adiponectin, adipsin, leptin, PAI-1, resistin, visfatin, insulin, C-peptide, ghrelin and incretins (GIP and GLP-1 using the flow fluorometry.ResultsSurgical treatment of obesity resulted in a significant decrease in BMI (from 45.67±9.87 to 32.45±5.35 kg/m2, p<0.05. Carbohydrate metabolism parameters and HOMA-IR index independent of BMI were comparable to the reference values after gastric bypass (18 months later. A direct correlation of plasma PAI-1 and leptin levels with BMI in groups with conservative (r=0.800, p=0.004 and r=0.780, p=0.010 and surgical treatment (r=-0.670, p=0.001 and r=0.760, p=0.01 was observed. Elevated leptin levels in patients with morbid obesity after gastric bypass with normal glucose and insulin levels indicated an indirect effect of leptin levels on the development of insulin resistance in metabolic syndrome.ConclusionsGastric bypass is a more efficient approach to reduce obesity. Adipokine (leptin and PAI-1 production and adipose tissue mass are directly

  11. Sports training and circulating adipokine levels 

    Directory of Open Access Journals (Sweden)

    Ryszard Plinta

    2013-01-01

    Full Text Available  The beneficial effect of regular moderate physical activity on metabolic profile is well documented. Sedentary lifestyle is a risk factor of excessive visceral fat accumulation, insulin resistance, type 2 diabetes and cardiovascular disease development. However, intensive training in athletes may be related to unfavorable changes in secretion of adipose tissue hormones and constitute a link in the pathogenesis of hormonal disturbances observed in athletes.In this paper we review the recently published data concerning the impact of sports training on circulating adipokine levels in athletes.

  12. Effect of weight loss on adipokine levels in obese patients

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    Hession M

    2011-08-01

    Full Text Available Catherine Rolland, Michelle Hession, Iain BroomCentre for Obesity Research and Epidemiology, Robert Gordon University, Aberdeen, Scotland, UKBackground: Adipose tissue functions as an endocrine organ by releasing adipokines which have important roles in the regulation of inflammation and insulin sensitivity. Although there is evidence of improvement in circulating levels of adipokines with weight loss, few studies relate such changes to specific diets. We investigated the effects of weight loss achieved by two different diets on circulating adipokine levels in obese individuals.Methods: A total of 120 obese patients (body mass index ≥ 35 kg/m2 underwent a three-month screening period on a low-fat, reduced-calorie diet. Patients failing to achieve a 5% weight loss using this approach were randomly allocated to either a low carbohydrate/high protein diet (n = 17 or to a commercial very low calorie diet (LighterLife®, n = 14 for a period of nine months.Results: At nine months, a significant weight loss was only maintained for LighterLife® (−32.3 ± 22.7 kg, P < 0.0001 but not on the low carbohydrate/high protein diet. Changes in adiponectin (15.8 ± 17.1 ng/mL versus −0.8 ± 6.2 ng/mL, P = 0.003 and leptin (−17.6 ± 24.3 ng/mL versus −3.0 ± 9.2 ng/mL, P = 0.049 at nine months were significantly greater for LighterLife® than for the low carbohydrate/high protein diet, which may reflect greater weight loss and decrease in fat mass. Changes in tumor necrosis factor-alpha, interleukin-6, and plasminogen activator inhibitor type 1 did not differ significantly between the dietary interventions at nine months.Conclusion: A significant weight loss of 23.8% from baseline weight was observed using a very low calorie diet and resulted in significant improvements in circulating levels of leptin, plasminogen activator inhibitor type 1, and adiponectin, which are likely to be due to weight loss and not macronutrient intake.Keywords: weight loss

  13. Effects of high-fat diets composed of different oils on adipokine production in mice

    Science.gov (United States)

    Dysregulation of adipokines is a hallmark of obesity. Polyunsaturated (n3) fatty acids in fish oil are shown to exert anti-inflammatory effects on adipose tissue mitigating the dysregulation of adipokines. In this study, we compared high-fat diets composed of different dietary oils with various le...

  14. Maternal bisphenol A alters fetal endocrine system: Thyroid adipokine dysfunction.

    Science.gov (United States)

    Ahmed, R G

    2016-09-01

    Because bisphenol A (BPA) has been detected in animals, the aim of this study was to investigate the possible effects of maternal BPA exposure on the fetal endocrine system (thyroid-adipokine axis). BPA (20 or 40 μg/kg body weight) was orally administered to pregnant rats from gestation day (GD) 1-20. In both treated groups, the dams and their fetuses had lower serum thyroxine (T4) and triiodothyronine (T3) levels, and higher thyrotropin (TSH) level than control dams and fetuses at GD 20. Some histopathological changes in fetal thyroid glands were observed in both maternal BPA groups at embryonic day (ED) 20, including fibroblast proliferation, hyperplasia, luminal obliteration, oedema, and degeneration. These disorders resulted in the suppression of fetal serum growth hormone (GH), insulin growth factor-1 (IGF1) and adiponectin (ADP) levels, and the elevation of fetal serum leptin, insulin and tumor necrosis factor-alpha (TNFα) levels in both treated groups with respect to control. The depraved effects of both treated groups were associated with reduced maternal and fetal body weight compared to the control group. These alterations were dose dependent. Thus, BPA might penetrate the placental barrier and perturb the fetal thyroid adipokine axis to influence fat metabolism and the endocrine system.

  15. Expression of adipokines in osteoarthritis osteophytes and their effect on osteoblasts.

    Science.gov (United States)

    Junker, Susann; Frommer, Klaus W; Krumbholz, Grit; Tsiklauri, Lali; Gerstberger, Rüdiger; Rehart, Stefan; Steinmeyer, Jürgen; Rickert, Markus; Wenisch, Sabine; Schett, Georg; Müller-Ladner, Ulf; Neumann, Elena

    2017-10-01

    Osteophyte formation in osteoarthritis (OA) is mediated by increased osteoblast activity, which is -in turn- regulated by the Wnt signaling pathway. Obesity is regarded a risk factor in OA, yet little is known about the interaction between adipose tissue-derived factors, the adipokines, and bone formation, although adipokines are associated with the pathogenesis of OA. Therefore, the effect of adipokines on bone and cartilage forming cells and osteophyte development was analyzed. Human OA osteophytes were histologically characterized and adipokine expression was evaluated by immunohistochemistry. Osteoblasts and chondrocytes were isolated from OA tissue and stimulated with adiponectin, resistin, or visfatin. Cytokine and osteoblast/chondrocyte markers were quantified and activation of Wnt and p38 MAPK signaling was analyzed. Adiponectin, resistin, and visfatin were expressed in OA osteophytes by various articular cell types. Stimulation of OA osteoblasts with adiponectin and of OA chondrocytes with visfatin led to an increased release of proinflammatory mediators but not to osteoblast differentiation or activation. Additionally, visfatin increased matrix degrading factors in chondrocytes. Wnt signaling was not altered by adipokines, but adiponectin induced p38 MAPK signaling in osteoblasts. Adipokines are present in OA osteophytes, and adiponectin and visfatin increase the release of proinflammatory mediators by osteoblasts and chondrocytes. The effects of adiponectin were mediated by p38 MAPK but not Wnt signaling in osteoblasts. Therefore, the results support the idea that adipokines do not directly influence osteophyte development but the proinflammatory conditions in OA. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Metabolic Syndrome, Chronic Kidney, and Cardiovascular Diseases: Role of Adipokines

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    Manfredi Tesauro

    2011-01-01

    Full Text Available Obesity is a chronic disease, whose incidence is alarmingly growing. It is associated with metabolic abnormalities and cardiovascular complications. These complications are clustered in the metabolic syndrome (MetS leading to high cardiovascular morbidity and mortality. Obesity predisposes to diabetic nephropathy, hypertensive nephrosclerosis, and focal and segmental glomerular sclerosis and represents an independent risk factor for the development and progression of chronic kidney disease (CKD. Albuminuria is a major risk factor for cardiovascular diseases (CVDs. Microalbuminuria has been described as early manifestation of MetS-associated kidney damage and diabetic nephropathy. Obesity and MetS affect renal physiology and metabolism through mechanisms which include altered levels of adipokines such as leptin and adiponectin, oxidative stress, and inflammation. Secretory products of adipose tissue also deeply and negatively influence endothelial function. A better understanding of these interactions will help in designing more effective treatments aimed to protect both renal and cardiovascular systems.

  17. Circulating adipokines data associated with insulin secretagogue use in breast cancer patients

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    Zachary A.P. Wintrob

    2017-02-01

    Full Text Available Oral drugs stimulating endogenous insulin production (insulin secretagogues may have detrimental effects on breast cancer outcomes. The data presented shows the relationship between pre-existing insulin secretagogues use, adipokine profiles at the time of breast cancer (BC diagnosis and subsequent cancer outcomes in women diagnosed with BC and type 2 diabetes mellitus (T2DM. The Pearson correlation analysis evaluating the relationship between adipokines stratified by T2DM pharmacotherapy and controls is also provided. This information is the extension of the data presented and discussed in “Insulin use, adipokine profiles and breast cancer prognosis” (Wintrob et al., in press [1].

  18. Adipokines in reproductive function: a link between obesity and polycystic ovary syndrome.

    Science.gov (United States)

    Chen, Xinwang; Jia, Xiao; Qiao, Jie; Guan, Youfei; Kang, Jihong

    2013-04-01

    Polycystic ovary syndrome (PCOS) is the most common endocrinopathy associated with infertility and metabolic disorder in women of reproductive age. Dysfunction of adipose tissue has been implicated in the pathophysiology of PCOS. Increasing evidence shows that the dysregulated expression of adipokines, the secreted products of adipose tissue, plays an important role in the pathology of PCOS. Here, we review the role of several identified adipokines that may act as a link between obesity and PCOS. PCOS also reciprocally influences the profile of adipokines. Insight into the underlying mechanisms will help better understand the pathology of PCOS and identify new therapeutic targets of this syndrome.

  19. Beyond Fat Mass: Exploring the Role of Adipokines in Rheumatic Diseases

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    Morena Scotece

    2011-01-01

    Full Text Available The cloning of leptin in 1994 by Zhang et al. introduced a novel concept about white adipose tissue (WAT as a very dynamic organ that releases a plethora of immune and inflammatory mediators, such as adipokines and cytokines, which are involved in multiple diseases. Actually, adipokines exert potent modulatory actions on target tissues involved in rheumatic diseases including cartilage, synovial, bone and immune cells. The goal of this paper is to elucidate the recent findings concerning the involvement of adipokines in rheumatic diseases, such as rheumatoid arthritis (RA, osteoarthritis (OA, and systemic lupus erythematosus (SLE.

  20. Adipokines and Osteoarthritis: Novel Molecules Involved in the Pathogenesis and Progression of Disease

    Directory of Open Access Journals (Sweden)

    Javier Conde

    2011-01-01

    Full Text Available Obesity has been considered a risk factor for osteoarthritis and it is usually accepted that obesity contributes to the development and progression of osteoarthritis by increasing mechanical load of the joints. Nevertheless, recent advances in the physiology of white adipose tissue evidenced that fat cells produce a plethora of factors, called adipokines, which have a critical role in the development of ostearthritis, besides to mechanical effects. In this paper, we review the role of adipokines and highlight the cellular and molecular mechanisms at play in osteoarthritis elicited by adipokines. We also emphasize how defining the role of adipokines has broadned our understanding of the diversity of factors involved in the genesis and progression of osteoarthritis in the hope of modifying it to prevent and treat diseases.

  1. Exercise Training Attenuates the Dysregulated Expression of Adipokines and Oxidative Stress in White Adipose Tissue

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    Takuya Sakurai

    2017-01-01

    Full Text Available Obesity-induced inflammatory changes in white adipose tissue (WAT, which caused dysregulated expression of inflammation-related adipokines involving tumor necrosis factor-α and monocyte chemoattractant protein-1, contribute to the development of insulin resistance. Moreover, current literature reports state that WAT generates reactive oxygen species (ROS, and the enhanced production of ROS in obese WAT has been closely associated with the dysregulated expression of adipokines in WAT. Therefore, the reduction in excess WAT and oxidative stress that results from obesity is thought to be one of the important strategies in preventing and improving lifestyle-related diseases. Exercise training (TR not only brings about a decrease in WAT mass but also attenuates obesity-induced dysregulated expression of the adipokines in WAT. Furthermore, some reports indicate that TR affects the generation of oxidative stress in WAT. This review outlines the impact of TR on the expression of inflammation-related adipokines and oxidative stress in WAT.

  2. Insulin resistance, adipokine profile and hepatic expression of SOCS-3 gene in chronic hepatitis C

    OpenAIRE

    Wójcik, Kamila; Jabłonowska, Elżbieta; Omulecka, Aleksandra; Piekarska, Anna

    2014-01-01

    AIM: To analyze adipokine concentrations, insulin resistance and hepatic expression of suppressor of cytokine signaling 3 (SOCS-3) in patients with chronic hepatitis C genotype 1 with normal body weight, glucose and lipid profile.

  3. Identification and validation of novel adipokines released from primary human adipocytes.

    Science.gov (United States)

    Lehr, Stefan; Hartwig, Sonja; Lamers, Daniela; Famulla, Susanne; Müller, Stefan; Hanisch, Franz-Georg; Cuvelier, Claude; Ruige, Johannes; Eckardt, Kristin; Ouwens, D Margriet; Sell, Henrike; Eckel, Juergen

    2012-01-01

    Adipose tissue is a major endocrine organ, releasing signaling and mediator proteins, termed adipokines, via which adipose tissue communicates with other organs. Expansion of adipose tissue in obesity alters adipokine secretion, which may contribute to the development of metabolic diseases. Although recent profiling studies have identified numerous adipokines, the amount of overlap from these studies indicates that the adipokinome is still incompletely characterized. Therefore, we conducted a complementary protein profiling on concentrated conditioned medium derived from primary human adipocytes. SDS-PAGE/liquid chromatography-electrospray ionization tandem MS and two-dimensional SDS-PAGE/matrix-assisted laser desorption ionization/time of flight MS identified 347 proteins, 263 of which were predicted to be secreted. Fourty-four proteins were identified as novel adipokines. Furthermore, we validated the regulation and release of selected adipokines in primary human adipocytes and in serum and adipose tissue biopsies from morbidly obese patients and normal-weight controls. Validation experiments conducted for complement factor H, αB-crystallin, cartilage intermediate-layer protein, and heme oxygenase-1 show that the release and expression of these factors in adipocytes is regulated by differentiation and stimuli, which affect insulin sensitivity, as well as by obesity. Heme oxygenase-1 especially reveals to be a novel adipokine of interest. In vivo, circulating levels and adipose tissue expression of heme oxygenase-1 are significantly increased in obese subjects compared with lean controls. Collectively, our profiling study of the human adipokinome expands the list of adipokines and further highlights the pivotal role of adipokines in the regulation of multiple biological processes within adipose tissue and their potential dysregulation in obesity.

  4. The Action of D-Dopachrome Tautomerase as an Adipokine in Adipocyte Lipid Metabolism

    OpenAIRE

    2012-01-01

    Adipose tissue is a critical exchange center for complex energy transactions involving triacylglycerol storage and release. It also has an active endocrine role, releasing various adipose-derived cytokines (adipokines) that participate in complex pathways to maintain metabolic and vascular health. Here, we found D-dopachrome tautomerase (DDT) as an adipokine secreted from human adipocytes by a proteomic approach. DDT mRNA levels in human adipocytes were negatively correlated with obesity-rela...

  5. Adiponectin and Intelectin-1: Important Adipokine Players in Obesity-Related Colorectal Carcinogenesis

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    Keisuke Kawashima

    2017-04-01

    Full Text Available Overweight is believed to be associated with colorectal cancer risk. Adipose tissue is loose connective tissue composed of adipocytes. It is now recognized as a major endocrine organ, secreting humoral factors collectively called adipokines. Aberrant hormonal systems consisting of modulated adipokines and their receptors are thought to play a role in colorectal carcinogenesis and cancer progression in obese conditions. However, it is still unclear whether and how each adipokine relates to colorectal carcinogenesis. Notably, a couple of molecules that were initially proposed to be obesity-related adipokines were disqualified by subsequent studies. The adipokines, adiponectin, and intelectin-1 (also known as omentin-1, whose levels are decreased in obesity, act as tumor suppressor factors in various cancers. Numerous studies have demonstrated a link between the insufficient expression and function of adiponectin and its receptor, T-cadherin, in colorectal carcinogenesis. Moreover, our recent study indicated that loss of TMEM207, which is critical for the proper processing of intelectin-1 in the colon mucosa, leads to insufficient intelectin-1 production, thus participating in colorectal carcinogenesis. Here, we discuss the recent understanding of the role of adipokines in colorectal carcinogenesis and subsequently describe the potent tumor suppressor roles of intelectin-1 and TMEM207 in colorectal cancer.

  6. Adiponectin and Intelectin-1: Important Adipokine Players in Obesity-Related Colorectal Carcinogenesis.

    Science.gov (United States)

    Kawashima, Keisuke; Maeda, Kenichi; Saigo, Chiemi; Kito, Yusuke; Yoshida, Kazuhiro; Takeuchi, Tamotsu

    2017-04-19

    Overweight is believed to be associated with colorectal cancer risk. Adipose tissue is loose connective tissue composed of adipocytes. It is now recognized as a major endocrine organ, secreting humoral factors collectively called adipokines. Aberrant hormonal systems consisting of modulated adipokines and their receptors are thought to play a role in colorectal carcinogenesis and cancer progression in obese conditions. However, it is still unclear whether and how each adipokine relates to colorectal carcinogenesis. Notably, a couple of molecules that were initially proposed to be obesity-related adipokines were disqualified by subsequent studies. The adipokines, adiponectin, and intelectin-1 (also known as omentin-1), whose levels are decreased in obesity, act as tumor suppressor factors in various cancers. Numerous studies have demonstrated a link between the insufficient expression and function of adiponectin and its receptor, T-cadherin, in colorectal carcinogenesis. Moreover, our recent study indicated that loss of TMEM207, which is critical for the proper processing of intelectin-1 in the colon mucosa, leads to insufficient intelectin-1 production, thus participating in colorectal carcinogenesis. Here, we discuss the recent understanding of the role of adipokines in colorectal carcinogenesis and subsequently describe the potent tumor suppressor roles of intelectin-1 and TMEM207 in colorectal cancer.

  7. [Novel adipokines: their potential role in the pathogenesis of obesity and metabolic disorders].

    Science.gov (United States)

    Korek, Emilia; Krauss, Hanna

    2015-01-02

    Since identification in 1994 of leptin, a hormone produced by adipocytes, adipose tissue has become the subject of intensive research. These studies contributed to the discovery that adipocytes have the ability to synthesize and secrete biologically active substances called "adipokines". Adipokines include a variety of cytokines, peptide hormones and enzymes that play a role in a wide variety of biological functions. For example, they are involved in the regulation of appetite, energy homeostasis, vascular hemostasis, blood pressure, inflammatory and immune processes and play a role in the metabolism of carbohydrates and fats. In obese patients, the secretion of adipokines is frequently abnormal. These changes may predispose to the development of insulin resistance, hypertension and inflammation. Therefore, adipokines are the subject of ongoing clinical trials. The family of adipokines is increasing by the newly discovered peptides. This paper presents the current state of knowledge about retinol binding protein 4 (RBP-4), fasting-induced adipose factor/angiopoietin-like protein 4 (FIAF/ANGPTL4), fibroblast growth factor-21 (FGF21), dipeptidyl peptidase-4 (DPP-4), irisin and their potential role in the pathogenesis of metabolic disorders associated with obesity. The knowledge of the role of newly discovered adipokines may help in the treatment of metabolic syndrome.

  8. Association of dietary patterns with serum adipokines among Japanese: a cross-sectional study.

    Science.gov (United States)

    Kashino, Ikuko; Nanri, Akiko; Kurotani, Kayo; Akter, Shamima; Yasuda, Kazuki; Sato, Masao; Hayabuchi, Hitomi; Mizoue, Tetsuya

    2015-06-11

    Diet may influence disease risk by modulating adipokines. Although some foods and nutrients have been linked to circulating adipokine levels, little is known about the role of dietary patterns on adipokines. We investigated the association between major dietary patterns and circulating levels of adiponectin, leptin, resistin, visfatin, and plasminogen activator inhibitor-1 (PAI-1) in a working population. The subjects were 509 employees (296 men and 213 women), aged 20 to 65 years, of two municipal offices. Serum adipokines were measured using a Luminex suspension bead-based multiplexed array. Dietary patterns were derived by using principal component analysis of the consumption of 52 food and beverage items, which were ascertained by a validated diet history questionnaire. Multiple regression analysis was performed to assess the association between dietary pattern scores and adipokine concentrations, with adjustment for potential confounders. Three major dietary patterns were extracted: a Japanese, a Westernized breakfast, and a meat food patterns. Of these, we found significant, inverse associations of the Westernized breakfast pattern, which was characterized by higher intake of confectioneries, bread, and milk and yogurt but lower intake of alcoholic beverages and rice, with serum leptin and PAI-1 concentrations in a fully adjusted model (P for trend = 0.04 for both leptin and PAI-1). The other adipokines were not significantly associated with any dietary pattern. The Westernized breakfast dietary pattern may be associated with lower circulating levels of leptin and PAI-1.

  9. The usefulness of circulating adipokine levels for the assessment of obesity-related health problems

    Directory of Open Access Journals (Sweden)

    Hidekuni Inadera

    2008-01-01

    Full Text Available Because the prevalence of obesity has increased dramatically in recent years, one of the key targets of public health is obesity and its associated pathological conditions. Obesity occurs as a result of white adipose tissue enlargement, caused by adipocyte hyperplasia and/or hypertrophy. Recently, endocrine aspects of adipose tissue have become an active research area and these adipose tissue-derived factors are referred to as adipokines. These adipokines interact with a range of processes in many different organ systems and influence a various systemic phenomena. Therefore, dysregulated production of adipokines has been found to participate in the development of metabolic and vascular diseases related to obesity. The obese state is also known to be associated with increased local and systemic inflammation. Adipokines influence not only systemic insulin resistance and have pathophysiological roles in the metabolic syndrome and cardiovascular disease, but also contribute toward an increase in local and systemic inflammation. Thus, circulating levels of adipokines can be used as high-throughput biomarkers to assess the obesity-related health problems, including low grade inflammation. This review focuses on the usefulness of measuring circulating adipokine levels for the assessment of obesity-related health problems.

  10. Adipokines in the HIV/HAART-associated lipodystrophy syndrome.

    Science.gov (United States)

    Paruthi, Jason; Gill, Natasha; Mantzoros, Christos S

    2013-09-01

    The use of highly active antiretroviral therapy (HAART) in the treatment of human immunodeficiency virus has dramatically altered both the landscape of this disease and the prognosis for those affected. With more patients now receiving HAART, adverse effects such as lipodystrophy and metabolic syndrome have emerged. In HIV/HAART-associated lipodystrophy syndrome (HALS), patients demonstrate fat maldistribution with dyslipidemia, insulin resistance, and other metabolic complications. Recent studies have contributed to the elucidation of the pathophysiological abnormalities seen in this syndrome and have provided guidance for the study and use of potential treatments for these patients, but widely accepted guidelines have not yet been established. Two adipokines, leptin and adiponectin, are decreased in patients with HALS and lipoatrophy or lipodystrophy. Further, recent proof-of-concept clinical trials have proven the efficacy of leptin replacement and medications that increase circulating adiponectin levels in improving the metabolic profile of HALS patients. This review article highlights recent evidence on leptin replacement and compares leptin's efficacy to that of other treatments, including metformin and thiazolidinediones, on metabolic abnormalities such as impaired insulin-glucose homeostasis associated with lipodystrophy in patients receiving HAART. It is hoped that forthcoming large phase III clinical trials will allow the addition of leptin to our therapeutic armamentarium for use in patients suffering from this disease state.

  11. Multiple Sclerosis and Obesity: Possible Roles of Adipokines

    Science.gov (United States)

    Guerrero-García, José de Jesús; Márquez-Aguirre, Ana Laura

    2016-01-01

    Multiple Sclerosis (MS) is an autoimmune disorder of the Central Nervous System that has been associated with several environmental factors, such as diet and obesity. The possible link between MS and obesity has become more interesting in recent years since the discovery of the remarkable properties of adipose tissue. Once MS is initiated, obesity can contribute to increased disease severity by negatively influencing disease progress and treatment response, but, also, obesity in early life is highly relevant as a susceptibility factor and causally related risk for late MS development. The aim of this review was to discuss recent evidence about the link between obesity, as a chronic inflammatory state, and the pathogenesis of MS as a chronic autoimmune and inflammatory disease. First, we describe the main cells involved in MS pathogenesis, both from neural tissue and from the immune system, and including a new participant, the adipocyte, focusing on their roles in MS. Second, we concentrate on the role of several adipokines that are able to participate in the mediation of the immune response in MS and on the possible cross talk between the latter. Finally, we explore recent therapy that involves the transplantation of adipocyte precursor cells for the treatment of MS. PMID:27721574

  12. Multiple Sclerosis and Obesity: Possible Roles of Adipokines

    Directory of Open Access Journals (Sweden)

    José de Jesús Guerrero-García

    2016-01-01

    Full Text Available Multiple Sclerosis (MS is an autoimmune disorder of the Central Nervous System that has been associated with several environmental factors, such as diet and obesity. The possible link between MS and obesity has become more interesting in recent years since the discovery of the remarkable properties of adipose tissue. Once MS is initiated, obesity can contribute to increased disease severity by negatively influencing disease progress and treatment response, but, also, obesity in early life is highly relevant as a susceptibility factor and causally related risk for late MS development. The aim of this review was to discuss recent evidence about the link between obesity, as a chronic inflammatory state, and the pathogenesis of MS as a chronic autoimmune and inflammatory disease. First, we describe the main cells involved in MS pathogenesis, both from neural tissue and from the immune system, and including a new participant, the adipocyte, focusing on their roles in MS. Second, we concentrate on the role of several adipokines that are able to participate in the mediation of the immune response in MS and on the possible cross talk between the latter. Finally, we explore recent therapy that involves the transplantation of adipocyte precursor cells for the treatment of MS.

  13. The Role of Adipokines in Understanding the Associations between Obesity and Depression

    Directory of Open Access Journals (Sweden)

    Valerie H. Taylor

    2010-01-01

    Full Text Available Objective. Two major causes of disability, major depression and obesity, share overlapping psychosocial and pathophysiological etiologies. Studies are now focused on biological mechanisms linking the two illnesses, and there is interest in the role that adipokines may have in mediating the association between obesity and depression. We reviewed the literature to look at what is currently known about this association, focusing on the adipokines leptin, adiponectin, and resistin. Methods. A MEDLINE search, citing articles from 1966 onward, supplemented by a review of bibliographies, was conducted to identify relevant studies. Results. This paper identified plausible pathways underlying a link between adipokines and depression. Only a few studies have yet been conducted specifically examining these biomarkers in patients with depression, but the results are intriguing. Conclusion. This paper is one of the first to examine the association between adipokines and depression. It provides an overview of the physiological role of adipokines and summarizes the data suggesting that they may be dysregulated in major depression. This area of research may become increasingly important as new treatment strategies are developed.

  14. Identification of novel adipokines in the joint. Differential expression in healthy and osteoarthritis tissues.

    Directory of Open Access Journals (Sweden)

    Javier Conde

    Full Text Available Emerging data suggest that several metabolic factors, released mainly by white adipose tissue (WAT and joint tissues, and collectively named adipokines, might have a role in the pathophysiology of OA. Recently, novel adipokines such as SERPINE2, WISP2, GPNMB and ITIH5 have been identified in WAT. The main goal of this study was to analyse the expression of these novel adipokines in synovium, infrapatellar fat pad and chondrocytes and to compare the expression of these molecules in healthy and OA tissues.Synovial tissues, infrapatellar fat pad and chondrocytes were obtained from 36 OA patients (age 52-85; mean BMI 28.9 who underwent total knee replacement surgery. Healthy synovial tissues and infrapatellar fat pad were obtained from 15 traumatic knee patients (age 23-53; mean BMI 23.5. mRNA and protein expression were determined by qRT-PCR and western blot analysis respectively.All the novel adipokines, matter of our study, are expressed in OA synovium, infrapatellar fat pad and chondrocytes. Moreover, we detected a differential expression of SERPINE2 and ITIH5 in OA synovial tissues as compared to healthy samples. Finally, we also observed an increased expression of WISP2 in OA infrapatellar fat pad in comparison to healthy controls.In this study we demonstrated for the first time the expression of four novel adipokines in different joint tissues and how these molecules are differentially expressed in healthy and OA joint tissues.

  15. Adipokines: Potential Therapeutic Targets for Vascular Dysfunction in Type II Diabetes Mellitus and Obesity

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    Mostafa Wanees Ahmed El husseny

    2017-01-01

    Full Text Available Adipokines are bioactive molecules that regulate several physiological functions such as energy balance, insulin sensitization, appetite regulation, inflammatory response, and vascular homeostasis. They include proinflammatory cytokines such as adipocyte fatty acid binding protein (A-FABP and anti-inflammatory cytokines such as adiponectin, as well as vasodilator and vasoconstrictor molecules. In obesity and type II diabetes mellitus (DM, insulin resistance causes impairment of the endocrine function of the perivascular adipose tissue, an imbalance in the secretion of vasoconstrictor and vasodilator molecules, and an increased production of reactive oxygen species. Recent studies have shown that targeting plasma levels of adipokines or the expression of their receptors can increase insulin sensitivity, improve vascular function, and reduce the risk of cardiovascular morbidity and mortality. Several reviews have discussed the potential of adipokines as therapeutic targets for type II DM and obesity; however, this review is the first to focus on their therapeutic potential for vascular dysfunction in type II DM and obesity.

  16. Effects of Bariatric Surgery on Adipokine-Induced Inflammation and Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Zeynep eGoktas

    2013-06-01

    Full Text Available Over a third of the US population is obese and at high risk for developing type 2 diabetes, insulin resistance and other metabolic disorders. Obesity is considered a chronic low grade inflammatory condition that is primarily attributed to expansion and inflammation of adipose tissues. Indeed, adipocytes produce and secrete numerous proinflammatory and anti-inflammatory cytokines known as adipokines. When the balance of these adipokines is shifted towards higher production of proinflammatory factors, local inflammation within adipose tissues and subsequently systemic inflammation occur. These adipokines including leptin, visfatin, resistin, apelin, vaspin, and retinol binding protein-4 can regulate inflammatory responses and contribute to the pathogenesis of diabetes. These effects are mediated by key inflammatory signaling molecules including activated serine kinases such as c-Jun N-terminal kinase (JNK and serine kinases inhibitor κB kinase (IKK and insulin signaling molecules including insulin receptor substrates, protein kinase B (PKB, also known as Akt, and nuclear factor kappa B (NF-kB. Bariatric surgery can decrease body weight and improve insulin resistance in morbidly obese subjects. However, despite reports suggesting reduced inflammation and weight-independent effects of bariatric surgery on glucose metabolism, mechanisms behind such improvements are not yet well understood. This review article focuses on some of these novel adipokines and discusses their changes after bariatric surgery and their relationship to insulin resistance, fat mass, inflammation, and glucose homeostasis.

  17. The Potential Interplay of Adipokines with Toll-Like Receptors in the Development of Hepatocellular Carcinoma

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    Shen-Nien Wang

    2011-01-01

    Full Text Available Toll-like receptors (TLRs are not only crucial to the initiation of the immune system, but also play a key role in several human inflammatory diseases. Hepatocellular carcinoma (HCC is among those human cancers, which arise from sites of chronic inflammation. Therefore, a number of studies have explored the potential contribution of TLRs to HCC occurrence, which is initiated by exposure to chronic hepatic inflammation of different etiologies (including ethanol, and chronic B and C viral infections. Recent epidemiological data have shown the association of obesity and HCC development. Given the fact that adipose tissues can produce a variety of inflammation-related adipokines, obesity has been characterized as a state of chronic inflammation. Adipokines are therefore considered as important mediators linking inflammation to several metabolic diseases, including cancers. More recently, many experts have also shown the bridging role of TLRs between inflammation and metabolism. Hopefully, to retrieve the potential interaction between TLRs and adipokines in carcinogenesis of HCC will shed a new light on the therapeutic alternative for HCC. In this paper, the authors first review the respective roles of TLRs and adipokines, discuss their mutual interaction in chronic inflammation, and finally anticipate further investigations of this interaction in HCC development.

  18. Lifestyle intervention and adipokine levels in subjects at high risk for type 2 diabetes

    NARCIS (Netherlands)

    Corpeleijn, Eva; Feskens, Edith J. M.; Jansen, Eugene H. J. M.; Mensink, Marco; Saris, Wim H. M.; Blaak, Ellen E.

    2007-01-01

    OBJECTIVE - We investigated whether circulating adipokine concentrations can be altered by lifestyle intervention according to general recommendations in subjects at risk for diabetes as well as the potential of leptin, adiponectin, and resistin as biomarkers for lifestyle-induced improvements in gl

  19. Role of adipokines in the pathogenesis of nonalcoholic fatty liver disease

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    Pallavi M

    2015-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is the hepatic manife-station of metabolic syndrome. The increased prevalence of obesity, diabetes, hypertension, hypertriglyceridaemia and hypercholesterolemia are considered to be the potential causative factors for NAFLD. NAFLD is emerging as a major clinical problem worldwide. Recently much attention has been focused in India as the prevalence of obesity and diabetes is rising. NAFLD is responsible for unexplained raise in transaminases, and an important cause of cryptogenic cirrhosis and cryptogenic hepatocellular carcinoma in India. NAFLD is a spectrum of disease ranging from simple steatosis to nonalcoholic steatohepatitis (NASH, potentially leading to fibrosis and cirrhosis. Studies have suggested that the adipokines are involved in the pathogenesis of NAFLD and its progression to NASH, through their metabolic and pro- or anti-inflammatory activity. Adipokines in particular tumor necrosis factor-α and interleukin-6 are believed to mediate the shift in pathology from steatosis to steatohepatitis. In addition, other adipokines such as adiponectin, leptin and resistin also play a crucial role in the development and progression of NAFLD through their metabolic and pro–or anti-inflammatory activity. This suggests that imbalance between pro-inflammatory and anti-inflammatory cytokines may have a role in the development of liver damage in NAFLD. Understanding the relationship between adipokines and NAFLD may play an important role in the early identification /diagnosis, treatment and also help in preventing disease progression.

  20. Adipokines in umbilical cord blood from children born large for gestational age

    DEFF Research Database (Denmark)

    Lausten-Thomsen, Ulrik; Christiansen, Michael; Hedley, Paula Louise

    2016-01-01

    of adipokines and their mutual relationship at birth in children born to non-diabetic mothers. METHODS: Adiponectin, leptin and sOB-R were measured using ELISA-based commercial kits in umbilical cord blood from 60 neonates (30 born large for gestational age [LGA] and 30 born appropriate for gestational age [AGA...

  1. The association between polycystic ovary syndrome, obesity, and the serum concentration of adipokines.

    Science.gov (United States)

    Behboudi-Gandevani, S; Ramezani Tehrani, F; Bidhendi Yarandi, R; Noroozzadeh, M; Hedayati, M; Azizi, F

    2017-08-01

    This study aimed to investigate the interactive effect of polycystic ovary syndrome (PCOS) status and obesity status on the serum levels of adipokines. In this comparative case-control cross-sectional study, 58 women with PCOS and 104 eumenorrheic non-hirsute women as the control group were recruited. They were further divided into two subgroups of overweight/obese and normal weight. The interactive effect of the PCOS status and obesity status on the circulating levels of adipokines was assessed using general linear model with the adjustment of age. A statistically significant negative interaction was reported between obesity status and PCOS status in the determination of serum adiponectin and resistin concentrations (effect size = -0.14, interaction P = 0.001, effect size = -0.15, P = 0.016). It indicated that adiponectin and resistin were significantly decreased in overweight/obese patients with PCOS compared with other subgroups. Statistically significant positive interactive effects were found between PCOS status obesity status and leptin (effect size = 0.321, interaction P = 0.036), indicating that the overweight/obese women with PCOS had the higher levels of leptin compared with the control group. Also, no interaction was reported between PCOS status and obesity status with regard to the serum levels of other adipokines. While no sufficient evidence is available with regard to the causal association between adipokines and PCOS, they may contribute to the development of PCOS and regarded as the novel biomarkers of PCOS.

  2. Changes of inflammatory factors and adipokines in patients with diabetic osteoporosis

    Institute of Scientific and Technical Information of China (English)

    Ning-Xu Li; Yan Tu; Xiao-Xia Liu; Ying Shen; Li-Hua Zhang

    2016-01-01

    Objective:This study aimed to investigate the changes of inflammatory factors and adipokines in patients with diabetic osteoporosis.Methods:A total of 142 type 2 diabetic patients were divided into osteoporosis group (OP,n=78) and non-osteoporosis group (NOP,n=64) according to the conditions of bone density. Then levels of blood lipid, inflammatory factors and adipokines were detected and compared.Results:As for blood lipids, the levels of low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) were not significantly different between the two groups (P>0.05), while the levels of total cholesterol (TC) and triglyceride (TG) in the OP group were significantly higher than those in the NOP group (P<0.05); referring to inflammatory factors, the levels of monocyte chemoattractant protein-1 (MCP-1), hyper-sensitive C-reactive protein (hs-CRP) and tumor necrosis factor-α (TNF-α) in the OP group were significantly increased compared with the NOP group (P<0.05); speaking to adipokines, the levels of visceral adipose tissue-derived serine protease inhibitor (vaspin) and adiponectin rose obviously and the level of visfatin declined apparently in the OP group compared with the NOP group (P<0.05).Conclusions:The alterations of the levels of inflammatory factors and adipokines might increase the risk of osteoporosis in patients with type 2 diabetes mellitus.

  3. Even- and odd-chain saturated fatty acids in serum phospholipids are differentially associated with adipokines

    Science.gov (United States)

    Sato, Masao; Yasuda, Kazuki; Kashima, Kentaro; Tanaka, Shoji; Hayashi, Takuya; Shirouchi, Bungo; Akter, Shamima; Kashino, Ikuko; Hayabuchi, Hitomi; Mizoue, Tetsuya

    2017-01-01

    Background Saturated fatty acids are generally thought to have detrimental effects on health. However, a recent study showed that even- and odd-chain saturated fatty acids had opposite associations with type 2 diabetes. Limited studies of Western populations examined the associations of circulating saturated fatty acids with adipokines, an important role in glucose metabolism. Objective We examined the associations of saturated fatty acids in serum phospholipids with circulating levels of adipokines among a Japanese population. Design A cross-sectional study was conducted among 484 Japanese employees (284 men and 200 women) aged 20–65 years. The serum fatty acid composition in the phospholipid fraction was measured by gas-chromatography. Serum leptin, adiponectin, plasminogen activator inhibitor-1 (PAI-1), resistin, and visfatin were measured using a Luminex suspension bead-based multiplexed array. Multiple linear regression analysis was performed to assess the association between saturated fatty acids and adipokines, with adjustment for potential confounding variables. Results Even- and odd-chain saturated fatty acids were differentially associated with adipokines. Higher levels of even-chain saturated fatty acids (14:0 myristic, 16:0 palmitic, and 18:0 stearic acids) were associated with higher levels of resistin (P for trend = 0.048) and lower levels of adiponectin (P for trend = 0.003). By contrast, odd-chain saturated fatty acids (15:0 pentadecanoic and 17:0 heptadecanoic acids) showed inverse associations with leptin and PAI-1 (P for trend = 0.048 and 0.02, respectively). Visfatin was positively associated with both even- and odd-chain saturated fatty acids. Conclusions The results suggest that even- and odd-chain saturated fatty acids are differentially associated with adipokine profile. PMID:28552966

  4. Adipokines in psoriatic arthritis patients: the correlations with osteoclast precursors and bone erosions.

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    Yu Xue

    Full Text Available Significant bone remodeling with disordered osteoclastogenesis has been implicated in the pathogenesis of psoriatic arthritis (PsA. And there is a high prevalence of the metabolic syndrome (MS in PsA patients. Adipokines, especially leptin and adiponectin, have recently been reported to be involved in the development and regulation of some autoimmune diseases. In this study, we examined the alternation of circulating osteoclastogenesis related cytokines [tumor necrosis factor-α (TNF-α, osteoprotegerin (OPG and receptor activator of nuclear factor-κB ligand (RANKL] and adipokines (leptin, adiponectin, resistin, chemerin, omentin in PsA patients, and analysed the correlations between these factors and osteoclast precursors numbers, radiographic damage scores, and disease activity index. 41 PsA patients, 20 psoriasis patients, and 24 healthy controls were recruited. Blood samples were obtained for detecting the levels of TNF-α, OPG, RANKL and the adipokines. The numbers of osteoclast precursors (OCs in peripheral blood were assessed. Radiographs of affected joints in PsA patients were scored for erosion, joint-space narrowing, osteolysis, and new bone formation. Compared with healthy controls, patients with PsA had higher TNF-α, RANKL, OCs, leptin and omentin but lower adiponectin and chemerin. Increased serum levels of TNF-α, RANKL, leptin, and omentin were positively correlated with OCs numbers. In contrast, serum adiponectin levels were decreased in PsA patients and negatively correlated with OCs numbers. TNF-α, RANKL and leptin were positively correlated with Psoriatic Arthritis Joint Activity Index (PsAJAI. Only TNF-α was positively correlated with radiographic damage scores. Our data demonstrated that systemic expression of soluble mediators of osteoclastogenesis and adipokines were disordered in PsA. Certain adipokines were elevated in the circulation of patients with PsA and might contribute to pathogenesis of arthritis. Prospective

  5. Molecular mechanisms linking adipokines to obesity-related colon cancer: focus on leptin.

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    Drew, Janice E

    2012-02-01

    Obesity is linked to increased risk of colon cancer, currently the third most common cancer. Consequently rising levels of obesity worldwide are likely to significantly impact on obesity-related colon cancers in the decades to come. Understanding the molecular mechanisms whereby obesity increases colon cancer risk is thus a focus for research to inform strategies to prevent the increasing trend in obesity-related cancers. This review will consider research on deregulation of adipokine signalling, a consequence of altered adipokine hormone secretion from excess adipose tissue, with a focus on leptin, which has been studied extensively as a potential mediator of obesity-related colon cancer. Numerous investigations using colon cell lines in vitro, in vivo studies in rodents and investigations of colon cancer patients illuminate the complexity of the interactions of leptin with colon tissues via leptin receptors expressed by the colon epithelium. Although evidence indicates a role for leptin in proliferation of colon epithelial cells in vitro, this has been contradicted by studies in rodent models. However, recent studies have indicated that leptin may influence inflammatory mediators linked with colon cancer and also promote cell growth dependent on genotype and is implicated in growth promotion of colon cancer cells. Studies in human cancer patients indicate that there may be different tumour sub-types with varying levels of leptin receptor expression, indicating the potential for leptin to induce variable responses in the different tumour types. These studies have provided insights into the complex interplay of adipokines with responsive tissues prone to obesity-related colon cancer. Deregulation of adipokine signalling via adipokine receptors located in the colon appears to be a significant factor in obesity-related colon cancer. Molecular profiling of colon tumours will be a useful tool in future strategies to characterise the influence that adipokines may have

  6. Role of Adipokines in Atherosclerosis: Interferences with Cardiovascular Complications in Rheumatic Diseases

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    Morena Scotece

    2012-01-01

    Full Text Available Patients with rheumatic diseases have an increased risk of mortality by cardiovascular events. In fact, several rheumatic diseases such as rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, and ankylosing spondylitis are associated with a higher prevalence of cardiovascular diseases (CVDs. Although traditional cardiovascular risk factors have been involved in the pathogenesis of cardiovascular diseases in rheumatic patients, these alterations do not completely explain the enhanced cardiovascular risk in this population. Obesity and its pathologic alteration of fat mass and dysfunction, due to an altered pattern of secretion of proinflammatory adipokines, could be one of the links between cardiovascular and rheumatic diseases. Indeed, the incidence of CVDs is augmented in obese individuals with rheumatic disorders. Thus, in this paper we explore in detail the relationships among adipokines, rheumatic diseases, and cardiovascular complications by giving to the reader a holistic vision and several suggestions for future perspectives and potential clinical implications.

  7. Recently Discovered Adipokines and Cardio-Metabolic Comorbidities in Childhood Obesity

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    Gloria Maria Barraco

    2014-10-01

    Full Text Available White adipose tissue (WAT asset, in terms of cell number, fat storage capacity and endocrine function, is largely determined in early stages of life and is pivotal for shaping the WAT pro-inflammatory behavior. WAT derived adipokines have been shown to play a main role in several cardio-metabolic abnormalities of obesity. This review focuses on the most recently identified adipokines, namely adipocyte-fatty acid-binding protein, chemerin, fibroblast growth factor-21, lipocalin-2, omentin-1 and vaspin; their role in the pathogenesis of obesity and associated cardio-metabolic abnormalities; and on their adaptive response to body weight change. Evidence consistently suggests a pathogenic role for A-FABP, chemerin and FGF-21. Nevertheless, large population studies are needed to verify whether they can be useful to predict the risk of cardio-metabolic abnormalities in adulthood and/or monitor the clinical response to therapeutic interventions.

  8. The control of insulin secretion by adipokines: current evidence for adipocyte-beta cell endocrine signalling in metabolic homeostasis.

    Science.gov (United States)

    Cantley, James

    2014-10-01

    Metabolic homeostasis is maintained by the coordinated action of multiple organ systems. Insulin secretion is often enhanced during obesity or insulin resistance to maintain glucose and lipid homeostasis, whereas a loss of insulin secretion is associated with type 2 diabetes. Adipocytes secrete hormones known as adipokines which act on multiple cell types to regulate metabolism. Many adipokines have been shown to influence beta cell function by enhancing or inhibiting insulin release or by influencing beta cell survival. Insulin, in turn, regulates lipolysis and promotes glucose uptake and lipid storage in adipocytes. As adipokine secretion and action is strongly influenced by obesity, this provides a potential route by which beta cell function is coordinated with adiposity, independently of alterations in blood glucose or lipid levels. In this review, I assess the evidence for the direct regulation of beta cell function by the adipokines leptin, adiponectin, extracellular nicotinamide phosphoribosyltransferase, apelin, resistin, retinol binding protein 4, fibroblast growth factor 21, nesfatin-1 and fatty acid binding protein 4. I summarise in vitro and in vivo data and discuss the influence of obesity and diabetes on circulating adipokine concentrations, along with the potential for influencing beta cell function in human physiology. Finally, I highlight future research questions that are likely to yield new insights into the exciting field of insulinotropic adipokines.

  9. Inflammation Activation Contributes to Adipokine Imbalance in Patients with Acute Coronary Syndrome.

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    Li, Rong; Chen, Lu-zhu; Zhao, Shui-ping; Huang, Xian-sheng

    2016-01-01

    Inflammation can be activated as a defensive response by the attack of acute coronary syndrome (ACS) for ischemic tissue injury. The aim of the present study was to investigate the impact of ACS-activated inflammation on adipokine imbalance and the effects of statins on the crosstalk between inflammation and adipokine imbalance during ACS. In this study, 586 subjects were categorized into: (1) control group; (2) SA (stable angina) group; and (3) ACS group. Circulating levels of hs-CRP, adiponectin and resistin were measured by ELISA. Furthermore, forty C57BL/6 mice were randomized into: sham, AMI, low-statin (atorvastatin, 2 mg/kg/day) and high-statin (atorvastatin, 20 mg/kg/day) group. After 3 weeks, AMI models were established by surgical coronary artery ligation. Circulating levels and adipose expressions of adiponectin and resistin were assessed in animals. Besides, we investigate the effects of atorvastatin on ox-LDL-induced adipokine imbalance in vitro. As a result, we found that ACS patients had higher hs-CRP and resistin levels and lower adiponectin levels. Our correlation analysis demonstrated hs-CRP concentrations were positively correlated with resistin but negatively with adiponectin levels in humans. Our animal findings indicated higher circulating hs-CRP and resistin levels and lower adiponectin levels in AMI mice. Atorvastatin pre-treatment dose-dependently decreased hs-CRP and resistin levels but increased adiponectin levels in mice. The consistent findings were observed about the adipose expressions of resistin and adiponectin in mice. In study in vitro, ox-LDL increased cellular resistin expressions and otherwise for adiponectin expressions, which dose-dependently reversed by the addition of atorvastatin. Therefore, our study indicates that the ACS attack activates inflammation leading to adipokine imbalance that can be ameliorated by anti-inflammation of atorvastatin.

  10. A prospective study of circulating adipokine levels and risk of multiple myeloma

    OpenAIRE

    Hofmann, Jonathan N.; Liao, Linda M.; Pollak, Michael N.; Wang, Ye; Pfeiffer, Ruth M.; Baris, Dalsu; Andreotti, Gabriella; Lan, Qing; Landgren, Ola; Rothman, Nathaniel; Purdue, Mark P.

    2012-01-01

    It has been hypothesized that the observed excess risk of multiple myeloma (MM) among obese persons could be the result of altered circulating levels of adipokines, polypeptide hormones with pro- and anti-inflammatory properties secreted by adipose tissue. We investigated whether circulating levels of leptin, total adiponectin, and high molecular weight adiponectin are associated with subsequent MM risk among 174 MM patients and 348 controls within the Prostate, Lung, Colorectal, and Ovarian ...

  11. Inflammation Activation Contributes to Adipokine Imbalance in Patients with Acute Coronary Syndrome.

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    Rong Li

    Full Text Available Inflammation can be activated as a defensive response by the attack of acute coronary syndrome (ACS for ischemic tissue injury. The aim of the present study was to investigate the impact of ACS-activated inflammation on adipokine imbalance and the effects of statins on the crosstalk between inflammation and adipokine imbalance during ACS. In this study, 586 subjects were categorized into: (1 control group; (2 SA (stable angina group; and (3 ACS group. Circulating levels of hs-CRP, adiponectin and resistin were measured by ELISA. Furthermore, forty C57BL/6 mice were randomized into: sham, AMI, low-statin (atorvastatin, 2 mg/kg/day and high-statin (atorvastatin, 20 mg/kg/day group. After 3 weeks, AMI models were established by surgical coronary artery ligation. Circulating levels and adipose expressions of adiponectin and resistin were assessed in animals. Besides, we investigate the effects of atorvastatin on ox-LDL-induced adipokine imbalance in vitro. As a result, we found that ACS patients had higher hs-CRP and resistin levels and lower adiponectin levels. Our correlation analysis demonstrated hs-CRP concentrations were positively correlated with resistin but negatively with adiponectin levels in humans. Our animal findings indicated higher circulating hs-CRP and resistin levels and lower adiponectin levels in AMI mice. Atorvastatin pre-treatment dose-dependently decreased hs-CRP and resistin levels but increased adiponectin levels in mice. The consistent findings were observed about the adipose expressions of resistin and adiponectin in mice. In study in vitro, ox-LDL increased cellular resistin expressions and otherwise for adiponectin expressions, which dose-dependently reversed by the addition of atorvastatin. Therefore, our study indicates that the ACS attack activates inflammation leading to adipokine imbalance that can be ameliorated by anti-inflammation of atorvastatin.

  12. A murine model of obesity implicates the adipokine milieu in the pathogenesis of severe acute pancreatitis.

    Science.gov (United States)

    Zyromski, Nicholas J; Mathur, Abhishek; Pitt, Henry A; Lu, Debao; Gripe, John T; Walker, Julia J; Yancey, Kyle; Wade, Terence E; Swartz-Basile, Deborah A

    2008-09-01

    Obesity is clearly an independent risk factor for increased severity of acute pancreatitis (AP), although the mechanisms underlying this association are unknown. Adipokines (including leptin and adiponectin) are pleiotropic molecules produced by adipocytes that are important regulators of the inflammatory response. We hypothesized that the altered adipokine milieu observed in obesity contributes to the increased severity of pancreatitis. Lean (C57BL/6J), obese leptin-deficient (LepOb), and obese hyperleptinemic (LepDb) mice were subjected to AP by six hourly intraperitoneal injections of cerulein (50 microg/kg). Severity of AP was assessed by histology and by measuring pancreatic concentration of the proinflammatory cytokines IL-1beta and IL-6, the chemokine MCP-1, and the marker of neutrophil activation MPO. Both congenitally obese strains of mice developed significantly more severe AP than wild-type lean animals. Severity of AP was not solely related to adipose tissue volume: LepOb mice were heaviest; however, LepDb mice developed the most severe AP both histologically and biochemically. Circulating adiponectin concentrations inversely mirrored the severity of pancreatitis. These data demonstrate that congenitally obese mice develop more severe AP than lean animals when challenged by cerulein hyperstimulation and suggest that alteration of the adipokine milieu exacerbates the severity of AP in obesity.

  13. Differential Effect of Electroacupuncture on Inflammatory Adipokines in Two Rat Models of Obesity

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    Jacqueline J.T. Liaw

    2016-08-01

    Full Text Available Chronic inflammation is known to be associated with visceral obesity and insulin resistance which are characterized by altered levels of production of pro- and anti-inflammatory adipokines. The dysregulation of the production of inflammatory adipokines and their functions in obese individuals leads to a state of chronic low-grade inflammation and may promote obesity-linked metabolic disorders and cardiovascular diseases such as insulin resistance, metabolic syndrome, and atherosclerosis. Electroacupuncture (EA was tested to see if there was a difference in its effect on pro- and anti-inflammatory adipokine levels in the blood serum and the white adipose tissue of obese Zucker fatty rats and high-fat diet-induced obese Long Evans rats. In the two rat models of obesity, on Day 12 of treatment, repeated applications of EA were seen to have had a significant differential effect for serum tumor necrosis factor-α, adiponectin, the adiponectin:leptin ratio, and blood glucose. For the adipose tissue, there was a differential effect for adiponectin that was on the borderline of significance. To explore these changes further and how they might affect insulin resistance would require a modification to the research design to use larger group sizes for the two models or to give a greater number of EA treatments.

  14. Adipokines Do Not Mediate the Association of Obesity and Colorectal Adenoma

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    Heather M. Ochs-Balcom

    2014-01-01

    Full Text Available Purpose. The association between obesity and colon neoplasia is well established but the underlying biological mechanisms are not fully understood. Rates of both obesity and colon cancer differ by race. Adipokines have been postulated as contributors to the observed association; however, few studies have examined the mediating effect of adipokines on the obesity-colon adenoma association with consideration of racial differences. Methods. We determined prediagnostic levels of adiponectin and leptin in Caucasians (217 cases and 650 controls and African Americans (175 cases and 378 controls participating in the Case Transdisciplinary Research on Energetics and Cancer Colon Adenoma Study. We evaluated mediating effects of adiponectin and leptin on the association of abdominal adiposity and colon adenoma separately according to race using mediational pathway analysis. Results. We observed differences in circulating adipokine concentrations by race; African Americans had higher levels of leptin and lower levels of adiponectin than Caucasians for both adenoma cases and controls (P values 0.27. Conclusions. We found no evidence that leptin or adiponectin mediates the abdominal obesity-colorectal adenoma pathway. Larger studies on how these associations vary by race, sex, and obesity are needed.

  15. Early changes in adipokines from overweight to obesity in children and adolescents

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    Rafael Machado Mantovani

    Full Text Available Abstract Objective: Childhood obesity has been associated with metabolic syndrome and cardiovascular diseases. This study aimed to compare plasma levels of traditional metabolic markers, adipokines and soluble tumor necrosis factor receptor type 1 (sTNFR1 in overweight, obese and lean children. We also assessed the relationships of these molecules with classical metabolic risk factors. Methods: This study included 104 children and adolescents, which were grouped as: lean (n = 24, overweight (n = 30, and obese subjects (n = 50. They were subjected to anthropometrical, clinical and laboratorial measurements. All measurements were compared between groups. Correlation analyses were also performed to evaluate the association between clinical data, traditional metabolic markers, adipokines and sTNFR1. Results: Fasting glucose, insulin, homeostatic model assessment of insulin resistance (HOMA-IR, LDL-cholesterol and triglycerides were comparable in lean, overweight and obese subjects. Plasma levels of sTNFR1 were similar in lean and overweight subjects, but significantly increased in obese group. Leptin, adiponectin and resistin levels did not differ when overweight were compared to obese subjects. However, all adipokines differed significantly when lean subjects were compared to overweight and obese individuals. Plasma levels of adiponectin were negatively correlated with body mass index (BMI, whereas leptin, resistin and sTNFR1 concentrations positively correlated with BMI. Conclusion: Our results showed significant differences in circulating levels of the evaluated markers when lean, overweight and obese individuals were compared, suggesting that these biomarkers may change from lean to overweight and from overweight to obesity.

  16. Differential regulation of adipokines may influence migratory behavior in the white-throated sparrow (Zonotrichia albicollis.

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    Erica F Stuber

    Full Text Available White-throated sparrows increase fat deposits during pre-migratory periods and rely on these fat stores to fuel migration. Adipose tissue produces hormones and signaling factors in a rhythmic fashion and may be controlled by a clock in adipose tissue or driven by a master clock in the brain. The master clock may convey photoperiodic information from the environment to adipose tissue to facilitate pre-migratory fattening, and adipose tissue may, in turn, release adipokines to indicate the extent of fat energy stores. Here, we present evidence that a change in signal from the adipokines adiponectin and visfatin may act to indicate body condition, thereby influencing an individual's decision to commence migratory flight, or to delay until adequate fat stores are acquired. We quantified plasma adiponectin and visfatin levels across the day in captive birds held under constant photoperiod. The circadian profiles of plasma adiponectin in non-migrating birds were approximately inverse the profiles from migrating birds. Adiponectin levels were positively correlated to body fat, and body fat was inversely related to the appearance of nocturnal migratory restlessness. Visfatin levels were constant across the day and did not correlate with fat deposits; however, a reduction in plasma visfatin concentration occurred during the migratory period. The data suggest that a significant change in the biological control of adipokine expression exists between the two migratory conditions and we propose a role for adiponectin, visfatin and adipose clocks in the regulation of migratory behaviors.

  17. Inflammatory markers and adipokines alter adipocyte-derived ASP production through direct and indirect immune interaction.

    Science.gov (United States)

    Lu, H; Gauvreau, D; Tom, F-Q; Lapointe, M; Luo, X P; Cianflone, K

    2013-04-01

    Obesity and related metabolic diseases are associated with chronic low-grade inflammation, characterized by increased pro-inflammatory proteins. Several studies have demonstrated increases in acylation stimulating protein (ASP) and its precursor protein C3 in obesity, diabetes and dyslipidemia. To evaluate the effects of acute inflammatory factors and adipokines on ASP production and potential mechanisms of action, 3T3-L1 adipocytes were treated for 24 h with adipokines, cytokines, macrophage-conditioned media and direct co-culture with J774 macrophages. ASP and C3 in the media were evaluated in relation to changes in adipocyte lipid metabolism (cellular triglyceride stores). Leptin, adiponectin, IL-10, LPS and TNF-α increased ASP production (151%, 153%, 190%, 318%, 134%, PASP production ( - 34%, - 47%, PASP and C3 secretion. By contrast, apelin, omentin and visfatin also decreased ASP ( - 27%, - 49%, - 22%, PASP, while co-culture of adipocytes with macrophages markedly increased ASP and C3 production (272%, 167%, PASP production through increased precursor C3 production and/or by changing the rate of C3 conversion to ASP. As an adipokine, ASP could constitute a new link between adipocytes and macrophages. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

  18. Adipokines in the skeleton: influence on cartilage function and joint degenerative diseases.

    Science.gov (United States)

    Gomez, Rodolfo; Lago, Francisca; Gomez-Reino, Juan; Dieguez, Carlos; Gualillo, Oreste

    2009-07-01

    The discovery of leptin in 1994 marked the beginning of a new understanding about white adipose tissue (WAT) and modified a static vision of this tissue which was viewed up to the end of the 20th century as an inert tissue, devoted to body protection from heat loss and to passively storing energy. The identification of the product of the gene obese accentuated the role of adipose tissue in the physiopathology of obesity-linked diseases, and led to the discovery of various adipokines, many of a pro-inflammatory nature. It has become progressively manifest that WAT-derived adipokines can now be considered as the fulcrum between obesity-related environmental causes, such as nutrition and lifestyle, and the biochemical shifts that lead to metabolic syndrome, inflammatory and/or autoimmune conditions, and rheumatic diseases. Herein, we review recent adipokine research, with particular emphasis to the role of leptin, adiponectin, resistin, and visfatin in chondrocyte function and skeleton, as well as in inflammatory and degenerative cartilage joint diseases.

  19. Associations of objective physical activity with insulin sensitivity and circulating adipokine profile: the Framingham Heart Study.

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    Spartano, N L; Stevenson, M D; Xanthakis, V; Larson, M G; Andersson, C; Murabito, J M; Vasan, R S

    2017-04-01

    The purpose of this study was to explore the relation of physical activity (PA) and sedentary time (SED) to insulin sensitivity and adipokines. We assessed PA and SED using Actical accelerometers and insulin resistance (HOMA-IR) in 2109 participants (free of type 1 and 2 diabetes mellitus) from Framingham Generation 3 and Omni 2 cohorts (mean age 46 years, 54% women). Systemic inflammation (C-reactive protein [CRP]) and circulating adipokines were measured 6 years earlier. Steps per day, moderate-to-vigorous PA (MVPA) and SED per wear time (%SED) were predictor variables in multivariable regression analyses, with HOMA-IR, CRP and circulating adipokines as outcome measures. We reported that higher MVPA and more steps per day were associated with lower HOMA-IR, adjusting for %SED (β = -0.036, P = 0.002; β = -0.041, P = 0.005). Steps were inversely associated with CRP, but were directly associated with insulin-like growth factor (IGF)-1 levels (β = -0.111, P = 0.002; β = 3.293, P = 0.007). %SED was positively associated with HOMA-IR (β = 0.033, P insulin resistance and inflammation, whereas SED influences FABPs.

  20. Value of adipokines in predicting the severity of acute pancreatitis: Comprehensive review

    Institute of Scientific and Technical Information of China (English)

    Andrius Karpavicius; Zilvinas Dambrauskas; Audrius Sileikis; Dalius Vitkus; Kestutis Strupas

    2012-01-01

    AIM:To analyze the prognostic value of adipokines in predicting the course,complications and fatal outcome of acute pancreatitis (AP).METHODS:We performed the search of PubMed database and the systemic analysis of the literature for both experimental and human studies on prognostic value of adipokines in AP for period 2002-2012.Only the papers that described the use of adipokines for prediction of severity and/or complications of AP were selected for further analysis.Each article had to contain information about the levels of measured adipokines,diagnosis and verification of AP,to specify presence of pancreatic necrosis,organ dysfunction and/or mortality rates.From the very beginning,study was carried out adhering to the PRISMA checklist and flowchart for systemic reviews.To assess quality of all included human studies,the Quality Assessment of Diagnostic Accuracy Studies tool was used.Because of the high heterogeneity between the studies,it was decided to refrain from the statistical processing or meta-analysis of the available data.RESULTS:Nine human and three experimental studies were included into review.In experimental studies significant differences between leptin concentrations at 24 and 48 h in control,acute edematous and acute necrotizing pancreatitis groups were found (P =0.027 and P < 0.001).In human studies significant differences between leptin and resitin concentrations in control and acute pancreatitis groups were found.1-3 d serum adiponectin threshold of 4.5 μg/mL correctly classified the severity of 81% of patients with AR This threshold yielded a sensitivity of 70%,specificity 85%,positive predictive value 64%,negative predictive value88% (area under curve 0.75).Resistin and visfatin concentrations differ significantly between mild and severe acute pancreatitis groups,they correlate with severity of disease,need for interventions and outcome.Both adipokines are good markers for parapancreatic necrosis and the cut-off values of 11

  1. Taurine chloramine modulates the expression of adipokines through inhibition of the STAT-3 signaling pathway in differentiated human adipocytes.

    Science.gov (United States)

    Kim, Kyoung Soo; Ji, Hye-In; Chung, Hyunju; Kim, Chakyeun; Lee, Sang Hoon; Lee, Yeon-Ah; Yang, Hyung-In; Yoo, Myung Chul; Hong, Seung Jae

    2013-12-01

    To examine the possible role of taurine chloramine (TauCl) in modulating the expression of adipokines in adipose tissue associated with obesity, we evaluated the effect of TauCl in human differentiated adipocytes in response to IL-1β. To study the physiological effects of TauCl on adipokine expression, differentiated adipocytes were treated with IL-1β in the presence or absence of TauCl at concentrations ranging from 200 to 600 μM for 7 days. Cell culture supernatants and total RNA were analyzed by ELISA and real-time PCR, respectively, to determine protein and mRNA levels of adipokines, including adiponectin, leptin, IL-6, and IL-8. Levels of proteins involved in relevant signaling pathways were investigated by western blotting. Stimulation with IL-1β significantly decreased levels of adiponectin and leptin in adipocytes, but increased levels of IL-6 and IL-8 in a dose-dependent manner. Treatment with TauCl significantly reversed the modulation of adipokine expression by inhibiting STAT-3 signaling in IL-1β-stimulated adipocytes, independent of MAPK signaling. TauCl treatment more significantly modulated the expression of adipokines in adipocytes stimulated with IL-1β than that of non-stimulated adipocytes, suggesting that TauCl plays a significant role in modulating the expression of adipokines under inflammatory conditions. In conclusion, TauCl and other taurine derivatives that inhibit the STAT-3 signaling pathway can modulate expression of adipokines and thus may be useful as therapeutic agents for obesity-related diseases.

  2. Cold-Induced Browning Dynamically Alters the Expression Profiles of Inflammatory Adipokines with Tissue Specificity in Mice

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    Xiao Luo

    2016-05-01

    Full Text Available Cold exposure or β3-adrenoceptor agonist treatment induces the adipose tissues remodeling, relevant for beige adipogenesis within white adipose tissue (WAT. It remains unclear whether this process influences inflammatory adipokines expression in adipose tissues. We determine the temporal profile of cold or β3-adrenoceptor agonist (CL316,243-induced changes in the expression of inflammatory adipokines in adipose tissues in mice or primary mice adipocytes. Male C57BL/6J mice at eight weeks old were exposed to 4 °C for 1–5 days. Interscapular brown adipose tissue (iBAT, inguinal subcutaneous WAT (sWAT and epididymal WAT (eWAT were harvested for gene and protein expression analysis. In addition, cultured primary mice brown adipocyte (BA and white adipocyte (WA treated with or without CL316,243 were harvested for gene expression analysis. The inflammatory adipokines expressed significantly higher in WAT than BAT at baseline. They were rapidly changed in iBAT, while down-regulated in sWAT and up-regulated in eWAT during the cold acclimation. Upon CL316,243 treatment, detected inflammatory adipokines except Leptin were transiently increased in both BA and WA. Our in vivo and in vitro data demonstrate that the browning process alters the inflammatory adipokines expression in adipose tissues, which is acutely responded to in iBAT, dynamically decreased in sWAT whilst increased in eWAT for compensation.

  3. Systematic review of saturated fatty acids on inflammation and circulating levels of adipokines.

    Science.gov (United States)

    Santos, Susana; Oliveira, Andreia; Lopes, Carla

    2013-09-01

    Diet is one factor that plays a part in coronary heart disease risk through multiple biological mechanisms including subclinical inflammation. In this review, we aimed to systematically assess and summarize evidence regarding the association of saturated fatty acids (SFAs) with inflammatory markers and adipokines. An electronic search of the literature was conducted up to September 2010 using Medline, Scopus, Web of Science, and Science Direct (updated from September 2010 to August 2011 through Medline). Original studies that were written in Portuguese, English, Spanish, or French, and addressed the effects of SFA (not dietary sources or SFA-rich diets) on inflammatory markers or adipokines in adult populations were considered eligible. Data from 15 studies providing adjusted estimates were extracted. The publication year varied from 1995 to 2010 and the sample size from 54 to 4900. Most studies were cross sectional, with 3 studies using a prospective design. Twelve studies assessed total SFA, and 3 studies considered their subtypes, which were measured through dietary assessments (11 studies) or in blood samples (4 studies). Significant positive associations were observed between SFA and soluble intercellular adhesion molecule-1 and interleukin-6, whereas no significant associations were observed with E-selectin, tumor necrosis factor α, granulocyte-macrophage colony-stimulating factor, fibrinogen, and adiponectin. For high-sensitivity C-reactive protein, 2 studies showed significant positive associations, whereas 3 studies reported no significant associations. One study reported a significant inverse association of SFA with leptin, although the other 3 found no significant associations. Based on this systematic review, a potential positive association of SFA with high-sensitivity C-reactive protein but not with adipokines is suggested, which should be confirmed by future research.

  4. The role of adipokines in the rapid antidepressant effects of ketamine

    Science.gov (United States)

    Machado-Vieira, R; Gold, PW; Luckenbaugh, DA; Ballard, ED; Richards, EM; Henter, ID; De Sousa, RT; Niciu, MJ; Yuan, P; Zarate, CA

    2016-01-01

    We previously found that body mass index (BMI) strongly predicted response to ketamine. Adipokines have a key role in metabolism (including BMI). They directly regulate inflammation and neuroplasticity pathways and also influence insulin sensitivity, bone metabolism and sympathetic outflow; all of these have been implicated in mood disorders. Here, we sought to examine the role of three key adipokines—adiponectin, resistin and leptin—as potential predictors of response to ketamine or as possible transducers of its therapeutic effects. Eighty treatment-resistant subjects who met DSM-IV criteria for either major depressive disorder (MDD) or bipolar disorder I/II and who were currently experiencing a major depressive episode received a single ketamine infusion (0.5 mg kg −1 for 40 min). Plasma adipokine levels were measured at three time points (pre-infusion baseline, 230 min post infusion and day 1 post infusion). Overall improvement and response were assessed using percent change from baseline on the Montgomery–Asberg Depression Rating Scale and the Hamilton Depression Rating Scale. Lower baseline levels of adiponectin significantly predicted ketamine’s antidepressant efficacy, suggesting an adverse metabolic state. Because adiponectin significantly improves insulin sensitivity and has potent anti-inflammatory effects, this finding suggests that specific systemic abnormalities might predict positive response to ketamine. A ketamine-induced decrease in resistin was also observed; because resistin is a potent pro-inflammatory compound, this decrease suggests that ketamine’s anti-inflammatory effects may be transduced, in part, by its impact on resistin. Overall, the findings suggest that adipokines may either predict response to ketamine or have a role in its possible therapeutic effects. PMID:27046644

  5. Bone health as a function of adipokines and vitamin D pattern in elderly patients.

    Science.gov (United States)

    Pedone, Claudio; Napoli, Nicola; Pozzilli, Paolo; Lauretani, Fulvio; Bandinelli, Stefania; Ferrucci, Luigi; Rossi, Francesca Flavia; Antonelli-Incalzi, Raffaele

    2013-12-01

    Adiponectin, leptin, and resistin are involved in bone metabolism, but the evidence regarding their effects is not conclusive. We analyzed the relationship between these adipokines, vitamin D, and bone health using a cluster analysis approach. We used cross-sectional data coming from the InCHIANTI study, in which bone density and area were estimated using computed tomography. The sample size was 690 (women, 57.5%; mean age, 75.2 years; range, 65-102). Five clusters were generated on the basis of gender, age, adipokines, and vitamin D concentrations. The clusters were characterized, respectively, by higher resistin and older age (hR-O, n=134), higher vitamin D and younger age (hD-Y, n=152), higher adiponectin (hA, n=65), and higher leptin (hL, n=52). The last cluster had intermediate values of all the constituting variables (I, n=287). The clusters were compared with respect to bone parameters and clinical characteristics. Cluster hR-O had the lowest total and cortical bone density. Cluster hD-Y had the lowest adiponectin (9.29 g/mL) and leptin (7.9 ng/mL) serum concentrations, the highest prevalence of men (71.1%), and total/cortical bone density and area. No statistically significant difference across clusters was observed for age- and sex-standardized measures of bone mineral density and bone area, but leptin was associated with these parameters in a linear model adjusted for age, gender, vitamin D, resistin, and leptin. In an elderly population, age and sex almost completely explain the variability in bone status across cluster characterized by different levels of circulating adipokines and vitamin D. The role of leptin, however, seems worthy of consideration.

  6. Role of adipokines and peroxisome proliferator-activated receptors in nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Vettickattuparambil; George; Giby; Thekkuttuparambil; Ananthanarayanan; Ajith

    2014-01-01

    Intrahepatic fat deposition has been demonstrated in patients with nonalcoholic fatty liver disease(NAFLD). Genetic and environmental factors are important for the development of NAFLD. Diseases such as obesity, diabetes, and hypertension have been found to be closely associated with the incidence of NAFLD. Evi-dence suggests that obesity and insulin resistance are the major factors that contribute to the development of NAFLD. In comparing the factors that contribute to the buildup of excess calories in obesity, an imbalance of energy homeostasis can be considered as the basis. Among the peripheral signals that are generated to regulate the uptake of food, signals from adipose tissue are of major relevance and involve the maintenance of energy homeostasis through processes such as lipo-genesis, lipolysis, and oxidation of fatty acids. Advances in research on adipose tissue suggest an integral role played by adipokines in NAFLD. Cytokines secreted by adipocytes, such as tumor necrosis factor-α, transform-ing growth factor-β, and interleukin-6, are implicated in NAFLD. Other adipokines, such as leptin and adiponectin and, to a lesser extent, resistin and retinol binding protein-4 are also involved. Leptin and adiponectin can augment the oxidation of fatty acid in liver by activating the nuclear receptor super-family of transcription fac-tors, namely peroxisome proliferator-activated receptor(PPAR)-α. Recent studies have proposed downregula-tion of PPAR-α in cases of hepatic steatosis. This re-view discusses the role of adipokines and PPARs with regard to hepatic energy metabolism and progression of NAFLD.

  7. The Role of Adipose Tissue and Adipokines in Obesity-Related Inflammatory Diseases

    Directory of Open Access Journals (Sweden)

    Carmela Rita Balistreri

    2010-01-01

    Full Text Available Obesity is an energy-rich condition associated with overnutrition, which impairs systemic metabolic homeostasis and elicits stress. It also activates an inflammatory process in metabolically active sites, such as white adipose tissue, liver, and immune cells. As consequence, increased circulating levels of proinflammatory cytokines, hormone-like molecules, and other inflammatory markers are induced. This determines a chronic active inflammatory condition, associated with the development of the obesity-related inflammatory diseases. This paper describes the role of adipose tissue and the biological effects of many adipokines in these diseases.

  8. Interstitial concentrations of adipokines in subcutaneous abdominal and femoral adipose tissue

    DEFF Research Database (Denmark)

    Nielsen, Ninna Bo; Højbjerre, Lise; Sonne, Mette P

    2009-01-01

    ) in subcutaneous, abdominal and femoral adipose tissue using calibrated, large-pore microdialysis technique in 8 healthy, lean men on 2 experimental days. The interstitial leptin concentration was 2.5-fold higher in subcutaneous, femoral than abdominal adipose tissue (P... found for the remaining adipokines (P>0.05). Adiponectin and leptin concentrations were higher in plasma than subcutaneous adipose tissue (approximately 25-fold and approximately 2-fold, respectively, Padipose tissue than...... plasma (approximately 100-fold, approximately 200-fold and approximately 1000-fold, respectively, PAdipose tissue blood flow (ATBF) showed no regional difference (P>0.05). The intra- and inter-subject variations of all...

  9. Improvement in coronary heart disease risk factors during an intermittent fasting/calorie restriction regimen: Relationship to adipokine modulations

    Directory of Open Access Journals (Sweden)

    Kroeger Cynthia M

    2012-10-01

    Full Text Available Abstract Background The ability of an intermittent fasting (IF-calorie restriction (CR regimen (with or without liquid meals to modulate adipokines in a way that is protective against coronary heart disease (CHD has yet to be tested. Objective Accordingly, we examined the effects of an IFCR diet on adipokine profile, body composition, and markers of CHD risk in obese women. Methods Subjects (n = 54 were randomized to either the IFCR-liquid (IFCR-L or IFCR-food based (IFCR-F diet for 10 weeks. Results Greater decreases in body weight and waist circumference were noted in the IFCR-L group (4 ± 1 kg; 6 ± 1 cm versus the IFCR-F group (3 ± 1 kg; 4 ± 1 cm. Similar reductions (P Conclusion These findings suggest that IFCR with a liquid diet favorably modulates visceral fat and adipokines in a way that may confer protection against CHD.

  10. Determining the association between adipokine expression in multiple tissues and phenotypic features of non-alcoholic fatty liver disease in obesity

    NARCIS (Netherlands)

    Wolfs, M. G. M.; Gruben, N.; Rensen, S. S.; Verdam, F. J.; Greve, J. W.; Driessen, A.; Wijmenga, C.; Buurman, W. A.; Franke, L.; Scheja, L.; Koonen, D. P. Y.; Shiri-Sverdlov, R.; van Haeften, T. W.; Hofker, M. H.; Fu, J.

    2015-01-01

    OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is an obesity-associated disease, and in obesity adipokines are believed to be involved in the development of NAFLD. However, it is still not clear whether adipokines in the liver and/or adipose tissues can be related to the development of specif

  11. Adipokines (Leptin, Adiponectin, Resistin) Differentially Regulate All Hormonal Cell Types in Primary Anterior Pituitary Cell Cultures from Two Primate Species.

    Science.gov (United States)

    Sarmento-Cabral, André; Peinado, Juan R; Halliday, Lisa C; Malagon, María M; Castaño, Justo P; Kineman, Rhonda D; Luque, Raúl M

    2017-03-06

    Adipose-tissue (AT) is an endocrine organ that dynamically secretes multiple hormones, the adipokines, which regulate key physiological processes. However, adipokines and their receptors are also expressed and regulated in other tissues, including the pituitary, suggesting that locally- and AT-produced adipokines might comprise a regulatory circuit that relevantly modulate pituitary cell-function. Here, we used primary pituitary cell-cultures from two normal nonhuman-primate species [Papio-anubis/Macaca-fascicularis] to determine the impact of different adipokines on the functioning of all anterior-pituitary cell-types. Leptin and resistin stimulated GH-release, a response that was blocked by somatostatin. Conversely, adiponectin decreased GH-release, and inhibited GHRH-, but not ghrelin-stimulated GH-secretion. Furthermore: 1) Leptin stimulated PRL/ACTH/FSH- but not LH/TSH-release; 2) adiponectin stimulated PRL-, inhibited ACTH- and did not alter LH/FSH/TSH-release; and 3) resistin increased ACTH-release and did not alter PRL/LH/FSH/TSH-secretion. These effects were mediated through the activation of common (AC/PKA) and distinct (PLC/PKC, intra-/extra-cellular calcium, PI3K/MAPK/mTOR) signaling-pathways, and by the gene-expression regulation of key receptors/transcriptional-factors involved in the functioning of these pituitary cell-types (e.g. GHRH/ghrelin/somatostatin/insulin/IGF-I-receptors/Pit-1). Finally, we found that primate pituitaries expressed leptin/adiponectin/resistin. Altogether, these and previous data suggest that local-production of adipokines/receptors, in conjunction with circulating adipokine-levels, might comprise a relevant regulatory circuit that contribute to the fine-regulation of pituitary functions.

  12. Role of adipokines signaling in the modulation of T cells function

    Directory of Open Access Journals (Sweden)

    Claudio eProcaccini

    2013-10-01

    Full Text Available The field that links immunity and metabolism is rapidly expanding. Apparently non-immunological disorders such as obesity and type 2 diabetes have been linked to immune dysregulation, suggesting that metabolic alterations can be induced by or be consequence of an altered self-immune tolerance. In this context, adipose tissue produces and releases a variety of proinflammatory and anti-inflammatory factors, termed adipokines, which can be considered as the bridge between obesity-related exogenous factors, such as nutrition and lifestyle, and the molecular events leading to metabolic syndrome, inflammatory and/or autoimmune conditions. In obesity, increased production of most adipokines impacts on multiple functions such as appetite and energy balance, modulation of immune responses, insulin sensitivity, angiogenesis, blood pressure, lipid metabolism, and so on. This report aims to discuss some of the recent topics of adipocytokine research and their related signaling pathways, that may be of particular importance as could lead to effective therapeutic strategies for obesity-associated diseases.

  13. Assessment of serum IGF-1 and adipokines related to metabolic dysfunction in HIV-infected adults.

    Science.gov (United States)

    Parfieniuk-Kowerda, Anna; Czaban, Sławomir Lech; Grzeszczuk, Anna; Jaroszewicz, Jerzy; Flisiak, Robert

    2013-10-01

    HIV/HAART associated metabolic syndrome (HAMS) seems to result from direct influence of HIV, adverse effects of combined antiretroviral therapy (cART) and individual genetic predisposition. This study aimed to assess the influence of HIV infection and cART on serum concentration of insulin-like growth factor-1 (IGF-1) and adipokines related to metabolic abnormalities. Seventy-two HIV infected patients including 48 HIV/HCV coinfected were enrolled in this study. Insulin resistance was evaluated by Homeostatic Model Assessment (HOMA) indexes. Serum concentrations of IGF-1, adiponectin, chemerin and visfatin were measured by ELISA. Significant correlation between serum IGF-1 level and CD4 lymphocytes count was demonstrated and the lowest values were observed in subjects with CD4obesity, was found. There were significant positive correlations between serum concentration of chemerin and HOMA1-IR and serum IGF-1 concentration. Serum chemerin was increased in patients with insulin resistance vs. those with preserved insulin sensitivity. According to these results HAMS is associated with insulin resistance and imbalance of adipokines serum concentration, therefore identification of pathways related to HAMS development might be helpful in management of the syndrome. Serum IGF-1 largely depends on level of immunodeficiency in HIV-infection and may provide a link between immune dysfunction and development of HIV-associated lipodystrophy, AIDS wasting syndrome, diabetes and/or cardiovascular diseases in HIV-infected patients. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  14. Association of adipokines and adhesion molecules with indicators of obesity in women undergoing mammography screening

    Directory of Open Access Journals (Sweden)

    Isoppo de Souza Caroline

    2012-10-01

    Full Text Available Abstract Background The soluble cell adhesion molecules and adipokines are elevated in patients with obesity, hypertension, type 2 diabetes mellitus, breast cancer and atherosclerosis. Objective To investigate the relationship between anthropometric profile, dietary intake, lipid profile and fasting glycemia with serum levels of adipokines (adiponectin and PAI-1 and adhesion molecules (ICAM-1 and VCAM-1 in women without breast cancer undergoing routine mammographic screening. Design Transversal study. Subjects One hundred and forty-five women over 40-years old participated in this study. Results In 39.3% of cases the BMI was above 30 kg/m2; 46.9% had hypertension, 14.5% had type 2 Diabetes Mellitus, 31.7% had dyslipidemia and 88.3% presented a waist-to-hip ratio ≥ 0.8. A linear correlation was found between serum levels of PAI-1 and triglycerides, between serum levels of PAI-1 and WHR and between serum levels of VCAM-1 and BMI. Conclusion We found a high prevalence of obesity and metabolic syndrome. PAI-1 and VCAM-1 levels were correlated with clinical indicators of obesity and overweight.

  15. Role of adipokines and cytokines in obesity-associated breast cancer: therapeutic targets.

    Science.gov (United States)

    Khan, Sajid; Shukla, Samriddhi; Sinha, Sonam; Meeran, Syed Musthapa

    2013-12-01

    Obesity is the cause of a large proportion of breast cancer incidences and mortality in post-menopausal women. In obese people, elevated levels of various growth factors such as insulin and insulin-like growth factors (IGFs) are found. Elevated insulin level leads to increased secretion of estrogen by binding to the circulating sex hormone binding globulin (SHBG). The increased estrogen-mediated downstream signaling favors breast carcinogenesis. Obesity leads to altered expression profiles of various adipokines and cytokines including leptin, adiponectin, IL-6, TNF-α and IL-1β. The increased levels of leptin and decreased adiponectin secretion are directly associated with breast cancer development. Increased levels of pro-inflammatory cytokines within the tumor microenvironment promote tumor development. Efficacy of available breast cancer drugs against obesity-associated breast cancer is yet to be confirmed. In this review, we will discuss different adipokine- and cytokine-mediated molecular signaling pathways involved in obesity-associated breast cancer, available therapeutic strategies and potential therapeutic targets for obesity-associated breast cancer. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Chemerin is a novel adipokine associated with obesity and metabolic syndrome.

    Science.gov (United States)

    Bozaoglu, Kiymet; Bolton, Kristy; McMillan, Janine; Zimmet, Paul; Jowett, Jeremy; Collier, Greg; Walder, Ken; Segal, David

    2007-10-01

    Soluble protein hormones are key regulators of a number of metabolic processes, including food intake and insulin sensitivity. We have used a signal sequence trap to identify genes that encode secreted or membrane-bound proteins in Psammomys obesus, an animal model of obesity and type 2 diabetes (T2D). Using this signal sequence trap, we identified the chemokine chemerin as being a novel adipokine. Gene expression of chemerin and its receptor, chemokine-like receptor 1 (CMKLR1), was significantly higher in adipose tissue of obese and type 2 diabetic P. obesus compared with lean, normoglycemic P. obesus. Fractionation of P. obesus adipose tissue confirmed that chemerin was predominantly expressed in adipocytes, whereas CMKLR1 was expressed in both adipocytes and stromal-vascular cells of adipose tissue. In 3T3-L1 adipocytes, chemerin was markedly induced during differentiation, whereas CMKLR1 was down-regulated during differentiation. Serum chemerin levels were measured by ELISA in human plasma samples from 114 subjects with T2D and 142 normal glucose tolerant controls. Plasma chemerin levels were not significantly different between subjects with T2D and normal controls. However, in normal glucose tolerant subjects, plasma chemerin levels were significantly associated with body mass index, circulating triglycerides, and blood pressure. Here we report, for the first time, that chemerin is an adipokine, and circulating levels of chemerin are associated with several key aspects of metabolic syndrome.

  17. Adipokines and proinflammatory cytokines, the key mediators in the pathogenesis of nonalcoholic fatty liver disease.

    Science.gov (United States)

    Stojsavljević, Sanja; Gomerčić Palčić, Marija; Virović Jukić, Lucija; Smirčić Duvnjak, Lea; Duvnjak, Marko

    2014-12-28

    Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient with no history of alcohol abuse or other causes for secondary hepatic steatosis. The pathogenesis of NAFLD and nonalcoholic steatohepatitis (NASH) has not been fully elucidated. The "two-hit" hypothesis is probably a too simplified model to elaborate complex pathogenetic events occurring in patients with NASH. It should be better regarded as a multiple step process, with accumulation of liver fat being the first step, followed by the development of necroinflammation and fibrosis. Adipose tissue, which has emerged as an endocrine organ with a key role in energy homeostasis, is responsive to both central and peripheral metabolic signals and is itself capable of secreting a number of proteins. These adipocyte-specific or enriched proteins, termed adipokines, have been shown to have a variety of local, peripheral, and central effects. In the current review, we explore the role of adipocytokines and proinflammatory cytokines in the pathogenesis of NAFLD. We particularly focus on adiponectin, leptin and ghrelin, with a brief mention of resistin, visfatin and retinol-binding protein 4 among adipokines, and tumor necrosis factor-α, interleukin (IL)-6, IL-1, and briefly IL-18 among proinflammatory cytokines. We update their role in NAFLD, as elucidated in experimental models and clinical practice.

  18. Adipokines, biomarkers of endothelial activation, and metabolic syndrome in patients with ankylosing spondylitis.

    Science.gov (United States)

    Genre, Fernanda; López-Mejías, Raquel; Miranda-Filloy, José A; Ubilla, Begoña; Carnero-López, Beatriz; Blanco, Ricardo; Pina, Trinitario; González-Juanatey, Carlos; Llorca, Javier; González-Gay, Miguel A

    2014-01-01

    Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease associated with accelerated atherosclerosis and increased risk of cardiovascular (CV) disease. AS patients also display a high prevalence of features clustered under the name of metabolic syndrome (MeS). Anti-TNF- α therapy was found to be effective to treat AS patients by suppressing inflammation and also improving endothelial function. Previously, it was demonstrated that a short infusion of anti-TNF- α monoclonal antibodyinfliximab induced a rapid and dramatic reduction in serum insulin levels and insulin resistance along with a rapid improvement of insulin sensitivity in nondiabetic AS patients. The role of adipokines, MeS-related biomarkers and biomarkers of endothelial cell activation and inflammation seem to be relevant in different chronic inflammatory diseases. However, its implication in AS has not been fully established. Therefore, in this review we summarize the recent advances in the study of the involvement of these molecules in CV disease or MeS in AS. The assessment of adipokines and biomarkers of endothelial cell activation and MeS may be of potential relevance in the stratification of the CV risk of patients with AS.

  19. Adipokines and the role of visceral adipose tissue in inflammatory bowel disease

    Science.gov (United States)

    Karrasch, Thomas; Schaeffler, Andreas

    2016-01-01

    Recently, adipocytes have been recognized as actively participating in local and systemic immune responses via the secretion of peptides detectable in relevant levels in the systemic circulation, the so-called “adipo(cyto)kines”. Multiple studies appearing within the last 10-15 years have focused on the possible impact of adipose tissue depots on inflammatory bowel disease (IBD). Consequently, various hypotheses regarding the role of different adipokines in inflammatory diseases in general and in intestinal inflammatory processes in particular have been developed and have been further refined in recent years. After a focused summary of the data reported concerning the impact of visceral adipose tissue on IBD, such as Crohn’s disease and ulcerative colitis, our review focuses on recent developments indicating that adipocytes as part of the innate immune system actively participate in antimicrobial host defenses in the context of intestinal bacterial translocation, which are of utmost importance for the homeostasis of the whole organism. Modulators of adipose tissue function and regulators of adipokine secretion, as well as modifiers of adipocytic pattern recognition molecules, might represent future potential drug targets in IBD. PMID:27708507

  20. Adipokines, Biomarkers of Endothelial Activation, and Metabolic Syndrome in Patients with Ankylosing Spondylitis

    Directory of Open Access Journals (Sweden)

    Fernanda Genre

    2014-01-01

    Full Text Available Ankylosing spondylitis (AS is a chronic inflammatory rheumatic disease associated with accelerated atherosclerosis and increased risk of cardiovascular (CV disease. AS patients also display a high prevalence of features clustered under the name of metabolic syndrome (MeS. Anti-TNF-α therapy was found to be effective to treat AS patients by suppressing inflammation and also improving endothelial function. Previously, it was demonstrated that a short infusion of anti-TNF-α monoclonal antibodyinfliximab induced a rapid and dramatic reduction in serum insulin levels and insulin resistance along with a rapid improvement of insulin sensitivity in nondiabetic AS patients. The role of adipokines, MeS-related biomarkers and biomarkers of endothelial cell activation and inflammation seem to be relevant in different chronic inflammatory diseases. However, its implication in AS has not been fully established. Therefore, in this review we summarize the recent advances in the study of the involvement of these molecules in CV disease or MeS in AS. The assessment of adipokines and biomarkers of endothelial cell activation and MeS may be of potential relevance in the stratification of the CV risk of patients with AS.

  1. Leukocyte Telomere Length in Healthy Caucasian and African-American Adolescents : Relationships with Race, Sex, Adiposity, Adipokines, and Physical Activity

    NARCIS (Netherlands)

    Zhu, Haidong; Wang, Xiaoling; Gutin, Bernard; Davis, Catherine L.; Keeton, Daniel; Thomas, Jeffrey; Stallmann-Jorgensen, Inger; Mooken, Grace; Bundy, Vanessa; Snieder, Harold; van der Harst, Pim; Dong, Yanbin

    2011-01-01

    Objective To examine the relationships of race, sex, adiposity, adipokines, and physical activity to telomere length in adolescents. Study design Leukocyte telomere length (T/S ratio) was assessed cross-sectionally in 667 adolescents (aged 14-18 years; 48% African-Americans; 51% girls) using a quant

  2. The Effects of Exercise Training on Obesity-Induced Dysregulated Expression of Adipokines in White Adipose Tissue

    Science.gov (United States)

    Sakurai, Takuya; Ogasawara, Junetsu; Kizaki, Takako; Ishibashi, Yoshinaga; Takahashi, Motoko; Kobayashi, Osamu; Nagasawa, Junichi; Takahashi, Kazuto; Ishida, Hitoshi; Ohno, Hideki

    2013-01-01

    Obesity is recognized as a risk factor for lifestyle-related diseases such as type 2 diabetes and cardiovascular disease. White adipose tissue (WAT) is not only a static storage site for energy; it is also a dynamic tissue that is actively involved in metabolic reactions and produces humoral factors, such as leptin and adiponectin, which are collectively referred to as adipokines. Additionally, because there is much evidence that obesity-induced inflammatory changes in WAT, which is caused by dysregulated expression of inflammation-related adipokines involving tumor necrosis factor-α and monocyte chemoattractant protein 1, contribute to the development of insulin resistance, WAT has attracted special attention as an organ that causes diabetes and other lifestyle-related diseases. Exercise training (TR) not only leads to a decrease in WAT mass but also attenuates obesity-induced dysregulated expression of the inflammation-related adipokines in WAT. Therefore, TR is widely used as a tool for preventing and improving lifestyle-related diseases. This review outlines the impact of TR on the expression and secretory response of adipokines in WAT. PMID:24369466

  3. The Effects of Exercise Training on Obesity-Induced Dysregulated Expression of Adipokines in White Adipose Tissue

    Directory of Open Access Journals (Sweden)

    Takuya Sakurai

    2013-01-01

    Full Text Available Obesity is recognized as a risk factor for lifestyle-related diseases such as type 2 diabetes and cardiovascular disease. White adipose tissue (WAT is not only a static storage site for energy; it is also a dynamic tissue that is actively involved in metabolic reactions and produces humoral factors, such as leptin and adiponectin, which are collectively referred to as adipokines. Additionally, because there is much evidence that obesity-induced inflammatory changes in WAT, which is caused by dysregulated expression of inflammation-related adipokines involving tumor necrosis factor-α and monocyte chemoattractant protein 1, contribute to the development of insulin resistance, WAT has attracted special attention as an organ that causes diabetes and other lifestyle-related diseases. Exercise training (TR not only leads to a decrease in WAT mass but also attenuates obesity-induced dysregulated expression of the inflammation-related adipokines in WAT. Therefore, TR is widely used as a tool for preventing and improving lifestyle-related diseases. This review outlines the impact of TR on the expression and secretory response of adipokines in WAT.

  4. The glucocorticoid receptor, not the mineralocorticoid receptor, plays the dominant role in adipogenesis and adipokine production in human adipocytes.

    Science.gov (United States)

    Lee, M-J; Fried, S K

    2014-09-01

    Both the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR) are expressed in adipose tissue and assumed to mediate cortisol actions on adipose tissue. The relative significance of the two receptors in mediating glucocorticoid regulation of adipogenesis and adipokine expression in human adipocytes has not been addressed. We investigated the differential roles of the GR and MR in mediating glucocorticoid actions on adipogenesis and adipokine production using RNA interference in primary cultures of human preadipocytes and adipocytes. Both types of receptors are expressed, but levels of GR were several hundred fold higher than MR in both human preadipocytes and adipocytes. As expected, cortisol added during adipogenesis increased the differentiation of human preadipocytes. Silencing of GR, but not MR, blocked these proadipogenic actions of cortisol. In differentiated human adipocytes, addition of cortisol increased leptin and adiponectin, while suppressing interleukin-6 (IL-6), messenger RNA levels and protein secretion. Knockdown of GR by 65% decreased leptin and adiponectin while increasing IL-6 production. In addition, GR silencing blocked the effects of cortisol on adipokine expression. In contrast, although MR knockdown increased leptin, it did not affect adiponectin and IL-6 expression. Our data demonstrate that although both GR and MR have roles in regulating leptin expression, GR plays more important roles in mediating the actions of cortisol to regulate adipogenesis and adipokine production in human adipocytes.

  5. The concentrations of adipokines in goat milk: relation to plasma levels, inflammatory status, milk quality and composition

    Science.gov (United States)

    GUZEL, Saime; YIBAR, Artun; BELENLI, Deniz; CETIN, Ismail; TANRIVERDI, Meltem

    2017-01-01

    The main objectives of our study were to measure the major adipokines adiponectin, leptin and resistin in goat milk, to assess their interrelationships and to assess their relationships with the plasma and serum concentrations of total protein, cholesterol, total lipids, plasma C-reactive protein (CRP), milk somatic cell count (SCC), milk total aerobic colony and lactobacillus count, and milk components in lactating Saanen goats. The study was performed on eighteen lactating Saanen goats. Milk and blood samples were collected on days 20, 35, 50, 65 and 80 of lactation postpartum. The milk and plasma adiponectin levels on days 50, 65 and 80 postpartum were significantly higher than those on day 20. The milk and plasma leptin levels were lower on day 20 than on days 35, 50, 65 and 80. The milk concentrations of these major adipokines were positively intercorrelated. The milk and plasma concentrations of these three adipokines were also positively correlated. The plasma CRP concentrations correlated positively with milk leptin and resistin concentrations and inversely with milk adiponectin concentration. Milk adiponectin concentration was inversely related with its SCC. These data confirm that adiponectin, leptin and resistin are present in goat milk. The milk concentrations of these three adipokines were interrelated and interacted with the general inflammatory marker, CRP. The inverse relationship between milk adiponectin concentrations and its SCC suggests that variations in milk adiponectin might be involved in the udder health of lactating goats, but clinical trials are needed to support this hypothesis. PMID:28111374

  6. Effect of moderate alcohol consumption on adipokines and insulin sensitivity in lean and overweight men: A diet intervention study

    NARCIS (Netherlands)

    Beulens, J.W.J.; Zoete, E.C.de; Kok, F.J.; Schaafsma, G.; Hendriks, H.F.J.

    2008-01-01

    Objective: Moderate alcohol consumption is associated with a decreased risk of type II diabetes. This study investigates the effect of moderate alcohol consumption on adipokines and insulin sensitivity. Subjects: Twenty healthy, lean (body mass index (BMI) 18.5-25 kg/m2; n=11) or overweight (BMI>27

  7. Specific Strains of Lactic Acid Bacteria Differentially Modulate the Profile of Adipokines In Vitro

    Science.gov (United States)

    Fabersani, Emanuel; Abeijon-Mukdsi, María Claudia; Ross, Romina; Medina, Roxana; González, Silvia; Gauffin-Cano, Paola

    2017-01-01

    Obesity induces local/systemic inflammation accompanied by increases in macrophage infiltration into adipose tissue and production of inflammatory cytokines, chemokines, and hormones. Previous studies have shown that probiotics could improve the intestinal dysbiosis induced by metabolic diseases such as obesity, diabetes, and metabolic syndrome. Microorganisms could (directly or indirectly) affect adipokine levels due to their capacity to induce translocation of several intestinal microbial antigens into systemic circulation, which could lead to metabolic endotoxemia or produce immunomodulation in different organs. The aim of the present study was to select non-inflammatory lactic acid bacteria (LAB) strains with the capacity to modulate adipokine secretion by the adipose tissue. We wish to elucidate the role of potential probiotic strains in the regulation of the cross talking between immune cells such as macrophages and adipose cells. Mouse macrophage cell line RAW 264.7 was used for evaluating the ability of 14 LAB strains to induce cytokine production. The LAB strains were chosen based on their previously studied beneficial properties in health. Then, in murine adipocyte culture and macrophage–adipocyte coculture, we determined the ability of these strains to induce cytokines and leptin secretion. Tumor necrosis factor alpha, interleukin 6 (IL-6), IL-10, monocyte chemoattractant protein-1, and leptin levels were measured in cell supernatants. We also performed the detection and quantification of leptin receptor (Ob-Rb) expression in macrophage cell lines stimulated by these LAB strains. Differential secretion profile of cytokines in macrophage cells induced by LAB strains was observed. Also, the levels of Ob-Rb expression diverged among different LAB strains. In LAB-stimulated coculture cells (adipocytes and macrophages), we observed differential production of leptin and cytokines. Furthermore, we detected lower production levels in single culture than

  8. Adipokines, hormones related to body composition, and insulin resistance in HIV fat redistribution syndrome.

    Science.gov (United States)

    Freitas, Paula; Carvalho, Davide; Santos, Ana Cristina; Madureira, António José; Martinez, Esteban; Pereira, Jorge; Sarmento, António; Medina, José Luís

    2014-06-23

    Lipodystrophies are characterized by adipose tissue redistribution, insulin resistance (IR) and metabolic complications. Adipokines and hormones related to body composition may play an important role linking these alterations. Our aim was to evaluate adipocyte-derived hormones (adiponectin, leptin, resistin, TNF-α, PAI-1) and ghrelin plasma levels and their relationship with IR in HIV-infected patients according to the presence of lipodystrophy and fat redistribution. Anthropometric and metabolic parameters, HOMA-IR, body composition by DXA and CT, and adipokines were evaluated in 217 HIV-infected patients on cART and 74 controls. Fat mass ratio defined lipodystrophy (L-FMR) was defined as the ratio of the percentage of the trunk fat mass to the percentage of the lower limb fat mass by DXA. Patient's fat redistribution was classified into 4 different groups according the presence or absence of either clinical lipoatrophy or abdominal prominence: no lipodystrophy, isolated central fat accumulation (ICFA), isolated lipoatrophy and mixed forms (MXF). The associations between adipokines levels and anthropometric, metabolic and body composition were estimated by Spearman correlation. Leptin levels were lower in patients with FMR-L and isolated lipoatrophy, and higher in those with ICFA and MXF. Positive correlations were found between leptin and body fat (total, trunk, leg, arm fat evaluated by DXA, and total, visceral (VAT), subcutaneous adipose tissue (SAT), and VAT/SAT ratio evaluated by CT) regardless of FMR-L, and with HOMA-IR only in patients with FMR-L. Adiponectin correlated negatively with VAT, and its mean levels were lower in patients with ICFA and higher in those with no lipodystrophy. Resistin was not correlated with adipose tissue but positively correlated with HOMA-IR in FMR-L patients. PAI-1 levels were higher in MXF-patients and their levels were positively correlated with VAT in those with FMR-L. Ghrelin was higher in HIV-infected patients than

  9. The association of physical activity with novel adipokines in patients with type 2 diabetes.

    Science.gov (United States)

    Kadoglou, Nikolaos P E; Vrabas, Ioannis S; Kapelouzou, Alkistis; Angelopoulou, Nikoletta

    2012-03-01

    Adipose-tissue derivatives, known as adipokines, have been involved in the inflammatory-mediated metabolic and cardiovascular disorders of type 2 diabetes mellitus (T2DM). This study examined the association between novel adipokines and self-reported physical activity, a potential anti-inflammatory mediator. We enrolled 247 men and women with T2DM, free from overt cardiovascular disease. Based on a physical activity questionnaire, patients were classified into groups: A) sedentary, who did not report any physical activity or reported light activitiesactive, referring to low or moderate-intensity physical activities>2 h/week. Among them, 88 patients were randomly selected to perform a cardiorespiratory ergocycle testing. Clinical parameters, glycemic and lipid profiles, HOMA-IR, and serum levels of visfatin, apelin, vaspin, ghrelin and adiponectin were assessed. With the exception of fat-mass, our groups did not differ in anthropometric parameters and pharmaceutical regimen. Active patients showed ameliorated glucose regulation, HOMA-IR, hsCRP and exercise capacity compared to sedentary counterparts (pActive rather than sedentary patients showed lower visfatin (10.16±5.53 ng/ml vs 14.77±8.48 ng/ml, p=0.013), higher apelin (1.39±0.65 ng/ml vs 1.04±0.35 ng/ml, p=0.018) and adiponectin (11.82±3.06 μg/ml vs 7.81±2.11 μg/ml, p=0.033) levels. There were non-significant differences in the rest of parameters between groups. After adjusting for age, sex and BMI, physical activity along with hsCRP and ghrelin remained independent determinants of visfatin levels (R(2)=0.328, p=0.032), while physical activity was independently associated with apelin (R(2)=0.221, p=0.022). Self-controlled physical activity of, even, moderate intensity ameliorates adipokines, such as visfatin, apelin and adiponectin, in patients with T2DM. Prospective interventional studies will confirm our results. The ClinicalTrials.gov identifier is: NCT00306176. Copyright © 2011 European Federation

  10. Lipid accumulation in overweight type 2 diabetic subjects: relationships with insulin sensitivity and adipokines.

    Science.gov (United States)

    Sambataro, Maria; Perseghin, Gianluca; Lattuada, Guido; Beltramello, Giampietro; Luzi, Livio; Pacini, Giovanni

    2013-06-01

    Adipokines are known to play a fundamental role in the etiology of obesity, that is, in the impaired balance between increased feeding and decreased energy expenditure. While the adipokine-induced changes of insulin resistance in obese diabetic and nondiabetic subjects are well known, the possible role of fat source in modulating insulin sensitivity (IS) remains controversial. The aim of our study was to explore in overweight type 2 diabetic patients (T2DM) with metabolic syndrome IS in different energy storage conditions (basal and dynamic) for relating it to leptin and adiponectin. Sixteen T2DM (5/11 F/M; 59 ± 2 years; 29.5 ± 1.1 kg/m(2)) and 16 control (CNT 5/11; 54 ± 2; 29.1 ± 1.0) underwent an oral glucose tolerance test. Fasting IS was measured by QUICKI, while the dynamic one with OGIS. The insulinogenic index (IGI) described beta cell function. Also, the lipid accumulation product parameter (LAP) was assessed. LAP accounts for visceral abdominal fat and triglycerides, and it is known to be related to IS. Possible interrelationships between LAP and adipokines were explored. In T2DM and CNT, adiponectin (7.4 ± 0.5 vs. 7.8 ± 0.9 μg/mL), leptin (13.3 ± 3.0 vs. 12.4 ± 2.6 ng/mL), and QUICKI (0.33 ± 0.01 vs. 0.33 ± 0.01) were not different (P > 0.40), at variance with OGIS (317 ± 11 vs. 406 ± 13 mL/min/m(2); P = 0.006) and IGI (0.029 ± 0.005 vs. 0.185 ± 0.029 × 10(3) pmolI/mmolG; P = 0.00001). LAP was 85 ± 15 cm × mg/dL in T2DM and 74 ± 10 in CNT (P > 0.1), correlated with OGIS in all subjects (R = -0.42, P = 0.02) and QUICKI (R = -0.56, P = 0.025) in T2DM. Leptin correlated with QUICKI (R = -0.45, P = 0.009), and adiponectin correlated with OGIS (R = 0.43, P = 0.015). In overweight T2DM, insulin sensitivity in basal condition appears to be multifaceted with respect to the dynamic one, because it should be more fat-related. Insulin sensitivity appears to be incompletely described by functions of fasting glucose and insulin values alone and the

  11. Adipokine regulation of colon cancer: adiponectin attenuates interleukin-6-induced colon carcinoma cell proliferation via STAT-3.

    Science.gov (United States)

    Fenton, Jenifer I; Birmingham, Janette M

    2010-07-01

    Obesity results in increased circulating levels of specific adipokines, which are associated with colon cancer risk. The disease state is associated with increased leptin, insulin, IGF-1, and IL-6. Conversely, adiponectin levels are decreased in obese individuals. Previously, we demonstrated adipokine-enhanced cell proliferation in preneoplastic, but not normal, colon epithelial cells, demonstrating a differential effect of adipokines on colon cancer progression in vitro. Using a model of late stage carcinoma cancer cell, namely murine MC-38 colon carcinoma cells, we compared the effect of obesity-associated adipokines (leptin, insulin, IGF-1, and IL-6) on MC-38 cell proliferation and determined whether adiponectin (full length or globular) could modulate adipokine-induced cell proliferation. We show that insulin and IL-6, but not leptin and IGF-1, induce proliferation in MC-38 cells. Adiponectin treatment of MC-38 cells did not inhibit insulin-induced cell proliferation but did inhibit IL-6-induced cell proliferation by decreasing STAT-3 phosphorylation and activation. Nitric oxide (NO) production was increased in MC-38 cells treated with IL-6; co-treatment with adiponectin blocked IL-6-induced iNOS and subsequent NO production. These data are compared to previously reported findings from our laboratory using the YAMC (model normal colon epithelial cells) and IMCE (model preneoplastic) cells. The cell lines are utilized to construct a model summarizing the hormonal consequences of obesity and the impact on the differential regulation of colon epithelial cells along the continuum to carcinoma. These data, taken together, highlight mechanisms involved in obesity-associated cancers and may lead to potential-targeted therapies.

  12. Serum levels of adipokines resistin and leptin in patients with colon cancer.

    Science.gov (United States)

    Sălăgeanu, Aurora; Tucureanu, Catalin; Lerescu, Lucian; Caraş, Iuliana; Pitica, Ramona; Gangurà, Gabriel; Costea, Radu; Neagu, Stefan

    2010-01-01

    Adipose tissue displays characteristics of an endocrine organ releasing a number of adipocyte-specific factors known as adipocytokines. It has been recently suggested that adipocytokines may play a role in pathogenesis and progression of certain cancers, in particular in colorectal cancer. The aim of this study was to investigate the association between several blood adipocytokine levels and clinicopathological characteristics of colon cancer patients undergoing surgery. The study group comprised of 29 patients who underwent surgical resection for colon cancer at Emergency University Hospital Bucharest and 27 healthy volunteers. The serum levels of adipocytokines were measured using multianalyte xMap profiling technology (Luminex). Resistin levels were significantly higher in colon cancer patients while leptin serum levels were significantly lower as compared to controls. Leptin levels decreased gradually with tumor stage and aggressiveness. Taken together, these results of this study suggest that adipokines, in particular resistin and leptin may be involved in development and progression of colon cancer.

  13. Roles of FGFs as Adipokines in Adipose Tissue Development, Remodeling, and Metabolism.

    Science.gov (United States)

    Ohta, Hiroya; Itoh, Nobuyuki

    2014-01-01

    White and brown adipose tissues (BATs), which store and burn lipids, respectively, play critical roles in energy homeostasis. Fibroblast growth factors (FGFs) are signaling proteins with diverse functions in development, metabolism, and neural function. Among 22 FGFs, FGF1, FGF10, and FGF21 play roles as adipokines, adipocyte-secreted proteins, in the development and function of white and BATs. FGF1 is a critical transducer in white adipose tissue (WAT) remodeling. The peroxisome proliferator-activated receptor γ-FGF1 axis is critical for energy homeostasis. FGF10 is essential for embryonic white adipocyte development. FGF21 activates BAT in response to cold exposure. FGF21 also stimulates the accumulation of brown-like cells in WAT during cold exposure and is an upstream effector of adiponectin, which controls systemic energy metabolism. These findings provide new insights into the roles of FGF signaling in white and BATs and potential therapeutic strategies for metabolic disorders.

  14. New obesity indices and adipokines in normotensive patients and patients with hypertension: comparative pilot analysis.

    Science.gov (United States)

    Stepien, Mariusz; Stepien, Anna; Banach, Maciej; Wlazel, Rafal N; Paradowski, Marek; Rizzo, Manfredi; Toth, Peter P; Rysz, Jacek

    2014-04-01

    We compared the obesity parameters and selected adipokines-leptin, adiponectin, and resistin-in obese patients with hypertension and normotensive patients. A total of 67 nondiabetic obese outpatients were divided into 2 groups: A-hypertensive and B-normotensive. Serum levels of leptin, adiponectin, resistin, and insulin were measured. Weight, height, waist circumference, and hip circumference were measured to calculate waist-to-hip ratio (WHR), weight-to-height ratio, visceral adiposity index, and body adiposity index (BAI). Among patients with hypertension, significant positive correlations were observed between leptin and body mass index and BAI (r = .31 and r = .63, respectively). In normotensive patients, leptin positively correlated with BAI (r = .73, P obesity and leptin are associated with hypertension in obese patients.

  15. Peroxiredoxin 3 is a key molecule regulating adipocyte oxidative stress, mitochondrial biogenesis, and adipokine expression.

    Science.gov (United States)

    Huh, Joo Young; Kim, Yunghee; Jeong, Jaeho; Park, Jehyun; Kim, Inok; Huh, Kyu Ha; Kim, Yu Seun; Woo, Hyun Ae; Rhee, Sue Goo; Lee, Kong-Joo; Ha, Hunjoo

    2012-02-01

    Increased oxidative stress and mitochondrial dysfunction in obese adipocytes contribute to adipokine dysregulation, inflammation, and insulin resistance. Through an advanced proteomic analysis, we found that peroxiredoxin 3 (Prx3), a thioredoxin-dependent mitochondrial peroxidase, is highly expressed in 3T3-L1 adipocytes compared to preadipocytes. Interestingly, in obese db/db mice and human subjects, adipose Prx3 levels were significantly decreased, indicating its association with obesity. We therefore employed Prx3 knockout (KO) mice and transfected 3T3-L1 cells to examine the role of endogenous Prx3 in adipocyte metabolism. Prx3 KO mice had increased fat mass compared to wild-type due to adipocyte hypertrophy. Increased adipogenic transcription factors and lipogenic gene expression during differentiation of adipose tissue-derived stem cells from Prx3-deficient mice confirmed that these adipocytes are likely to accumulate fat. Mitochondrial protein carbonylation in Prx3 KO adipose tissue and mitochondrial superoxide level in Prx3 knockdown 3T3-L1 cells were increased showing aberrant regulation of oxidative stress. Proteomic analysis and gene expression analysis of Prx3 KO mice adipocytes also showed defect in mitochondria biogenesis along with enzymes involved in glucose/lipid metabolism and oxidative phosphorylation. In addition, expression level of adiponectin was downregulated and plasminogen activator inhibitor-1 was upregulated in Prx3 KO adipocytes. Impaired glucose tolerance and insulin resistance further implied metabolic dysregulation in Prx3 KO mice. These data suggest that endogenous Prx3 may play an essential role in maintaining normal characteristics of adipocytes and that defect in Prx3 alters mitochondrial redox state and function, and adipokine expression in adipocytes leading to metabolic alteration.

  16. Adipokines and obesity are associated with colorectal polyps in adult males: a cross-sectional study.

    Directory of Open Access Journals (Sweden)

    Sarah S Comstock

    Full Text Available BACKGROUND: Obesity increases the risk of colon cancer. It is also known that most colorectal cancers develop from adenomatous polyps. However, the effects of obesity and adipokines on colonic polyp formation are unknown. METHODS: To determine if BMI, waist circumference or adipokines are associated with colon polyps in males, 126 asymptomatic men (48-65 yr were recruited at time of colonoscopy, and anthropometric measures as well as blood were collected. Odds ratios were determined using polytomous logistic regression for polyp number (0 or ≥3 and polyp type (no polyp, hyperplastic polyp, tubular adenoma. RESULTS: 41% of the men in our study were obese (BMI ≥30. The odds of an obese individual having ≥3 polyps was 6.5 (CI: 1.3-33.0 times greater than those of a lean (BMI<25 individual. Additionally, relative to lean individuals, obese individuals were 7.8 (CI: 2.0-30.8 times more likely to have a tubular adenoma than no polyp. As BMI category increased, participants were 2.9 (CI: 1.5-5.4 times more likely to have a tubular adenoma than no polyps. Serum leptin, IP-10 and TNF-α were significantly associated with tubular adenoma presence. Serum leptin and IP-10 were significantly associated with increased likelihood of ≥3 polyps, and TNF-α showed a trend (p = 0.09. CONCLUSIONS: Obese men are more likely to have at least three polyps and adenomas. This cross-sectional study provides evidence that colonoscopy should be recommended for obese, white males.

  17. Adipokines: A Possible Contribution to Vascular and Bone Remodeling in Idiopathic Pulmonary Arterial Hypertension.

    Science.gov (United States)

    Kochetkova, Evgenia A; Ugai, Ludmila G; Maistrovskaia, Yuliya V; Nevzorova, Vera A

    2017-04-01

    Osteoporosis is a major comorbidity of cardio-respiratory diseases, but the mechanistic links between pulmonary arterial hypertension and bone remain elusive. The purpose of the stud was to evaluate serum adipokines and endothelin-1 (ET-1) levels in the patients with idiopathic pulmonary arterial hypertension (IPAH) NYHA class III-IV and to determine its associations with bone mineral density (BMD). Pulmonary and hemodynamic parameters, BMD Z-scores at the lumbar spine (LS) and femoral neck (FN), serum leptin, adiponectin, visfatin and endothelin-1 (ET-1), were evaluated in 32 patients with IPAH NYHA class III-IV and 30 healthy volunteers. Leptin, adiponectin and ET-1 were higher in the patients with IPAH than in healthy subjects. Visfatin level showed a tendency to increase compared to that of healthy subjects (p = 0.076). The univariate analysis revealed a positive correlation between BMD Z-scores at both sites and 6-min walk test, and inverse relation with pulmonary vascular resistance (PVR) and mean pulmonary arterial pressure (mPAP). Adiponectin and visfatin showed positive correlations with PVR (p = 0.009 and p = 0.006). Serum adiponectin, visfatin and leptin were inversely associated with Z-scores. After adjusting for BMI and FMI, such associations persisted between visfatin and adiponectin levels and Z-scores at both sites. ET-1 related to mPAP, cardiac index and PVR. Negative correlation was observed between ET-1 and FN BMD (p = 0.01). Positive correlations have revealed between ET-1 and adiponectin (p = 0.02), visfatin (p = 0.004) in IPAH patients. These results provide further evidence that adipokine and endothelial dysregulation may cause not only a decrease in BMD, but also an increase in hemodynamic disorders of IPAH.

  18. Lipoprotein composition in patients with type 1 diabetes mellitus: Impact of lipases and adipokines.

    Science.gov (United States)

    Hughes, Thomas A; Calderon, Rossana M; Diaz, Sylvia; Mendez, Armando J; Goldberg, Ronald B

    2016-01-01

    High cardiovascular mortality in patients with type 1 diabetes (T1DM) is widely recognized. Paradoxically, these patients have been shown to have elevated HDL-C and reduced apoB-containing lipoproteins. The purpose of this investigation was to further characterize the lipoprotein composition in T1DM and to assess the role that lipases and adipokines may play in these differences. T1DM patients (89) attending the Diabetes Clinic at the University of Miami and 42 healthy controls were recruited. Clinical characteristics, lipoprotein composition (by ultracentrifugation and HPLC), leptin, and adiponectin were measured in the full cohort, while a subgroup had LPL and hepatic lipase measured. Subjects were predominately Caucasian and Hispanic. HgbA1c's were above goal while their mean duration of diabetes was >20 years. LPL was 2-fold elevated in diabetic women versus controls (+107%{p=0.001}) with no difference in men. Hepatic lipase was reduced 50% {pdiabetic men (-33%{pdiabetic women (-25%{p=0.015}). LPL activity correlated primarily with IDL(-), LDL(-), HDL-L(+), and HDL-D(-) only in the women. HL correlated weakly with VLDL(+), LDL(+), HDL-L(-), and HDL-D(+) in women but had much stronger correlations with VLDL(-), IDL(-), and HDL-L(+). Adiponectin correlated with VLDL(-), IDL(-), LDL(-), HDL-L(+), and HDL-D(-) in women but only HDL-L(+) and HDL-D(-) in men. Leptin correlated with very few parameters in women but did correlate weakly with several HDL-L(-) and HDL-M(-) parameters. Lipoprotein composition and adipokine concentrations in both genders as well as lipase activities in the women would be expected to reduce the atherosclerotic risk in these patients with T1DM. These data suggest that there are functional lipoprotein abnormalities responsible for their CV risk that are not reflected in their plasma concentrations. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. The action of D-dopachrome tautomerase as an adipokine in adipocyte lipid metabolism.

    Directory of Open Access Journals (Sweden)

    Takeo Iwata

    Full Text Available Adipose tissue is a critical exchange center for complex energy transactions involving triacylglycerol storage and release. It also has an active endocrine role, releasing various adipose-derived cytokines (adipokines that participate in complex pathways to maintain metabolic and vascular health. Here, we found D-dopachrome tautomerase (DDT as an adipokine secreted from human adipocytes by a proteomic approach. DDT mRNA levels in human adipocytes were negatively correlated with obesity-related clinical parameters such as BMI, and visceral and subcutaneous fat areas. Experiments using SGBS cells, a human preadipocyte cell line, revealed that DDT mRNA levels were increased in an adipocyte differentiation-dependent manner and DDT was secreted from adipocytes. In DDT knockdown adipocytes differentiated from SGBS cells that were infected with the adenovirus expressing shRNA against the DDT gene, mRNA levels of genes involved in both lipolysis and lipogenesis were slightly but significantly increased. Furthermore, we investigated AMP-activated protein kinase (AMPK signaling, which phosphorylates and inactivates enzymes involved in lipid metabolism, including hormone-sensitive lipase (HSL and acetyl-CoA carboxylase (ACC, in DDT knockdown adipocytes. The AMPK phosphorylation of HSL Ser-565 and ACC Ser-79 was inhibited in DDT knockdown cells and recovered in the cells treated with recombinant DDT (rDDT, suggesting that down-regulated DDT in adipocytes brings about a state of active lipid metabolism. Furthermore, administration of rDDT in db/db mice improved glucose intolerance and decreased serum free fatty acids levels. In the adipose tissue from rDDT-treated db/db mice, not only increased levels of HSL phosphorylated by AMPK, but also decreased levels of HSL phosphorylated by protein kinase A (PKA, which phosphorylates HSL to promote its activity, were observed. These results suggested that DDT acts on adipocytes to regulate lipid metabolism through

  20. Cellular Expression of Cyclooxygenase, Aromatase, Adipokines, Inflammation and Cell Proliferation Markers in Breast Cancer Specimen.

    Directory of Open Access Journals (Sweden)

    Samar Basu

    Full Text Available Current evidences suggest that expression of Ki67, cyclooxygenase (COX, aromatase, adipokines, prostaglandins, free radicals, β-catenin and α-SMA might be involved in breast cancer pathogenesis. The main objective of this study was to compare expression/localization of these potential compounds in breast cancer tissues with tissues collected adjacent to the tumor using immunohistochemistry and correlated with clinical pathology. The breast cancer specimens were collected from 30 women aged between 49 and 89 years who underwent breast surgery following cancer diagnosis. Expression levels of molecules by different stainings were graded as a score on a scale based upon staining intensity and proportion of positive cells/area or individually. AdipoR1, adiponectin, Ob-R, leptin, COX-1, COX-2, aromatase, PGF2α, F2-isoprostanes and α-SMA were localised on higher levels in the breast tissues adjacent to the tumor compared to tumor specimens when considering either score or staining area whereas COX-2 and AdipoR2 were found to be higher considering staining intensity and Ki67 on score level in the tumor tissue. There was no significant difference observed on β-catenin either on score nor on staining area and intensity between tissues adjacent to the tumor and tumor tissues. A positive correlation was found between COX-1 and COX-2 in the tumor tissues. In conclusion, these suggest that Ki67, COXs, aromatase, prostaglandin, free radicals, adipokines, β-catenin and α-SMA are involved in breast cancer. These further focus the need of examination of tissues adjacent to tumor, tumor itself and compare them with normal or benign breast tissues for a better understanding of breast cancer pathology and future evaluation of therapeutic benefit.

  1. Ceruloplasmin Is a Novel Adipokine Which Is Overexpressed in Adipose Tissue of Obese Subjects and in Obesity-Associated Cancer Cells: e80274

    National Research Council Canada - National Science Library

    Erik Arner; Alistair R R Forrest; Anna Ehrlund; Niklas Mejhert; Masayoshi Itoh; Hideya Kawaji; Timo Lassmann; Jurga Laurencikiene; Mikael Rydén; Peter Arner; the FANTOM consortium

    2014-01-01

    ...(s) and the tissues prone to develop cancer among obese. We searched for novel adipokines that were overexpressed in adipose tissue of obese subjects as well as in tumor cells derived from cancers commonly associated with obesity...

  2. Ceruloplasmin is a novel adipokine which is overexpressed in adipose tissue of obese subjects and in obesity-associated cancer cells

    National Research Council Canada - National Science Library

    Arner, Erik; Forrest, Alistair R R; Ehrlund, Anna; Mejhert, Niklas; Itoh, Masayoshi; Kawaji, Hideya; Lassmann, Timo; Laurencikiene, Jurga; Rydén, Mikael; Arner, Peter; Clevers, Hans

    2014-01-01

    ...(s) and the tissues prone to develop cancer among obese. We searched for novel adipokines that were overexpressed in adipose tissue of obese subjects as well as in tumor cells derived from cancers commonly associated with obesity...

  3. The association of depressive symptoms with inflammatory factors and adipokines in middle-aged and older Chinese.

    Directory of Open Access Journals (Sweden)

    An Pan

    Full Text Available BACKGROUND: Studies in Western populations find that depression is associated with inflammation and obesity. The present study aimed to evaluate the relation of depressive symptoms with inflammatory factors and adipose-derived adipokines in middle-aged and older Chinese. METHODOLOGY/PRINCIPAL FINDINGS: Data were from 3289 community residents aged 50-70 from Beijing and Shanghai who participated in the Nutrition and Health of Aging Population in China project. Depressive symptoms were defined as a Center for Epidemiological Studies of Depression Scale (CES-D score of 16 or higher. Plasma concentrations of C-reactive protein (CRP, interleukin-6 (IL-6, adiponectin, resistin, plasminogen activator inhibitor-1 (PAI-1 and retinol binding protein 4 (RBP4 were measured. Of the 3289 participants, 312 (9.5% suffered from current depressive symptoms. IL-6 level was higher in participants with depressive symptoms compared to their counterparts in the crude analyses (1.17 vs. 1.05 pg/mL, p = 0.023 and this association lost statistical significance after multiple adjustments (1.13 vs. 1.10 pg/mL, p = 0.520. Depressive symptoms were not associated with increased mean levels of any other inflammatory factors or adipokines in the unadjusted or adjusted analyses. CONCLUSIONS/SIGNIFICANCE: We found no evidence that depressive symptoms were associated with inflammatory factors and adipokines in the middle-aged and older Chinese populations. Prospective studies and studies in clinically diagnosed patients are needed to confirm our results and clarify the relation of depression with inflammatory factors and adipokines.

  4. Resveratrol supplementation and plasma adipokines concentrations? A systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Mohammadi-Sartang, Mohsen; Mazloom, Zohreh; Sohrabi, Zahra; Sherafatmanesh, Saeed; Barati-Boldaji, Reza

    2017-03-01

    The results of human clinical trials have revealed that the effects of resveratrol on adipokines are inconsistent. Our objective was to elucidate the role of resveratrol supplementation on adipokines through a systematic review and a meta-analysis of available randomized placebo-controlled trials (RCTs).(1) The search included PubMed-MEDLINE, SCOPUS and ISI web of sciences database till up to 6th November 2016. Weight mean differences (WMD)(2) were calculated for net changes in adipokines using fixed-effects or random-effects models; meta-regression analysis and publication bias were conducted in accordance with standard methods. Nine RCTs with 11 treatment arms were eligible for inclusion in this systematic review and meta-analysis. Meta-analysis of data from 10 treatment arms showed a significant change in plasma adiponectin concentrations following resveratrol supplementation (WMD: 1.10μg/ml, 95%CI: 0.88, 1.33, p<0.001); Q=11.43, I(2)=21.29%, p=0.247). There was a significant greater adiponectin-reducing effect in trials with higher than or equal to 100mg/day (WMD: 1.11μg/ml, 95%CI: 0.88, 1.34, p<0.001), versus those with less than 100 mg/day dosage (WMD: 0.84μg/ml, 95%CI: -0.62, 2.31, p=0.260). Meta-analysis of data from 5 treatment arms did not find any significant change in plasma leptin concentrations following resveratrol supplementation (WMD: 3.77ng/ml, 95% CI: -2.28, 9.83, p=0.222; Q=8.00, I(2)=50.01%). Resveratrol significantly improves adiponectin but does not affect leptin concentrations. Additional studies are required to further evaluate the potential benefits of resveratrol on adipokines in humans.

  5. The Effect of Renal Denervation on Plasma Adipokine Profile in Patients with Treatment Resistant Hypertension

    Directory of Open Access Journals (Sweden)

    Nina Eikelis

    2017-05-01

    Full Text Available Background: We previously demonstrated the effectiveness of renal denervation (RDN to lower blood pressure (BP at least partially via the reduction of sympathetic stimulation to the kidney. A number of adipocyte-derived factors are implicated in BP control in obesity.Aim: The aim of this study was to examine whether RDN may have salutary effects on the adipokine profile in patients with resistant hypertension (RH.Methods: Fifty seven patients with RH undergoing RDN program have been included in this study (65% males, age 60.8 ± 1.5 years, BMI 32.6 ± 0.7 kg/m2, mean ± SEM. Throughout the study, the patients were on an average of 4.5 ± 2.7 antihypertensive drugs. Automated seated office BP measurements and plasma concentrations of leptin, insulin, non-esterified fatty acids (NEFA, adiponectin and resistin were assessed at baseline and the 3 months after RDN.Results: There was a significant reduction in mean office systolic (168.75 ± 2.57 vs. 155.23 ± 3.17 mmHg, p < 0.001 and diastolic (90.68 ± 2.31 vs. 83.74 ± 2.36 mmHg, p < 0.001 BP 3 months after RDN. Body weight, plasma leptin and resistin levels and heart rate remained unchanged. Fasting insulin concentration significantly increased 3 months after the procedure (20.05 ± 1.46 vs. 29.70 ± 2.51 uU/ml, p = 0.002. There was a significant drop in circulating NEFA at follow up (1.01 ± 0.07 vs. 0.47 ± 0.04 mEq/l, p < 0.001. Adiponectin concentration was significantly higher after RDN (5,654 ± 800 vs. 6,644 ± 967 ng/ml, p = 0.024.Conclusions: This is the first study to demonstrate that RDN is associated with potentially beneficial effects on aspects of the adipokine profile. Increased adiponectin and reduced NEFA production may contribute to BP reduction via an effect on metabolic pathways.Clinical Trial Registration Number: NCT00483808, NCT00888433.

  6. Influence of insulin resistance and adipokines in the grade of steatosis of nonalcoholic fatty liver disease.

    Science.gov (United States)

    Aller, Rocio; de Luis, Daniel A; Fernandez, Luis; Calle, Fernando; Velayos, Benito; Olcoz, Jose Luis; Izaola, Olatz; Sagrado, Manuel Gonzalez; Conde, Rosa; Gonzalez, Jose Manuel

    2008-04-01

    The objective of this work was to study the influence of insulin resistance and adipokines on the grade of steatosis in patients with NAFLD (nonalcoholic fatty liver disease) diagnosed by liver biopsy. A sample of 24 NAFLD patients was analyzed in a cross-sectional study. All patients with a two-week weight-stabilization period before recruitment were enrolled. A liver biopsy was realized. Weight, basal glucose, insulin, insulin resistance (HOMA), total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, and adipokines blood levels were measured. A nutritional evaluation (dietary intake, indirect calorimetry, and bioimpedance) was performed. The mean age was 41.6 +/- 8.7 years and the mean body mass index (BMI) 29.4 +/- 4.7. Twelve patients had a low grade of steatosis (grade 1 of the Brunt classification) and 12 patients had a high grade of steatosis (grade 2 or 3). Only HOMA was higher in patients with a high grade of steatosis (1.4 +/- 0.5 vs. 2.8 +/- 1.7 units; P < 0.05). Anthropometric data and dietary intake were similar for both groups. Blood levels of adiponectin were higher in patients with a low grade of steatosis (37.7 +/- 22.5 vs. 24.2 +/- 33 ng mL(-1); P < 0.05). Blood levels of resistin were higher in patients with a high grade of steatosis (2.36 +/- 0.6 vs. 2.8 +/- 0.6 mg mL(-1); P < 0.05), without differences in TNF-alpha or leptin levels. In logistic regression analysis, the HOMA-IR remained in the model, with an odds ratio to develop high grade of steatosis of 7.8 (95% CI: 1.8-75) with each 1 unit of HOMA-IR adjusted by age, sex, BMI, and dietary intake. This study demonstrates that insulin resistance determined with the HOMA model is associated with a high grade of steatosis in patients with NAFLD.

  7. Adiposity Trajectory and Its associations with Plasma Adipokine Levels in Children and Adolescents – A Prospective Cohort Study

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    Li, Shenghui; Liu, Rong; Arguelles, Lester; Wang, Guoying; Zhang, Jun; Shen, Xiaoming; Wang, Xiaobin

    2015-01-01

    Objective This study aimed to examine the associations of longitudinal adiposity measures with two adipokines, leptin and adiponectin, and their ratio in children and adolescents. Methods A total of 953 children and adolescents participated in a 6-year longitudinal study. Body mass index (BMI), percentage body fat (%BF), and fat mass index (FMI) were used to assess adiposity status. Results After adjusting for possible confounders, our regression models revealed that BMI, %BF, and FMI, in both the baseline and follow-up survey, were independently associated with a higher level of leptin and the leptin/adiponectin ratio at the follow-up survey, whereas the significant association with adiponectin only partly existed in adiposity measures at the follow-up visit. Moreover, the longitudinal change in adiposity measures was found to be a significant predictor for follow-up plasma adipokine levels. Compared with the low→low group, the medium→medium group, up-trend group, and high→high group all showed a significantly increased level of leptin and leptin/adiponectin ratio. The up-trend group and high→high group also had significantly decreased adiponectin levels. Conclusions Our findings highlight the importance of adiposity surveillance and the utility of adipokines as biomarkers for adverse metabolic consequences of childhood adiposity. PMID:26704698

  8. Circulating adipokine levels and endometrial cancer risk in the prostate, lung, colorectal, and ovarian cancer screening trial.

    Science.gov (United States)

    Luhn, Patricia; Dallal, Cher M; Weiss, Jocelyn M; Black, Amanda; Huang, Wen-Yi; Lacey, James V; Hayes, Richard B; Stanczyk, Frank Z; Wentzensen, Nicolas; Brinton, Louise A

    2013-07-01

    Circulating adipokine levels may be associated with endometrial cancer risk, yet few studies have evaluated these markers prospectively. We conducted a nested case-control study of postmenopausal women in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (n = 78,216), including 167 incident endometrial cancer cases and 327 controls that were matched on age, study center, race, study year of diagnosis, year of blood draw, time of day of blood draw, and menopausal hormone therapy (MHT) use. Adipokine and estradiol levels were categorized into tertiles (T). ORs and 95% confidence intervals (CIs) for the associations of adiponectin, leptin, and visfatin with endometrial cancer risk were estimated by conditional logistic regression, adjusting for known endometrial cancer risk factors, including body mass index (BMI) and circulating estradiol levels. Adiponectin levels were inversely associated with risk of endometrial cancer [ORT3vsT1 = 0.48; 95% CI, 0.29-0.80); Ptrend cancer risk through pathways other than estrogen-mediated cell growth in postmenopausal women not currently on MHT. Understanding how adipokines influence endometrial cancer risk may help to elucidate biological mechanisms important for the observed obesity-endometrial cancer association.

  9. Sequence analysis of three canine adipokine genes revealed an association between TNF polymorphisms and obesity in Labrador dogs.

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    Mankowska, M; Stachowiak, M; Graczyk, A; Ciazynska, P; Gogulski, M; Nizanski, W; Switonski, M

    2016-04-01

    Obesity is an emerging health problem in purebred dogs. Due to their crucial role in energy homeostasis control, genes encoding adipokines are considered candidate genes, and their variants may be associated with predisposition to obesity. Searching for polymorphism was carried out in three adipokine genes (TNF, RETN and IL6). The study was performed on 260 dogs, including lean (n = 109), overweight (n = 88) and obese (n = 63) dogs. The largest cohort was represented by Labrador Retrievers (n = 136). Altogether, 24 novel polymorphisms were identified: 12 in TNF (including one missense SNP), eight in RETN (including one missense SNP) and four in IL6. Distributions of five common SNPs (two in TNF, two in RETN and one in IL6) were further analyzed with regard to body condition score. Two SNPs in the non-coding parts of TNF (c.-40A>C and c.233+14G>A) were associated with obesity in Labrador dogs. The obtained results showed that the studied adipokine genes are highly polymorphic and two polymorphisms in the TNF gene may be considered as markers predisposing Labrador dogs to obesity.

  10. Relationship among serum taurine, serum adipokines, and body composition during 8-week human body weight control program.

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    You, Jeong Soon; Park, Ji Yeon; Zhao, Xu; Jeong, Jin Seok; Choi, Mi Ja; Chang, Kyung Ja

    2013-01-01

    Human adipose tissue is not only a storage organ but also an active endocrine organ to release adipokines. This study was conducted to investigate the relationship among serum taurine and adipokine levels, and body composition during 8-week human body weight control program in obese female college students. The program consisted of diet therapy, exercise, and behavior modification. After the program, body weight, body fat mass, percent body fat, and body mass index (BMI) were significantly decreased. Serum triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels were significantly decreased. Also serum adiponectin level was significantly increased and serum leptin level was significantly decreased. There were no differences in serum taurine and homocysteine levels. The change of serum adiponectin level was positively correlated with change of body fat mass and percent body fat. These results may suggest that body fat loss by human body weight control program is associated with an increase in serum adiponectin in obese female college students. Therefore, further study such as taurine intervention study is needed to know more exact correlation between dietary taurine intake and serum adipokines or body composition.

  11. FNDC5/irisin is not only a myokine but also an adipokine.

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    Arturo Roca-Rivada

    Full Text Available Exercise provides clear beneficial effects for the prevention of numerous diseases. However, many of the molecular events responsible for the curative and protective role of exercise remain elusive. The recent discovery of FNDC5/irisin protein that is liberated by muscle tissue in response to exercise might be an important finding with regard to this unsolved mechanism. The most striking aspect of this myokine is its alleged capacity to drive brown-fat development of white fat and thermogenesis. However, the nature and secretion form of this new protein is controversial. The present study reveals that rat skeletal muscle secretes a 25 kDa form of FNDC5, while the 12 kDa/irisin theoretical peptide was not detected. More importantly, this study is the first to reveal that white adipose tissue (WAT also secretes FNDC5; hence, it may also behave as an adipokine. Our data using rat adipose tissue explants secretomes proves that visceral adipose tissue (VAT, and especially subcutaneous adipose tissue (SAT, express and secrete FNDC5. We also show that short-term periods of endurance exercise training induced FNDC5 secretion by SAT and VAT. Moreover, we observed that WAT significantly reduced FNDC5 secretion in fasting animals. Interestingly, WAT of obese animals over-secreted this hormone, which might suggest a type of resistance. Because 72% of circulating FNDC5/irisin was previously attributed to muscle secretion, our findings suggest a muscle-adipose tissue crosstalk through a regulatory feedback mechanism.

  12. Vitamin D Deficiency in Obese Children and Its Relationship to Insulin Resistance and Adipokines

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    Christian L. Roth

    2011-01-01

    Full Text Available Low-serum concentrations of 25-hydroxyvitamin D [25(OHD] are associated with insulin resistance in adults. Less data are available in pediatric populations. Serum 25(OHD serum concentrations were assessed in 125 obese and 31 nonobese children (age 11.9±2.7 y, range 6–16 y, 49% male living in Bonn, Germany. The relationship between 25(OHD, measured by liquid chromatography-tandem mass spectrometry, and measures of insulin sensitivity and adipokines adiponectin and resistin were analyzed. Seventy-six % of subjects were 25(OHD deficient (<20 ng/mL. Higher insulin, homeostasis model assessment-insulin resistance (HOMA-IR r=−0.269, P=0.023, and hemoglobin A1c (HbA1c as well as lower quantitative insulin-sensitivity check index (QUICKI r=0.264, P=0.030 values were found in obese children with lower 25(OHD concentrations even after adjustment for gender, age, and body mass index. Furthermore, 25(OHD correlated significantly with adiponectin, but not with resistin. Our results suggest that hypovitaminosis D is a risk factor for developing insulin resistance independent of adiposity.

  13. Adipokines, asymmetrical dimethylarginine, and pulmonary function in adolescents with asthma and obesity.

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    Huang, Fengyang; Del-Río-Navarro, Blanca Estela; Torres-Alcántara, Saúl; Pérez-Ontiveros, José Alfredo; Ruiz-Bedolla, Eliseo; Saucedo-Ramírez, Omar Josué; Villafaña, Santiago; Sánchez Muñoz, Fausto; Bravo, Guadalupe; Hong, Enrique

    2017-03-01

    This study was to investigate whether the metabolic abnormalities of adipokines and asymmetrical dimethylarginine (ADMA) associate with pulmonary function deficits in adolescents with obesity and asthma. This study enrolled 28 obese adolescents with asthma, 46 obese adolescents without asthma, 58 normal-weight adolescents with asthma, and 63 healthy control subjects. Serum levels of leptin, high-molecule-weight (HMW) adiponectin, retinol binding protein 4 (RBP4), asymmetrical dimethylarginine (ADMA), and pulmonary function were qualified. The obese subjects had higher levels of leptin and ADMA but lower levels of HMW adiponectin than the normal-weight subjects with or without asthma. The subjects with asthma had higher levels of RBP4 than those without asthma. The obese adolescents with asthma had lowest forced expiratory lung volume in the first second (FEV1)/forced vital capacity (FVC) ratio among the four study groups. In all the study subjects and in the subjects with asthma alone, the FEV1/FVC ratio associated negatively with leptin, however, such association was rendered non-significant when adjusted for BMI. The pulmonary function deficits associated inversely with BMI percentile in the subjects with asthma. However, the decreased FEV1/FVC ratio was not correlated with HMW adiponectin, RBP4 or ADMA. Our present study confirmed obstructive pattern of pulmonary function characterized by the reduced FEV1/FVC ratio in the obese adolescents with asthma. These pulmonary deficits were associated inversely with the increased BMI percentile.

  14. Adipokines, cytokines and body fat stores in hepatitis Cvirus liver steatosis

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    AIM To identify patients with or without liver steatosisand its severity in treatment-na?ve patients affected byhepatitis C virus (HCV) infection.METHODS: We included 56 HCV infected patients, andassessed the amount of liver fat by histomorphometry,and its relationships with fat and lean mass at differentparts of the body (by densitometry), hormones [insulin,homeostatic model assessment (HOMA)], adipokines(resistin, adiponectin, leptin), and cytokines (tumornecrosis factor α, interleukin-6).RESULTS: Although the intensity of liver steatosis isrelated to trunk fat mass and HOMA, 33% of patientsshowed no liver steatosis, and this finding was notrelated to body mass index or genotype. Besides trunk fat mass, no other factor was related to the presenceor not of liver steatosis, or to the intensity of it, by multivariateanalysis. Lean mass was not related to liversteatosis. Adiponectin levels were lower among patients.No differences were observed in leptin and resistin.CONCLUSION: Steatosis in HCV infection is common(67.2%), and closely related to trunk fat, and insulinresistance, but not with leg fat mass or adipokines.

  15. Evaluation of Adipokines, Inflammatory Markers, and Sex Hormones in Simple and Complex Breast Cysts’ Fluid

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    Paweł Madej

    2016-01-01

    Full Text Available Objective. The aim of the study was to analyze the association between levels of adipokines in the breast cyst fluid and in the circulation in relation to the type of cysts. Material and Measurements. A cross-sectional study involved 86 women with breast cysts (42 with simple cysts and 44 with complex cysts. Plasma and breast cyst fluid leptin, adiponectin, visfatin/NAMPT, resistin, TNF-α, and IL-6 levels, in addition to serum levels of estradiol, progesterone and prolactin, and anthropometric parameters and body composition (by bioimpedance method, were measured. Results. The levels of leptin, adiponectin, and resistin were significantly lower in breast cyst fluid than in plasma regardless of the cyst type. Contrarily, the levels of visfatin/NAMPT and TNF-α were significantly increased, and IL-6 levels were similar in the breast cyst fluid and plasma in both study groups. There was no correlation between corresponding levels of leptin, adiponectin, resistin, visfatin/NAMPT, TNF-α, and IL-6 in breast cyst fluid and plasma. Conclusions. Higher levels of visfatin/NAMPT and TNF-α in the fluid from simple and complex breast cysts than in plasma suggest that their local production is related to inflammation.

  16. WISP1 is a novel adipokine linked to inflammation in obesity.

    Science.gov (United States)

    Murahovschi, Veronica; Pivovarova, Olga; Ilkavets, Iryna; Dmitrieva, Renata M; Döcke, Stephanie; Keyhani-Nejad, Farnaz; Gögebakan, Özlem; Osterhoff, Martin; Kemper, Margrit; Hornemann, Silke; Markova, Mariya; Klöting, Nora; Stockmann, Martin; Weickert, Martin O; Lamounier-Zepter, Valeria; Neuhaus, Peter; Konradi, Alexandra; Dooley, Steven; von Loeffelholz, Christian; Blüher, Matthias; Pfeiffer, Andreas F H; Rudovich, Natalia

    2015-03-01

    WISP1 (Wnt1-inducible signaling pathway protein-1, also known as CCN4) is a member of the secreted extracellular matrix-associated proteins of the CCN family and a target gene of the Wingless-type (WNT) signaling pathway. Growing evidence links the WNT signaling pathway to the regulation of adipogenesis and low-grade inflammation in obesity. We aimed to validate WISP1 as a novel adipokine. Human adipocyte differentiation was associated with increased WISP1 expression and secretion. Stimulation of human macrophages with WISP1 led to a proinflammatory response. Circulating WISP1 and WISP1 subcutaneous adipose tissue expression were regulated by weight changes in humans and mice. WISP1 expression in visceral and subcutaneous fat tissue was associated with markers of insulin resistance and inflammation in glucose-tolerant subjects. In patients with nonalcoholic fatty liver disease, we found no correlation among disease activity score, liver fat content, and WISP1 expression. Insulin regulated WISP1 expression in adipocytes in vitro but had no acute effect on WISP1 gene expression in subcutaneous fat tissue in overweight subjects who had undergone hyperinsulinemic clamp experiments. The data suggest that WISP1 may play a role in linking obesity to inflammation and insulin resistance and could be a novel therapeutic target for obesity. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  17. Maternal and Fetal Lipid and Adipokine Profiles and Their Association with Obesity

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    Mario Solis-Paredes

    2016-01-01

    Full Text Available Background. Maternal metabolic changes impact fetal metabolism resulting in a higher risk for developing chronic diseases later in life. The aim of this study was to assess the association between maternal and fetal adipokine and lipid profiles, as well as the influence of maternal weight on this association. Methods. Healthy pregnant women at term who delivered by C-section were enrolled. Maternal and fetal glucose, lipid profile, adiponectin, leptin, and resistin levels were analyzed by obesity and maternal weight gain. Statistics included descriptives, correlations, and mean differences (SPSS v20.0. Results. Adiponectin and resistin concentrations were higher in fetal blood, while leptin was lower (p<0.05. A significant inverse association between maternal resistin and fetal LDL-cholesterol (LDL-C (r=-0.327; p=0.022 was observed. A positive correlation was found between maternal and fetal resistin (r=0.358; p=0.013. Women with excessive weight gain had higher leptin levels and their fetuses showed higher LDL-C levels (p<0.05. Conclusions. Maternal resistin showed an inverse association with fetal LDL-C, suggesting that maternal adiposity status may play an active role in the regulation of fetal lipid profile and consequently, in fetal programming. Excessive maternal weight gain during pregnancy may exert an effect over metabolic mediators in both mother and newborn.

  18. Experimental Hyperthyroidism Decreases Gene Expression and Serum Levels of Adipokines in Obesity

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    Renata de Azevedo Melo Luvizotto

    2012-01-01

    Full Text Available Aims. To analyze the influence of hyperthyroidism on the gene expression and serum concentration of leptin, resistin, and adiponectin in obese animals. Main Methods. Male Wistar rats were randomly divided into two groups: control (C—fed with commercial chow ad libitum—and obese (OB—fed with a hypercaloric diet. After group characterization, the OB rats continued receiving a hypercaloric diet and were randomized into two groups: obese animals (OB and obese with 25 μg triiodothyronine (T3/100 BW (OT. The T3 dose was administered every day for the last 2 weeks of the study. After 30 weeks the animals were euthanized. Samples of blood and adipose tissue were collected for biochemical and hormonal analyses as well as gene expression of leptin, resistin, and adiponectin. Results. T3 treatment was effective, increasing fT3 levels and decreasing fT4 and TSH serum concentration. Administration of T3 promotes weight loss, decreases all fat deposits, and diminishes serum levels of leptin, resistin, and adiponectin by reducing their gene expression. Conclusions. Our results suggest that T3 modulate serum and gene expression levels of leptin, resistin, and adiponectin in experimental model of obesity, providing new insights regarding the relationship between T3 and adipokines in obesity.

  19. Bilirubin Increases Insulin Sensitivity by Regulating Cholesterol Metabolism, Adipokines and PPARγ Levels.

    Science.gov (United States)

    Liu, Jinfeng; Dong, Huansheng; Zhang, Yong; Cao, Mingjun; Song, Lili; Pan, Qingjie; Bulmer, Andrew; Adams, David B; Dong, Xiao; Wang, Hongjun

    2015-05-28

    Obesity can cause insulin resistance and type 2 diabetes. Moderate elevations in bilirubin levels have anti-diabetic effects. This study is aimed at determining the mechanisms by which bilirubin treatment reduces obesity and insulin resistance in a diet-induced obesity (DIO) mouse model. DIO mice were treated with bilirubin or vehicle for 14 days. Body weights, plasma glucose, and insulin tolerance tests were performed prior to, immediately, and 7 weeks post-treatment. Serum lipid, leptin, adiponectin, insulin, total and direct bilirubin levels were measured. Expression of factors involved in adipose metabolism including sterol regulatory element-binding protein (SREBP-1), insulin receptor (IR), and PPARγ in liver were measured by RT-PCR and Western blot. Compared to controls, bilirubin-treated mice exhibited reductions in body weight, blood glucose levels, total cholesterol (TC), leptin, total and direct bilirubin, and increases in adiponectin and expression of SREBP-1, IR, and PPARγ mRNA. The improved metabolic control achieved by bilirubin-treated mice was persistent: at two months after treatment termination, bilirubin-treated DIO mice remained insulin sensitive with lower leptin and higher adiponectin levels, together with increased PPARγ expression. These results indicate that bilirubin regulates cholesterol metabolism, adipokines and PPARγ levels, which likely contribute to increased insulin sensitivity and glucose tolerance in DIO mice.

  20. Effect of zinc supplementation on inflammatory markers and adipokines in young obese women.

    Science.gov (United States)

    Kim, Jihye; Ahn, Juhee

    2014-02-01

    Obesity is a chronic inflammatory state characterized by altered adipokine production and increased levels of inflammatory cytokines. The study explored the effect of zinc supplementation on inflammatory markers and adipocyte hormones in young obese women. Twenty five non-obese women and forty obese women (body mass index ≥25 kg/m(2)) aged 19-28 years were recruited for this study. Twenty obese women of the study group took 30 mg/day of supplemental zinc as zinc gluconate for 8 weeks and 20 obese women of control group took placebo. Usual dietary zinc intake was estimated from 3-day diet records. Serum zinc and urinary zinc concentration were measured by Atomic Absorption Spectrophotometry. Inflammatory markers such as high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), and interleukin (IL)-6 and adipocyte hormones such as lepin and adiponectin were measured by enzyme immunoassay. Inflammatory markers and leptin were significantly higher, but adiponectin was significantly lower in obese women than non-obese women. Zinc supplementation increased serum zinc by 15% and urinary zinc by 56% (P zinc supplementation, but not in placebo group. Serum leptin and plasma adiponectin concentration did not differ with either zinc supplementation or placebo. The levels of IL-6 and leptin were inversely associated with dietary zinc intake. These results suggest that zinc may have a favorable effect on obesity-related inflammation in young adults.

  1. FGF21 as a hepatokine, adipokine, and myokine in metabolism and diseases

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    Nobuyuki eItoh

    2014-07-01

    Full Text Available Fibroblast growth factor (FGF family members are mostly secreted as signaling proteins with diverse functions in development and metabolism. FGF21 is a unique FGF with metabolic, but not proliferative activities. FGF21 is mostly induced by different kinds of stress and acts though FGF receptor 1c with β−Klotho as a cofactor in an endocrine or, in parts, autocirne/paracrine manner. Hepatic FGF21 directly acts on white adipocytes to inhibit lipolysis and acts through the brain to increase systemic glucocorticoid levels and suppress physical activity in response to starvation. It also protects against dioxin toxicity. Adipocytic FGF21 induces the browning of white adipose tissue (WAT and activates brown adipocytes in response to cold exposure. It also acts as an upstream effector of adiponectin in white adipocytes. Myocytic FGF21 protects against diet-induced obesity and insulin resistance, induces the browning of WAT, and protects against cardiac hypertrophy. In addition, Fgf21 polymorphisms are possibly related with metabolic diseases and FGF21 are biomarker of metabolic diseases. These findings indicate that FGF21 plays roles as a hepatokine, adipokine, and myokine in metabolism, injury protection, and diseases.

  2. Impact of glucocorticoid hormones on adipokine secretion and human adipose tissue metabolism.

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    Fain, John N

    2013-08-01

    The glucocorticoid hormones alter the metabolism of the adipose tissue after an approximately 2-h lag period. The effects are mediated through the nuclear receptors that alter the expression of a wide variety of genes through the mechanisms that are similar to those seen in the other cells. There are many direct metabolic effects of the glucocorticoids on the adipose tissue metabolism, and every year, new effects are added to the list of proteins whose expression is influenced by the glucocorticoids. Furthermore, some enzymatic processes are affected by these hormones only in the presence of the other hormones such as growth hormone (GH) or insulin. Most of the effects of the glucocorticoids are on the gene transcription, and the effects on the mRNA are reflected in the altered levels of the target proteins. The glucocorticoids enhance the leptin release, while reducing that of the inflammatory adipokines and stimulating that of the lipoprotein lipase (LPL) in the presence of insulin. The activity of 11β-hydroxysteroid dehydrogenase type 1 (HSD1) is enhanced by the glucocorticoids along with that of α1 glycoprotein 1 and serum amyloid A release by the adipose tissue. In contrast, the tumor necrosis factor α (TNF)-stimulated lipolysis in the adipose tissue is blocked by the glucocorticoids. It is still unclear which, if any, of these effects account for the insulin resistance due to the glucocorticoids in the adipose tissue. However, recent work suggests that, at least in mice, the reduction in the osteocalcin release by the osteoblasts in the presence of the glucocorticoids accounts for much of the in vivo insulin resistance. In summary, there are multiple direct effects of the glucocorticoids, both anti-inflammatory and proinflammatory, on the adipose tissue.

  3. Obesity induced rapid melanoma progression is reversed by orlistat treatment and dietary intervention: role of adipokines.

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    Malvi, Parmanand; Chaube, Balkrishna; Pandey, Vimal; Vijayakumar, Maleppillil Vavachan; Boreddy, Purushotham Reddy; Mohammad, Naoshad; Singh, Shivendra Vikram; Bhat, Manoj Kumar

    2015-03-01

    Obesity, owing to adiposity, is associated with increased risk and development of various cancers, and linked to their rapid growth as well as progression. Although a few studies have attempted to understand the relationship between obesity and melanoma, the consequences of controlling body weight by reducing adiposity on cancer progression is not well understood. By employing animal models of obesity, we report that controlling obesity either by orlistat treatment or by restricting caloric intake significantly slows down melanoma progression. The diminished tumor progression was correlated with decreased fat mass (adiposity) in obese mice. Obesity associated factors contributing to tumor progression were decreased in the experimental groups compared to respective controls. In tumors, protein levels of fatty acid synthase (FASN), caveolin (Cav)-1 and pAkt, which are tumor promoting molecules implicated in melanoma growth under obese state, were decreased. In addition, increased necrosis and reduction in angiogenesis as well as proliferative markers PCNA and cyclin D1 were observed in tumors of the orlistat treated and/or calorically restricted obese mice. We observed that growth of melanoma cells cultured in conditioned medium (CM) from orlistat-treated adipocytes was reduced. Adipokines (leptin and resistin), via activating Akt and modulation of FASN as well as Cav-1 respectively, enhanced melanoma cell growth and proliferation. Together, we demonstrate that controlling body weight reduces adipose mass thereby diminishing melanoma progression. Therefore, strategic means of controlling obesity by reduced caloric diet or with antiobesity drugs treatment may render obesity-promoted tumor progression in check and prolong survival of patients.

  4. Adipokine Imbalance in the Pericardial Cavity of Cardiac and Vascular Disease Patients.

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    Atlanta G I M Elie

    Full Text Available Obesity and especially hypertrophy of epicardial adipose tissue accelerate coronary atherogenesis. We aimed at comparing levels of inflammatory and atherogenic hormones from adipose tissue in the pericardial fluid and circulation of cardiovascular disease patients.Venous plasma (P and pericardial fluid (PF were obtained from elective cardiothoracic surgery patients (n = 37. Concentrations of leptin, adipocyte fatty acid-binding protein (A-FABP and adiponectin (APN were determined by enzyme-linked immunosorbent assays (ELISA. The median concentration of leptin in PF (4.3 (interquartile range: 2.8-9.1 μg/L was comparable to that in P (5.9 (2.2-11 μg/L and these were significantly correlated to most of the same patient characteristics. The concentration of A-FABP was markedly higher (73 (28-124 versus 8.4 (5.2-14 μg/L and that of APN was markedly lower (2.8 (1.7-4.2 versus 13 (7.2-19 mg/L in PF compared to P. APN in PF was unlike in P not significantly related to age, body mass index, plasma triglycerides or coronary artery disease. PF levels of APN, but not A-FABP, were related to the size of paracardial adipocytes. PF levels of APN and A-FABP were not related to the immunoreactivity of paracardial adipocytes for these proteins.In cardiac and vascular disease patients, PF is enriched in A-FABP and poor in APN. This adipokine microenvironment is more likely determined by the heart than by the circulation or paracardial adipose tissue.

  5. Adipokines and biochemical changes in Egyptian obese subjects: possible variation with sex and degree of obesity.

    Science.gov (United States)

    El-Haggar, Sahar Mohamed; Mostafa, Tarek Mohamed

    2015-04-01

    The purpose of this study was firstly to evaluate the adipokines and biochemical changes in obese subjects in relation to different grades of obesity and in relation to gender difference (males versus females) and secondly to evaluate the role of TNF-α in obesity. From January 2013 to February 2014, a total number of 120 non-diabetic subjects of both sexes were recruited and randomly selected from Dr. Abd-Elhamid Elsheikh center for physiotherapy and weight control, El-menofia-Egypt. Those subjects were classified according to their sex into two main groups; the female group and the male group. The female group (60 women) was distributed according to BMI into group 1 (15 lean women), group 2 (15 class I obese women), group 3 (15 class II obese women), and group 4 (15 class III obese women). The male group (60 men) was also distributed according to the BMI into group 1 (15 lean men), group 2 (15 class I obese men), group 3 (15 class II obese men), and group 4 (15 class III obese men). All individuals enrolled in the study were submitted to weight and height measurements with subsequent calculation of body mass index. Fasting blood samples were collected from all participants for quantitative determination of blood glucose, serum lipid, TNF-α, leptin, and adiponectin levels. One-way analysis of variance followed by LSD post hoc test was used for comparison of variables. In obese subjects of both sexes, it was found that circulating leptin and TNF-α levels were significantly high (Pgender difference, although serum leptin and adiponectin levels were higher in women than men, men showed higher atherogenic parameters. We conclude that leptin, TNF-α, and adiponectin were related to both BMI and grades of obesity. Furthermore, TNF-α may play a role in obesity.

  6. Early weaning PCB 95 exposure alters the neonatal endocrine system: thyroid adipokine dysfunction.

    Science.gov (United States)

    Ahmed, R G

    2013-12-01

    Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that can severely disrupt the endocrine system. In the present study, early-weaned male rats were administered a single dose of 2,3,6-2',5'-pentachlorinated biphenyl (PCB 95; 32 mg/kg per day, by i.p. injection) for two consecutive days (postnatal days (PNDs) 15 and 16) and killed 24 and 48 h after the administration of the last dose. Compared with the control group, administration of PCB 95 induced a reduction (P<0.01) in serum concentrations of thyroxine, triiodothyronine, and GH and an increase (P<0.01) in the serum concentration of TSH at PNDs 17 and 18. These conspicuous perturbations led to some histopathological deterioration in the thyroid gland characterized by follicular degeneration, edema, fibrosis, hemorrhage, luminal obliteration, and hypertrophy with reduced colloidal contents at PND 18. The dyshormonogenesis and thyroid dysgenesis may be attributed to the elevation of DNA fragmentation at PNDs 17 and 18. Furthermore, this hypothyroid state revealed higher (P<0.01) serum concentrations of leptin, adiponectin, and tumor necrosis factor and lower (P<0.01) serum concentrations of IGF1 and insulin at both PNDs compared with the control group. Interestingly, the body weight of the neonates in the PCB 95 group exhibited severe decreases throughout the experimental period in relation to that of the control group. These results imply that PCB 95 may act as a disruptor of the developmental hypothalamic-pituitary-thyroid axis. Hypothyroidism caused by PCB 95 may impair the adipokine axis, fat metabolism, and in general postnatal development. Thus, further studies need to be carried out to understand this concept.

  7. Obesity and Its Metabolic Complications: The Role of Adipokines and the Relationship between Obesity, Inflammation, Insulin Resistance, Dyslipidemia and Nonalcoholic Fatty Liver Disease

    Science.gov (United States)

    Jung, Un Ju; Choi, Myung-Sook

    2014-01-01

    Accumulating evidence indicates that obesity is closely associated with an increased risk of metabolic diseases such as insulin resistance, type 2 diabetes, dyslipidemia and nonalcoholic fatty liver disease. Obesity results from an imbalance between food intake and energy expenditure, which leads to an excessive accumulation of adipose tissue. Adipose tissue is now recognized not only as a main site of storage of excess energy derived from food intake but also as an endocrine organ. The expansion of adipose tissue produces a number of bioactive substances, known as adipocytokines or adipokines, which trigger chronic low-grade inflammation and interact with a range of processes in many different organs. Although the precise mechanisms are still unclear, dysregulated production or secretion of these adipokines caused by excess adipose tissue and adipose tissue dysfunction can contribute to the development of obesity-related metabolic diseases. In this review, we focus on the role of several adipokines associated with obesity and the potential impact on obesity-related metabolic diseases. Multiple lines evidence provides valuable insights into the roles of adipokines in the development of obesity and its metabolic complications. Further research is still required to fully understand the mechanisms underlying the metabolic actions of a few newly identified adipokines. PMID:24733068

  8. Influence of resveratrol on endoplasmic reticulum stress and expression of adipokines in adipose tissues/adipocytes induced by high-calorie diet or palmitic acid.

    Science.gov (United States)

    Chen, Li; Wang, Ting; Chen, Guanjun; Wang, Nuojin; Gui, Li; Dai, Fang; Fang, Zhaohui; Zhang, Qiu; Lu, Yunxia

    2017-03-01

    This study aimed to determine whether resveratrol treatment alleviates endoplasmic reticulum stress and changes the expression of adipokines in adipose tissues and cells. 8-week-old male C57BL/6 mice were fed a high-calorie diet (HCD group) or high-calorie diet supplemented with resveratrol (high-calorie diet  + resveratrol group) for 3 months. Insulin resistance, serum lipids and proinflammatory indices, the size and inflammatory cell infiltration in subcutaneous and visceral adipose tissues were analyzed. The gene expressions of endoplasmic reticulum stress, adipokines, and inflammatory cytokines were determined. The induced mature 3T3-L1 cells were pretreated with resveratrol and then palmitic acid, and the gene expressions of endoplasmic reticulum stress, adipokines, and inflammatory cytokines were determined. Subcutaneous and visceral adipose tissues in the high-calorie diet-fed mice exhibited adipocyte hypertrophy, inflammatory activation, and endoplasmic reticulum stress. Resveratrol alleviated high-calorie diet-induced insulin resistance and endoplasmic reticulum stress, increased expression of SIRT1, and reversed expression of adipokines in varying degrees in both subcutaneous and visceral adipose tissues. The effects of resveratrol on palmitic acid-treated adipocytes were similar to those shown in the tissues. Resveratrol treatment obviously reversed adipocyte hypertrophy and insulin resistance by attenuating endoplasmic reticulum stress and inflammation, thus increasing the expression of SIRT1 and inverting the expression of adipokines in vivo and in vitro.

  9. Adipokine profile in celiac patients: differences in comparison with patients suffering from diarrhea-predominant IBS and healthy subjects.

    Science.gov (United States)

    Russo, Francesco; Chimienti, Guglielmina; Clemente, Caterina; D'Attoma, Benedetta; Linsalata, Michele; Orlando, Antonella; De Carne, Massimo; Cariola, Filomena; Semeraro, Francesco P; Pepe, Gabriella; Riezzo, Giuseppe

    2013-12-01

    OBJECTIVE. The role of adipokines such as resistin, leptin, and adiponectin could be pivotal in the molecular crosstalk between the inflamed intestine and the surrounding mesenteric adipose tissue. Our aims were to a) evaluate their circulating concentrations in patients with active celiac disease (ACD) and compare them to those in patients with diarrhea-predominant irritable bowel syndrome (IBS-d) and healthy subjects; b) establish the impact of genetic variability in resistin; and c) evaluate whether a 1-year gluten-free diet (GFD) modifies circulating concentrations of resistin, leptin, and adiponectin in celiac patients. MATERIAL AND METHODS. The study included 34 ACD patients, 29 IBS-d patients, and 27 healthy controls. Circulating concentrations of resistin, leptin, adiponectin, IL-6, and IL-8 were evaluated at the time of enrollment. Resistin +299 G/A polymorphism was also analysed. In CD patients, biochemical measurements were repeated after a 1-year GFD. RESULTS. Along with higher IL-6 and IL-8 plasma levels, higher resistin and adiponectin concentrations were found in ACD and IBS-d patients compared with controls (p: 0.0351 and p: 0.0020, respectively). Resistin values proved to be predictable from a linear combination of IL-8 and +299 polymorphism. GFD affected resistin (p: 0.0009), but not leptin and adiponectin concentrations. CONCLUSIONS. Our data suggest that these adipokines are involved in modulating inflammatory processes in both CD and IBS-d patients. Alterations in the adipokine profile as well as the higher prevalence of the resistin +299 G/A SNP A allele compared to controls support the hypothesis that, at least in well-defined cases of IBS, a genetic component may also be supposed.

  10. Breast cancer and obesity: in vitro interferences between adipokines and proangiogenic features and/or antitumor therapies?

    Science.gov (United States)

    Dubois, Virginie; Delort, Laetitia; Billard, Hermine; Vasson, Marie-Paule; Caldefie-Chezet, Florence

    2013-01-01

    Obesity is now considered as a risk factor for breast cancer in postmenopausal women. Adipokine levels are modulated in obesity, and may play a role in carcinogenesis. Moreover, obesity increases risk of cancer mortality. Here, we hypothesized that this increase could be due to a modification in angiogenesis, capital event in the development of metastases, and/or in effectiveness of cancer treatments. To test these assumptions, following a same experimental design and simultaneously the effects of leptin and adiponectin on angiogenesis were investigated, and the impact of hyperleptinemia on anticancer drug effectiveness was measured in physiological and obesity situations. Focusing on angiogenesis, the proliferation of endothelial cells (HUVEC), which expressed leptin and adiponectin receptors, was stimulated by leptin and inhibited by adiponectin. Both adipokines globally reduced apoptosis and caspase activity. Leptin increased migration whereas adiponectin decreased migration, and leptin enhanced the area of the tubes formed by HUVEC cells while adiponectin inhibited their formation. MCF7 and MDA-MB-231 cells treated with leptin secreted more VEGF than untreated cells, whereas adiponectin treatment inhibited VEGF secretion. Finally, MCF7 cells pre-treated with leptin were more invasive than untreated cells. This effect was not reproduced in MDA-MB-231 cells. In the MCF7 breast cancer cell line, leptin could induce cell proliferation and reduced the efficacy of all breast cancer therapies (tamoxifen, 5-fluorouracil, taxol and vinblastin). These results suggest that, in obesity situation, leptin- in contrast to adiponectin - may promote tumor invasion and angiogenesis, leading to metastases 'apparition, and reduce treatment efficacy, which could explain the increased risk of cancer mortality in cases of overweight. The evidence suggests adipokines influence breast cancer issue and could play a significant role, especially in obese patients for which hyperleptinemia

  11. Modulation of visceral fat adipokine secretion by dietary fatty acids and ensuing changes in skeletal muscle inflammation.

    Science.gov (United States)

    Tishinsky, Justine M; De Boer, Anna A; Dyck, David J; Robinson, Lindsay E

    2014-01-01

    Given the link between obesity and insulin resistance, the role of adipose-derived factors in communicating with skeletal muscle to affect its function is important. We sought to determine if high fat diets modulate visceral adipose tissue (VAT) adipokines with subsequent effects on skeletal muscle inflammation and insulin sensitivity. Rats were fed (i) low fat (LF), (ii) high saturated fatty acid (SFA), or (iii) high SFA with n-3 polyunsaturated fatty acid (SFA/n-3 PUFA) diets for 4 weeks. VAT-derived adipokines were measured in adipose conditioned medium (ACM) after 72 h. Next, skeletal muscles from LF-fed rats were incubated for 8 h in (i) control buffer (CON), (ii) CON with 2 mmol·L(-1) palmitate (PALM, positive control), (iii) ACM from LF, (iv) ACM from SFA, or (v) ACM from SFA/n-3 PUFA. ACM from rats fed SFA and SFA/n-3 PUFA had increased (P ≤ 0.05) interleukin-6 (IL-6) (+31%) and monocyte chemoattractant protein-1 (MCP-1) (+30%). Adiponectin was decreased (-29%, P ≤ 0.05) in ACM from SFA, and this was prevented in SFA/n-3 PUFA ACM. Toll-like receptor 4 (TLR4) gene expression was increased (P ≤ 0.05) in PALM soleus muscle (+356%) and all ACM groups (+175%-191%). MCP-1 gene expression was elevated (P ≤ 0.05) in PALM soleus muscle (+163%) and soleus muscle incubated in ACM from animals fed SFA (+159%) and SFA/n-3 PUFA (+151%). Glucose transport was impaired (P ≤ 0.05) in PALM muscles but preserved in ACM groups. Acute exposure of muscle to fatty acid modulated adipokines affects skeletal muscle inflammatory gene expression but not insulin sensitivity.

  12. Effects of a multi-component camp-based intervention on inflammatory markers and adipokines in children

    DEFF Research Database (Denmark)

    Huang, T.; Larsen, K. T.; Moller, N. C.

    2015-01-01

    arm (DCIA) or the standard intervention arm (SIA). The intervention for the DCIA consisted of a 6-week camp-based intervention and a 46-week family-based intervention. The SIA was offered one weekly physical activity session for 6 weeks and one educational meeting. C-reactive protein (CRP), monocyte......Objective. To examine the effects of a multi-component camp-based intervention on inflammatory markers and adipokines in children. Methods. One hundred and fifteen children were recruited in Odense, Denmark (2012-2014). The participants were randomly allocated to either the day camp intervention...

  13. Cardiotrophin-1 Regulates Adipokine Production in 3T3-L1 Adipocytes and Adipose Tissue From Obese Mice.

    Science.gov (United States)

    López-Yoldi, Miguel; Marcos-Gomez, Beatriz; Romero-Lozano, María Asunción; Sáinz, Neira; Prieto, Jesús; Martínez, Jose Alfredo; Bustos, Matilde; Moreno-Aliaga, Maria J

    2017-09-01

    Cardiotrophin-1 (CT-1) belongs to the IL-6 family of cytokines. Previous studies of our group revealed that CT-1 is a key regulator of glucose and lipid metabolism. The aim of the present study was to analyze the in vitro and in vivo effects of CT-1 on the production of several adipokines involved in body weight regulation, nutrient metabolism, and inflammation. For this purpose, 3T3-L1 adipocytes were incubated with recombinant protein CT-1 (rCT-1) (1-40 ng/ml) for 1 and 18 h. Moreover, the acute effects of rCT-1 administration (0.2 mg/kg, i.v.) for 30 min and 3 h on adipokines levels were also evaluated in high-fat fed obese mice. In 3T3-L1 adipocytes, rCT-1 treatment downregulated the expression and secretion of leptin, resistin, and visfatin. However, rCT-1 significantly stimulated apelin mRNA and secretion. rCT-1 (18 h) also promoted the activation by phosphorylation of AKT, ERK 1/2, and STAT3. Interestingly, pre-treatment with the PI3K inhibitor LY294002 reversed the stimulatory effects of rCT-1 on apelin expression, suggesting that this pathway could be mediating the effects of rCT-1 on apelin production. In contrast, acute administration of rCT-1 (30 min and 3 h) to diet-induced obese mice downregulated leptin and resistin, without significantly modifying apelin or visfatin mRNA in adipose tissue. Furthermore, CT-1 null mice exhibited altered expression of adipokines in adipose tissue. The present study demonstrates that rCT-1 modulates the production of adipokines in vitro and in vivo, suggesting that the regulation of the secretory function of adipocytes could be involved in the metabolic actions of this cytokine. J. Cell. Physiol. 232: 2469-2477, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  14. A prospective study of gynecological cancer risk in relation to adiposity factors: cumulative incidence and association with plasma adipokine levels.

    Directory of Open Access Journals (Sweden)

    Meei-Maan Wu

    Full Text Available BACKGROUND: Associations of obesity and obesity-related metabolic factors (adiposity factors with uterine corpus cancer (UCC and ovarian cancer (OVC risk have been described. Still, a cause-effect relationship and the underlying mediators remain unclear, particularly for low-incidence populations. We aimed to prospectively determine whether adiposity factors could predict the development of UCC and OVC in Taiwanese women. To explore the biological mediators linking adiposity factors to cancer risk, we examined the association of two adipokines, leptin and adiponectin, with the gynecological cancers. METHODS: Totally, 11,258 women, aged 30-65, were recruited into the Community-Based Cancer Screening Program (CBCSP study during 1991-1993, and were followed for UCC and OVC cases until December 31, 2011. Cox proportional hazard models were used to estimate hazard ratios (HRs. Adiposity factors and risk covariates were assessed at recruitment. Newly-developed cancer cases were determined from data in the government's National Cancer Registry and Death Certification System. For adipokienes study, a nested case-control study was conducted within the cohort. Baseline plasma samples of 40 incident gynecological cancer cases and 240 age-menopause-matched controls were assayed for adipokines levels. FINDINGS: There were 38 and 30 incident cases of UCC and OVC, respectively, diagnosed during a median 19.9 years of follow-up. Multivariate analysis showed that alcohol intake (HR = 16.00, 95%  = 4.83-53.00, high triglyceride levels (HR = 2.58, 95% = 1.28-5.17, and years of endogenous estrogen exposure per 5-year increment (HR = 1.91, 95%  = 1.08-3.38 were associated with increased UCC risk. High body mass index (BMI ≥ 27 kg/m(2, HR = 2.90, 95%  = 1.30-6.46 was associated with increased OVC risk. Analysis further showed an independent effect of adipokines on UCC and OVC risk after adjustment of the risk covariates. CONCLUSION: We provided evidence

  15. Targeting AMP-activated protein kinase in adipocytes to modulate obesity-related adipokine production associated with insulin resistance and breast cancer cell proliferation

    Directory of Open Access Journals (Sweden)

    Grisouard Jean

    2011-07-01

    Full Text Available Abstract Background Adipokines, e.g. TNFα, IL-6 and leptin increase insulin resistance, and consequent hyperinsulinaemia influences breast cancer progression. Beside its mitogenic effects, insulin may influence adipokine production from adipocyte stromal cells and paracrine enhancement of breast cancer cell growth. In contrast, adiponectin, another adipokine is protective against breast cancer cell proliferation and insulin resistance. AMP-activated protein kinase (AMPK activity has been found decreased in visceral adipose tissue of insulin-resistant patients. Lipopolysaccharides (LPS link systemic inflammation to high fat diet-induced insulin resistance. Modulation of LPS-induced adipokine production by metformin and AMPK activation might represent an alternative way to treat both, insulin resistance and breast cancer. Methods Human preadipocytes obtained from surgical biopsies were expanded and differentiated in vitro into adipocytes, and incubated with siRNA targeting AMPKalpha1 (72 h, LPS (24 h, 100 μg/ml and/or metformin (24 h, 1 mM followed by mRNA extraction and analyses. Additionally, the supernatant of preadipocytes or derived-adipocytes in culture for 24 h was used as conditioned media to evaluate MCF-7 breast cancer cell proliferation. Results Conditioned media from preadipocyte-derived adipocytes, but not from undifferentiated preadipocytes, increased MCF-7 cell proliferation (p Conclusions Adipocyte-secreted factors enhance breast cancer cell proliferation, while AMPK and metformin improve the LPS-induced adipokine imbalance. Possibly, AMPK activation may provide a new way not only to improve the obesity-related adipokine profile and insulin resistance, but also to prevent obesity-related breast cancer development and progression.

  16. Prediction of Nonalcoholic Fatty Liver Disease Via a Novel Panel of Serum Adipokines.

    Science.gov (United States)

    Jamali, Raika; Arj, Abbas; Razavizade, Mohsen; Aarabi, Mohammad Hossein

    2016-02-01

    Considering limitations of liver biopsy for diagnosis of nonalcoholic liver disease (NAFLD), biomarkers' panels were proposed. The aims of this study were to establish models based on serum adipokines for discriminating NAFLD from healthy individuals and nonalcoholic steatohepatitis (NASH) from simple steatosis.This case-control study was conducted in patients with persistent elevated serum aminotransferase levels and fatty liver on ultrasound. Individuals with evidence of alcohol consumption, hepatotoxic medication, viral hepatitis, and known liver disease were excluded. Liver biopsy was performed in the remaining patients to distinguish NAFLD/NASH. Histologic findings were interpreted using "nonalcoholic fatty liver activity score." Control group consisted of healthy volunteers with normal physical examination, liver function tests, and liver ultrasound. Binary logistic regression analysis was applied to ascertain the effects of independent variables on the likelihood that participants have NAFLD/NASH.Decreased serum adiponectin and elevated serum visfatin, IL-6, TNF-a were associated with an increased likelihood of exhibiting NAFLD. NAFLD discriminant score was developed as the following: [(-0.298 × adiponectin) + (0.022 × TNF-a) + (1.021 × Log visfatin) + (0.709 × Log IL-6) + 1.154]. In NAFLD discriminant score, 86.4% of original grouped cases were correctly classified. Discriminant score threshold value of (-0.29) yielded a sensitivity and specificity of 91% and 83% respectively, for discriminating NAFLD from healthy controls. Decreased serum adiponectin and elevated serum visfatin, IL-8, TNF-a were correlated with an increased probability of NASH. NASH discriminant score was proposed as the following: [(-0.091 × adiponectin) + (0.044 × TNF-a) + (1.017 × Log visfatin) + (0.028 × Log IL-8) - 1.787] In NASH model, 84% of original cases were correctly classified. Discriminant score threshold value of (-0.22) yielded a sensitivity and specificity of 90

  17. Different modulation by dietary restriction of adipokine expression in white adipose tissue sites in the rat

    Directory of Open Access Journals (Sweden)

    Esteve Montserrat

    2009-07-01

    Full Text Available Abstract Background White adipose tissue (WAT is a disperse organ acting as energy storage depot and endocrine/paracrine controlling factor in the management of energy availability and inflammation. WAT sites response under energy-related stress is not uniform. In the present study we have analyzed how different WAT sites respond to limited food restriction as a way to better understand the role of WAT in the pathogenesis of the metabolic syndrome. Methods Overweight male rats had their food intake reduced a 40% compared with free-feeding controls. On day ten, the rats were killed; circulating glucose, insulin, leptin, adiponectin, triacylglycerols and other parameters were measured. The main WAT sites were dissected: mesenteric, retroperitoneal, epididymal and subcutaneous inguinal, which were weighed and frozen. Later all subcutaneous WAT was also dissected and weighed. Samples were used for DNA (cellularity analysis and mRNA extraction and semiquantitarive RT-PCR analysis of specific cytokine gene expressions. Results There was a good correlation between serum leptin and cumulative WAT leptin gene mRNA, but not for adiponectin. Food restriction reduced WAT size, but not its DNA content (except for epididymal WAT. Most cytokines were correlated to WAT site weight, but not to DNA. There was WAT site specialization in the differential expression (and probably secretion of adipokines: subcutaneous WAT showed the highest concentration for leptin, CD68 and MCP-1, mesenteric WAT for TNFα (and both tissues for the interleukins 1β and 6; resistin was highly expressed in subcutaneous and retroperitoneal WAT. Conclusion Food restriction induced different patterns for mesenteric and the other WAT sites, which may be directly related to both the response to intestine-derived energy availability, and an inflammatory-related response. However, retroperitoneal WAT, and to a lower extent, subcutaneous and epididymal, reacted decreasing the expression of

  18. Resveratrol metabolites modify adipokine expression and secretion in 3T3-L1 pre-adipocytes and mature adipocytes.

    Directory of Open Access Journals (Sweden)

    Itziar Eseberri

    Full Text Available OBJECTIVE: Due to the low bioavailability of resveratrol, determining whether its metabolites exert any beneficial effect is an interesting issue. METHODS: 3T3-L1 maturing pre-adipocytes were treated during differentiation with 25 µM of resveratrol or with its metabolites and 3T3-L1 mature adipocytes were treated for 24 hours with 10 µM resveratrol or its metabolites. The gene expression of adiponectin, leptin, visfatin and apelin was assessed by Real Time RT-PCR and their concentration in the incubation medium was quantified by ELISA. RESULTS: Resveratrol reduced mRNA levels of leptin and increased those of adiponectin. It induced the same changes in leptin secretion. Trans-resveratrol-3-O-glucuronide and trans-resveratrol-4'-O-glucuronide increased apelin and visfatin mRNA levels. Trans-resveratrol-3-O-sulfate reduced leptin mRNA levels and increased those of apelin and visfatin. CONCLUSIONS: The present study shows for the first time that resveratrol metabolites have a regulatory effect on adipokine expression and secretion. Since resveratrol has been reported to reduce body-fat accumulation and to improve insulin sensitivity, and considering that these effects are mediated in part by changes in the analyzed adipokines, it may be proposed that resveratrol metabolites play a part in these beneficial effects of resveratrol.

  19. Lack of Platelet-Activating Factor Receptor Attenuates Experimental Food Allergy but Not Its Metabolic Alterations regarding Adipokine Levels

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    Nathália Vieira Batista

    2016-01-01

    Full Text Available Platelet-activating factor (PAF is known to be an important mediator of anaphylaxis. However, there is a lack of information in the literature about the role of PAF in food allergy. The aim of this work was to elucidate the participation of PAF during food allergy development and the consequent adipose tissue inflammation along with its alterations. Our data demonstrated that, both before oral challenge and after 7 days receiving ovalbumin (OVA diet, OVA-sensitized mice lacking the PAF receptor (PAFR showed a decreased level of anti-OVA IgE associated with attenuated allergic markers in comparison to wild type (WT mice. Moreover, there was less body weight and adipose tissue loss in PAFR-deficient mice. However, some features of inflamed adipose tissue presented by sensitized PAFR-deficient and WT mice after oral challenge were similar, such as a higher rate of rolling leukocytes in this tissue and lower circulating levels of adipokines (resistin and adiponectin in comparison to nonsensitized mice. Therefore, PAF signaling through PAFR is important for the allergic response to OVA but not for the adipokine alterations caused by this inflammatory process. Our work clarifies some effects of PAF during food allergy along with its role on the metabolic consequences of this inflammatory process.

  20. Metabolic syndrome, inflammation and atherosclerosis - the role of adipokines in health and in systemic inflammatory rheumatic diseases.

    Science.gov (United States)

    Santos, Maria José; Fonseca, João Eurico

    2009-01-01

    Cardiovascular (CV) events are among the leading causes of morbidity and mortality in patients with inflammatory rheumatic diseases. It has been hypothesized that, in addition to the traditional CV risk factors, inflammation is a major contributor to atherogenesis. Metabolic syndrome (MetS) stands for a cluster of risk factors associated with insulin resistance and increased abdominal fat. Inflammation and MetS are intimately linked. Inflammatory biomarkers are frequently elevated in people with MetS and, conversely, the prevalence of MetS is higher in patients with chronic inflammatory rheumatic diseases, such as Rheumatoid Arthritis and Systemic Lupus Erythematosus. Inflammatory cytokines impair insulin sensitivity and can induce an adverse lipoprotein profile as seen in MetS. Furthermore, the presence of MetS correlates with increased subclinical atherosclerosis, major adverse CV events and death, making an important contribution to the CV burden in inflammatory diseases. Adipose tissue has recently emerged as an active organ that produces and secretes numerous mediators - adipokines - particularly relevant in energy homeostasis, inflammation, immune regulation and angiogenesis. These mediators arise as a potential link between MetS, inflammation and atherogenesis. Understanding the complex regulation and function of adipokines in health and disease is a priority since it may lead to new preventive and therapeutic interventions aiming to decrease CV risk.

  1. 脂肪细胞因子与妊娠期糖尿病%Adipokines and gestational diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    刘冰

    2012-01-01

    妊娠期糖尿病严重威胁母婴健康,是社会公共卫生事业的关注重点.目前妊娠期糖尿病的发病机制尚未完全阐明,近年来脂肪因子在其发病机制中的作用备受关注.这些脂肪因子包括脂联素、瘦素、视黄醇结合蛋白-4、visfatin、vaspin、抵抗素和chemerin等.%Gestational diabetes meilitus is the diabetes firstly found or occurring after pregnancy, which is the one of high risk states in pregnancy. However, its etiology and pathogenesis is not very clear at present. Recent data suggest that various adipokines are dysregulated in gestational diabetes mellitus. These adipokines including adi-ponectin, leptin , retinol-binding protein 4, visfatin, vaspin, resistin and chemerin etc might be of pathophysiologi-cal and prognostic significance in these complications of pregnancy.

  2. Lack of Platelet-Activating Factor Receptor Attenuates Experimental Food Allergy but Not Its Metabolic Alterations regarding Adipokine Levels

    Science.gov (United States)

    Batista, Nathália Vieira; Fonseca, Roberta Cristelli; Perez, Denise; Pereira, Rafaela Vaz Sousa; de Lima Alves, Juliana; Pinho, Vanessa; Faria, Ana Maria Caetano; Cara, Denise Carmona

    2016-01-01

    Platelet-activating factor (PAF) is known to be an important mediator of anaphylaxis. However, there is a lack of information in the literature about the role of PAF in food allergy. The aim of this work was to elucidate the participation of PAF during food allergy development and the consequent adipose tissue inflammation along with its alterations. Our data demonstrated that, both before oral challenge and after 7 days receiving ovalbumin (OVA) diet, OVA-sensitized mice lacking the PAF receptor (PAFR) showed a decreased level of anti-OVA IgE associated with attenuated allergic markers in comparison to wild type (WT) mice. Moreover, there was less body weight and adipose tissue loss in PAFR-deficient mice. However, some features of inflamed adipose tissue presented by sensitized PAFR-deficient and WT mice after oral challenge were similar, such as a higher rate of rolling leukocytes in this tissue and lower circulating levels of adipokines (resistin and adiponectin) in comparison to nonsensitized mice. Therefore, PAF signaling through PAFR is important for the allergic response to OVA but not for the adipokine alterations caused by this inflammatory process. Our work clarifies some effects of PAF during food allergy along with its role on the metabolic consequences of this inflammatory process. PMID:27314042

  3. Changes in IGF-I, urinary free cortisol and adipokines during dronabinol therapy in anorexia nervosa: Results from a randomised, controlled trial

    DEFF Research Database (Denmark)

    Andries, Alin; Frystyk, Jan; Flyvbjerg, Allan

    2015-01-01

    , separated by a four-week washout period. Bioactive IGF was determined by a cell-based bioassay, whereas total IGF-I, IGFBP-2 and -3 and the two adipokines leptin and adiponectines were measured by immunoassays. The UFC excretion was determined by mass spectrometry. RESULTS: As previously reported...

  4. Effects of regular exercise on obesity and type 2 diabete mellitus in Korean children: improvements glycemic control and serum adipokines level

    Science.gov (United States)

    Lee, Sung Soo; Kang, Sunghwun

    2015-01-01

    [Purpose] The aim of the study was to clarify the effects of regular exercise on lipid profiles and serum adipokines in Korean children. [Subjects and Methods] Subjects were divided into controls (n=10), children who were obese (n=10), and children with type 2 diabetes mellitus (n=10). Maximal oxygen uptake (VO2max), body composition, lipid profiles, glucagon, insulin and adipokines (leptin, resistin, visfatin and retinol binding protein 4) were measured before to and after a 12-week exercise program. [Results] Body weight, body mass index, and percentage body fat were significantly higher in the obese and diabetes groups compared with the control group. Total cholesterol, triglycerides, low-density lipoprotein cholesterol and glycemic control levels were significantly decreased after the exercise program in the obese and diabetes groups, while high-density lipoprotein cholesterol levels were significantly increased. Adipokines were higher in the obese and diabetes groups compared with the control group prior to the exercise program, and were significantly lower following completion. [Conclusion] These results suggest that regular exercise has positive effects on obesity and type 2 diabetes mellitus in Korean children by improving glycemic control and reducing body weight, thereby lowering cardiovascular risk factors and adipokine levels. PMID:26180345

  5. Ceruloplasmin is a novel adipokine which is overexpressed in adipose tissue of obese subjects and in obesity-associated cancer cells

    NARCIS (Netherlands)

    Arner, Erik; Forrest, Alistair R R; Ehrlund, Anna; Mejhert, Niklas; Itoh, Masayoshi; Kawaji, Hideya; Lassmann, Timo; Laurencikiene, Jurga; Rydén, Mikael; Arner, Peter; Clevers, Hans

    2014-01-01

    Obesity confers an increased risk of developing specific cancer forms. Although the mechanisms are unclear, increased fat cell secretion of specific proteins (adipokines) may promote/facilitate development of malignant tumors in obesity via cross-talk between adipose tissue(s) and the tissues prone

  6. Ceruloplasmin is a novel adipokine which is overexpressed in adipose tissue of obese subjects and in obesity-associated cancer cells.

    Science.gov (United States)

    Arner, Erik; Forrest, Alistair R R; Ehrlund, Anna; Mejhert, Niklas; Itoh, Masayoshi; Kawaji, Hideya; Lassmann, Timo; Laurencikiene, Jurga; Rydén, Mikael; Arner, Peter

    2014-01-01

    Obesity confers an increased risk of developing specific cancer forms. Although the mechanisms are unclear, increased fat cell secretion of specific proteins (adipokines) may promote/facilitate development of malignant tumors in obesity via cross-talk between adipose tissue(s) and the tissues prone to develop cancer among obese. We searched for novel adipokines that were overexpressed in adipose tissue of obese subjects as well as in tumor cells derived from cancers commonly associated with obesity. For this purpose expression data from human adipose tissue of obese and non-obese as well as from a large panel of human cancer cell lines and corresponding primary cells and tissues were explored. We found expression of ceruloplasmin to be the most enriched in obesity-associated cancer cells. This gene was also significantly up-regulated in adipose tissue of obese subjects. Ceruloplasmin is the body's main copper carrier and is involved in angiogenesis. We demonstrate that ceruloplasmin is a novel adipokine, which is produced and secreted at increased rates in obesity. In the obese state, adipose tissue contributed markedly (up to 22%) to the total circulating protein level. In summary, we have through bioinformatic screening identified ceruloplasmin as a novel adipokine with increased expression in adipose tissue of obese subjects as well as in cells from obesity-associated cancers. Whether there is a causal relationship between adipose overexpression of ceruloplasmin and cancer development in obesity cannot be answered by these cross-sectional comparisons.

  7. Effect of weight loss with or without exercise on inflammatory markers and adipokines in postmenopausal women : The SHAPE-2 Trial, a randomized controlled trial

    NARCIS (Netherlands)

    Van Gemert, Willemijn A.; May, Anne M.|info:eu-repo/dai/nl/304818658; Schuit, Albertine J.; Oosterhof, Blanche Y M; Peeters, Petra H.|info:eu-repo/dai/nl/074099655; Monninkhof, Evelyn M.|info:eu-repo/dai/nl/260610178

    2016-01-01

    Background: We investigated the effect of equivalent weight loss, by a hypocaloric diet or mainly exercise, on inflammatory markers and adipokines in overweight postmenopausal women. Methods: Women were randomized to a diet (n = 97), mainly exercise (n = 98), or control group (n = 48). Goal of both

  8. Lifestyle intervention and adipokine levels in subjects at high risk for type 2 diabetes: the study on lifestyle intervention and impaired glucose tolerance Maastricht (SLIM)

    NARCIS (Netherlands)

    Corpeleijn, E.; Feskens, E.J.M.; Jansen, E.H.; Mensink, M.R.; Saris, W.H.M.; Blaak, E.E.

    2007-01-01

    OBJECTIVE¿We investigated whether circulating adipokine concentrations can be altered by lifestyle intervention according to general recommendations in subjects at risk for diabetes as well as the potential of leptin, adiponectin, and resistin as biomarkers for lifestyle-induced improvements in gluc

  9. Effect of weight loss with or without exercise on inflammatory markers and adipokines in postmenopausal women : The SHAPE-2 Trial, a randomized controlled trial

    NARCIS (Netherlands)

    Van Gemert, Willemijn A.; May, Anne M.; Schuit, Albertine J.; Oosterhof, Blanche Y M; Peeters, Petra H.; Monninkhof, Evelyn M.

    2016-01-01

    Background: We investigated the effect of equivalent weight loss, by a hypocaloric diet or mainly exercise, on inflammatory markers and adipokines in overweight postmenopausal women. Methods: Women were randomized to a diet (n = 97), mainly exercise (n = 98), or control group (n = 48). Goal of both

  10. Ceruloplasmin is a novel adipokine which is overexpressed in adipose tissue of obese subjects and in obesity-associated cancer cells

    NARCIS (Netherlands)

    Arner, Erik; Forrest, Alistair R R; Ehrlund, Anna; Mejhert, Niklas; Itoh, Masayoshi; Kawaji, Hideya; Lassmann, Timo; Laurencikiene, Jurga; Rydén, Mikael; Arner, Peter; Clevers, Hans

    2014-01-01

    Obesity confers an increased risk of developing specific cancer forms. Although the mechanisms are unclear, increased fat cell secretion of specific proteins (adipokines) may promote/facilitate development of malignant tumors in obesity via cross-talk between adipose tissue(s) and the tissues prone

  11. Effects of regular exercise on obesity and type 2 diabete mellitus in Korean children: improvements glycemic control and serum adipokines level.

    Science.gov (United States)

    Lee, Sung Soo; Kang, Sunghwun

    2015-06-01

    [Purpose] The aim of the study was to clarify the effects of regular exercise on lipid profiles and serum adipokines in Korean children. [Subjects and Methods] Subjects were divided into controls (n=10), children who were obese (n=10), and children with type 2 diabetes mellitus (n=10). Maximal oxygen uptake (VO2max), body composition, lipid profiles, glucagon, insulin and adipokines (leptin, resistin, visfatin and retinol binding protein 4) were measured before to and after a 12-week exercise program. [Results] Body weight, body mass index, and percentage body fat were significantly higher in the obese and diabetes groups compared with the control group. Total cholesterol, triglycerides, low-density lipoprotein cholesterol and glycemic control levels were significantly decreased after the exercise program in the obese and diabetes groups, while high-density lipoprotein cholesterol levels were significantly increased. Adipokines were higher in the obese and diabetes groups compared with the control group prior to the exercise program, and were significantly lower following completion. [Conclusion] These results suggest that regular exercise has positive effects on obesity and type 2 diabetes mellitus in Korean children by improving glycemic control and reducing body weight, thereby lowering cardiovascular risk factors and adipokine levels.

  12. Effect of a low-carbohydrate diet versus a low-fat, calorie-restricted diet on adipokine levels in obese, diabetic participants

    Directory of Open Access Journals (Sweden)

    Marion L Vetter

    2010-10-01

    Full Text Available Marion L Vetter1,2,3, Alisha Wade1, Leslie G Womble3, Cornelia Dalton-Bakes1, Thomas A Wadden3, Nayyar Iqbal1,21Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA; 2Division of Endocrinology, Department of Medicine, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA; 3Department of Psychiatry, Center for Weight and Eating Disorders, University of Pennsylvania School of Medicine, Philadelphia, PA, USAAbstract: The effect of dietary macronutrient composition on adipokine concentrations remains unclear. Greater reductions in leptin have been reported in participants who followed low-carbohydrate versus low-fat diets, although these studies did not adjust for the important effects of weight loss on adipokines. We investigated the effect of macronutrient composition on adipokine levels in 144 obese, diabetic participants who were randomly assigned to a low-carbohydrate (<30 g/day or low-fat diet (≤30% of calories from fat with a deficit of 500 kcal/day. Weight, adipokines, and dietary intake were assessed at baseline and 6 months. Complete data were available for 79 participants. At month 6, weight, leptin, adiponectin, and tumor necrosis factor-a concentrations did not differ significantly between groups (P > 0.05 for all variables. However, significant changes in leptin and adiponectin occurred over time (P < 0.001 and P < 0.012, respectively. Modest weight loss, rather than macronutrient composition, likely accounted for the favorable changes observed in leptin and adiponectin over time.Keywords: diet, adipokine, obesity, diabetes, carbohydrate, hormone

  13. [Role of the fatty acids in ovarian functions: involvement of peroxisome proliferator-activated receptors (PPAR) and adipokines].

    Science.gov (United States)

    Dupont, J; Froment, P; Ramé, C; Pierre, P; Coyral-Castel, S; Chabrolle, C

    2008-12-01

    The impact of nutrition and energy reserves on the reproductive functions is known for a very long time. However, the metabolic factors involved in the interactions between nutrition and reproduction are still poorly understood. These factors may be hormones or nutrients (glucose, protein and fatty acids). However, it remains to determine whether these factors act directly or indirectly on the reproductive tissues. In this issue, we briefly summarize the impact of fatty acids on the development of ovarian follicles, oocyte and embryo. We then discuss the current hypotheses about the mechanisms of action of these fatty acids on the ovarian functions. We describe more particularly the role of some receptors of fatty acids, Peroxisome Proliferator-Activated Receptors (PPAR) and Liver X Receptors (LXR) and two adipokines, leptin and adiponectin on ovarian cells.

  14. Nrg4 promotes fuel oxidation and a healthy adipokine profile to ameliorate diet-induced metabolic disorders.

    Science.gov (United States)

    Chen, Zhimin; Wang, Guo-Xiao; Ma, Sara L; Jung, Dae Young; Ha, Hyekyung; Altamimi, Tariq; Zhao, Xu-Yun; Guo, Liang; Zhang, Peng; Hu, Chun-Rui; Cheng, Ji-Xin; Lopaschuk, Gary D; Kim, Jason K; Lin, Jiandie D

    2017-08-01

    Brown and white adipose tissue exerts pleiotropic effects on systemic energy metabolism in part by releasing endocrine factors. Neuregulin 4 (Nrg4) was recently identified as a brown fat-enriched secreted factor that ameliorates diet-induced metabolic disorders, including insulin resistance and hepatic steatosis. However, the physiological mechanisms through which Nrg4 regulates energy balance and glucose and lipid metabolism remain incompletely understood. The aims of the current study were: i) to investigate the regulation of adipose Nrg4 expression during obesity and the physiological signals involved, ii) to elucidate the mechanisms underlying Nrg4 regulation of energy balance and glucose and lipid metabolism, and iii) to explore whether Nrg4 regulates adipose tissue secretome gene expression and adipokine secretion. We examined the correlation of adipose Nrg4 expression with obesity in a cohort of diet-induced obese mice and investigated the upstream signals that regulate Nrg4 expression. We performed metabolic cage and hyperinsulinemic-euglycemic clamp studies in Nrg4 transgenic mice to dissect the metabolic pathways regulated by Nrg4. We investigated how Nrg4 regulates hepatic lipid metabolism in the fasting state and explored the effects of Nrg4 on adipose tissue gene expression, particularly those encoding secreted factors. Adipose Nrg4 expression is inversely correlated with adiposity and regulated by pro-inflammatory and anti-inflammatory signaling. Transgenic expression of Nrg4 increases energy expenditure and augments whole body glucose metabolism. Nrg4 protects mice from diet-induced hepatic steatosis in part through activation of hepatic fatty acid oxidation and ketogenesis. Finally, Nrg4 promotes a healthy adipokine profile during obesity. Nrg4 exerts pleiotropic beneficial effects on energy balance and glucose and lipid metabolism to ameliorate obesity-associated metabolic disorders. Biologic therapeutics based on Nrg4 may improve both type 2

  15. Effects of C-reactive protein on adipokines genes expression in 3T3-L1 adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, Guoyue, E-mail: yuanguoyue@hotmail.com [Department of Endocrinology, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001 (China); Jia, Jue; Di, Liangliang [Department of Endocrinology, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001 (China); Zhou, Libin [Ruijin Hospital, Center of Molecular Medicine, Shanghai Institute of Endocrine and Metabolic Diseases, State Key Laboratory of Medical Genomics, Shanghai Jiaotong University Medical School, 197, Ruijin Road II, Shanghai 200025 (China); Dong, Sijing; Ye, Jingjing; Wang, Dong; Yang, Ling; Wang, Jifang [Department of Endocrinology, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001 (China); Li, Lianxi [Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People' s Hospital, 600, Yishan Road, Shanghai 200233 (China); Yang, Ying [Ruijin Hospital, Center of Molecular Medicine, Shanghai Institute of Endocrine and Metabolic Diseases, State Key Laboratory of Medical Genomics, Shanghai Jiaotong University Medical School, 197, Ruijin Road II, Shanghai 200025 (China); Mao, Chaoming [Department of Endocrinology, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001 (China); Chen, Mingdao, E-mail: mingdaochensh@yahoo.com [Ruijin Hospital, Center of Molecular Medicine, Shanghai Institute of Endocrine and Metabolic Diseases, State Key Laboratory of Medical Genomics, Shanghai Jiaotong University Medical School, 197, Ruijin Road II, Shanghai 200025 (China)

    2012-08-03

    Highlights: Black-Right-Pointing-Pointer CRP increases TNF-{alpha} and IL-6 genes expression in matured 3T3-L1 adipocytes. Black-Right-Pointing-Pointer CRP suppresses adiponectin, leptin and PPAR-{gamma} mRNA levels in matured 3T3-L1 cells. Black-Right-Pointing-Pointer Wortmannin reverses effects of CRP on adiponectin, TNF-{alpha} and leptin mRNA levels. Black-Right-Pointing-Pointer CRP may regulate IR, obesity and metabolic syndrome by this mechanism. -- Abstract: Adipose tissue is now recognized to be an important endocrine organ, secreting a variety of adipokines that are involved in the regulation of energy metabolism, insulin resistance and metabolic syndrome. C-reactive protein (CRP) is considered as one of the most sensitive markers of inflammation. A number of studies have shown that elevation of CRP concentrations is an independent predictive parameter of type 2 diabetes mellitus, which is also strongly associated with various components of the metabolic syndrome. The aim of the present study is to investigate the effects of CRP on adipokines genes expression in 3T3-L1 adipocytes. Quantitative real-time PCR analysis revealed that CRP inhibited adiponectin, leptin and peroxisome proliferator-activated receptor-gamma (PPAR-{gamma}) genes expression and raised tumor necrosis factor-{alpha} (TNF-{alpha}) and interleukin-6 (IL-6) mRNA levels in matured 3T3-L1 adipocytes in a dose and time-dependent manner. Pharmacological inhibition of phosphatidylinositol (PI)-3 kinase by wortmannin partially reversed the effects of CRP on adiponectin, TNF-{alpha} and leptin genes expression. These results collectively suggest that CRP regulates adiponectin, TNF-{alpha}, leptin, IL-6 and PPAR-{gamma} genes expression, and that might represent a mechanism by which CRP regulates insulin resistance, obesity and metabolic syndrome.

  16. The impact of aerobic exercise training on novel adipokines, apelin and ghrelin, in patients with type 2 diabetes.

    Science.gov (United States)

    Kadoglou, Nikolaos P E; Vrabas, Ioannis S; Kapelouzou, Alkistis; Lampropoulos, Stilianos; Sailer, Nikolaos; Kostakis, Alkiviadis; Liapis, Christos D; Angelopoulou, Nikoletta

    2012-05-01

    Accumulating data support the atheroprotective role of the novel adipokines, apelin and ghrelin. The aim of the present randomized study was to investigate the effects of aerobic exercise training on these adipokines in patients with type 2 diabetes mellitus (T2DM). Fifty-four overweight (BMI >25 kg/m²) patients with T2DM, but without vascular complications, were randomized to either the aerobic exercise training group (EG, N=27), 4 times/week, 45-60 min/session; or to the control group (CG, N=27), orally instructed to increase physical activity. Clinical glycemic and lipid parameters, exercise capacity (VO₂peak), insulin, HOMA-IR, and serum levels of apelin and ghrelin were assessed at baseline and after 12 weeks. Aerobic exercise significantly improved lipid and glycemic profile and insulin sensitivity compared to CG (pexercise-induced upregulation in apelin (p=0.007) and VO₂peak (pghrelin concentrations were detected within and between groups after the completion of the study (p>0.05). However, subgroup analysis revealed a considerable increment in ghrelin levels only in the exercise-treated women compared to their control counterparts (p=0.038). LDL and HOMA-IR reduction were found to be independent predictors of apelin increment in multiple regression analysis (R²=0.391, p=0.011). In patients with T2DM, systemic, long-term, aerobic exercise exerts positive effects on apelin and ghrelin (only in women), even in the absence of significant weight loss, suggesting its pleiotropic effects.

  17. Ectopic fat and adipokines in metabolically benign overweight/obese women: the Kronos Early Estrogen Prevention Study.

    Science.gov (United States)

    Ogorodnikova, Alexandra D; Khan, Unab I; McGinn, Aileen P; Zeb, Irfan; Budoff, Matthew J; Harman, S M; Miller, Virginia M; Brinton, Eliot A; Manson, JoAnn E; Hodis, Howard N; Merriam, George R; Cedars, Marcelle I; Taylor, Hugh S; Naftolin, Frederick; Lobo, Rogerio A; Santoro, Nanette; Wildman, Rachel P

    2013-08-01

    It is unclear why despite a comparable cardiometabolic risk profile, "metabolically benign" overweight/obese individuals show an elevated risk of cardiovascular disease compared to normal weight individuals. In cross-sectional analyses, we compared levels of ectopic fat (epicardial, pericardial, and hepatic fat) and adipokines (leptin, soluble leptin receptor, and high molecular weight [HMW] adiponectin) among metabolically benign (MBO) and at-risk overweight/obese (ARO), and metabolically benign normal weight (MBNW) women, screened for the Kronos Early Estrogen Prevention Study. We defined "metabolically benign" with ≤ 1, and "at-risk" with ≥2 components of the metabolic syndrome. Compared to MBO women, ARO women had significantly elevated odds of being in the top tertile of epicardial fat (OR: 1.76, 95% CI: 1.04-2.99), hepatic fat (OR: 1.90, 95% CI:1.12-3.24) and leptin (OR: 2.15, 95% CI: 1.23-3.76), and the bottom tertile of HMW-adiponectin (OR: 2.90, 95% CI: 1.62-5.19). Compared to MBNW women, MBO women had significantly higher odds of being in the top tertile of epicardial fat (OR: 5.17, 95% CI: 3.22-8.29), pericardial fat (OR: 9.27, 95% CI: 5.52-15.56) and hepatic fat (OR: 2.72, 95% CI: 1.77-4.19) and the bottom tertile of HMW adiponectin levels (OR: 2.51, 95% CI: 1.60-3.94). Levels of ectopic fat and the adverse adipokine profile increase on a continuum of BMI, suggesting that the metabolically benign phenotype may be a transient state. Copyright © 2013 The Obesity Society.

  18. Effect of exercise training combined with phytoestrogens on adipokines and C-reactive protein in postmenopausal women: a randomized trial.

    Science.gov (United States)

    Riesco, Eléonor; Choquette, Stéphane; Audet, Mélisa; Lebon, Johann; Tessier, Daniel; Dionne, Isabelle J

    2012-02-01

    Phytoestrogens and training could be effective to reduce cardiovascular and type 2 diabetes mellitus risk factors in postmenopausal women. Nevertheless, the impact of their combination on adipokines and systemic inflammation was never investigated. The objective was to verify if 6 months of mixed training combined with phytoestrogens could have an additional effect on adipokine levels and systemic inflammation in obese postmenopausal women. Fifty-two obese women aged between 50 and 70 years were randomly assigned to (1) exercise with placebo (EX + PL; n = 25) or (2) exercise with phytoestrogens (EX + PHY; n = 27). Body weight, waist circumference, fat mass, and lean body mass (dual-energy x-ray absorptiometry) were assessed. Fasting plasma glucose and insulin, adiponectin, leptin, and C-reactive protein (CRP) levels were obtained after a 12-hour overnight fast. Total energy intake was measured with a 3-day dietary record. All measurements were performed before and after the 6-month intervention. Although energy intake remained unchanged, body composition was improved in all women (all Ps phytoestrogens. Correlation analyses showed that homeostasis model assessment of insulin resistance (r = -0.58, P = .02) and fasting insulin levels (r = -0.42, P = .02) at baseline were both correlated with changes in leptin levels. Baseline fasting glucose (r = -0.36, P = .03) and adiponectin (r = 0.45, P = .005) levels were associated with changes in CRP concentrations. Although mixed exercise program combined with phytoestrogens does not seem to provide any additional effect, mixed training improves systemic inflammation and leptin concentrations in obese postmenopausal women.

  19. Pro-inflammatory adipokines as predictors of incident cancers in a Chinese cohort of low obesity prevalence in Hong Kong.

    Directory of Open Access Journals (Sweden)

    Chun-Yip Yeung

    Full Text Available BACKGROUND: Cytokines released from adipose tissues induce chronic low-grade inflammation, which may enhance cancer development. We investigated whether indices of obesity and circulating adipokine levels could predict incident cancer risk. MATERIALS AND METHODS: This longitudinal community-based study included subjects from the Hong Kong Cardiovascular Risk Factors Prevalence Study (CRISPS study commenced in 1995-1996 (CRISP-1 with baseline assessments including indices of obesity. Subjects were reassessed in 2000-2004 (CRISPS-2 with measurement of serum levels of adipokines including interleukin-6 (IL-6, soluble tumor necrosis factor receptor 2 (sTNFR2; as a surrogate marker of tumor necrosis factor-α activity, leptin, lipocalin 2, adiponectin and adipocyte-fatty acid binding protein (A-FABP. Incident cancer cases were identified up to 31 December 2011. RESULTS: 205 of 2893 subjects recruited at CRISPS-1 had developed incident cancers. More of the subjects who developed cancers were obese (22.1 vs 16.1% or had central obesity (36.6 vs 24.5% according to Asian cut-offs. Waist circumference (adjusted HR 1.02 [1.00-1.03] per cm; p=0.013, but not body mass index (adjusted HR 1.04 [1.00-1.08] per kg/m²; p=0.063, was a significant independent predictor for incident cancers after adjustment for age, sex and smoking status. 99 of 1899 subjects reassessed at CRISPS-2 had developed cancers. Subjects who developed cancers had significantly higher level of hsCRP, IL-6, sTNFR2 and lipocalin 2. After adjustment for conventional risk factors, only IL-6 (HR 1.51, 95% CI 1.18-1.95 and sTNFR2 (HR 3.27, 95%CI 1.65-6.47 predicted cancer development. CONCLUSIONS: Our data supported the increased risk of malignancy by chronic low grade inflammation related to central obesity.

  20. Effect of the Pro12Ala Polymorphism of the Peroxisome Proliferator-activated Receptor γ2 Gene on Lipid Profile and Adipokines Levels in Obese Subjects.

    Science.gov (United States)

    Becer, E; Çırakoğlu, A

    2017-06-30

    Peroxisome proliferator-activated receptor γ (PPARγ) is a key regulator of metabolism, adipokines production and secretion. The aim of this study was to investigate the association between the PPARγ2 gene Pro12Ala polymorphism in obesity in terms of body mass index (BMI), lipid parameters, homeostasis model assessment of insulin resistance (HOMA-IR), serum lipid, leptin, adiponectin, resistin and chemerin levels. The study included 160 obese and 140 non obese subjects. The Pro12Ala polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Serum lipid, leptin, adiponectin, resistin and chemerin levels were measured. No association was found between the Pro12Ala polymorphism and BMI. Strikingly, in the study group, obese subjects with the AA genotype had significantly higher triglycerides (p = 0.046) and resistin (p Pro12Ala polymorphism has no direct association with obesity but does have significant influences on lipid profiles and adipokines levels.

  1. The effects of an eight-week aerobic training program on plasma adipokine concentrations in middle-aged men

    Directory of Open Access Journals (Sweden)

    Rashidlamir A

    2011-05-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Obesity is currently a worldwide health epidemic which has incited major interest among researchers to look for the underlying mechanisms that regulate body weight. In fact, adiponectin and leptin concentrations that are called adipokines are altered in obesity with a decreased production of adiponectin and an increased production of leptin. Adiponectin has anti-inflammatory, anti-atherosclerotic and anti-insulin resistance properties, but increased levels of leptin are observed in patients with diabetes and cardiovascular diseases. The aim of the present study was to investigate the effects of an 8-week aerobic training program on the plasma levels of adiponectin and leptin in healthy middle-aged men. "n"nMethods : Thirty healthy middle-aged men were selected based on their body fat percentage and were assigned to two equal groups. The experimental group took the 8-week training, four days a week on alternate days with an intensity of 60-80% of their heart rate reserve but the control group lived their sedentary life. Blood samples were collected before and after the training program from all subjects and plasma adipokine levels were measured."n"nResults : Plasma adiponectin concentration increased while

  2. Influence of Weight Loss, Body Composition, and Lifestyle Behaviors on Plasma Adipokines: A Randomized Weight Loss Trial in Older Men and Women with Symptomatic Knee Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Gary D. Miller

    2012-01-01

    Full Text Available Objective. To investigate effects of weight loss on adipokines and health measures in obese older adults with symptomatic knee osteoarthritis. Methods. Participants were randomly assigned to either weight loss (WL (men: 12, women: 14 or weight stable (WS group (men: 12, women: 13. WL intervention included meal replacements and structured exercise training. Measurements of leptin, adiponectin, soluble leptin receptor, lifestyle behaviors, and body composition were collected at baseline and 6 months. Univariate analysis of covariance was performed on 6 month variables, and Spearman and partial correlations were made between variables. Results. Weight loss was 13.0% and 6.7% in WL for men and women, respectively. Women in WL had lower whole body and trunk fat than WS. The leptin : adiponectin ratio was lower for women in WL than WS at 6 months, with no group differences in adipokines for men. Leptin and free leptin index correlated with body fat in both genders at baseline. Interestingly, only women showed reductions in leptin (P<0.100 and correlations between the percentage change leptin and trunk fat and the percentage changes in free leptin index with total fat and trunk fat. Partial correlations between 6 month adipokines after adjustments for covariates and group/time period show potential multivariate influences. Conclusions. In the presence of an effective weight loss intervention in older obese adults, there are significant relationships between weight and fat loss and leptin in women, but not men, suggesting gender-specific features of adipokine metabolism in this age group.

  3. Effects of a walking intervention using mobile technology and interactive voice response on serum adipokines among postmenopausal women at increased breast cancer risk

    Science.gov (United States)

    Llanos, Adana A.M.; Krok, Jessica L.; Peng, Juan; Pennell, Michael L.; Vitolins, Mara Z.; Degraffinreid, Cecilia R.; Paskett, Electra D.

    2014-01-01

    Practical methods to reduce the risk of obesity-related breast cancer among high-risk subgroups are lacking. Few studies have investigated the effects of exercise on circulating adipokines, which have been shown to be associated with obesity and breast cancer. The aim of this study was to examine the effects of a walking intervention on serum adiponectin, leptin and the adiponectin-to-leptin ratio (A/L). Seventy-one overweight and obese postmenopausal women at increased risk of developing breast cancer were stratified by BMI (25-30 kg/m2 or >30 kg/m2) and randomized to a 12-week, 2-arm walking intervention administered through interactive voice response (IVR) and mobile devices. The intervention arms were: IVR + coach and IVR + no coach condition. Pre-post changes in serum adiponectin, leptin and the A/L ratio were examined using mixed regression models, with ratio estimates (and 95% confidence intervals [CI]) corresponding to post-intervention adipokine concentrations relative to pre-intervention concentrations. While post-intervention effects included statistically significant improvements in anthropometric measures, the observed decreases in adiponectin and leptin (Ratio=0.86, 95% CI 0.74-1.01 and Ratio=0.94, 95% CI 0.87-1.01, respectively) and increase in A/L (Ratio=1.09, 95% CI 0.94-1.26) were not significant. Thus, these findings do not support significant effects of the walking intervention on circulating adipokines among overweight and obese postmenopausal women. Additional studies are essential to determine the most effective and practical lifestyle interventions that can promote beneficial modification of serum adipokine concentrations, which may prove useful for obesity-related breast cancer prevention. PMID:24435584

  4. Inflammatory adipokines, high molecular weight adiponectin, and insulin resistance: a population-based survey in prepubertal schoolchildren.

    Directory of Open Access Journals (Sweden)

    Giuseppe Murdolo

    Full Text Available BACKGROUND: The aim of this study was to investigate sex differences and associations of high molecular weight (HMW adiponectin, leptin and proinflammatory adipokines, individually or in combinations, with adiposity and insulin resistance (IR measures in prepubertal childhood. METHODOLOGY: We studied 305 prepubertal children (boys/girls: 144/161; Tanner stage 1; age: 5-13 yr, included in a cohort of 44,231 adolescents who participated in an extensive Italian school-based survey. According to Cole's criteria, 105 individuals were lean (L; boys/girls: 59/46, 60 overweight (OW; boys/girls: 32/28 and 140 obese (OB; boys/girls: 70/70. Measurements comprised total and HMW adiponectin, leptin, as well as a panel of proinflammatory adipokines/chemokines associated with diabetes risk. PRINCIPAL FINDINGS: Leptin-, and the leptin-to-HMW adiponectin ratio (L/HMW-, increased progressively (p<0.0001 from L to OW to OB boys and girls. When compared with L peers, OW and OB girls exhibited lower (p<0.001 HMW adiponectin levels, while in boys the HMW multimers did not differ significantly across the BMI-stratified groups. OB girls displayed higher (p<0.05 IL-8, IL-18, monocyte chemoattractant protein-1 (MCP-1 and soluble intercellular adhesion molecule-1 levels (sICAM-1 than L girls, whereas increased macrophage migration inhibitory factor (MIF concentrations in OB vs OW boys were seen. HMW adiponectin (negatively, leptin or inflammatory markers (positively correlated with adiposity and IR measures. In multivariate models, leptin represented a strong and independent determinant of HOMA-IR (R(2 0.378; p<0.01. Adjustment for age, BMI(z-score, lipids and inflammatory mediators abolished the association between leptin and HOMA-IR in boys, while in girls leptin remained still a significant predictor of IR (R(2 0.513; p<0.01. Finally, in both sexes, the joint effect of the L/HMW did not improve the prediction of basal IR as compared with leptin levels alone, which were

  5. Metabolic hormones, apolipoproteins, adipokines, and cytokines in the alveolar lining fluid of healthy adults: compartmentalization and physiological correlates.

    Directory of Open Access Journals (Sweden)

    Carlos O Mendivil

    Full Text Available Our current understanding of hormone regulation in lung parenchyma is quite limited. We aimed to quantify a diverse array of biologically relevant protein mediators in alveolar lining fluid (ALF, compared to serum concentrations, and explore factors associated with protein compartmentalization on either side of the air-blood barrier.Participants were 24 healthy adult non-smoker volunteers without respiratory symptoms or significant medical conditions, with normal lung exams and office spirometry. Cell-free bronchoalveolar lavage fluid and serum were analyzed for 24 proteins (including enteric and metabolic hormones, apolipoproteins, adipokines, and cytokines using a highly sensitive multiplex ELISA. Measurements were normalized to ALF concentrations. The ALF:serum concentration ratios were examined in relation to measures of protein size, hydrophobicity, charge, and to participant clinical and spirometric values.ALF measurements from 24 individuals detected 19 proteins, including adiponectin, adipsin, apoA-I, apoA-II, apoB, apoC-II, apoC-III, apoE, C-reactive protein, ghrelin, glucose-dependent insulinotropic peptide (GIP, glucagon-like peptide-1 (GLP-1, glucagon, insulin, leptin, monocyte chemoattractant protein-1, plasminogen activator inhibitor-1, resistin, and visfatin. C-peptide and serpin E1 were not detected in ALF for any individual, and IL-6, IL-10, and TNF-alpha were not detected in either ALF or serum for any individual. In general, ALF levels were similar or lower in concentration for most proteins compared to serum. However, ghrelin, resistin, insulin, visfatin and GLP-1 had ALF concentrations significantly higher compared to serum. Importantly, elevated ALF:serum ratios of ghrelin, visfatin and resistin correlated with protein net charge and isoelectric point, but not with molecular weight or hydrophobicity.Biologically relevant enteric and metabolic hormones, apolipoproteins, adipokines, and cytokines can be detected in the ALF of

  6. Soy isoflavones modulate adipokines and myokines to regulate lipid metabolism in adipose tissue, skeletal muscle and liver of male Huanjiang mini-pigs.

    Science.gov (United States)

    Yang, Huansheng; Li, Fengna; Xiong, Xia; Kong, Xiangfeng; Zhang, Bin; Yuan, Xiaoxue; Fan, Juexin; Duan, Yefei; Geng, Meimei; Li, Lili; Yin, Yulong

    2013-01-05

    Although a growing body of evidence suggests that soy isoflavones help regulate lipid metabolism, the underlying mechanism has not yet been thoroughly clarified. The present study was undertaken to determine the effects of soy isoflavones on the expression of genes involved in lipid metabolism in different adipose tissue depots, skeletal muscle and liver of male Huanjiang mini-pigs, as well as the expression of adipokines and myokines. A total of 36 male Huanjiang mini-pigs were fed basal diet (control, Con), low-dose soy isoflavones (LSI) and high-dose soy isoflavones (HSI). The results showed that LSI and HSI regulated the expression of genes involved in the anabolism and catabolism of fatty acids in dorsal subcutaneous (DSA), abdominal subcutaneous (ASA) and perirenal (PRA) adipose tissue depots, as well as longissimus dorsi muscle (LDM) and liver. LSI and HSI also regulated the expression of adipokines in DSA, ASA and PRA, and the expression of myokines in LDM in male Huanjiang mini-pigs. In addition, soy isoflavones regulated plasma glucose, leptin and adiponectin contents after treatment for two months. Our results indicate that soy isoflavones, by regulating the expression of adipokines and myokines, may regulate the metabolism of lipids and could have potential therapeutic applications in lipid abnormalities.

  7. 脂肪因子在肝硬化发病机制中的作用%Role of adipokine in the pathogenesis of cirrhosis of the liver

    Institute of Scientific and Technical Information of China (English)

    魏思忱; 郑国启

    2012-01-01

    脂肪组织不再只是一个储存过剩能量的惰性组织,同时也是一个活跃的内分泌器官.脂肪组织作为旺盛的内分泌器官已得到广泛认可,其分泌的大量脂肪因子如瘦素、细胞因子等参与维持机体能量稳态和调控糖、脂代谢平衡,对全身器官系统有重要的调节功能.研究发现脂肪因子影响肝脏的炎症、纤维化和细胞死亡.本文就各种脂肪因子与肝硬化的关系作一综述.%Adipose tissue not only can store excess energy, but also can be an active endocrine organ. It was widely recognized that adipose tissue is a vigorous endocrine organ. Many of adipokines secreted by adipose tissue, such as leptin, cytokines ,can participate in keeping energy balance, regulating metabolism balance of sugar and fat. They also have many important regulatory effect on the organs and systems of the whole body. Studies found that adipokines can influence inflammation, fibrosis and cell apoptosis of the liver. We summarize the relationship of adipokines and cirrhosis of the liver.

  8. Effects of paeoniflorin on tumor necrosis factor-α-induced insulin resistance and changes of adipokines in 3T3-L1 adipocytes.

    Science.gov (United States)

    Kong, Poren; Chi, Rongxiang; Zhang, Linlin; Wang, Ningjian; Lu, Yingli

    2013-12-01

    TNFα plays an important role in the adipocyte dysfunction, including lipolysis acceleration, insulin resistance and changes of adipokines. Recently, we showed that paeoniflorin attenuates adipocyte lipolysis and inhibits the phosphorylation of ERK, JNK, IKK stimulated by TNFα. However, the effects of paeoniflorin on adipocytes insulin resistance and changes of adipokines remain unknown. The aim of the current study was to investigate the role of paeoniflorin in preventing insulin resistance or inflammation in 3T3-L1 adipocytes treated with TNFα. Our results showed that paeoniflorin restored insulin-stimulated [(3)H]2-DOG uptake, which was reduced by TNFα, with concomitant restoration in serine phosphorylation of IRS-1 and insulin-stimulated phosphorylation of AKT in adipocytes. Paeoniflorin attenuated TNFα-mediated suppression of the expressions of PPARγ and PPARγ target genes, and the improvement of paeoniflorin on TNFα-induced insulin resistance was attenuated by GW9662, an antagonist of PPARγ activity. Moreover, paeoniflorin could inhibit the expressions and secretions of IL-6 and MCP-1 from adipocytes induced by TNFα. These results, together with our previous data, indicate that paeoniflorin exerts a beneficial effect on adipocytes to prevent TNFα-induced insulin resistance and inflammatory adipokine release. Our studies provide important evidence for an ability of paeoniflorin in amelioration of TNFα-induced adipocyte dysfunction, which would be helpful to clarify its potential role in the treatment of obesity. © 2013.

  9. Inhibitory effects of harpagoside on TNF-α-induced pro-inflammatory adipokine expression through PPAR-γ activation in 3T3-L1 adipocytes.

    Science.gov (United States)

    Kim, Tae Kon; Park, Kyoung Sik

    2015-12-01

    Obesity is closely associated with increased production of pro-inflammatory adipokines, including interleukin (IL)-6, plasminogen activator inhibitor (PAI)-1, and adipose-tissue-derived monocyte chemoattractant protein (MCP)-1, which contribute to chronic and low-grade inflammation in adipose tissue. Harpagoside, a major iridoid glycoside present in devil's claw, has been reported to show anti-inflammatory activities by suppression of lipopolysaccharide (LPS)-induced production of inflammatory cytokines in murine macrophages. The present study is aimed to investigate the effects of harpagoside on both tumor necrosis factor (TNF)-α-induced inflammatory adipokine expression and its underlying signaling pathways in differentiated 3T3-L1 cells. Harpagoside significantly inhibited TNF-α-induced mRNA synthesis and protein production of the atherogenic adipokines including IL-6, PAI-1, and MCP-1. Further investigation of the molecular mechanism revealed that pretreatment with harpagoside activated peroxisome proliferator-activated receptor (PPAR)-γ. These findings suggest that the clinical application of medicinal plants which contain harpagoside may lead to a partial prevention of obesity-induced atherosclerosis by attenuating inflammatory responses.

  10. Relationship of adipokine to insulin sensitivity and glycemic regulation in obese women: The effect of body weight reduction by caloric restriction

    Directory of Open Access Journals (Sweden)

    Velojić-Golubović Milena

    2013-01-01

    Full Text Available Bacground/Aim. Visceral fat is highly active metabolic and endocrine tissue which secretes many adipokines that act both on local and systemic level. It is believed that adipokines and "low-grade inflammatory state" represent a potential link between obesity, metabolic syndrome, insulin resistance and cardiovascular disease. Leptin and adiponectin are considered to be the most important adipokines with the potential metabolic and cardiovascular effects. Body weight loss improves insulin sensitivity and decreases risk for most complications associated with obesity. The aim of this study was to determine the effects of moderate loss of body weight on the level of leptin and adiponectin, insulin sensitivity and abnormalities of glycoregulation in obese women, to determine whether and to what extent the secretory products of adipose tissue, leptin and adiponectin contribute to insulin sensitivity, as well as to assess their relationship and influence on glycemia and insulinemia during the period of losing body weight using a calorie restricted diet. Methods. The study involved 90 obese female subjects (BMI

  11. Effect of atorvastatin and fenofibric acid on adipokine release from visceral and subcutaneous adipose tissue of patients with mixed dyslipidemia and normolipidemic subjects.

    Science.gov (United States)

    Krysiak, Robert; Labuzek, Krzysztof; Okopień, Bogusław

    2009-01-01

    Because of methodological limitations and conflicting results of studies conducted thus far, the possible involvement of human adipose tissue in pleiotropic effects of statins and fibrates requires better understanding. Samples of visceral and subcutaneous adipose tissue obtained from 23 mixed dyslipidemic patients and 23 normolipidemic subjects were treated in vitro for 48 h with atorvastatin, fenofibric acid or both these agents. Visceral and subcutaneous fat of mixed dyslipidemic patients released more leptin, resistin, interleukin-6, tumor necrosis factor alpha (TNFalpha and plasminogen activator inhibitor-1 (PAI-1), and less adiponectin than respective adipose tissue of patients without lipid abnormalities. In both groups of patients, visceral and subcutaneous tissue varied in the amount of secreted adipokines. In dyslipidemic patients both drugs administered alone affected adipose tissue adiponectin and resistin secretion. Additionally, atorvastatin decreased PAI-1 while fenofibric acid reduced leptin release. A combined administration of atorvastatin and fenofibric acid changed the release of all studied markers by visceral fat but did not affect interleukin-6 and TNFalpha release by subcutaneous tissue. In normolipidemic subjects the effect on adipokine release was more pronounced in visceral fat, in which it was strongest if the drugs were given together. Adipose tissue hormonal activity differs between mixed dyslipidemic and normolipidemic patients and between visceral and subcutaneous adipose tissue. Atorvastatin and fenofibrate exhibit their pleiotropic effects in part by changing the adipokine release by human adipose tissue, regardless of its origin. These effects are stronger in patients with mixed dyslipidemia and are particularly pronounced if atorvastatin and fenofibric acid are given together.

  12. High-density lipoprotein inhibits ox-LDL-induced adipokine secretion by upregulating SR-BI expression and suppressing ER Stress pathway.

    Science.gov (United States)

    Song, Guohua; Wu, Xia; Zhang, Pu; Yu, Yang; Yang, Mingfeng; Jiao, Peng; Wang, Ni; Song, Haiming; Wu, You; Zhang, Xiangjian; Liu, Huaxia; Qin, Shucun

    2016-07-29

    Endoplasmic reticulum stress (ERS) in adipocytes can modulate adipokines secretion. The aim of this study was to explore the protective effect of high-density lipoprotein (HDL) on oxidized low-density lipoprotein (ox-LDL)-induced ERS-C/EBP homologous protein (CHOP) pathway-mediated adipokine secretion. Our results showed that serum adipokines, including visfatin, resistin and TNF-α, correlated inversely with serum HDL cholesterol level in patients with abdominal obesity. In vitro, like ERS inhibitor 4-phenylbutyric acid (PBA), HDL inhibited ox-LDL- or tunicamycin (TM, an ERS inducer)-induced increase in visfatin and resistin secretion. Moreover, HDL inhibited ox-LDL-induced free cholesterol (FC) accumulation in whole cell lysate and in the endoplasmic reticulum. Additionally, like PBA, HDL inhibited ox-LDL- or TM-induced activation of ERS response as assessed by the decreased phosphorylation of protein kinase-like ER kinase and eukaryotic translation initiation factor 2α and reduced nuclear translocation of activating transcription factor 6 as well as the downregulation of Bip and CHOP. Furthermore, HDL increased scavenger receptor class B type I (SR-BI) expression and SR-BI siRNA treatment abolished the inhibitory effects of HDL on ox-LDL-induced FC accumulation and CHOP upregulation. These data indicate that HDL may suppress ox-LDL-induced FC accumulation in adipocytes through upregulation of SR-BI, subsequently preventing ox-LDL-induced ER stress-CHOP pathway-mediated adipocyte inflammation.

  13. [The role of adipokines in formation of lipid and carbohydrate metabolic disorders in patients with cardiovascular disease].

    Science.gov (United States)

    Kravchun, P; Kadykova, O; Gabisoniia, T

    2012-12-01

    Cardio-vascular disease is an important public health problem in all developed countries.The challenge isto learn thepathogenic mechanisms of this disease.Attention of scientists of the world are drown to the role of hormones in the development of adipose tissue metabolic disorders. Adipose tissue is composed of adipocytes embedded in a loose connective tissue meshwork containing adipocyte precursors, fibroblasts, immune cells, and various other cell types. Adipose tissue was traditionally considered an energy storage depot with few interesting attributes. Due to the dramatic rise in obesity and its metabolic sequelae during the past decades, adipose tissue gained tremendous scientific interest. It is now regarded as an active endocrine organ that, in addition to regulating fat mass and nutrient homeostasis, releases a large number of bioactive mediators (adipokines) modulating hemostasis, blood pressure, lipid and glucose metabolism, inflammation, and atherosclerosis. The aim of our study was to examine the metabolic disorders in patients with cardiovascular disease. Based on identifying the nature of changes of insulin antagonists and of insulin sensitizers. We were investigated 68 patients with hypertension, which included 35 women and 33 men.Estimated distance of carbohydrate and lipid metabolism and adipose tissue hormone imbalance. Our results suggest that the mechanisms underlying the progression of diabetes and obesity in patients with hypertension against metabolic disorders that manifest dysfunction of carbohydrate and lipid metabolism are associated with insulinorezistense and hypervisfatinemia and hyperrezistinemia against hypoadiponektinemia occur in hypertensive patients by having diabetes mellitus type 2.

  14. Effects of clozapine on adipokine secretions/productions and lipid droplets in 3T3-L1 adipocytes

    Directory of Open Access Journals (Sweden)

    Tomomi Tsubai

    2017-02-01

    Full Text Available Clozapine, a second-generation antipsychotic (SGA, is a cause of side effects related to metabolic syndrome. The participation of serotonin 5-HT2C and histamine H1 receptors in the central nervous system has been reported as a mechanism of the weight gain caused by clozapine. In the present study, we investigated the direct pharmacological action of clozapine on the 3T3-L1 adipocytes and compared it to that of blonanserin, an SGA with low affinity for both receptors. Short-term exposure to clozapine decreased secretion and mRNA expression of leptin. Long-term exposure decreased leptin as well as adiponectin secretion, and further increased lipid droplets accumulation. However, short- and long-term exposures to blonanserin did not affect these parameters. A selective serotonin 5-HT2C, but not a histamine H1, receptor antagonist enhanced the decreased secretion of leptin induced by short-term exposure to clozapine, but did not affect the increased accumulation of lipid droplets. Our findings indicate that clozapine, but not blonanserin, strongly and directly affected the secretion of adipokines, such as leptin, in adipocytes and caused adipocyte enlargement.

  15. Effects of clozapine on adipokine secretions/productions and lipid droplets in 3T3-L1 adipocytes.

    Science.gov (United States)

    Tsubai, Tomomi; Yoshimi, Akira; Hamada, Yoji; Nakao, Makoto; Arima, Hiroshi; Oiso, Yutaka; Noda, Yukihiro

    2017-02-01

    Clozapine, a second-generation antipsychotic (SGA), is a cause of side effects related to metabolic syndrome. The participation of serotonin 5-HT2C and histamine H1 receptors in the central nervous system has been reported as a mechanism of the weight gain caused by clozapine. In the present study, we investigated the direct pharmacological action of clozapine on the 3T3-L1 adipocytes and compared it to that of blonanserin, an SGA with low affinity for both receptors. Short-term exposure to clozapine decreased secretion and mRNA expression of leptin. Long-term exposure decreased leptin as well as adiponectin secretion, and further increased lipid droplets accumulation. However, short- and long-term exposures to blonanserin did not affect these parameters. A selective serotonin 5-HT2C, but not a histamine H1, receptor antagonist enhanced the decreased secretion of leptin induced by short-term exposure to clozapine, but did not affect the increased accumulation of lipid droplets. Our findings indicate that clozapine, but not blonanserin, strongly and directly affected the secretion of adipokines, such as leptin, in adipocytes and caused adipocyte enlargement. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  16. L-carnitine supplementation and adipokines in patients with end-stage renal disease on regular hemodialysis.

    Science.gov (United States)

    Csiky, B; Nyul, Z; Tóth, G; Wittmann, I; Melegh, B; Rauh, M; Rascher, W; Sulyok, E

    2010-11-01

    Chronic hemodialysis (HD) patients frequently encounter carnitine depletion, elevated adipose tissue-derived hormones/cytokines, that may contribute to accelerated arteriosclerosis. 10 non-diabetic HD patients were studied over 28 weeks. In the 12 weeks treatment period 1 g L-carnitine was given iv after each HD session. Measurements of plasma free- and acylcarnitines, insulin, leptin, adiponectin, resistin and ghrelin were performed at baseline, at weeks 2, 4, 8, 12 (treatment period) and at weeks 24-28 (post-treatment period). L-carnitine supplementation resulted in progressive increase of free- and acylcarnitine levels. Plasma levels of insulin, resistin, leptin and ghrelin remained at the already elevated baseline values. L-carnitine therapy induced a significant increase in plasma adiponectin from 20.2 ± 12.7 μg/ml (baseline) to 32.7 ± 20.2 μg/ml in week 2 (pcarnitine period. Plasma insulin levels correlated positively with leptin (r = 0.525, pcarnitine status. Plasma levels of adipokines and related hormones are greatly elevated in patients on regular HD. L-carnitine administration further augmented the plasma levels of protective adiponectin, therefore it may have a role in preventing cardiovascular complications of uremia.

  17. Mechanism of Butyrate Stimulation of Triglyceride Storage and Adipokine Expression during Adipogenic Differentiation of Porcine Stromovascular Cells.

    Directory of Open Access Journals (Sweden)

    Hui Yan

    Full Text Available Short chain fatty acids (SCFA, products of microbial fermentation of dietary fiber, exert multiple metabolic effects in cells. Previously, we had demonstrated that soluble fiber influenced fat mass accumulation, gut microbial community structure and SCFA production in pigs. The current study was designed to identify effects of SCFA treatment during adipogenic differentiation of porcine stromovascular cells on lipid metabolism and adipokine expression. Differentiating cells were treated with varying concentrations of butyrate. Results show that butyrate treatment enhanced adipogenesis and lipid accumulation, perhaps through upregulation of glucose uptake and de novo lipogenesis and other mechanisms that include induction of SREBP-1c, C/EBPα/β, GLUT4, LPL, PPARγ, GPAT4, DGAT1 and DGAT2 expression. In addition, butyrate induced adiponectin expression, resulting in activation of downstream target genes, such as AMPK and AKT. Activation of AMPK by butyrate led to phosphorylation of ACC. Although increased ACO gene expression was seen with butyrate treatment, experiments with the peroxisomal fatty acid inhibitor, thioridazine, suggest that butyrate may have an inhibitory effect on peroxisomal fatty acid oxidation. Our studies also provide evidence that butyrate may inhibit lipolysis, perhaps in an FFAR3-dependent manner. Therefore, this study presents a novel paradigm for butyrate action in adipocytes and shows that adipocytes are capable of utilizing butyrate, leading to increased expression of adiponectin for enhanced glucose uptake and improved insulin sensitivity.

  18. Mechanism of Butyrate Stimulation of Triglyceride Storage and Adipokine Expression during Adipogenic Differentiation of Porcine Stromovascular Cells.

    Science.gov (United States)

    Yan, Hui; Ajuwon, Kolapo M

    2015-01-01

    Short chain fatty acids (SCFA), products of microbial fermentation of dietary fiber, exert multiple metabolic effects in cells. Previously, we had demonstrated that soluble fiber influenced fat mass accumulation, gut microbial community structure and SCFA production in pigs. The current study was designed to identify effects of SCFA treatment during adipogenic differentiation of porcine stromovascular cells on lipid metabolism and adipokine expression. Differentiating cells were treated with varying concentrations of butyrate. Results show that butyrate treatment enhanced adipogenesis and lipid accumulation, perhaps through upregulation of glucose uptake and de novo lipogenesis and other mechanisms that include induction of SREBP-1c, C/EBPα/β, GLUT4, LPL, PPARγ, GPAT4, DGAT1 and DGAT2 expression. In addition, butyrate induced adiponectin expression, resulting in activation of downstream target genes, such as AMPK and AKT. Activation of AMPK by butyrate led to phosphorylation of ACC. Although increased ACO gene expression was seen with butyrate treatment, experiments with the peroxisomal fatty acid inhibitor, thioridazine, suggest that butyrate may have an inhibitory effect on peroxisomal fatty acid oxidation. Our studies also provide evidence that butyrate may inhibit lipolysis, perhaps in an FFAR3-dependent manner. Therefore, this study presents a novel paradigm for butyrate action in adipocytes and shows that adipocytes are capable of utilizing butyrate, leading to increased expression of adiponectin for enhanced glucose uptake and improved insulin sensitivity.

  19. Characterization of In Vitro Engineered Human Adipose Tissues: Relevant Adipokine Secretion and Impact of TNF-α.

    Science.gov (United States)

    Aubin, Kim; Safoine, Meryem; Proulx, Maryse; Audet-Casgrain, Marie-Alice; Côté, Jean-François; Têtu, Félix-André; Roy, Alphonse; Fradette, Julie

    2015-01-01

    Representative modelling of human adipose tissue functions is central to metabolic research. Tridimensional models able to recreate human adipogenesis in a physiological tissue-like context in vitro are still scarce. We describe the engineering of white adipose tissues reconstructed from their cultured adipose-derived stromal precursor cells. We hypothesize that these reconstructed tissues can recapitulate key functions of AT under basal and pro-inflammatory conditions. These tissues, featuring human adipocytes surrounded by stroma, were stable and metabolically active in long-term cultures (at least 11 weeks). Secretion of major adipokines and growth factors by the reconstructed tissues was determined and compared to media conditioned by human native fat explants. Interestingly, the secretory profiles of the reconstructed adipose tissues indicated an abundant production of leptin, PAI-1 and angiopoietin-1 proteins, while higher HGF levels were detected for the human fat explants. We next demonstrated the responsiveness of the tissues to the pro-inflammatory stimulus TNF-α, as reflected by modulation of MCP-1, NGF and HGF secretion, while VEGF and leptin protein expression did not vary. TNF-α exposure induced changes in gene expression for adipocyte metabolism-associated mRNAs such as SLC2A4, FASN and LIPE, as well as for genes implicated in NF-κB activation. Finally, this model was customized to feature adipocytes representative of progressive stages of differentiation, thereby allowing investigations using newly differentiated or more mature adipocytes. In conclusion, we produced tridimensional tissues engineered in vitro that are able to recapitulate key characteristics of subcutaneous white adipose tissue. These tissues are produced from human cells and their neo-synthesized matrix elements without exogenous or synthetic biomaterials. Therefore, they represent unique tools to investigate the effects of pharmacologically active products on human stromal cells

  20. Instigation of endothelial Nlrp3 inflammasome by adipokine visfatin promotes inter-endothelial junction disruption: role of HMGB1.

    Science.gov (United States)

    Chen, Yang; Pitzer, Ashley L; Li, Xiang; Li, Pin-Lan; Wang, Lei; Zhang, Yang

    2015-12-01

    Recent studies have indicated that the inflammasome plays a critical role in the pathogenesis of vascular diseases. However, the pathological relevance of this inflammasome activation, particularly in vascular cells, remains largely unknown. Here, we investigated the role of endothelial (Nucleotide-binding Oligomerization Domain) NOD-like receptor family pyrin domain containing three (Nlrp3) inflammasomes in modulating inter-endothelial junction proteins, which are associated with endothelial barrier dysfunction, an early onset of obesity-associated endothelial injury. Our findings demonstrate that the activation of Nlrp3 inflammasome by visfatin markedly decreased the expression of inter-endothelial junction proteins including tight junction proteins ZO-1, ZO-2 and occludin, and adherens junction protein VE-cadherin in cultured mouse vascular endothelial (VE) cell monolayers. Such visfatin-induced down-regulation of junction proteins in endothelial cells was attributed to high mobility group box protein 1 (HMGB1) release derived from endothelial inflammasome-dependent caspase-1 activity. Similarly, in the coronary arteries of wild-type mice, high-fat diet (HFD) treatment caused a down-regulation of inter-endothelial junction proteins ZO-1, ZO-2, occludin and VE-cadherin, which was accompanied with enhanced inflammasome activation and HMGB1 expression in the endothelium as well as transmigration of CD43(+) T cells into the coronary arterial wall. In contrast, all these HFD-induced alterations in coronary arteries were prevented in mice with Nlrp3 gene deletion. Taken together, these data strongly suggest that the activation of endothelial Nlrp3 inflammasomes as a result of the increased actions of injurious adipokines such as visfatin produces HMGB1, which act in paracrine or autocrine fashion to disrupt inter-endothelial junctions and increase paracellular permeability of the endothelium contributing to the early onset of endothelial injury during metabolic

  1. ER stress in adipocytes inhibits insulin signaling, represses lipolysis, and alters the secretion of adipokines without inhibiting glucose transport.

    Science.gov (United States)

    Xu, L; Spinas, G A; Niessen, M

    2010-08-01

    The endoplasmic reticulum (ER) is the intra-cellular site, where secreted and membrane proteins are synthesized. ER stress and activation of the unfolded protein response (UPR) contribute to insulin resistance and the development of diabetes in obesity. It was shown previously in hepatocytes that the UPR activates c-jun N-terminal kinase (JNK), which phosphorylates insulin receptor substrate (IRS) proteins on serine residues thereby inhibiting insulin signal transduction. Here we describe how ER stress affects insulin signaling and the biological function of adipocytes. In addition to inhibition of IRS we found that ER stress downregulates the expression of the insulin receptor. Concomitantly, insulin-induced activation of Akt/PKB and of ERK1/2 was strongly inhibited. Ectopic expression of IRS1 or IRS2 strongly counteracted the inhibitory effect of ER stress on insulin signaling while pharmacological inhibition of JNK with SP600125 resulted only in a mild improvement. ER stress decreased the secretion of the adipokines adiponectin and leptin, but strongly increased secretion of IL-6. ER stress inhibited expression and insulin-induced phosphorylation of AS160, reduced lipolysis but did not inhibit glucose transport. Finally, supernatants collected from 3T3-L1 adipocytes undergoing ER stress improved or impaired proliferation when used to condition the culture medium of INS-1E beta-cells dependent on the degree of ER stress. It appears that ER stress in adipocytes might initially lead to changes resembling early prediabetic stages, which at least in part support the regulation of systemic energy homeostasis. Copyright Georg Thieme Verlag KG Stuttgart New York.

  2. Adipokines : rôle dans l’obésité et l’insulino‐résistance

    Directory of Open Access Journals (Sweden)

    Aubert Roberte

    2003-03-01

    Full Text Available Le tissu adipeux longtemps considéré comme un organe de stockage est maintenant reconnu comme un organe endocrine. Cette revue étudie l’action de 3 adipokines sécrétées par le tissu adipeux et impliquées dans le contrôle de l’homéostasie énergétique et l’insulino‐résistance, la leptine, l’adiponectine et la résistine. La découverte de la leptine a permis la compréhension des mécanismes centraux de la prise alimentaire et de la dépense énergétique. L’espoir que la leptine puisse intervenir dans le traitement de l’obésité a été déçu, mais elle joue un rôle important dans l’insulino‐sensibilité. L’adiponectine circulante est diminuée dans l’obésité et la perte pondérale augmente son taux. Elle améliore la sensibilité à l’insuline en agissant sur le métabolisme glucidique et lipidique. Bien que pour le moment le rôle de la résistine soit encore mal défini, les études chez l’animal suggèrent qu’elle soit impliqués dans l’insulino‐résistance. Chez l’homme il n’y a pas de relation entre l’expression de la résistine et l’obésité. On peut donc se demander si la résistine, dans l’espèce humaine, est bien le lien entre obésité et diabète de type 2.

  3. Characterization of In Vitro Engineered Human Adipose Tissues: Relevant Adipokine Secretion and Impact of TNF-α

    Science.gov (United States)

    Aubin, Kim; Safoine, Meryem; Proulx, Maryse; Audet-Casgrain, Marie-Alice; Côté, Jean-François; Têtu, Félix-André; Roy, Alphonse; Fradette, Julie

    2015-01-01

    Representative modelling of human adipose tissue functions is central to metabolic research. Tridimensional models able to recreate human adipogenesis in a physiological tissue-like context in vitro are still scarce. We describe the engineering of white adipose tissues reconstructed from their cultured adipose-derived stromal precursor cells. We hypothesize that these reconstructed tissues can recapitulate key functions of AT under basal and pro-inflammatory conditions. These tissues, featuring human adipocytes surrounded by stroma, were stable and metabolically active in long-term cultures (at least 11 weeks). Secretion of major adipokines and growth factors by the reconstructed tissues was determined and compared to media conditioned by human native fat explants. Interestingly, the secretory profiles of the reconstructed adipose tissues indicated an abundant production of leptin, PAI-1 and angiopoietin-1 proteins, while higher HGF levels were detected for the human fat explants. We next demonstrated the responsiveness of the tissues to the pro-inflammatory stimulus TNF-α, as reflected by modulation of MCP-1, NGF and HGF secretion, while VEGF and leptin protein expression did not vary. TNF-α exposure induced changes in gene expression for adipocyte metabolism-associated mRNAs such as SLC2A4, FASN and LIPE, as well as for genes implicated in NF-κB activation. Finally, this model was customized to feature adipocytes representative of progressive stages of differentiation, thereby allowing investigations using newly differentiated or more mature adipocytes. In conclusion, we produced tridimensional tissues engineered in vitro that are able to recapitulate key characteristics of subcutaneous white adipose tissue. These tissues are produced from human cells and their neo-synthesized matrix elements without exogenous or synthetic biomaterials. Therefore, they represent unique tools to investigate the effects of pharmacologically active products on human stromal cells

  4. Periodontitis contributes to aberrant metabolism in type 2 diabetes mellitus rats by stimulating the expression of adipokines.

    Science.gov (United States)

    Luo, S; Yang, X; Wang, D; Ni, J; Wu, J; Xu, Z; Xuan, D; Zhang, J

    2016-08-01

    Periodontitis has been associated with type 2 diabetes mellitus. We investigated the effects of local aberrant secretion of adipokines in diabetic rats on systemic metabolism. Otsuka Long-Evans Tokushima Fatty (OLETF) and non-diabetic Long-Evans Tokushima Otsuka rats were used as a diabetic model and associated control, respectively. Periodontitis was induced using a silk ligature for 36 wk. Rats were grouped into OLETF with (OP+) or without (OP-) periodontitis and Long-Evans Tokushima Otsuka with (LP+) or without (LP-) periodontitis. Alveolar bone resorption and destruction were evaluated by micro-computed tomography and hematoxylin and eosin staining. After 20 wk of periodontitis induction, lipids, insulin, interleukin-1, leptin and plasminogen activator inhibitor-1 were analyzed, and mRNA expressions of NF-κB, Mark8, TLR2 and -4, IKBKB and Nampt were evaluated by quantitative polymerase chain reaction in adipose tissue. After ligation, OLETF rats exhibited typical periodontitis lesions with the clinical features of type 2 diabetes mellitus. When compared with the OP(-) group, the area under curve of the oral glucose tolerance test and homeostatic model assessment-insulin resistance values were significantly higher in the OP(+) group. Micro-computed tomography showed that the OP(+) group had more bone resorption than the OP(-) group. When compared with the OP(-) group, the OP(+) group also exhibited higher total cholesterol (p 0.05) and higher expression of Nampt (p periodontitis can alter lipid profiles in affected rats, elevate adipose tissue expression of Nampt and affect the metabolism of adipose tissue through the NF-κB pathway to inflame diabetes. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Levels of Adipokines in Amniotic Fluid and Cord Blood Collected from Dichorionic-Diamniotic Twins Discordant for Fetal Growth.

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    Seung Mi Lee

    Full Text Available To compare the concentrations of adipokines in amniotic fluid (AF and cord blood collected from discordant dichorionic-diamniotic (DCDA twin fetuses.The study population included DCDA twins discordant for fetal growth (birth weight difference >10% who either underwent mid-trimester amniocentesis for routine clinical indication (Cohort 1 or whose amniotic fluid was collected at the time of delivery (Cohort 2. In both cohorts, cord blood was collected at delivery.A total of 92 twin pairs were enrolled (n = 49 in Cohort 1; n = 43 in Cohort 2. In Cohort 1, the concentrations of adiponectin (median, 68.5 ng/mL vs 61.4 ng/mL; p<0.05 and leptin (median, 13.9 ng/mL vs 11.2 ng/mL; p<0.1 in mid-trimester AF were significantly higher in smaller compared with larger twins. In Cohort 2, the concentration of serpin E1 (median, 246.0 ng/mL vs 182.8 ng/mL; p<0.01 in AF at delivery was significantly higher in smaller twins, but no difference was noted in adiponectin and leptin concentrations. Levels of adiponectin (median, 10425.5 ng/mL vs 11552.0 ng/mL; p<0.005 and leptin (median, 2.1 ng/mL vs 2.6 ng/mL; p<0.005 were significantly lower in the cord blood of smaller twins whereas cord blood concentrations of serpin E1 (median, 15.5 ng/mL vs 13.3 ng/mL; p<0.05 was higher in the smaller twins.In discordant DCDA twin pairs, concentrations of adiponectin, leptin, and serpin E1 in mid-trimester AF, AF at delivery, and cord blood at birth vary significantly but predictably between the smaller and larger twins.

  6. New adipokines vaspin and omentin. Circulating levels and gene expression in adipose tissue from morbidly obese women

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    Aguilar Carmen

    2011-04-01

    Full Text Available Abstract Background Vaspin and omentin are recently described molecules that belong to the adipokine family and seem to be related to metabolic risk factors. The objectives of this study were twofold: to evaluate vaspin and omentin circulating levels and mRNA expression in subcutaneous and visceral adipose tissues in non-diabetic morbidly obese women; and to assess the relationship of vaspin and omentin with anthropometric and metabolic parameters, and other adipo/cytokines. Design We analysed vaspin and omentin circulating levels in 71 women of European descent (40 morbidly obese [BMI ≥ 40 kg/m2] and 31 lean [BMI ≤ 25]. We assessed vaspin and omentin gene expression in paired samples of visceral and subcutaneous abdominal adipose tissue from 46 women: 40 morbidly obese and 6 lean. We determined serum vaspin and plasma omentin levels with an Enzyme-Linked Immunosorbent Assay and adipose tissue mRNA expression by real time RT-PCR. Results Serum vaspin levels in the morbidly obese were not significantly different from those in controls. They correlated inversely with levels of lipocalin 2 and interleukin 6. Vaspin mRNA expression was significantly higher in the morbidly obese, in both subcutaneous and visceral adipose tissue. Plasma omentin levels were significantly lower in the morbidly obese and they correlated inversely with glucidic metabolism parameters. Omentin circulating levels, then, correlated inversely with the metabolic syndrome (MS. Omentin expression in visceral adipose tissue was significantly lower in morbidly obese women than in controls. Conclusions The present study indicates that vaspin may have a compensatory role in the underlying inflammation of obesity. Decreased omentin circulating levels have a close association with MS in morbidly obese women.

  7. Sex hormone imbalances and adipose tissue dysfunction impacting on metabolic syndrome; a paradigm for the discovery of novel adipokines.

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    Zhang, Hui; Sairam, M Ram

    2014-02-01

    Sex hormone imbalance is causally related with visceral adipose tissue (AT) dysfunction and visceral obesity - an etiological component of metabolic syndrome (MetS), associated with high risk of both cardiovascular disease (CVD) and type 2 diabetes. In general, premenopausal women appear to be protected from CVD and the dramatic decline in sex steroid hormone occurring during menopausal transitions or other sex-related disorders influence the regional distribution, function, and metabolism of AT and increase the risk of CVD. Visceral AT dysfunction, manifesting as abnormality of fatty acid metabolism, increased oxidative stress, endothelial dysfunction, and excessive production of adipokines have been proposed in the pathogenesis of MetS. However, direct evidence of molecular mechanisms of depot-specific AT alterations, and dysfunction causally related to MetS is limited in studies on postmenopausal women due to difficulty in collecting discrete AT specimens at different ages and repeated sampling from different fat depots. This can be overcome using animal models that can mimic the cluster of pathology leading to MetS and help establish the molecular basis of links between loss of gonadal function on various AT depots and their contribution to MetS. Our group used sex hormone imbalance FSH receptor knock out (FORKO) female mice to recapitulate different aspects of the MetS and addressed the mechanism of visceral obesity related to MetS and discover two novel sex steroid hormone-regulated deep mesenteric estrogen-dependent adipose (MEDAs) genes. Taken together, such recent studies raise hopes for pharmacologic intervention strategies targeting sex steroid hormone signaling in AT to provide protection against AT dysfunction.

  8. Nε-(carboxymethyl)lysine-receptor for advanced glycation end product axis is a key modulator of obesity-induced dysregulation of adipokine expression and insulin resistance.

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    Gaens, Katrien H J; Goossens, Gijs H; Niessen, Petra M; van Greevenbroek, Marleen M; van der Kallen, Carla J H; Niessen, Hans W; Rensen, Sander S; Buurman, Wim A; Greve, Jan Willem M; Blaak, Ellen E; van Zandvoort, Marc A; Bierhaus, Angelika; Stehouwer, Coen D A; Schalkwijk, Casper G

    2014-06-01

    Dysregulation of inflammatory adipokines by the adipose tissue plays an important role in obesity-associated insulin resistance. Pathways leading to this dysregulation remain largely unknown. We hypothesized that the receptor for advanced glycation end products (RAGE) and the ligand N(ε)-(carboxymethyl)lysine (CML) are increased in adipose tissue and, moreover, that activation of the CML-RAGE axis plays an important role in obesity-associated inflammation and insulin resistance. In this study, we observed a strong CML accumulation and increased expression of RAGE in adipose tissue in obesity. We confirmed in cultured human preadipocytes that adipogenesis is associated with increased levels of CML and RAGE. Moreover, CML induced a dysregulation of inflammatory adipokines in adipocytes via a RAGE-dependent pathway. To test the role of RAGE in obesity-associated inflammation further, we constructed an obese mouse model that is deficient for RAGE (ie, RAGE(-/-)/Leptr(Db-/-) mice). RAGE(-/-)/Leptr(Db-/-) mice displayed an improved inflammatory profile and glucose homeostasis when compared with RAGE(+/+)/Leptr(Db-/-) mice. In addition, CML was trapped in adipose tissue in RAGE(+/+)/Leptr(Db-/-) mice but not in RAGE(-/-)/Leptr(Db-/-). RAGE-mediated trapping in adipose tissue provides a mechanism underlying CML accumulation in adipose tissue and explaining decreased CML plasma levels in obese subjects. Decreased CML plasma levels in obese individuals were strongly associated with insulin resistance. RAGE-mediated CML accumulation in adipose tissue and the activation of the CML-RAGE axis are important mechanisms involved in the dysregulation of adipokines in obesity, thereby contributing to the development of obesity-associated insulin resistance. © 2014 American Heart Association, Inc.

  9. The Roles of Adipokines, Proinflammatory Cytokines, and Adipose Tissue Macrophages in Obesity-Associated Insulin Resistance in Modest Obesity and Early Metabolic Dysfunction.

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    Kang, Yea Eun; Kim, Ji Min; Joung, Kyong Hye; Lee, Ju Hee; You, Bo Ram; Choi, Min Jeong; Ryu, Min Jeong; Ko, Young Bok; Lee, Min A; Lee, Junguee; Ku, Bon Jeong; Shong, Minho; Lee, Ki Hwan; Kim, Hyun Jin

    2016-01-01

    The roles of adipokines, proinflammatory cytokines, and adipose tissue macrophages in obesity-associated insulin resistance have been explored in both animal and human studies. However, our current understanding of obesity-associated insulin resistance relies on studies of artificial metabolic extremes. The purpose of this study was to explore the roles of adipokines, proinflammatory cytokines, and adipose tissue macrophages in human patients with modest obesity and early metabolic dysfunction. We obtained omental adipose tissue and fasting blood samples from 51 females undergoing gynecologic surgery. We investigated serum concentrations of proinflammatory cytokines and adipokines as well as the mRNA expression of proinflammatory and macrophage phenotype markers in visceral adipose tissue using ELISA and quantitative RT-PCR. We measured adipose tissue inflammation and macrophage infiltration using immunohistochemical analysis. Serum levels of adiponectin and leptin were significantly correlated with HOMA-IR and body mass index. The levels of expression of MCP-1 and TNF-α in visceral adipose tissue were also higher in the obese group (body mass index ≥ 25). The expression of mRNA MCP-1 in visceral adipose tissue was positively correlated with body mass index (r = 0.428, p = 0.037) but not with HOMA-IR, whereas TNF-α in visceral adipose tissue was correlated with HOMA-IR (r = 0.462, p = 0.035) but not with body mass index. There was no obvious change in macrophage phenotype or macrophage infiltration in patients with modest obesity or early metabolic dysfunction. Expression of mRNA CD163/CD68 was significantly related to mitochondrial-associated genes and serum inflammatory cytokine levels of resistin and leptin. These results suggest that changes in the production of inflammatory biomolecules precede increased immune cell infiltration and induction of a macrophage phenotype switch in visceral adipose tissue. Furthermore, serum resistin and leptin have specific

  10. Does vitamin D supplementation alter plasma adipokines concentrations? A systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Dinca, Madalina; Serban, Maria-Corina; Sahebkar, Amirhossein; Mikhailidis, Dimitri P; Toth, Peter P; Martin, Seth S; Blaha, Michael J; Blüher, Matthias; Gurban, Camelia; Penson, Peter; Michos, Erin D; Hernandez, Adrian V; Jones, Steven R; Banach, Maciej

    2016-05-01

    We aimed to elucidate the role of vitamin D supplementation on adipokines through a systematic review and a meta-analysis of randomized placebo-controlled trials (RCTs). The search included PUBMED, Scopus, Web of Science and Google Scholar through July 1st, 2015. Finally we identified 9 RCTs and 484 participants. Meta-analysis of data from 7 studies did not find a significant change in plasma adiponectin concentrations following vitamin D supplementation (mean difference [MD]: 4.45%, 95%CI: -3.04, 11.93, p=0.244; Q=2.18, I(2)=0%). In meta-regression, changes in plasma adiponectin concentrations following vitamin D supplementation were found to be independent of treatment duration (slope: 0.25; 95%CI: -0.69, 1.19; p=0.603) and changes in serum 25-hydroxy vitamin D [25(OH)D] levels (slope: -0.02; 95%CI: -0.15, 0.12; p=0.780). Meta-analysis of data from 6 studies did not find a significant change in plasma leptin concentrations following vitamin D supplementation (MD: -4.51%, 95%CI: -25.13, 16.11, p=0.668; Q=6.41, I(2)=21.97%). Sensitivity analysis showed that this effect size is sensitive to one of the studies; removing it resulted in a significant reduction in plasma leptin levels (MD: -12.81%, 95%CI: -24.33, -1.30, p=0.029). In meta-regression, changes in plasma leptin concentrations following vitamin D supplementation were found to be independent of treatment duration (slope: -1.93; 95%CI: -4.08, 0.23; p=0.080). However, changes in serum 25(OH)D were found to be significantly associated with changes in plasma leptin levels following vitamin D supplementation (slope: 1.05; 95%CI: 0.08, 2.02; p=0.033). In conclusion, current data did not indicate a significant effect of vitamin D supplementation on adiponectin and leptin levels.

  11. Acute-phase serum amyloid A: an inflammatory adipokine and potential link between obesity and its metabolic complications.

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    Rong-Ze Yang

    2006-06-01

    Full Text Available BACKGROUND: Obesity is associated with low-grade chronic inflammation, and serum markers of inflammation are independent risk factors for cardiovascular disease (CVD. However, the molecular and cellular mechanisms that link obesity to chronic inflammation and CVD are poorly understood. METHODS AND FINDINGS: Acute-phase serum amyloid A (A-SAA mRNA levels, and A-SAA adipose secretion and serum levels were measured in obese and nonobese individuals, obese participants who underwent weight-loss, and persons treated with the insulin sensitizer rosiglitazone. Inflammation-eliciting activity of A-SAA was investigated in human adipose stromal vascular cells, coronary vascular endothelial cells and a murine monocyte cell line. We demonstrate that A-SAA was highly and selectively expressed in human adipocytes. Moreover, A-SAA mRNA levels and A-SAA secretion from adipose tissue were significantly correlated with body mass index (r = 0.47; p = 0.028 and r = 0.80; p = 0.0002, respectively. Serum A-SAA levels decreased significantly after weight loss in obese participants (p = 0.006, as well as in those treated with rosiglitazone (p = 0.033. The magnitude of the improvement in insulin sensitivity after weight loss was significantly correlated with decreases in serum A-SAA (r = -0.74; p = 0.034. SAA treatment of vascular endothelial cells and monocytes markedly increased the production of inflammatory cytokines, e.g., interleukin (IL-6, IL-8, tumor necrosis factor alpha, and monocyte chemoattractant protein-1. In addition, SAA increased basal lipolysis in adipose tissue culture by 47%. CONCLUSIONS: A-SAA is a proinflammatory and lipolytic adipokine in humans. The increased expression of A-SAA by adipocytes in obesity suggests that it may play a critical role in local and systemic inflammation and free fatty acid production and could be a direct link between obesity and its comorbidities, such as insulin resistance and atherosclerosis. Accordingly, improvements

  12. Visceral adipose tissue activated macrophage content and inflammatory adipokine secretion is higher in pre-eclampsia than in healthy pregnancys.

    Science.gov (United States)

    Huda, Shahzya S; Jordan, Fiona; Bray, Jack; Love, Gillian; Payne, Reba; Sattar, Naveed; Freeman, Dilys J

    2017-07-01

    Obesity increases pre-eclampsia (PE) risk. Adipose tissue inflammation may contribute to the clinical syndrome of PE. We compared adipose tissue macrophage infiltration and release of pro-inflammatory adipokines in PE and healthy pregnancy. Subcutaneous and visceral adipose tissue biopsies were collected from healthy (n=13) and PE (n=13) mothers. Basal and lipopolysaccharide (LPS) stimulated adipocyte TNFα, IL-6, CCL-2, and CRP release was measured. Adipose tissue cell densities of activated (cfms(+)) and total (CD68(+)) macrophages were determined. In PE only, visceral adipose tissue TNFα release was increased after LPS stimulation (57 [76] versus 81 [97] pg/ml/µg DNA, P=0.030). Basal TNFα release was negatively correlated insulin sensitivity of visceral adipocytes (r = -0.61, P=0.030) in PE. Visceral adipocyte IL-6 release was increased after LPS stimulation in PE only (566 [696] versus 852 [914] pg/ml/µg DNA, P=0.019). Visceral adipocyte CCL-2 basal (67 [61] versus 187 [219] pg/ml/µgDNA, P=0.049) and stimulated (46 [46] versus 224 [271] pg/ml/µg DNA, P=0.003) release was greater than in subcutaneous adipocytes in PE only. In PE, median TNF mRNA expression in visceral adipose tissue was higher than controls (1.94 [1.13-4.14] versus 0.8 [0.00-1.27] TNF/PPIA ratio, P=0.006). In visceral adipose tissue, CSF1R (a marker of activated macrophages) mRNA expression (24.8[11.0] versus 51.0[29.9] CSF1R/PPIA ratio, P=0.011) and activated (cfms+) macrophage count (6.7[2.6] versus 15.2[8.8] % cfms+/adipocyte, P=0.031) were higher in PE than in controls. In conclusion, our study demonstrates dysregulation of inflammatory pathways predominantly in visceral adipose tissue in PE. Inflammation of visceral adipose tissue may mediate many of the adverse metabolic effects associated with PE. © 2017 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution

  13. The adipokine leptin increases skeletal muscle mass and significantly alters skeletal muscle miRNA expression profile in aged mice

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    Hamrick, Mark W., E-mail: mhamrick@mail.mcg.edu [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Herberg, Samuel; Arounleut, Phonepasong [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); He, Hong-Zhi [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Shiver, Austin [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Qi, Rui-Qun [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Zhou, Li [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Department of Internal Medicine, Henry Ford Health System, Detroit, MI (United States); Isales, Carlos M. [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); and others

    2010-09-24

    Research highlights: {yields} Aging is associated with muscle atrophy and loss of muscle mass, known as the sarcopenia of aging. {yields} We demonstrate that age-related muscle atrophy is associated with marked changes in miRNA expression in muscle. {yields} Treating aged mice with the adipokine leptin significantly increased muscle mass and the expression of miRNAs involved in muscle repair. {yields} Recombinant leptin therapy may therefore be a novel approach for treating age-related muscle atrophy. -- Abstract: Age-associated loss of muscle mass, or sarcopenia, contributes directly to frailty and an increased risk of falls and fractures among the elderly. Aged mice and elderly adults both show decreased muscle mass as well as relatively low levels of the fat-derived hormone leptin. Here we demonstrate that loss of muscle mass and myofiber size with aging in mice is associated with significant changes in the expression of specific miRNAs. Aging altered the expression of 57 miRNAs in mouse skeletal muscle, and many of these miRNAs are now reported to be associated specifically with age-related muscle atrophy. These include miR-221, previously identified in studies of myogenesis and muscle development as playing a role in the proliferation and terminal differentiation of myogenic precursors. We also treated aged mice with recombinant leptin, to determine whether leptin therapy could improve muscle mass and alter the miRNA expression profile of aging skeletal muscle. Leptin treatment significantly increased hindlimb muscle mass and extensor digitorum longus fiber size in aged mice. Furthermore, the expression of 37 miRNAs was altered in muscles of leptin-treated mice. In particular, leptin treatment increased the expression of miR-31 and miR-223, miRNAs known to be elevated during muscle regeneration and repair. These findings suggest that aging in skeletal muscle is associated with marked changes in the expression of specific miRNAs, and that nutrient

  14. Acute-phase serum amyloid A: an inflammatory adipokine and potential link between obesity and its metabolic complications.

    Directory of Open Access Journals (Sweden)

    Rong-Ze Yang

    2006-06-01

    Full Text Available Obesity is associated with low-grade chronic inflammation, and serum markers of inflammation are independent risk factors for cardiovascular disease (CVD. However, the molecular and cellular mechanisms that link obesity to chronic inflammation and CVD are poorly understood.Acute-phase serum amyloid A (A-SAA mRNA levels, and A-SAA adipose secretion and serum levels were measured in obese and nonobese individuals, obese participants who underwent weight-loss, and persons treated with the insulin sensitizer rosiglitazone. Inflammation-eliciting activity of A-SAA was investigated in human adipose stromal vascular cells, coronary vascular endothelial cells and a murine monocyte cell line. We demonstrate that A-SAA was highly and selectively expressed in human adipocytes. Moreover, A-SAA mRNA levels and A-SAA secretion from adipose tissue were significantly correlated with body mass index (r = 0.47; p = 0.028 and r = 0.80; p = 0.0002, respectively. Serum A-SAA levels decreased significantly after weight loss in obese participants (p = 0.006, as well as in those treated with rosiglitazone (p = 0.033. The magnitude of the improvement in insulin sensitivity after weight loss was significantly correlated with decreases in serum A-SAA (r = -0.74; p = 0.034. SAA treatment of vascular endothelial cells and monocytes markedly increased the production of inflammatory cytokines, e.g., interleukin (IL-6, IL-8, tumor necrosis factor alpha, and monocyte chemoattractant protein-1. In addition, SAA increased basal lipolysis in adipose tissue culture by 47%.A-SAA is a proinflammatory and lipolytic adipokine in humans. The increased expression of A-SAA by adipocytes in obesity suggests that it may play a critical role in local and systemic inflammation and free fatty acid production and could be a direct link between obesity and its comorbidities, such as insulin resistance and atherosclerosis. Accordingly, improvements in systemic inflammation and insulin resistance

  15. Comparison of the effects of short-term hypolipidaemic treatment on plasma adipokine levels in men and women with isolated hypercholesterolaemia.

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    Krysiak, Robert; Żmuda, Witold; Marek, Bogdan; Okopień, Bogusław

    2015-01-01

    Hypolipidaemic agents were found to affect plasma adipokine levels, but no previous study has investigated whether this effect is sex-dependent. We retrospectively analysed 61 patients participating in our previous studies, who because of isolated hypercholesterolaemia were treated with simvastatin (40 mg daily), ezetimibe (10 mg daily) or simvastatin (40 mg daily) plus ezetimibe (10 mg daily). Plasma levels of leptin, adiponectin, visfatin, tumour necrosis factor-alpha (TNF-alpha), free fatty acids (FFA), and high-sensitivity C-reactive protein (hsCRP) were assessed separately for men and women before and after 30 days of treatment. At baseline, plasma levels of adiponectin and leptin were lower, while plasma levels of TNF-alpha were higher in men than in women. Administration of simvastatin and statin/ezetimibe combination for 30 days reduced plasma levels of hsCRP, FFA, leptin, visfatin, and TNF-alpha but increased plasma levels of adiponectin, while the effect of ezetimibe was much more limited. The effect of simvastatin and ezetimibe, administered alone or in combination, on plasma hsCRP, FFA, leptin, adiponectin, visfatin, and TNF-alpha did not differ between men and women. Irrespectively of sex, the changes in plasma adipokines and systemic-anti-inflammatory effects were more expressed in simvastatin - than in ezetimibe-treated patients and were strongest when both these agents were administered together. Our results show that sex differences do not determine the effect of hypolipidaemic agents on adipose tissue and low-grade inflammation.

  16. Effect of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor γ2 gene on lipid profile and adipokines levels in obese subjects

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    Becer E

    2017-06-01

    Full Text Available Peroxisome proliferator-activated receptor γ (PPARγ is a key regulator of metabolism, adipokines production and secretion. The aim of this study was to investigate the association between the PPARγ2 gene Pro12Ala polymorphism in obesity in terms of body mass index (BMI, lipid parameters, homeostasis model assessment of insulin resistance (HOMA-IR, serum lipid, leptin, adiponectin, resistin and chemerin levels. The study included 160 obese and 140 non obese subjects. The Pro12Ala polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP. Serum lipid, leptin, adiponectin, resistin and chemerin levels were measured. No association was found between the Pro12Ala polymorphism and BMI. Strikingly, in the study group, obese subjects with the AA genotype had significantly higher triglycerides (p = 0.046 and resistin (p <0.001 levels than those with the wild-type PP and heterozygous PA genotypes. Serum leptin and chemerin levels were significantly associated with Pro-12Ala poymorphism in the obese and non obese groups (p <0.01. In the obese group, subjects with the homozygous AA genotype had significantly lower adiponectin (p = 0.010 activity than the PP genotype. Our results suggest that the PPARγ2 gene Pro12Ala polymorphism has no direct association with obesity but does have significant influences on lipid profiles and adipokines levels.

  17. Association between the chondrocyte phenotype and the expression of adipokines and their receptors: evidence for a role of leptin but not adiponectin in the expression of cartilage-specific markers.

    Science.gov (United States)

    Francin, Pierre-Jean; Guillaume, Cécile; Humbert, Anne-Claude; Pottie, Pascale; Netter, Patrick; Mainard, Didier; Presle, Nathalie

    2011-11-01

    Although extensive evidence support the key role of adipokines in cartilage homeostasis, contradictory data have been found for their expression and their effects in chondrocytes. This study was then undertaken to determine whether a phenotypic modulation may affect the expression of adipokines and their receptors in human chondrocytes. The expression of leptin, adiponectin and their receptors, as well as cartilage-specific genes was examined in chondrocytes obtained from patients with osteoarthritis either directly after cells harvest or after culture in monolayer or in alginate beads. The results showed major changes in the gene expression pattern after culture in monolayer with a shift from the adipokines to their receptors. Interestingly, this downregulation of adipokines was associated with a loss of chondrocyte phenotype, and chondrocytes recovered a cartilage-like expression profile of leptin and adiponectin when cultured in a tridimensional chondrocyte phenotype-inducing system, but ceased expressing their receptors. Further experiments clearly showed that leptin but not adiponectin promoted the expression of cartilage-specific markers through mitogen-activated protein kinase, Janus kinase and phosphatidylinositol-3 kinase signaling pathways. In conclusion, our data indicate that any phenotypic modulation could affect chondrocyte responsiveness to leptin or adiponectin, and provide evidence for an important role for leptin in regulating the expression of cartilage-specific markers.

  18. Effects of secoisolariciresinol diglucoside lignan-enriched flaxseed powder on body weight, visceral fat, lipid profile, adipokines, and blood pressure in rats fed a high-fructose and high-fat diet

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    The potential effects of secoisolariciresinol diglucoside (SDG) lignan-enriched flaxseed powder LEFP) on body weight, visceral fat, lipid profile, adipokines, and blood pressure were investigated using Sprague-Dawley rats. The animals were divided into three groups (n=8) that were fed either a norm...

  19. Time-course microarrays reveal early activation of the immune transcriptome and adipokine dysregulation leads to fibrosis in visceral adipose depots during diet-induced obesity

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    Kwon Eun-Young

    2012-09-01

    Full Text Available Abstract Background Visceral white adipose tissue (WAT hypertrophy, adipokine production, inflammation and fibrosis are strongly associated with obesity, but the time-course of these changes in-vivo are not fully understood. Therefore, the aim of this study was to establish the time-course of changes in adipocyte morphology, adipokines and the global transcriptional landscape in visceral WAT during the development of diet-induced obesity. Results C57BL/6 J mice were fed a high-fat diet (HFD or normal diet (ND and sacrificed at 8 time-points over 24 weeks. Excessive fat accumulation was evident in visceral WAT depots (Epidydimal, Perirenal, Retroperitoneum, Mesentery after 2–4 weeks. Fibrillar collagen accumulation was evident in epidydimal adipocytes at 24 weeks. Plasma adipokines, leptin, resistin and adipsin, increased early and time-dependently, while adiponectin decreased late after 20 weeks. Only plasma leptin and adiponectin levels were associated with their respective mRNA levels in visceral WAT. Time-course microarrays revealed early and sustained activation of the immune transcriptome in epididymal and mesenteric depots. Up-regulated inflammatory genes included pro-inflammatory cytokines, chemokines (Tnf, Il1rn, Saa3, Emr1, Adam8, Itgam, Ccl2, 3, 4, 6, 7 and 9 and their upstream signalling pathway genes (multiple Toll-like receptors, Irf5 and Cd14. Early changes also occurred in fibrosis, extracellular matrix, collagen and cathepsin related-genes, but histological fibrosis was only visible in the later stages. Conclusions In diet-induced obesity, early activation of TLR-mediated inflammatory signalling cascades by CD antigen genes, leads to increased expression of pro-inflammatory cytokines and chemokines, resulting in chronic low-grade inflammation. Early changes in collagen genes may trigger the accumulation of ECM components, promoting fibrosis in the later stages of diet-induced obesity. New therapeutic approaches

  20. Time-course microarrays reveal early activation of the immune transcriptome and adipokine dysregulation leads to fibrosis in visceral adipose depots during diet-induced obesity.

    Science.gov (United States)

    Kwon, Eun-Young; Shin, Su-Kyung; Cho, Yun-Young; Jung, Un Ju; Kim, Eunjung; Park, Taesun; Park, Jung Han Yoon; Yun, Jong Won; McGregor, Robin A; Park, Yong Bok; Choi, Myung-Sook

    2012-09-04

    Visceral white adipose tissue (WAT) hypertrophy, adipokine production, inflammation and fibrosis are strongly associated with obesity, but the time-course of these changes in-vivo are not fully understood. Therefore, the aim of this study was to establish the time-course of changes in adipocyte morphology, adipokines and the global transcriptional landscape in visceral WAT during the development of diet-induced obesity. C57BL/6 J mice were fed a high-fat diet (HFD) or normal diet (ND) and sacrificed at 8 time-points over 24 weeks. Excessive fat accumulation was evident in visceral WAT depots (Epidydimal, Perirenal, Retroperitoneum, Mesentery) after 2-4 weeks. Fibrillar collagen accumulation was evident in epidydimal adipocytes at 24 weeks. Plasma adipokines, leptin, resistin and adipsin, increased early and time-dependently, while adiponectin decreased late after 20 weeks. Only plasma leptin and adiponectin levels were associated with their respective mRNA levels in visceral WAT. Time-course microarrays revealed early and sustained activation of the immune transcriptome in epididymal and mesenteric depots. Up-regulated inflammatory genes included pro-inflammatory cytokines, chemokines (Tnf, Il1rn, Saa3, Emr1, Adam8, Itgam, Ccl2, 3, 4, 6, 7 and 9) and their upstream signalling pathway genes (multiple Toll-like receptors, Irf5 and Cd14). Early changes also occurred in fibrosis, extracellular matrix, collagen and cathepsin related-genes, but histological fibrosis was only visible in the later stages. In diet-induced obesity, early activation of TLR-mediated inflammatory signalling cascades by CD antigen genes, leads to increased expression of pro-inflammatory cytokines and chemokines, resulting in chronic low-grade inflammation. Early changes in collagen genes may trigger the accumulation of ECM components, promoting fibrosis in the later stages of diet-induced obesity. New therapeutic approaches targeting visceral adipose tissue genes altered early by HFD

  1. Substitution in Amino Acid 70 of Hepatitis C Virus Core Protein Changes the Adipokine Profile via Toll-Like Receptor 2/4 Signaling.

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    Satoko Uraki

    Full Text Available It has been suggested that amino acid (aa substitution at position 70 from arginine (70R to glutamine (70Q in the genotype 1b hepatitis C virus (HCV core protein is associated with insulin resistance and worse prognosis. However, the precise mechanism is still unclear. The aim of this study was to investigate the impact of the substitution at position 70 in HCV core protein on adipokine production by murine and human adipocytes.The influence of treatment with HCV core protein (70R or 70Q on adipokine production by both 3T3-L1 and human adipocytes were examined with real-time PCR and enzyme-linked immunosorbent assay (ELISA, and triglyceride content was also analyzed. The effects of toll-like receptor (TLR2/4 inhibition on IL-6 production by 3T3-L1 induced by HCV core protein were examined.IL-6 production was significantly increased and adiponectin production was reduced without a change in triglyceride content by treatment with 70Q compared to 70R core protein in both murine and human adipocytes. IL-6 induction of 3T3-L1 cells treated by 70Q HCV core protein was significantly inhibited with anti-TLR2 antibody by 42%, and by TLR4 inhibitor by 40%.Our study suggests that extracellular HCV core protein with substitution at position 70 enhanced IL-6 production and reduced adiponectin production from visceral adipose tissue, which can cause insulin resistance, hepatic steatosis, and ultimately development of HCC.

  2. A prospective 4-year study of insulin resistance and adipokines in morbidly obese diabetic and non-diabetic patients after gastric banding.

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    Urbanavicius, Vaidotas; Juodeikis, Zygimantas; Dzenkeviciute, Vilma; Galkine, Aiste; Petrulioniene, Zaneta; Sapoka, Virginijus; Brimiene, Vilma; Vitkus, Dalius; Brimas, Gintautas

    2017-06-01

    There are insufficient data regarding the changes in adipokine levels after laparoscopic adjustable gastric banding (LAGB) in diabetic and non-diabetic patients and their effects on insulin resistance and type 2 diabetes remission. To assess leptin, adiponectin, and insulin resistance changes after LAGB in diabetic and non-diabetic morbidly obese patients. One hundred and three patients (37 with and 66 without type 2 diabetes) underwent LAGB from January 2009 to January 2010. Glycated hemoglobin, insulin, adipokine levels and insulin resistance were evaluated preoperatively, and 1 and 4 years after LAGB. The mean patient age was 45.9 ±11.7 years and mean preoperative body mass index was 47.5 ±7.3 kg/m(2). A total of 80 of 103 patients (77.6%) completed the 4-year follow-up. After 4 years the mean excess weight loss was 38.8% and 39.5% in diabetic and non-diabetic patients respectively. Leptin levels decreased significantly in both groups at 1 year, but after 4 years this was noted only in non-diabetic patients. After 1 year adiponectin levels increased significantly only in non-diabetic patients (p = 0.003) and remained almost the same at 4 years. A significant decrease in insulin resistance was noted in both groups 1 year after LAGB and diabetes remission was observed in 23 (62.1%) patients. There was a negative correlation between preoperative insulin resistance and adiponectin levels throughout the follow-up period. Leptin levels positively correlated with BMI throughout the study period (baseline r = 0.45; p year r = 0.71; p years r = 0.68; p year; however, at 4 years it was significant (r = 0.27; p year after LAGB. The 4-year follow-up revealed stabilization in metabolic indices rather than significant improvement.

  3. Research progress of the association of adipokines and bronchial asthma%脂肪因子与支气管哮喘相关性的研究进展

    Institute of Scientific and Technical Information of China (English)

    刘榴; 崇蕾; 李昌崇

    2015-01-01

    Epidemiologic data indicate an increasing morbidity of obesity and bronchial asthma (asthma).Over the past decades,obesity and asthma have become the two major global public health challenges.Many researches show a significant association between obesity and asthma,and define obese asthma as a new disease.But the mechanism does not been clearly understood.Adipokines are characteristic substances of obesity,many studys have found a relationship between adipokines and asthma.This review focused on the effect of three main adipokines (leptin,adiponectin and resistin) in asthma,and explored the potential relationship between adipokines and asthma.%肥胖和支气管哮喘(简称哮喘)的发病率均逐年增加,已经成为重要的社会经济问题,给社会和家庭带来沉重的负担.近十年来大量研究提示肥胖和哮喘之间存在关联,甚至提出肥胖型哮喘是一种新的疾病.但其发病机制目前尚未明确.脂肪因子是肥胖的特征性物质,已有较多研究发现脂肪因子与哮喘之间存在相关性,本文就3种主要的脂肪因子(瘦素、脂联素和抵抗素)在哮喘中的作用作一综述,探讨哮喘与脂肪因子之间可能的关系.

  4. Fish oil prevents changes induced by a high-fat diet on metabolism and adipokine secretion in mice subcutaneous and visceral adipocytes.

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    de Sá, Roberta D C da Cunha; Crisma, Amanda R; Cruz, Maysa M; Martins, Amanda R; Masi, Laureane N; do Amaral, Catia L; Curi, R; Alonso-Vale, Maria I C

    2016-11-01

    Fish oil (FO), rich in omega-3 polyunsaturated fatty acids, has beneficial effects on changes induced by obesity and partially prevents associated comorbidities. The effects of FO on adipocytes from different adipose tissue depots in high-fat (HF) diet induced obese mice have not been uninvestigated. This is the first study to examine the effects of FO on changes in metabolism and adipokine production in adipocytes from s.c. (inguinal; ING) or visceral (retroperitoneal; RP) white adipose depots in a HF diet-induced obese mice. Unlike most studies performed previously, FO supplementation was initiated 4 weeks before the induction of obesity. HF diet caused marked changes in ING (glucose uptake and secretion of adiponectin, tumour necrosis factor-α and interleukin-6 in ING) and RP (lipolysis, de novo lipogenesis and secretion of pro-inflammatory cytokines) adipose depots. Previous and concomitant FO administration prevented the changes in ING and RP adipocytes induced by the HF diet. In the present study, we investigated the effect of fish oil (FO) on metabolism and adipokine production by adipocytes from s.c. (inguinal; ING) and visceral (retroperitoneal; RP) white adipose depots in high-fat (HF) diet-induced obese mice. Mice were divided into CO (control diet), CO+FO, HF and HF+FO groups. The HF group presented higher body weight, glucose intolerance, insulin resistance, higher plasma total and low-density lipoprotein cholesterol levels, and greater weights of ING and RP adipose depots accompanied by hypertrophy of the adipocytes. FO exerted anti-obesogenic effects associated with beneficial effects on dyslipidaemia and insulin resistance in mice fed a HF diet (HF+FO group). HF raised RP adipocyte lipolysis and the production of pro-inflammatory cytokines and reduced de novo synthesis of fatty acids, whereas, in ING adipocytes, it decreased glucose uptake and adiponectin secretion but did not change lipolysis. Therefore, the adipose depots play different roles in

  5. Transcriptional analysis of abdominal fat in genetically fat and lean chickens reveals adipokines, lipogenic genes and a link between hemostasis and leanness

    Science.gov (United States)

    2013-01-01

    Background This descriptive study of the abdominal fat transcriptome takes advantage of two experimental lines of meat-type chickens (Gallus domesticus), which were selected over seven generations for a large difference in abdominal (visceral) fatness. At the age of selection (9 wk), the fat line (FL) and lean line (LL) chickens exhibit a 2.5-fold difference in abdominal fat weight, while their feed intake and body weight are similar. These unique avian models were originally created to unravel genetic and endocrine regulation of adiposity and lipogenesis in meat-type chickens. The Del-Mar 14K Chicken Integrated Systems microarray was used for a time-course analysis of gene expression in abdominal fat of FL and LL chickens during juvenile development (1–11 weeks of age). Results Microarray analysis of abdominal fat in FL and LL chickens revealed 131 differentially expressed (DE) genes (FDR≤0.05) as the main effect of genotype, 254 DE genes as an interaction of age and genotype and 3,195 DE genes (FDR≤0.01) as the main effect of age. The most notable discoveries in the abdominal fat transcriptome were higher expression of many genes involved in blood coagulation in the LL and up-regulation of numerous adipogenic and lipogenic genes in FL chickens. Many of these DE genes belong to pathways controlling the synthesis, metabolism and transport of lipids or endocrine signaling pathways activated by adipokines, retinoid and thyroid hormones. Conclusions The present study provides a dynamic view of differential gene transcription in abdominal fat of chickens genetically selected for fatness (FL) or leanness (LL). Remarkably, the LL chickens over-express a large number of hemostatic genes that could be involved in proteolytic processing of adipokines and endocrine factors, which contribute to their higher lipolysis and export of stored lipids. Some of these changes are already present at 1 week of age before the divergence in fatness. In contrast, the FL chickens have

  6. Effects of varying degrees of intermittent hypoxia on proinflammatory cytokines and adipokines in rats and 3T3-L1 adipocytes.

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    Qing He

    Full Text Available OBJECTIVES: Intermittent hypoxia (IH, resulted from recurring episodes of upper airway obstruction, is the hallmark feature and the most important pathophysiologic pathway of obstructive sleep apnea (OSA. IH is believed to be the most important factor causing systemic inflammation. Studies suggest that insulin resistance (IR is positively associated with OSA. In this study, we hypothesized that the recurrence of IH might result in cellular and systemic inflammation, which was manifested through the levels of proinflammatory cytokines and adipokines after IH exposure, and because IR is linked with inflammation tightly, this inflammatory situation may implicate an IR status. METHODS: We developed an IH 3T3-L1 adipocyte and rat model respectively, recapitulating the nocturnal oxygen profile in OSA. In IH cells, nuclear factor kappa B (NF-κB DNA binding reactions, hypoxia-inducible factor-1α (HIF-1α, glucose transporter-1 (Glut-1, necrosis factor alpha (TNF-α, interleukin (IL -6, leptin, adiponectin mRNA transcriptional activities and protein expressions were measured. In IH rats, blood glucose, insulin, TNF-α, IL-6, leptin and adiponectin levels were analyzed. RESULTS: The insulin and blood glucose levels in rats and NF-κB DNA binding activities in cells had significantly statistical results described as severe IH>moderate IH>mild IH>sustained hypoxia>control. The mRNA and protein levels of HIF-1α and Glut-1 in severe IH group were the highest. In cellular and animal models, both the mRNA and protein levels of TNF-α, IL-6 and leptin were the highest in severe IH group, when the lowest in severe IH group for adiponectin. CONCLUSIONS: Oxidative stress and the release of pro-inflammatory cytokines/adipokines, which are the systemic inflammatory markers, are associated with IH closely and are proportional to the severity of IH. Because IR and glucose intolerance are linked with inflammation tightly, our results may implicate the clinical

  7. The novel adipokine progranulin counteracts IL-1 and TLR4-driven inflammatory response in human and murine chondrocytes via TNFR1

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    Abella, Vanessa; Scotece, Morena; Conde, Javier; López, Verónica; Pirozzi, Claudio; Pino, Jesús; Gómez, Rodolfo; Lago, Francisca; González-Gay, Miguel Ángel; Gualillo, Oreste

    2016-01-01

    Progranulin (PGRN) is a recently identified adipokine that is supposed to have anti-inflammatory actions. The proinflammatory cytokine interleukin-1β (IL1β) stimulates several mediators of cartilage degradation. Toll like receptor-4 (TLR4) can bind to various damage-associated molecular patterns, leading to inflammatory condition. So far, no data exist of PGRN effects in inflammatory conditions induced by IL1β or lipopolysaccharide (LPS). Here, we investigated the anti-inflammatory potential of PGRN in IL1β- or LPS-induced inflammatory responses of chondrocytes. Human osteoarthritic chondrocytes and ATDC-5 cells were treated with PGRN in presence or not of IL1β or LPS. First, we showed that recombinant PGRN had no effects on cell viability. We present evidence that PGRN expression was increased during the differentiation of ATDC-5 cell line. Moreover, PGRN mRNA and protein expression is increased in cartilage, synovial and infrapatellar fat pad tissue samples from OA patients. PGRN mRNA levels are upregulated under TNFα and IL1β stimulation. Our data showed that PGRN is able to significantly counteract the IL1β-induced expression of NOS2, COX2, MMP13 and VCAM-1. LPS-induced expression of NOS2 is also decreased by PGRN. These effects are mediated, at least in part, through TNFR1. Taken together, our results suggest that PGRN has a clear anti-inflammatory function. PMID:26853108

  8. A Comparison of the Effects of Aerobic and Intense Exercise on the Type 2 Diabetes Mellitus Risk Marker Adipokines, Adiponectin and Retinol Binding Protein-4

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    Amy Phillips

    2014-01-01

    Full Text Available With a more sedentary population comes growing rates of obesity and increased type 2 diabetes mellitus (T2DM risk. Exercise generally induces positive changes in traditional T2DM risk markers such as lipids, glucose tolerance, and insulin sensitivity; however alterations in concentrations of many circulating cytokines and their respective receptors are also becoming apparent. These cytokines may be early-response health risk factors otherwise overlooked in traditional T2DM risk marker analysis. Plasma levels of two adipocyte-originating cytokines, adiponectin and retinol binding protein 4 (RBP-4, alter following exercise. Adiponectin has anti-inflammatory, anti-atherosclerotic, and anti-insulin resistance roles and its secretion increases with physical activity, whilst elevated RBP-4 leads to increased insulin resistance, and secretion decreases with increasing physical activity; thus these plasma adipokine levels alter favourably following exercise. Although current data are limited, they do suggest that the more intense the exercise, the greater the positive effect on plasma RBP-4 levels, whilst lower intensity aerobic exercise may positively improve adiponectin concentrations. Therefore short-duration, high intensity training may provide a time-efficient alternative to the recommended 150 min moderate aerobic exercise per week in providing positive changes in RBP-4 and other traditional T2DM risk markers and due to increased compliance give greater health benefits over the longer term.

  9. Adipokines and Sexual Hormones Associated with the Components of the Metabolic Syndrome in Pharmacologically Untreated Subjects: Data from the Brisighella Heart Study

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    Arrigo F. G. Cicero

    2011-01-01

    Full Text Available We evaluated the association of the sex hormone pattern and the serum level of the main adipokines to metabolic syndrome (MS and its components in 199 pharmacologically untreated subjects. Men and women included in the age-class subgroups were matched for body mass index, waist circumference, blood pressure, heart rate, fasting plasma glucose, and plasma lipids. Men without MS had significantly lower leptin/adiponectin ratio than men with MS. Women without MS had lower leptin and leptin/adiponectin ratio than women with MS but had significantly higher adiponectin, estrone, and dehydroepiandrosterone levels. In men, the leptin/adiponectin ratio is the main factor associated to MS diagnosis (OR: 3.36, 95% CI 1.40–8.08, while in women adiponectin alone appears to be a protective factor (OR: 0.87, 95% CI 0.79–0.95. In conclusion, in a sample of pharmacologically untreated subjects, leptin/adiponectin ratio seems to be the factor more strongly associated to MS and its components.

  10. C1q/TNF-related Protein-12 (CTRP12), a Novel Adipokine That Improves Insulin Sensitivity and Glycemic Control in Mouse Models of Obesity and Diabetes*

    Science.gov (United States)

    Wei, Zhikui; Peterson, Jonathan M.; Lei, Xia; Cebotaru, Liudmila; Wolfgang, Michael J.; Baldeviano, G. Christian; Wong, G. William

    2012-01-01

    Despite the prevalence of insulin resistance and type 2 diabetes mellitus, their underlying mechanisms remain incompletely understood. Many secreted endocrine factors and the intertissue cross-talk they mediate are known to be dysregulated in type 2 diabetes mellitus. Here, we describe CTRP12, a novel adipokine with anti-diabetic actions. The mRNA and circulating levels of CTRP12 were decreased in a mouse model of obesity, but its expression in adipocytes was increased by the anti-diabetic drug rosiglitazone. A modest rise in circulating levels of CTRP12 by recombinant protein administration was sufficient to lower blood glucose in wild-type, leptin-deficient ob/ob, and diet-induced obese mice. A short term elevation of serum CTRP12 by adenovirus-mediated expression improved glucose tolerance and insulin sensitivity, normalized hyperglycemia and hyperinsulinemia, and lowered postprandial insulin resistance in obese and diabetic mice. CTRP12 improves insulin sensitivity in part by enhancing insulin signaling in the liver and adipose tissue. Further, CTRP12 also acts in an insulin-independent manner; in cultured hepatocytes and adipocytes, CTRP12 directly activated the PI3K-Akt signaling pathway to suppress gluconeogenesis and promote glucose uptake, respectively. Collectively, these data establish CTRP12 as a novel metabolic regulator linking adipose tissue to whole body glucose homeostasis through insulin-dependent and independent mechanisms. PMID:22275362

  11. Human breast milk and adipokines--A potential role for the soluble leptin receptor (sOb-R) in the regulation of infant energy intake and development.

    Science.gov (United States)

    Zepf, F D; Rao, P; Moore, J; Stewart, R; Ladino, Yuli Martinez; Hartmann, B T

    2016-01-01

    Concentrations of different adipokines in human breast milk are thought to be able to affect energy intake of the infant. Leptin is a hormone synthesized by adipose tissue and the human placenta and favors satiety. The availability of leptin in breast milk is influenced by epithelial cells of the mammary gland that are known to be able to produce leptin, as well as leptin from maternal circulation that is transported to the breast milk, and which can thus in turn reach neonatal blood after absorption. Research so far as mainly focused on leptin concentrations in breast milk. However, evidence suggests that in addition to leptin concentrations levels of the so-called soluble leptin receptor (sOb-R), the main high-affinity binding protein for leptin in humans, are necessary in order to calculate the free leptin index (FLI) and to assess function of the leptin axis. FLI is calculated from the ratio of leptin to the sOb-R, and serves as the main parameter for assessing function of the leptin axis throughout maturation and development. Here we propose that assessing sOb-R levels in addition to leptin concentrations in breast milk could serve as a valuable tool to investigate effects of the leptin axis in breast milk because sOb-R concentrations can impact available leptin levels, and which in turn can have significant implications for infant energy intake and related development.

  12. Vaspin is an adipokine ameliorating ER stress in obesity as a ligand for cell-surface GRP78/MTJ-1 complex.

    Science.gov (United States)

    Nakatsuka, Atsuko; Wada, Jun; Iseda, Izumi; Teshigawara, Sanae; Higashio, Kanji; Murakami, Kazutoshi; Kanzaki, Motoko; Inoue, Kentaro; Terami, Takahiro; Katayama, Akihiro; Hida, Kazuyuki; Eguchi, Jun; Horiguchi, Chikage Sato; Ogawa, Daisuke; Matsuki, Yasushi; Hiramatsu, Ryuji; Yagita, Hideo; Kakuta, Shigeru; Iwakura, Yoichiro; Makino, Hirofumi

    2012-11-01

    It is unknown whether adipokines derived from adipose tissues modulate endoplasmic reticulum (ER) stress induced in obesity. Here, we show that visceral adipose tissue-derived serine protease inhibitor (vaspin) binds to cell-surface 78-kDa glucose-regulated protein (GRP78), which is recruited from ER to plasma membrane under ER stress. Vaspin transgenic mice were protected from diet-induced obesity, glucose intolerance, and hepatic steatosis, while vaspin-deficient mice developed glucose intolerance associated with upregulation of ER stress markers. With tandem affinity tag purification using HepG2 cells, we identified GRP78 as an interacting molecule. The complex formation of vaspin, GRP78, and murine tumor cell DnaJ-like protein 1 (MTJ-1) (DnaJ homolog, subfamily C, member 1) on plasma membrane was confirmed by cell-surface labeling with biotin and immunoprecipitation in liver tissues and H-4-II-E-C3 cells. The addition of recombinant human vaspin in the cultured H-4-II-E-C3 cells also increased the phosphorylation of Akt and AMP-activated protein kinase (AMPK) in a dose-dependent manner, and anti-GRP78 antibodies completely abrogated the vaspin-induced upregulation of pAkt and pAMPK. Vaspin is a novel ligand for cell-surface GRP78/MTJ-1 complex, and its subsequent signals exert beneficial effects on ER stress-induced metabolic dysfunctions.

  13. Overexpressing the novel autocrine/endocrine adipokine WISP2 induces hyperplasia of the heart, white and brown adipose tissues and prevents insulin resistance

    Science.gov (United States)

    Grünberg, John R.; Hoffmann, Jenny M.; Hedjazifar, Shahram; Nerstedt, Annika; Jenndahl, Lachmi; Elvin, Johannes; Castellot, John; Wei, Lan; Movérare-Skrtic, Sofia; Ohlsson, Claes; Holm, Louise Mannerås; Bäckhed, Fredrik; Syed, Ismail; Bosch, Fatima; Saghatelian, Alan; Kahn, Barbara B.; Hammarstedt, Ann; Smith, Ulf

    2017-01-01

    WISP2 is a novel adipokine, most highly expressed in the adipose tissue and primarily in undifferentiated mesenchymal cells. As a secreted protein, it is an autocrine/paracrine activator of canonical WNT signaling and, as an intracellular protein, it helps to maintain precursor cells undifferentiated. To examine effects of increased WISP2 in vivo, we generated an aP2-WISP2 transgenic (Tg) mouse. These mice had increased serum levels of WISP2, increased lean body mass and whole body energy expenditure, hyperplastic brown/white adipose tissues and larger hyperplastic hearts. Obese Tg mice remained insulin sensitive, had increased glucose uptake by adipose cells and skeletal muscle in vivo and ex vivo, increased GLUT4, increased ChREBP and markers of adipose tissue lipogenesis. Serum levels of the novel fatty acid esters of hydroxy fatty acids (FAHFAs) were increased and transplantation of Tg adipose tissue improved glucose tolerance in recipient mice supporting a role of secreted FAHFAs. The growth-promoting effect of WISP2 was shown by increased BrdU incorporation in vivo and Tg serum increased mesenchymal precursor cell proliferation in vitro. In contrast to conventional canonical WNT ligands, WISP2 expression was inhibited by BMP4 thereby allowing normal induction of adipogenesis. WISP2 is a novel secreted regulator of mesenchymal tissue cellularity. PMID:28240264

  14. 减肥后与健康相关的脂肪因子在动物模型中的表达%Effects of weight loss on health-related adipokines expression in an animal model of obesity

    Institute of Scientific and Technical Information of China (English)

    尹琼; Dr. Tim Parr; Dr. Lisa Coneyworth; Dr. John Brameld

    2015-01-01

    Objective Some studies have been shown that reduced weight can increase serum anti-inflammatory cyto-kines and reduced pro-inflammatory cytokines, but whether the change of weight loss can alter mRNA expression of these adipokines are still unknown. Therefore, the research will investigate that after weight loss, the mRNA expres-sion of health-related adipokines in adipose tissue in obesity animal model. Method 12 LDLr (-/-) KO mice were induced obesity firstly and then 8 of them were subdivided into two subgroups, fed with high fat diet to keep obesity state or with low fat diet to lost weight for 82 days. After 82 days, mRNA expression of seven adipokines would be analyzed. Result There were no significant changes between HF×82 group and LF×82 group for seven adipokines mRNA expression. Conclusion These findings indicate that after weight loss by diet, health-related adipokines ex-pression in an animal model of obesity does not change.%目的:一些研究已经指出减低体重可以增加血液中抗炎因子的分泌并减少促炎因子,但是体重的减轻是否能改变这些脂肪因子mRNA的表达是未知的。因此本实验将会研究在减肥后,在肥胖小鼠脂肪组织里,与健康相关的脂肪因子的mRNA的表达情况。方法12只LDLr (-/-)敲除的老鼠将会先诱导为肥胖,然后其中8只分为两组,一组持续高脂肪喂养,另一组改为低脂肪喂养以达到减轻体重的目的。82天之后,7个脂肪因子的mRNA表达将会被测量。结果7个脂肪因子的表达在减肥组( HF ×82)和肥胖组(LF×82)中并没有显著的区别。结论结论通过饮食诱导减轻体重之后,与健康相关的脂肪因子mRNA表达在动物模型中并没有改变。

  15. Severely Obese Adolescents and Adults Exhibit a Different Association of Circulating Levels of Adipokines and Leukocyte Expression of the Related Receptors with Insulin Resistance

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    Antonello E. Rigamonti

    2013-01-01

    Full Text Available Obese adults frequently exhibit a low-grade inflammation and insulin resistance, which have been hypothesized to be established early in childhood. Aim of this study was to evaluate the age-dependent relationships between inflammatory state and insulin resistance in obese adolescents and adults. Clinical and metabolic parameters, circulating adipokines (TNF-α, adiponectin, and leptin, ghrelin, their leukocyte receptors (TNFR1, ADIPOR2, OBRL and GHSR1a, and acute phase reactants (CRP and white blood cells were assessed in lean and obese adolescents compared with the adult counterparts. Only obese adults had higher HOMA-IR, insulin, and triglycerides compared to the lean group. An inflammatory state was present in obese adolescents and adults, as demonstrated by the higher values of CRP and neutrophils. There were no group differences in circulating levels of TNF-α and leukocyte expression of TNFR1. Adiponectin concentrations and leukocyte expression of ADIPOR2 were higher in the lean groups than in the corresponding obese counterparts. For leptin and leukocyte expression of OBRL, the results were opposed. Circulating levels of ghrelin were higher in lean adolescents and adults than the related lean groups, while there was a higher leukocyte expression of GHSR1a in (only lean adults than obese adults. When the analysis was performed in (lean or obese adults, TNF-α, neutrophils, leptin, and GHSR1a were predictors of HOMA-IR. None of the considered independent variables accounted for the degree of insulin resistance in the adolescent group. In conclusion, a dissociation between the low-grade inflammation and insulin resistance is supposed to exist in the early phases of obesity.

  16. Impact of the adipokine adiponectin and the hepatokine fetuin-A on the development of type 2 diabetes: prospective cohort- and cross-sectional phenotyping studies.

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    Norbert Stefan

    Full Text Available BACKGROUND: Among adipokines and hepatokines, adiponectin and fetuin-A were consistently found to predict the incidence of type 2 diabetes, both by regulating insulin sensitivity. OBJECTIVE: To determine to what extent circulating adiponectin and fetuin-A are independently associated with incident type 2 diabetes in humans, and the major mechanisms involved. METHODS: Relationships with incident diabetes were tested in two cohort studies: within the European Prospective Investigation into Cancer and Nutrition (EPIC-Potsdam study (628 cases and the Nurses' Health Study (NHS; 470 cases. Relationships with body fat compartments, insulin sensitivity and insulin secretion were studied in the Tübingen Lifestyle Intervention Program (TULIP; N = 358. RESULTS: Circulating adiponectin and fetuin-A, independently of several confounders and of each other, associated with risk of diabetes in EPIC-Potsdam (RR for 1 SD: adiponectin: 0.45 [95% CI 0.37-0.54], fetuin-A: 1.18 [1.05-1.32] and the NHS (0.51 [0.42-0.62], 1.35 [1.16-1.58]. Obesity measures considerably attenuated the association of adiponectin, but not of fetuin-A. Subjects with low adiponectin and concomitantly high fetuin-A had the highest risk. Whereas both proteins were independently (both p<1.8×10(-7 associated with insulin sensitivity, circulating fetuin-A (r = -0.37, p = 0.0004, but not adiponectin, associated with insulin secretion in subjects with impaired glucose tolerance. CONCLUSIONS: We provide novel information that adiponectin and fetuin-A independently of each other associate with the diabetes risk. Furthermore, we suggest that they are involved in the development of type 2 diabetes via different mechanisms, possibly by mediating effects of their source tissues, expanded adipose tissue and nonalcoholic fatty liver.

  17. Obesidad, resistencia a la insulina y aumento de los niveles de adipoquinas: importancia de la dieta y el ejercicio físico Obesity, insulin resistance and increase in adipokines levels: importance of the diet and physical activity

    Directory of Open Access Journals (Sweden)

    E. Rodríguez-Rodríguez

    2009-08-01

    Full Text Available Con el padecimiento de obesidad el tejido adiposo aumenta la cantidad de adipoquinas pro y anti inflamatorias liberadas, sustancias que están implicadas en muchas de las manifestaciones clínicas de esta patología, como la diabetes, hipertensión arterial o enfermedad cardiovascular. En una primera etapa el tejido adiposo del paciente obeso se vuelve resistente a la acción de la insulina debido a la acción de alguna de estas adipoquinas, como el factor de necrosis tumoral α (TNF-α o la interleucina-6 (IL-6. En una segunda etapa aparece dicha resistencia en otros tejidos y se produce un aumento tanto en los niveles de glucosa como de insulina. Dicho aumento, junto con los altos niveles de adipoquinas que se producen en la obesidad, conducen a la aparición diferentes efectos adversos, entre los que se encuentran: aumento del estrés oxidativo, disfunción endotelial, aumento de la presión arterial y alteraciones del metabolismo lipoproteico, todos ellos perjudiciales para la salud. La realización de ejercicio físico, junto con el seguimiento de una dieta equilibrada, aproximada al patrón mediterráneo, con bajo consumo de grasa y sal, serían de ayuda para mejorar la resistencia a la insulina y los niveles de adipoquinas en las personas con obesidad, ayudando así a mejorar su estado de salud a largo plazo.With obesity the amount of pro- and anti-inflammatory adipokines released is increased within the fat tissue. These molecules are implicated in many clinical manifestations of this pathology such as diabetes, arterial hypertension, or cardiovascular disease. At the first stage, the fat tissue of the obese patient becomes resistant to the action of insulin due to the effect of some of these adipokines such as tumour necrosis alpha (TNF-α or interleukine-6 (IL-6. At a second stage, this resistance occurs at other tissues and glucose and insulin levels are increased. This increase, together with high adipokines levels that occur in

  18. Changes in Adipokines following Laparoscopic Roux-en-Y Gastric Bypass Surgery in Chinese Individuals with Type 2 Diabetes Mellitus and BMI of 22–30 kg·m−2

    Directory of Open Access Journals (Sweden)

    Chandrama Shrestha

    2013-01-01

    Full Text Available Aims. Although altered endocrine changes following bariatric surgery in morbidly obese patients with diabetes have been demonstrated by previous studies, little is known about their effects on low BMI patients of T2DM. We investigated the changes in adipokines and sICAM-1 in Chinese subjects with low BMI and T2DM after LRYGB and explored their relationship with postsurgical insulin sensitivity. Methods. Plasma levels of adiponectin, sICAM-1, fasting glucose, glycated hemoglobin, and fasting insulin and serum levels of visfatin were measured before and at three months after LRYGB in 33 T2DM patients with BMI of 22–30 kg·m−2. Results. Significant reductions in anthropometric measurements and indicators of glucose and lipid metabolism and moderate reductions in insulin resistance and fasting insulin were observed at three months after LRYGB. Postoperative adiponectin level ( was increased compared to the preoperative level, whereas visfatin ( and sICAM-1 ( were lower than that before surgery. Serum adiponectin negatively correlated with HOMA-IR and FIns both preoperatively and at three months after surgery, and visfatin positively correlated with HOMA-IR and FIns both preoperatively and postoperatively. Conclusion. Changes in adipokines were related to an improvement in postsurgical insulin sensitivity, which was predicted by weight loss after LRYGB even in low BMI patients with T2DM.

  19. Secretion of One Adipokine Nampt/Visfatin Suppresses the Inflammatory Stress-Induced NF-κB Activity and Affects Nampt-Dependent Cell Viability in Huh-7 Cells

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    Yi-Ching Lin

    2015-01-01

    Full Text Available Nampt/visfatin acts in both intracellular and extracellular compartments to regulate multiple biological roles, including NAD metabolism, cancer, inflammation, and senescence. However, its function in chronic inflammation and carcinogenesis in hepatocellular carcinoma (HCC has not been well-defined. Here we use Huh-7 hepatoma cells as a model to determine how Nampt/visfatin affects cellular survival under oxidative stress. We found that the transition of Nampt/visfatin from intracellular into extracellular form was induced by H2O2 treatment in 293T cells and confirmed that this phenomenon was not due to cell death but through the secretion of Nampt/visfatin. In addition, Nampt/visfatin suppressed cell viability in oxidative treatment in Huh-7 cells and acted on the inhibition of hepatoma cell growth. Oxidative stress also reduced the Nampt-mediated activation of NF-κB gene expression. In this study, we identify a novel feature of Nampt/visfatin which functions as an adipokine that can be secreted upon cellular stress. Our results provide an example to understand how adipokine interacts with chemotherapeutic treatment by oxidative stress in HCC.

  20. Obesidade e adipocinas inflamatórias: implicações práticas para a prescrição de exercício Obesity and inflammatory adipokines: practical implications for exercise prescription

    Directory of Open Access Journals (Sweden)

    Wagner Luiz do Prado

    2009-10-01

    tissue release a large amount of bioactive peptides called adipokines (which are proteins synthesized and released by adipose tissue. Thus, the aim of this review was to investigate the relationship between obesity and inflammatory adipokines, trying to discuss the role of physical exercise in the treatment of this pathology. The results have shown that one of the most important recent discoveries is the concept that obesity is characterized by a chronic inflammation state. Among all adipokines, IL-6, TNF- α, leptin (pro-inflammatory and adiponectin (anti-inflammatory, have received special attention from the specialized literature. High concentration of these adipokines promotes impact in several body functions, which is strongly linked with cardiovascular diseases. Since obesity is considered an inflammatory disease, and exercise directly modulates this process, it is essential that one of the main aims of exercise therapies is the improvement of the inflammatory response of obese individuals.

  1. Variations in Adipokine Genes AdipoQ, Lep, and LepR Are Associated with Risk for Obesity-Related Metabolic Disease: The Modulatory Role of Gene-Nutrient Interactions

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    Jennifer Emily Enns

    2011-01-01

    Full Text Available Obesity rates are rapidly increasing worldwide and facilitate the development of many related disease states, such as cardiovascular disease, the metabolic syndrome, type 2 diabetes mellitus, and various types of cancer. Variation in metabolically important genes can have a great impact on a population's susceptibility to becoming obese and/or developing related complications. The adipokines adiponectin and leptin, as well as the leptin receptor, are major players in the regulation of body energy homeostasis and fat storage. This paper summarizes the findings of single nucleotide polymorphisms in these three genes and their effect on obesity and metabolic disease risk. Additionally, studies of gene-nutrient interactions involving adiponectin, leptin, and the leptin receptor are highlighted to emphasize the critical role of diet in susceptible populations.

  2. Variations in Adipokine Genes AdipoQ, Lep, and LepR are Associated with Risk for Obesity-Related Metabolic Disease: The Modulatory Role of Gene-Nutrient Interactions

    Science.gov (United States)

    Enns, Jennifer Emily; Taylor, Carla G.; Zahradka, Peter

    2011-01-01

    Obesity rates are rapidly increasing worldwide and facilitate the development of many related disease states, such as cardiovascular disease, the metabolic syndrome, type 2 diabetes mellitus, and various types of cancer. Variation in metabolically important genes can have a great impact on a population's susceptibility to becoming obese and/or developing related complications. The adipokines adiponectin and leptin, as well as the leptin receptor, are major players in the regulation of body energy homeostasis and fat storage. This paper summarizes the findings of single nucleotide polymorphisms in these three genes and their effect on obesity and metabolic disease risk. Additionally, studies of gene-nutrient interactions involving adiponectin, leptin, and the leptin receptor are highlighted to emphasize the critical role of diet in susceptible populations. PMID:21773001

  3. Adipokines as potential biomarkers in rheumatoid arthritis%脂肪细胞因子在类风湿关节炎潜在生物标志物中的作用

    Institute of Scientific and Technical Information of China (English)

    常文静; 赵春江; 蔡辉

    2015-01-01

    类风湿关节炎( rheumatoid arthritis,RA)是一种累及多关节的慢性系统性炎性自身免疫性疾病。近年来,研究一直专注于预测疾病发病、疾病进展、关节损伤和治疗反应的生物标记物。白色脂肪组织作为一种多效性器官,不仅具有内分泌功能,而且参与多种病理生理过程,包括免疫和炎性反应。白色脂肪组织分泌的脂肪细胞因子,参与RA的发病。该文对可能作为疾病活动和治疗反应的潜在生物标记物的脂肪细胞因子的研究进展进行综述。%Rheumatoid arthritis ( RA) is a chronic multisystem systemic inflammatory utoimmune disease characterized by polyarticular injury.Recently,research has been focusing on the possible identification of predictor markers of disease onset and/or progression,of joint damage,and of therapeutic response.Recent findings have uncovered the role of white adipose tissue as a pleiotropic organ not on-ly specialized in endocrine functions but also able to control multiple physiopathological processes,including autoimmune and inflamma-tion.Adipokines are secreted by white adipose tissue which involved in the pathogenesis of RA.This review will focus on the recent advances on the adipokines as potential biomarkers of disease activity and therapeutic response.

  4. Possível papel das adipocinas no lúpus eritematoso sistêmico e na artrite reumatoide Possible role of adipokines in systemic lupus erythematosus and rheumatoid arthritis

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    Vitalina de Souza Barbosa

    2012-04-01

    Full Text Available Nos últimos anos têm sido descritos mediadores sintetizados no tecido adiposo, chamados adipocinas. Eles apresentam ação hormonal, regulando o apetite e o metabolismo da glicose, mas também atuam como citocinas, com efeitos sobre o sistema imune, incluindo efeitos na autoimunidade. As adipocinas mais importantes são: leptina, adiponectina, visfatina e resistina. Algumas delas vêm sendo estudadas nas doenças autoimunes reumáticas, particularmente no lúpus eritematoso sistêmico (LES e na artrite reumatoide (AR. Estudos mostram níveis elevados de leptina e de adiponectina no LES, porém a correlação com a atividade da doença ainda é discutida. Na AR, os estudos também mostram aumento dos níveis de leptina e de adiponectina, observando-se correlação com a atividade da doença e a erosão articular; os resultados, porém, são conflitantes. Esta revisão descreve os papéis da leptina e da adiponectina no sistema imune e suas atuações no LES e na AR.In recent years, mediators synthesized in the adipose tissue, the so-called adipokines, have been described. They have a hormonal action, regulating appetite and glucose metabolism, but also act as cytokines with effects on the immune system, including effects on autoimmunity. The most important adipokines are leptin, adiponectin, resistin and visfatin, and some of them have been assessed in autoimmune rheumatic diseases, especially systemic lupus erythematosus (SLE and rheumatoid arthritis (RA. Studies have shown high levels of leptin and adiponectin in SLE, but correlation with disease activity is questionable. In RA, studies have also reported increased levels of leptin and adiponectin, and correlation with disease activity and joint erosion, but the results are confl icting. This review describes the role of leptin and adiponectin on the immune system, as well as on SLE and RA.

  5. Adipocinas y síndrome metabólico: múltiples facetas de un proceso fisiopatológico complejo Adipokines and metabolic syndrome: multiple aspects of a complex pathophysiological process

    Directory of Open Access Journals (Sweden)

    Julio C Sánchez N

    2010-08-01

    Full Text Available Debido a la alta morbimortalidad de las enfermedades cardiovasculares y a su relación con trastornos de base como la obesidad y el síndrome metabólico, es crucial entender cuáles son los mecanismos y procesos que desencadenan la alteración del metabolismo y a su vez la generación de dichas enfermedades. En tal sentido, el tejido adiposo y el adipocito tienen un papel fundamental en este proceso, mediante la producción de múltiples adipocinas, algunas clásicas y otras de reciente descripción, pero que hasta ahora empieza a dilucidarse en medio del complejo panorama de interacciones fisiopatológicas conducentes al desarrollo de resistencia a la insulina y del complejo desequilibrio metabólico que conlleva un sinnúmero de complicaciones clínicas. Un grupo de estas adipocinas tiene claros efectos proinflamatorios, mientras que otras pueden clasificarse como anti-inflamatorias, las cuales contrarrestan en cierta medida y hasta cierto punto las acciones de las otras. Cuando esta homeostasis se rompe, la cascada de inflamación crónica allí originada desencadena resistencia a la insulina y se inicia el desarrollo del síndrome metabólico a partir de la obesidad, que a su vez genera alteraciones de la respuesta del adipocito a diferentes estímulos. Esto, sumado a los efectos de otros elementos, configura un complejo cuadro de factores que es necesario tener en cuenta para el abordaje correcto de la obesidad y sus patologías asociadas.Due to the high morbidity and mortality of cardiovascular diseases and their relationship with basic disorders such as obesity and metabolic syndrome, the understanding of the mechanisms and processes that trigger metabolic alterations and generate such diseases, is a crucial matter. In this regard, adipose tissue and adipocytes have a crucial role in this process through the production of multiple adipokines, some of them classical and others recently described; however, until now their role is beginning

  6. Adipokines, Metabolic Syndrome and Rheumatic Diseases

    OpenAIRE

    Vanessa Abella; Morena Scotece; Javier Conde; Verónica López; Verónica Lazzaro; Jesús Pino; Gómez-Reino, Juan J; Oreste Gualillo

    2014-01-01

    The metabolic syndrome (MetS) is a cluster of cardiometabolic disorders that result from the increasing prevalence of obesity. The major components of MetS include insulin resistance, central obesity, dyslipidemia, and hypertension. MetS identifies the central obesity with increased risk for cardiovascular diseases (CVDs) and type-2 diabetes mellitus (T2DM). Patients with rheumatic diseases, such as rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, and ankylosing spondylitis...

  7. Adipokines and ghrelin in gastric cancer cachexia

    Institute of Scientific and Technical Information of China (English)

    Mustafa Kerem; Zafer Ferahkose; Utku Tonguc Yilmaz; Hatice Pasaoglu; Ebru Ofluoglu; Abdulkadir Bedirli; Bulent Salman; Tevfik Tolga Sahin; Murat Akin

    2008-01-01

    AIM: To investigate the roles of the adipocytokines, ghrelin and leptin in gastric cancer cachexia.METHODS: Resistin, ghrelin, leptin, adiponectin, insulin and insulin-like growth factor (IGF-I), were measured in 30 healthy subjects, and 60 gastric cancer patients of which 30 suffered from cancer- induced cachexia and 30 served as a control group. The relationships between hormones, body mass index (BMI) loss ratio, age, gender, and Glasgow Prognostic Score (GPS) were investigated.RESULTS: Cachexia patients had higher tumor stage and GPS when compared with non-cachexia patients (P<0.05). Ghrelin, resistin, leptin, adiponectin and IGF-I, showed a significant correlation with BMI loss ratio and GPS (P < 0.05). A strong correlation was seen between GPS and BMI loss (R = -0.570, P < 0.0001). Multivariate analysis indicated that BMI loss was significantly independent as a predictor of ghrelin, resistin, leptin and IGF-I (P<0.05). Existence of an important significant relationship between resistin and insulin resistance was also noted.CONCLUSION: These results showed that serum ghrelin, leptin, adiponectin, and IGF-I play important roles in cachexia-related gastric cancers. No relationship was found between resistin and cancer cachexia. Also, because of the correlation between these parameters and GPS, these parameters might be used as a predictor factor.

  8. Adipokines: a link between obesity and dementia?

    NARCIS (Netherlands)

    Kiliaan, A.J.; Arnoldussen, I.A.C.; Gustafson, D.R.

    2014-01-01

    Being overweight or obese, as measured with body-mass index or central adiposity (waist circumference), and the trajectory of body-mass index over the life course have been associated with brain atrophy, white matter changes, disturbances of blood-brain barrier integrity, and risk of all-cause late-

  9. 代谢综合征患者心脏损害与脂肪因子变化的临床研究%Association of adipokines with cardiac abnormalities in patients with metabolic syndrome

    Institute of Scientific and Technical Information of China (English)

    韩露; 王彬; 牟晓梅; 巩会平; 闫会敏; 王志浩; 张运; 张薇; 钟明

    2011-01-01

    Objective To investigate the association of adipokine's levels with left systolic and diastolic function in patients with metabolic syndrome (MS). Methods We enrolled 48 patients with MS and 49 gender- and age-matched healthy subjects who served as the control. Tissue Doppler imaging echocardiography was performed to measure systolic and diastolic mitral annular velocities, including the peak systolic mitral annulus velocity (Sm), the peak early diastolic mitral annulus velocity (Em) and the peak late diastolic mitral annulus velocity (Am). Real-time PCR assays were applied to detect expressions of leptin receptor and ghrelin mRNA expressions in peripheral blood mononuclear cells (PBMCs). Results Compared with the control, the MS group showed significant increases in the peak late diastolic velocity (A) but decreases in the ratio of early and late diastolic peak velocity (E/A), Sm, Em, and the ratio of Em and Am (Em/Am) (P <0.01 ~0.001). mRNA expressions of leptin receptor and ghrelin were significantly decreased in the MS group (all P <0.05). Expression of leptin receptor mRNA level was significantly correlated with A, E/A, Sm, Em and Em/Am (P<0.05 -0.001), while the ghrelin mRNA level showed a significantly positive correlation with Em and Sm (P < 0.05 -0.01). Stepwise multiple linear regression analysis revealed a significant and independent association of E/A with decreases of leptin receptor mRNA level, as was the association of Sm with the decreases of ghrelin mRNA level. Decreases of leptin receptor mRNA level in PBMCs was an independent risk factor for left ventricular diastolic dysfunction,and the reduction of ghrelin mRNA expression was an independent risk factor for the early impairment of left ventricular systolic function. Conclusion The reduction of leptin receptor and ghrelin mRNA expression may contribute to impairments of left function in patients with metabolic syndrome.%目的 探讨代谢综合征(MS)患者心脏损害特点、脂肪因子的

  10. O impacto da obesidade sobre os componentes da síndrome metabólica e as adipocitoquinas em crianças pré-púberes Impact of obesity on metabolic syndrome components and adipokines in prepubertal children

    Directory of Open Access Journals (Sweden)

    Isabel R. Madeira

    2009-06-01

    Full Text Available OBJETIVO: Verificar o impacto da obesidade sobre os componentes da síndrome metabólica e sobre os níveis de adipocitoquinas em crianças pré-púberes. MÉTODOS: Estudo transversal comparando 30 crianças obesas, 31 com sobrepeso e 33 eutróficas, oriundas do ambulatório de pediatria geral de um hospital universitário, quanto às médias de glicose, lipídios séricos, insulina, HOMA-IR (homeostasis model assessment-insulin resistance, relação glicose/insulina, adiponectina e leptina. Compararam-se as frequências de acantose nigricans e das alterações de cintura, pressão arterial, glicose, lipídios séricos e insulina. Avaliou-se a correlação entre escore z de índice de massa corporal (IMC e adipocitoquinas. RESULTADOS: Houve diferença nas médias dos obesos, quanto a HDL-colesterol e adiponectina, e nas dos eutróficos, quanto a insulina, HOMA-IR, relação glicose/insulina e leptina (p OBJECTIVE: To verify the impact of obesity on metabolic syndrome components and adipokine levels in prepubertal children. METHODS: This cross-sectional study compared 30 obese, 31 overweight and 33 eutrophic children attending a university hospital-based outpatient pediatric clinic. Parameters assessed included glucose, serum lipids, insulin, homeostasis model assessment-insulin resistance (HOMA-IR, glucose/insulin relation, adiponectin, and leptin. We compared the frequency of acanthosis nigricans and changes in waist, blood pressure, glucose, serum lipids, and insulin. The correlation between body mass index (BMI z score and adipokines was evaluated. RESULTS: Among obese children, there was a difference in the mean values of HDL cholesterol and adiponectin, whereas among the eutrophic children, there was a difference in the mean values of insulin, HOMA-IR, glucose/insulin relation, and leptin (p < 0.001. A difference was also observed regarding the frequency of acanthosis nigricans and alteration in waist and HDL cholesterol (p < 0.005 in the

  11. Experimental study of diet and exercise intervention on plasma adipokine regulating gestational diabetes%饮食和运动干预对妊娠期糖尿病患者血浆脂肪因子调控的实验研究

    Institute of Scientific and Technical Information of China (English)

    高宇; 折瑞莲; 黎燕

    2014-01-01

    目的:观察饮食和运动干预对妊娠期糖尿病患者血浆脂肪因子调控的影响。方法选择妊娠期糖尿病孕妇139例:65例为观察组、74例为饮食和运动干预组;同期进行健康体检孕妇20例作为对照组;治疗前、后159例孕妇均为空腹采血。采用全自动生化分析仪检测血脂水平;采用 ELISA 法检测血浆中各脂肪因子的水平。结果治疗前与对照组比较,观察组和饮食、运动干预组血浆中血脂和各脂肪因子水平均明显增高有统计学意义(P <0.01);治疗后与对照组比较,观察组孕妇血浆中血脂和各脂肪因子水平仍处于高水平状态有统计学意义(P <0.01),饮食、运动干预组孕妇血浆中血脂和各脂肪因子水平均降低无统计学意义(P >0.05);治疗后与观察组比较,饮食、运动干预组孕妇血浆中血脂和各脂肪因子水平均降低有统计学意义(P <0.01)。结论饮食和运动干预对妊娠期糖尿病患者血浆中血脂和脂肪因子的调控疗效可靠,具有临床推广价值。%Objective To observe the diet and exercise intervention on patients with gestational diabetes fat factor regulation effect.Methods 139 cases of pregnant women with diabetes during pregnancy:65 cases in the observation group,74 cases of diet and exercise intervention group;concurrent healthy pregnant women,20 cases of the control group;before and after treatment were 159 cases of pregnant women,fasting blood.Using automatic biochemical analy-zer lipid levels;detected by ELISA in plasma levels of adipokines.Results Before treatment compared with the control group,the observation group and diet,exercise intervention group and the plasma lipid levels were significantly higher in fat factor was statistically significant(P 0.05);treatment with observation group,diet,exercise intervention group in maternal plasma lipids and various adipokines levels decreased statistically

  12. 维生素D对妊娠糖尿病胰岛素敏感性脂肪因子及肿瘤坏死因子-α的影响%Effects of Vitaimin D on Insulin Sensitivity and the Adipokine Factors APN,Visfatin, RBP4,TNF-αin Patients with Gestational Dellitus Mellitus

    Institute of Scientific and Technical Information of China (English)

    张黎明; 高凌; 帅红霞; 润袁敏; 邓晨盺; 田源; 马计; 肖婧

    2014-01-01

    Objective To investigate the relationship and mechanism of the serum vitamin D levels with insulin sensitivity and adipokines APN,RBP4,visfatin and TNF-α in patients with gestational diabetes mellitus(GDM). Methods A total of 101 patients with gestational diabetes( GDM group) and 50 pregnant women with normal blood sugar( control group) were recruited to detect the serum levels of correlative biochemical indexes,APN,RBP4,visfatin,TNF-α and 25OHD3 using an HPLC method. Twenty-four patients in the GDM group diagnosed with vitamin D deficiency(<25 nmol·L-1 ) were randomized to receive either 1,25(OH) 2D3(0. 25 μg·d-1) orally or no treatment. Serum levels of correlative biochemical indexes were detected after 1 month. Results GDM patients had 25OHD3 levels significantly lower than the control group(P<0. 05),APN levels lower than the control group,and RBP4,visfatin,TNF-α levels significantly higher than the control group(all P<0. 05). After 1 month of 1,25(OH) 2D3 treatment,HOMA-IR increased,while HOMA-β decreased. APN levels was positively correlated(r= 0. 526) with 25OHD3;RBP4,visfatin,TNF-α decreased and were negatively correlated with 25OHD3( r values were -0. 272,-0. 153,-0. 072). Conclusion Vitamin D can reduce the adipokines RBP4,visfatin,TNF-α,increase APN,and thus play a protective role for gestational diabetes.%目的:探讨血清维生素D水平与妊娠糖尿病( GDM)胰岛素敏感性及对脂肪因子脂联素( APN)、视黄醇结合蛋白4( RBP4)、内脂素(visfatin)及肿瘤坏死因子(TNF-α)的影响及作用机制。方法选择妊娠糖尿病患者101例( GDM组)和血糖正常孕妇50例(正常组),检测两组相关生化指标、APN、RBP4、visfatin、TNF-α及25羟化维生素 D3(25OHD3)。在GDM组中将诊断为维生素D缺乏患者24例随机分为治疗组及对照组各12例,治疗组口服1,25二羟维生素D3[1,25(OH)2D3]0.25μg·d-11个月,再行相关生化指标检查。结果GDM组患者25OHD3及APN水平明显低于

  13. Effects of Berberine on Inflammatory Factors, Adipokines and Fatty Acid Metabolism in 3T3-L1 Adipocytes%小檗碱对3T3-L1脂肪细胞炎症因子、脂肪因子及脂肪酸代谢的影响

    Institute of Scientific and Technical Information of China (English)

    李萍; 岳晶晶; 张达; 牛文彦; 何庆

    2014-01-01

    Objective To observe the effects of berberine on inflammatory factors, adipokines and fatty acid metabo-lism in 3T3-L1 adipocytes, and to investigate the molecular mechanism underlying berberine’s role of improving insulin re-sistance. Methods mRNA level of inflammatory molecules, adipokines, key enzymes and protein in fatty acid metabolism in 3T3-L1 cells were determined by quantitative real time polymerase chain reaction (qRT-PCR) after cells were treated with different concentrations of berberine (0, 5, 10, 20, 40μmol/L) for 24 hours and with 10μmol/L berberine at different du-rations (0,4,8,24,48 h). These factors mainly included interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), leptin, adipo-nectin, visfatin, fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), adipose triglyceride lipase (ATGL) and adipocyte fatty acid binding protein (AFABP). Results In 3T3-L1 adipocytes, transcription level of IL-6, TNF-α, leptin, FAS, AT-GL, AFABP reduced with addition of berberine dosage at 10~40μmol/L(P0.05). Tran-scription level of IL-6, TNF-α, leptin, AFABP, ATGL, FAS decreased with time after 10μmol/L berberine intervention (8-48 h) compared with the control group(P 0.05). Conclusion mRNA level of inflammatory factors, adipokines, key enzymes and protein in fatty acid metabolism in 3T3-L1 adipocytes can be affected by berberine and this effect depend on its dose and time . This might be the mechanisms underlying berber- ine to improve insulin resistance.%目的:观察小檗碱对3T3-L1脂肪细胞炎症因子、脂肪因子及脂肪酸代谢的影响,探讨小檗碱改善胰岛素抵抗的分子机制。方法3T3-L1脂肪细胞经不同浓度小檗碱(0、5、10、20和40μmol/L)处理24 h后,采用qRT-PCR技术检测相关因子mRNA表达水平,包括白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、瘦素、脂联素和内脂素以及脂肪酸合酶(FAS)、乙酰辅酶A羧化酶(ACC)、脂肪组织甘油三酯

  14. Relationship between adipokines, inflammation, and vascular reactivity in lean controls and obese subjects with metabolic syndrome Relação entre as adipocinas, inflamação e reatividade vascular em controles magros e pacientes obesos com síndrome metabólica

    Directory of Open Access Journals (Sweden)

    Luciana Bahia

    2006-10-01

    Full Text Available PURPOSE: Metabolic syndrome is an important risk factor for cardiovascular disease. Adipokines interfere with insulin action and endothelial cell function. We investigated the relationship among adipokines, metabolic factors, inflammatory markers, and vascular reactivity in obese subjects with metabolic syndrome and lean controls. METHODS: Cross-sectional study of 19 obese subjects with metabolic syndrome and 8 lean volunteers evaluated as controls. Vascular reactivity was assessed by venous occlusion pletysmography measuring braquial forearm blood flow (FBF and vascular resistance (VR responses to intra-arterial infusions of endothelium-dependent (acetylcholine-Ach and independent (sodium nitroprusside-SNP vasodilators. Blood samples were obtained to evaluate C reactive protein (CRP, plasminogen activator inhibitor 1 (PAI-1, fibrinogen, adiponectin, resistin, and lipid profile. Patients were classified with regard to insulin resistance through the HOMA-IR index. RESULTS: PAI-1, CRP and fibrinogen were higher and adiponectin was lower in metabolic syndrome subjects compared to controls. Metabolic syndrome subjects had impaired vascular reactivity. Adiponectin and PAI-1 were associated with insulin, HOMA-IR, triglycerides, and HDLc; and resistin with CRP. Adiponectin was associated with VR after Ach in the pooled group and resistin with D FBF after Ach in the metabolic syndrome group. CONCLUSION: Metabolic syndrome subjects exhibited low levels of adiponectin and high levels of CRP, fibrinogen, and PAI-1. Adiponectin and PAI-1 correlated with insulin resistance markers. Adiponectin and resistin correlated with vascular reactivity parameters. An adipocyte-endothelium interaction might be an important mechanism of inflammation and vascular dysfunction.A Síndrome Metabólica é um importante fator de risco para doenças cardiovasculares. As adipocinas interferem com a ação da insulina e com a função endotelial. OBJETIVO: Investigar a rela

  15. Promoting effects of the adipokine, apelin, on diabetic nephropathy.

    Directory of Open Access Journals (Sweden)

    Bao-hai Zhang

    Full Text Available Angiogenesis, increased glomerular permeability, and albuminuria are thought to contribute to the progression of diabetic nephropathy (DN. Apelin receptor (APLNR and the endogenous ligand of APLNR, apelin, induce the sprouting of endothelial cells in an autocrine or paracrine manner, which may be one of the mechanisms of DN. The aim of this study was to investigate the role of apelin in the pathogenesis of DN. Therefore, we observed apelin/APLNR expression in kidneys from patients with type 2 diabetes as well as the correlation between albuminuria and serum apelin in patients with type 2 diabetes. We also measured the proliferating, migrating, and chemotactic effects of apelin on glomerular endothelial cells. To measure the permeability of apelin in glomerular endothelial cells, we used transwells to detect FITC-BSA penetration through monolayered glomerular endothelial cells. The results showed that serum apelin was significantly higher in the patients with type 2 diabetes compared to healthy people (p<0.05, Fig. 1B and that urinary albumin was positively correlated with serum apelin (R = 0.78, p<0.05. Apelin enhanced the migration, proliferation, and chemotaxis of glomerular endothelial cells in a dose-dependent manner (p<0.05. Apelin also promoted the permeability of glomerular endothelial cells (p<0.05 and upregulated the expression of VEGFR2 and Tie2 in glomerular endothelial cells (p<0.05. These results indicated that upregulated apelin in type 2 diabetes, which may be attributed to increased fat mass, promotes angiogenesis in glomeruli to form abnormal vessels and that enhanced apelin increases permeability via upregulating the expression of VEGFR2 and Tie2 in glomerular endothelial cells.

  16. Adiponectin, a key adipokine in obesity related liver diseases

    Institute of Scientific and Technical Information of China (English)

    Christa Buechler; Josef Wanninger; Markus Neumeier

    2011-01-01

    Non-alcoholic fatty liver disease (NAFLD) comprising hepatic steatosis, non-alcoholic steatohepatitis (NASH),and progressive liver fibrosis is considered the most common liver disease in western countries. Fatty liver is more prevalent in overweight than normal-weight people and liver fat positively correlates with hepatic insulin resistance. Hepatic steatosis is regarded as a benign stage of NAFLD but may progress to NASH in a subgroup of patients. Besides liver biopsy no diagnostic tools to identify patients with NASH are available, and no effective treatment has been established. Visceral obesity is a main risk factor for NAFLD and inappropriate storage of triglycerides in adipocytes and higher concentrations of free fatty acids may add to increased hepatic lipid storage, insulin resistance, and progressive liver damage. Most of the adipose tissue-derived proteins are elevated in obesity and may contribute to systemic inflammation and liver damage. Adiponectin is highly abundant in human serum but its levels are reduced in obesity and are even lower in patients with hepatic steatosis or NASH. Adiponectin antagonizes excess lipid storage in the liver and protects from inflammation and fibrosis. This review aims to give a short survey on NAFLD and the hepatoprotective effects of adiponectin.

  17. Cardioprotective effects of adipokine apelin on myocardial infarction.

    Science.gov (United States)

    Zhang, Bao-Hai; Guo, Cai-Xia; Wang, Hong-Xia; Lu, Ling-Qiao; Wang, Ya-Jie; Zhang, Li-Ke; Du, Feng-He; Zeng, Xiang-Jun

    2014-09-01

    Angiogenesis plays an important role in myocardial infarction. Apelin and its natural receptor (angiotensin II receptor-like 1, AGTRL-1 or APLNR) induce sprouting of endothelial cells in an autocrine or paracrine manner. The aim of this study is to investigate whether apelin can improve the cardiac function after myocardial infarction by increasing angiogenesis in infarcted myocardium. Left ventricular end-diastolic pressure (LVEDP), left ventricular end systolic pressure (LVESP), left ventricular developed pressure (LVDP), maximal left ventricular pressure development (±LVdp/dtmax), infarct size, and angiogenesis were evaluated to analyze the cardioprotective effects of apelin on ischemic myocardium. Assays of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, 5-bromo-2'-deoxyuridine incorporation, wound healing, transwells, and tube formation were used to detect the effects of apelin on proliferation, migration, and chemotaxis of cardiac microvascular endothelial cells. Fluorescein isothiocyanate-labeled bovine serum albumin penetrating through monolayered cardiac microvascular endothelial cells was measured to evaluate the effects of apelin on permeability of microvascular endothelial cells. In vivo results showed that apelin increased ±LV dp/dtmax and LVESP values, decreased LVEDP values (all p myocardial infarction through promoting angiogenesis and decreasing permeability of microvascular endothelial cells via upregulating the expression of VEGFR2 and Tie-2 in cardiac microvascular endothelial cells.

  18. Obesity and dementia: Adipokines interact with the brain

    NARCIS (Netherlands)

    Arnoldussen, I.A.C.; Kiliaan, A.J.; Gustafson, D.R.

    2014-01-01

    Obesity is a pandemic and a serious global health concern. Obesity is a risk factor for multiple conditions and contributes to multi-morbidities, resulting in increased health costs and millions of deaths each year. Obesity has been associated with changes in brain structure, cognitive deficits, dem

  19. Relación del polimorfismo rs9939609 del gen FTO con factores de riesgo cardiovascular y niveles de adipocitoquinas en pacientes con obesidad mórbida Relation of the rs9939609 gene variant in FTO with cardiovascular risk factor and serum adipokine levels in morbid obese patients

    Directory of Open Access Journals (Sweden)

    D. A. de Luis

    2012-08-01

    Full Text Available Introducción: Algunos polimorfismos del gen asociado con la masa grasa y la obesidad (FTO se han relacionado con la obesidad y parámetros bioquímicos. Nuestro objetivo fue analizar la relación del polimorfismo rs9939609 del gen FTO con el peso corporal, factores de riesgo cardiovascular y los niveles séricos de adipocitoquinas en una muestra de pacientes con obesidad mórbida. Material y métodos: Una muestra de 129 pacientes con obesidad mórbida (IMC > 40 se analizó en un diseño de corte transversal. A todos los pacientes se les determinó el peso, presión arterial, glucemia basal, proteína C reactiva (PCR, insulina, resistencia a la insulina (HOMA-R, colesterol total, LDL-colesterol, HDL-colesterol, triglicéridos y adipocitoquinas (adiponectina leptina, resistina, TNF-alfa, y los niveles de interleucina-6. Se evaluó la masa grasa mediante bioimpedancia tetrapolar y registró prospectivamente la ingesta de nutrientes durante tres días. En todos ellos se genotipo el polimorfismo del gen FTO (rs9939609. Resultados: Cuarenta y un pacientes (31,8% tenían el genotipo TT (grupo genotipo salvaje, 55 pacientes (42,6% el genotipo TA y 33 pacientes (25,6% el genotipo AA. El índice de masa corporal (43,6 (2,6 kg/m² vs. 44,1 (2,9 kg/m²; p Background: Common polymorphisms of the fat mass and obesity associated gene (FTO have been linked to obesity in some populations. The aim of our study was to analyze the relationship of the rs9939609 FTO gene polymorphism on body weight, cardiovascular risk factors and serum adipokine levels in morbid obese patients. Material and methods: A sample of 129 patients with obesity was analyzed in a cross sectional design. Weight, blood pressure, basal glucose, creactive protein (CRP, insulin, insulin resistance (HOMA, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides blood and adipocytokines (leptin, adiponectin, resistin, TNF alpha, and interleukin 6 levels were measured. A tetrapolar

  20. 热应激对奶牛血液中胰岛素、脂肪因子、AMP激活蛋白激酶和热休克信号分子的影响%Effects of heat stress on serum insulin, adipokines, AMP-activated protein kinase, and heat shock signal molecules in dairy cows

    Institute of Scientific and Technical Information of China (English)

    Li MIN; Jian-bo CHENG; Bao-lu SHI; Hong-jian YANG; Nan ZHENG; Jia-qi WANG

    2015-01-01

    目 的:比较热应激和非热应激状态下,奶牛血液中胰岛素、脂肪因子(瘦素和脂联素)、AMP激活蛋白激酶(AMPK)和热休克信号分子的变化,探索奶牛对热应激的代谢响应.同时,通过比较不同程度热应激,寻找稳定生物标记物评估奶牛热应激.创新点:研究了热应激对奶牛血液中脂肪因子和AMPK的影响,验证了热应激条件下,脂联素和AMPK的关联性.科学假设了热休克信号分子作为生物标记物的可能性,通过比较不同程度热应激,得到了对热应激敏感性高的信号分子.方 法:通过牛属专一性的酶联免疫吸附试剂盒,快速检测奶牛血液中目标物的含量.结 论:热应激对奶牛胰岛素和瘦素的分泌无直接影响.然而,热应激导致干物质采食量降低,在相同的干物质采食量基础上,热应激提高了胰岛素和瘦素浓度.热应激导致脂联素和AMPK升高;脂联素和AMPK的协同作用是奶牛机体调节,适应热应激的重要途径.同时,建议将血液中的热休克转录因子(HSF)和热休克蛋白70(HSP70)作为生物标记物评估热应激,通过监测它们含量的变化预防热应激.%Heat stress affects feed intake, milk production, and endocrine status in dairy cows. The temperature- humidity index (THI) is employed as an index to evaluate the degree of heat stress in dairy cows. However, it is difficult to ascertain whether THI is the most appropriate measurement of heat stress in dairy cows. This experiment was conducted to investigate the effects of heat stress on serum insulin, adipokines (leptin and adiponectin), AMP-activated protein kinase (AMPK), and heat shock signal molecules (heat shock transcription factor (HSF) and heat shock proteins (HSP)) in dairy cows and to research biomarkers to be used for better understanding the meaning of THI as a bioclimatic index. To achieve these objectives, two experiments were performed. The first experiment: eighteen lactating Holstein

  1. Adipokines as Possible New Predictors of Cardiovascular Diseases: A Case Control Study

    Directory of Open Access Journals (Sweden)

    Laura Pala

    2012-01-01

    Full Text Available Background and Aims. The secretion of several adipocytokines, such as adiponectin, retinol-binding protein 4 (RBP4, adipocyte fatty acid binding protein (aFABP, and visfatin, is altered in subjects with abdominal adiposity; these endocrine alterations could contribute to increased cardiovascular risk. The aim of the study was to assess the relationship among adiponectin, RBP4, aFABP, and visfatin, and incident cardiovascular disease. Methods and Results. A case-control study, nested within a prospective cohort, on 2945 subjects enrolled for a diabetes screening program was performed. We studied 18 patients with incident fatal or nonfatal IHD (Ischemic Heart Disease or CVD (Cerebrovascular Disease, compared with 18 matched control subjects. Circulating adiponectin levels were significantly lower in cases of IHD with respect to controls. Circulating RBP4 levels were significantly increased in CVD and decreased in IHD with respect to controls. Circulating aFABP4 levels were significantly increased in CVD, while no difference was associated with IHD. Circulating visfatin levels were significantly lower in cases of both CVD and IHD with respect to controls, while no difference was associated with CVD. Conclusions. The present study confirms that low adiponectin is associated with increased incidents of IHD, but not CVD, and suggests, for the first time, a major effect of visfatin, aFABP, and RBP4 in the development of cardiovascular disease.

  2. Proinflammatory adipokine leptin mediates disinfection byproduct bromodichloromethane-induced early steatohepatitic injury in obesity

    Energy Technology Data Exchange (ETDEWEB)

    Das, Suvarthi [Environmental Health and Disease Laboratory, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208 (United States); Kumar, Ashutosh [Free Radical Metabolism Group, Laboratory of Toxicology and Pharmacology, Research Triangle Park, NC 27709 (United States); Seth, Ratanesh Kumar [Environmental Health and Disease Laboratory, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208 (United States); Tokar, Erik J. [Inorganic Toxicology Group, National Toxicology Program Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Kadiiska, Maria B. [Free Radical Metabolism Group, Laboratory of Toxicology and Pharmacology, Research Triangle Park, NC 27709 (United States); Waalkes, Michael P. [Inorganic Toxicology Group, National Toxicology Program Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Mason, Ronald P. [Free Radical Metabolism Group, Laboratory of Toxicology and Pharmacology, Research Triangle Park, NC 27709 (United States); Chatterjee, Saurabh, E-mail: schatt@mailbox.sc.edu [Environmental Health and Disease Laboratory, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208 (United States)

    2013-06-15

    Today's developed world faces a major public health challenge in the rise in the obese population and the increased incidence in fatty liver disease. There is a strong association among diet induced obesity, fatty liver disease and development of nonalcoholic steatohepatitis but the environmental link to disease progression remains unclear. Here we demonstrate that in obesity, early steatohepatitic lesions induced by the water disinfection byproduct bromodichloromethane are mediated by increased oxidative stress and leptin which act in synchrony to potentiate disease progression. Low acute exposure to bromodichloromethane (BDCM), in diet-induced obesity produced oxidative stress as shown by increased lipid peroxidation, protein free radical and nitrotyrosine formation and elevated leptin levels. Exposed obese mice showed histopathological signs of early steatohepatitic injury and necrosis. Spontaneous knockout mice for leptin or systemic leptin receptor knockout mice had significantly decreased oxidative stress and TNF-α levels. Co-incubation of leptin and BDCM caused Kupffer cell activation as shown by increased MCP-1 release and NADPH oxidase membrane assembly, a phenomenon that was decreased in Kupffer cells isolated from leptin receptor knockout mice. In obese mice that were BDCM-exposed, livers showed a significant increase in Kupffer cell activation marker CD68 and, increased necrosis as assessed by levels of isocitrate dehydrogenase, events that were decreased in the absence of leptin or its receptor. In conclusion, our results show that exposure to the disinfection byproduct BDCM in diet-induced obesity augments steatohepatitic injury by potentiating the effects of leptin on oxidative stress, Kupffer cell activation and cell death in the liver. - Highlights: ► BDCM acute exposure sensitizes liver to increased free radical stress in obesity. ► BDCM-induced higher leptin contributes to early steatohepatitic lesions. ► Increased leptin mediates protein radical and 3-nitrotyrosine formation. ► BDCM exposure in obesity activates Kupffer cells and NADPH oxidase. ► BDCM/leptin synergy promotes necrotic cell-death and augments steatohepatitis.

  3. Phobic Anxiety is Associated with Higher Serum Concentrations of Adipokines and Cytokines in Women with Diabetes

    OpenAIRE

    Brennan, Aoife M; Fargnoli, Jessica L.; Li, Tricia; Williams, Catherine J.; Willett, Walter C.; Kawachi, Ichiro; Qi, Lu; Hu, Frank B; Mantzoros, Christos S.

    2009-01-01

    OBJECTIVE: Phobic anxiety has been associated with increased risk of cardiovascular disease (CVD), but the underlying mechanisms are poorly understood. We aimed to determine whether associations of phobic anxiety with several known markers of CVD might be contributors. RESEARCH DESIGN AND METHODS: We used a 16-point validated index (Crown-Crisp) measured in 1988 to categorize 984 women with type 2 diabetes from the Nurses' Health Study as having low, moderate, or high phobic anxiety. Groups w...

  4. Immunomodulatory Role of Diet and Adipokines in Multiple Sclerosis and Its Animal Model

    Science.gov (United States)

    2015-09-01

    accompanied by cytokine release that can affect immune responses (Shoelson, Herrero et al. 2007). Indeed, white adipose tissue , is an active source of...adiponectin receptors on peripheral blood immune cells in MS patients and controls by flow cytometry and on autopsied human MS and non-MS tissues by...circulation in its full- length form, a functional proteolytic fragment (its globular domain) and in oligomeric forms. Adiponectin is an insulin

  5. Blood Pressure in Adolescence, Adipokines and Inflammation in Young Adults. The Rio de Janeiro Study

    Energy Technology Data Exchange (ETDEWEB)

    Campana, Erika Maria Gonçalves, E-mail: erikamaria@cardiol.br; Brandão, Andréa Araujo; Pozzan, Roberto; Magalhães, Maria Eliane Campos; Fonseca, Flávia Lopes; Pizzi, Oswaldo Luiz; Freitas, Elizabete Viana de; Brandão, Ayrton Pires [Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ (Brazil)

    2014-01-15

    The impact of blood pressure (BP) during adolescence on other cardiovascular risk factors in young adults is important for the primary prevention. To evaluate BP, anthropometric indexes, metabolic and inflammatory profiles in young individuals stratified by their BP behavior recorded for 18 years. A total of 116 individuals, of whom 63 were males, from the Rio de Janeiro study (follow-up of 17.76 ± 1.63 years), were assessed at two moments: A1 (12.40 ± 1.49 years) and A2 (30.09 ± 2.01 years). The 116 individuals were divided into two groups: GN (n = 71), of participants with normal BP at A1; and GH (n = 45), of those with abnormal BP at A1. BP, weight, height and body mass index (BMI) were measured at A1 and A2. At A2, abdominal circumference (AC) and laboratory, metabolic and inflammatory variables were included. 1) No difference was observed between the groups as regards age and gender; 2) At A2, GH showed higher mean weight, BMI, BP, insulin, HOMA-IR (p < 0.001), leptin (p < 0.02), apolipoprotein B100 and A1 (p < 0.02), apolipoprotein B100 / apolipoprotein A1 ratio (p < 0.010); and higher prevalences of overweight/obesity (p < 0.001), of increased AC (p < 0.001) and of hypertension (p < 0.02); 3) No difference was observed between the groups as regards the inflammatory variables; 4) There was a positive correlation of BP at A1 with BP, BMI, insulin, leptin and HOMA-IR at A2 (p < 0.05). BP in adolescence was associated with higher values of BP, and anthropometric and metabolic variables in young adulthood, but not with inflammatory variables.

  6. Severe Burn and Disuse in the Rat Independently Adversely Impact Body Composition and Adipokines

    Science.gov (United States)

    2013-10-07

    Scopus and Google Scholar • Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit Wade et al. Critical Care 2013, 17:R225 Page 12 of 12 http://ccforum.com/content/17/5/R225

  7. Solution structure of CXCL5--a novel chemokine and adipokine implicated in inflammation and obesity.

    Directory of Open Access Journals (Sweden)

    Krishna Mohan Sepuru

    Full Text Available The chemokine CXCL5 is selectively expressed in highly specialized cells such as epithelial type II cells in the lung and white adipose tissue macrophages in muscle, where it mediates diverse functions from combating microbial infections by regulating neutrophil trafficking to promoting obesity by inhibiting insulin signaling. Currently very little is known regarding the structural basis of how CXCL5 mediates its novel functions. Towards this missing knowledge, we have solved the solution structure of the CXCL5 dimer by NMR spectroscopy. CXCL5 is a member of a subset of seven CXCR2-activating chemokines (CAC that are characterized by the highly conserved ELR motif in the N-terminal tail. The structure shows that CXCL5 adopts the typical chemokine fold, but also reveals several distinct differences in the 30 s loop and N-terminal residues; not surprisingly, crosstalk between N-terminal and 30 s loop residues have been implicated as a major determinant of receptor activity. CAC function also involves binding to highly sulfated glycosaminoglycans (GAG, and the CXCL5 structure reveals a distinct distribution of positively charged residues, suggesting that differences in GAG interactions also influence function. The availability of the structure should now facilitate the design of experiments to better understand the molecular basis of various CXCL5 functions, and also serve as a template for the design of inhibitors for use in a clinical setting.

  8. Adipokines, Biomarkers of Endothelial Activation, and Metabolic Syndrome in Patients with Ankylosing Spondylitis

    OpenAIRE

    Fernanda Genre; Raquel López-Mejías; Miranda-Filloy, José A.; Begoña Ubilla; Beatriz Carnero-López; Ricardo Blanco; Trinitario Pina; Carlos González-Juanatey; Javier Llorca; González-Gay, Miguel A.

    2014-01-01

    Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease associated with accelerated atherosclerosis and increased risk of cardiovascular (CV) disease. AS patients also display a high prevalence of features clustered under the name of metabolic syndrome (MeS). Anti-TNF- α therapy was found to be effective to treat AS patients by suppressing inflammation and also improving endothelial function. Previously, it was demonstrated that a short infusion of anti-TNF- α monoclonal antib...

  9. Insulin sensitivity and related cytokines, chemokines, and adipokines in polymyalgia rheumatica

    DEFF Research Database (Denmark)

    Kreiner, F; Galbo, H

    2010-01-01

    To evaluate the insulin sensitivity (IS) and levels of peptides with impact on IS in polymyalgia rheumatica (PMR) before and after prednisolone treatment.......To evaluate the insulin sensitivity (IS) and levels of peptides with impact on IS in polymyalgia rheumatica (PMR) before and after prednisolone treatment....

  10. Signals from Fat After Injury: Plasma Adipokines and Ghrelin Concentrations in the Severely Burned

    Science.gov (United States)

    2012-09-26

    hor- mones , beta blockers and intensive insulin therapy. Furthermore, Table 1 Demographics of control and burn subjects. Values in the table are mean...possibilities to assess the status of the patient through the use of these hor- mones as biomarkers. This work also provides the basis on which to

  11. Effects of isolated GH deficiency on adipose tissue, feeding and adipokines in mice.

    Science.gov (United States)

    Recinella, Lucia; Shohreh, Rugia; Salvatori, Roberto; Orlando, Giustino; Vacca, Michele; Brunetti, Luigi

    2013-12-01

    Growth hormone deficiency (GHD) leads to growth failure and changes in body composition including increased fat accumulation and reduced lean body mass in both humans and rodents. The aim of this study was to characterize the consequences of isolated GHD (IGHD) on adiposity, total body weight (TBW), and food intake in a mouse model of autosomal recessive IGHD due to targeted ablation of the GH-releasing hormone (GHRH) gene [GHRH knockout (GHRHKO)]. Animals were also analyzed with respect to leptin, adiponectin and visfatin circulating levels and gene expression in both intra-abdominal and subcutaneous fat. We studied 8 male mice homozygous for GHRHKO allele (-/-) and 8 heterozygous (+/-) animals as controls. Feeding and TBW data were collected weekly from 3 through 5 months of age. Animals were then euthanized for measurement of body length and intra-abdominal (epididymal and retroperitoneal) and subcutaneous (interscapular, axillary, gluteal and inguinal) fat weights, and for blood collection for leptin, adiponectin and visfatin measurement. Gene expression of leptin, adiponectin and visfatin in adipose tissue was evaluated by real-time reverse transcription polymerase chain reaction. GHRHKO mice had significantly increased relative intra-abdominal (Pleptin mRNA levels were not different from controls. Conversely, serum adiponectin levels were higher in GHRHKO mice (Pleptin did not significantly differ from controls. IGHD due to targeted ablation of the GHRH gene in mice is associated with increased relative subcutaneous and intra-abdominal fat mass and higher food consumption which is not related to changes in circulating leptin. © 2013.

  12. Association of Adipokine Resistin With Homeostasis Model Assessment of Insulin Resistance in Type II Diabetes

    Directory of Open Access Journals (Sweden)

    Sokhanguei

    2015-03-01

    Full Text Available Background Resistin is a recently discovered signal molecule that has been linked to obesity, type II diabetes mellitus (T2DM and metabolic syndrome. Objectives This study aimed to assess whether serum resistin is associated with insulin resistance and glucose concentration in males with T2DM. Patients and Methods Thirty two adult non-trained males with type II diabetes, 34-48 years old and 88-110 kg of body weight, participated in this study by accessible sampling. Fasting blood samples were collected from all participants in order to measure serum resistin, insulin and glucose concentration. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR was calculated using fasting insulin and glucose. Relations between variables were determined by Pearson correlations. Results We found that serum resistin had a positive significant correlation with insulin resistance (P = 0.000, r = 0.64. No significant correlation was found between serum resistin and fasting glucose concentration in the studied patients (P = 0.21, r = 0.23. Conclusions Based on these data, we can argue that circulating glucose concentration is not directly affected by serum resistin in T2DM. It seems that resistin affects glucose indirectly, through insulin resistance.

  13. Hepatic steatosis,low-grade chronic inflammation and hormone/growth factor/adipokine imbalance

    Institute of Scientific and Technical Information of China (English)

    Giovanni; Tarantino; Silvia; Savastano; Annamaria; Colao

    2010-01-01

    Non-alcoholic fatty liver disease (NAFLD), a further expression of metabolic syndrome, strictly linked to obesity and diabetes mellitus, is characterized by insulin resistance (IR), elevated serum levels of free fatty acids and fatty infi ltration of the liver, which is known as hepatic steatosis. Hepatocyte apoptosis is a key feature of this disease and correlates with its severity. Free-fatty-acidinduced toxicity represents one of mechanisms for the pathogenesis of NAFLD and hormones, growth factors and a...

  14. Identification of Putative Receptors for the Novel Adipokine CTRP3 Using Ligand-Receptor Capture Technology

    Science.gov (United States)

    Li, Ying; Ozment, Tammy; Wright, Gary L.

    2016-01-01

    C1q TNF Related Protein 3 (CTRP3) is a member of a family of secreted proteins that exert a multitude of biological effects. Our initial work identified CTRP3’s promise as an effective treatment for Nonalcoholic fatty liver disease (NAFLD). Specifically, we demonstrated that mice fed a high fat diet failed to develop NAFLD when treated with CTRP3. The purpose of this current project is to identify putative receptors which mediate the hepatic actions of CTRP3. Methods We used Ligand-receptor glycocapture technology with TriCEPS™-based ligand-receptor capture (LRC-TriCEPS; Dualsystems Biotech AG). The LRC-TriCEPS experiment with CTRP3-FLAG protein as ligand and insulin as a control ligand was performed on the H4IIE rat hepatoma cell line. Results Initial analysis demonstrated efficient coupling of TriCEPS to CTRP3. Further, flow cytometry analysis (FACS) demonstrated successful oxidation and crosslinking of CTRP3-TriCEPS and Insulin-TriCEPS complexes to cell surface glycans. Demonstrating the utility of TriCEPS under these conditions, the insulin receptor was identified in the control dataset. In the CTRP3 treated cells a total enrichment of 261 peptides was observed. From these experiments 5 putative receptors for CTRP3 were identified with two reaching statistically significance: Lysosomal-associated membrane protein 1 (LAMP-1) and Lysosome membrane protein 2 (LIMP II). Follow-up Co-immunoprecipitation analysis confirmed the association between LAMP1 and CTRP3 and further testing using a polyclonal antibody to block potential binding sites of LAMP1 prevented CTRP3 binding to the cells. Conclusion The LRC-TriCEPS methodology was successful in identifying potential novel receptors for CTRP3. Relevance The identification of the receptors for CTRP3 are important prerequisites for the development of small molecule drug candidates, of which none currently exist, for the treatment NAFLD. PMID:27727322

  15. Reduction of CTRP9, a novel anti-platelet adipokine, contributes to abnormal platelet activity in diabetic animals.

    Science.gov (United States)

    Wang, Wenqing; Lau, Wayne Bond; Wang, Yajing; Ma, Xinliang; Li, Rong

    2016-01-11

    Platelet hyper-reactivity is a crucial cause of accelerated atherosclerosis increasing risk of thrombotic vascular events in diabetic patients. The mechanisms leading to abnormal platelet activity during diabetes are complex and not fully defined. The current study attempted to clarify the role of CTRP9, a novel adiponectin paralog, in enhanced platelet activity and determined whether CTRP9 may inhibit platelet activity. Adult male C57BL/6 J mice were randomized to receive high-fat diet (HFD) or normal diet (ND). 8 weeks after HFD, animals were sacrificed, and both plasma CTRP9 and platelet aggregation were determined. HFD-fed animals increased weight gain significantly, and became hyperglycemic and hyperinsulinemic 8 weeks post-HFD. Compared to ND animals, HFD animals exhibited significantly decreased plasma CTRP9 concentration and increased platelet response to ADP, evidenced by augmented aggregation amplitude, steeper aggregation slope, larger area under the curve, and shorter lag time (P animals. Taken together, our results suggest reduced plasma CTRP9 concentration during diabetes plays a causative role in platelet hyper-activity, contributing to platelet-induced cardiovascular damage during this pathologic condition. Enhancing CTRP9 production and/or exogenous supplementation of CTRP9 may protect against diabetic cardiovascular injury via inhibition of abnormal platelet activity.

  16. Blood lipids and adipokines concentrations during a 6-month nutritional and physical activity intervention for metabolic syndrome treatment

    Directory of Open Access Journals (Sweden)

    Courteix Daniel

    2010-12-01

    Full Text Available Abstract Background To report changes in body weight, total and central fat mass, metabolic, hormonal and inflammatory parameters in overweight people who participated in a six months weight loss intervention associating diet management and exercise. Subjects and Methods Fourteen subjects (10 M, 4 F, mean age 62.9 ± 6.9 years, BMI 30.4+/- 3.8 kg/m2 presenting the characteristics of the Metabolic Syndrome (MS were included in the survey. They followed a three weeks (D0 to D20 cure in a medical establishment and a six months (D20 to M3 and M6 follow up at home. During the cure, they receive a balanced diet corresponding to 500 Kcal deficit vs their dayly energy expenditure (DEE and they exercised 2 to 3 hours per day. At D0, D20, M3 and M6, body composition (lean mass, total and central fat mass was analyzed with DEXA, blood pressure was taken and blood was collected to evaluate glycaemia, triglycerides, total, LDL and HDL cholesterol, insulin, leptin and adiponectin levels, CRP and pro-inflammatory interleukines IL1, IL.6 and TNFalpha. Results All parameters listed above except the cytokine were improved at D20, so that 4 subjects among 14 still presented the MS. After returning to home, these parameters remained stable. Conclusion The efficacy of therapeutic lifestyle modifications with education and exercise and diet was demonstrated, but the compliance to the new healthy lifestyle initiated during the cure was not optimal.

  17. Adipocitocinas: uma nova visão do tecido adiposo Adipokines: a new view of adipose tissue

    Directory of Open Access Journals (Sweden)

    Daniella Esteves Duque Guimarães

    2007-10-01

    Full Text Available A identificação da leptina, hormônio secretado pelos adipócitos, cujo efeito sobre o sistema nervoso simpático e a função endócrina confere participação ativa no controle do dispêndio energético, bem como do apetite, acrescentou às funções do tecido adiposo no organismo humano o papel de órgão multifuncional, produtor e secretor de inúmeros peptídeos e proteínas bioativas, denominadas adipocitocinas. Alterações na quantidade de tecido adiposo, como ocorrem na obesidade, afetam a produção da maioria desses fatores secretados pelos adipócitos. Ainda que essas alterações estejam freqüentemente associadas às inúmeras disfunções metabólicas e ao aumento do risco de doenças cardiovasculares, permanece sob investigação o envolvimento do tecido adiposo no desenvolvimento dessas complicações, considerada a sua função endócrina. As concentrações de várias adipocitocinas elevam-se na obesidade e têm sido relacionadas à hipertensão (angiotensinogênio, ao prejuízo da fibrinólise (inibidor do ativador de plasminogênio-1 e à resistência à insulina (proteína estimuladora de acilação, fator de necrose tumoral-alfa, interleucina-6 e resistina. De outro modo, leptina e adiponectina têm efeitos sobre a sensibilidade à insulina. Na obesidade, a resistência insulínica também está relacionada à resistência à leptina e aos teores plasmáticos reduzidos de adiponectina. Leptina e adiponectina ainda exercem efeitos orgânicos adicionais distintos: frente à participação da leptina no controle da ingestão alimentar, a adiponectina apresenta potente ação anti-aterogênica. Algumas drogas utilizadas no controle do diabetes elevam a produção endógena de adiponectina, em roedores e humanos, indicando que o desenvolvimento de novos medicamentos com alvo nas adipocitocinas pode representar uma alternativa terapêutica de prevenção da resistência insulínica e da aterosclerose em indivíduos obesos.Leptin is a hormone secreted by adipocytes whose effect on the sympathetic nervous system and endocrine function confers active participation in the control of energy expenditure and appetite. Its identification added to the fat tissues in the human body the role of a multifunctional organ that produces and secretes a number of bioactive peptides and proteins, called adipocytokines. Changes in the amount of fat tissue, such as the ones that occur in obesity, affect the production of most of these factors secreted by adipocytes. Even if these changes are frequently associated with many metabolic disorders and increased risk for cardiovascular diseases, the role of fat tissue in the development of these complications, considered its endocrine function, continue to be investigated. The concentration of various adipocytokines increase in obesity and have been associated with hypertension (angiotensinogen, fibrinolysis impairment (plasminogen activator inhibitor-1 and insulin resistance (protein that stimulates acylation, tumor necrosis factor-alpha, interleukine-6 and resistin. On the other hand, leptin and adiponectin affect insulin sensitivity. In obesity, insulin resistance is also associated with leptin resistance and reduced plasma levels of adiponectin. Leptin and adiponectin still have complementary and distinct organic functions: adiponectin has potent antiatherogenic activity while leptin participates in the control of food intake. Some medications used to control diabetes increase adiponectin production in rodents and humans, suggesting that the development of new medications that target the adipocytokines can represent a new therapeutic alternative to prevent insulin resistance and atherosclerosis in obese individuals.

  18. BEHAVIOR OF ADIPOKINES AFTER A YEAR FOLLOW-UP IN THE OBESITY OUTPATIENT CLINIC FOR CHILDREN AND ADOLESCENTS.

    Science.gov (United States)

    Miraglia, Fernanda; de Moraes Silveira, Carla Rosane; Gomes Beghetto, Mariur; dos Santos Oliveira, Fernanda; de Mello, Elza Daniel

    2015-10-01

    Objetivo: demostrar la evolución de las adipocinas a lo largo de 12 meses en niños obesos usuarios del Ambulatorio de Obesidad Infantojuvenil. Metodología: se hizo el seguimiento de niños y adolescentes en tratamiento clínico para obesidad a lo largo de 12 meses. Se los evaluó en lo tocante a antropometría, presión arterial, circunferencia de cintura, perfil lipídico, glicemia e insulina en ayuno, interleucina 6, factor de necrosis tumoral alfa y adiponectina en dos instancias: inclusión y después de 12 meses de seguimiento en el Ambulatorio de Obesidad Infantojuvenil. Resultados: se evaluaron 27 niños y adolescentes con una media de edad de 10,3 años. Los valores promedio de la puntuación-z del IMC bajaron en el período (p adiponectina (p = 0,943). No hubo correlación entre la IL-6 y el TNF-con obesidad central y global a lo largo de los 12 meses de seguimiento. El 45% de la muestra aumentó sus valores de adiponectina, siendo mayor este aumento en el sexo femenino. Conclusión: los niños y adolescentes en tratamiento clínico para obesidad tras un año de seguimiento no mejoraron su perfil de adipocinas.

  19. Visceral adiposity index (VAI is predictive of an altered adipokine profile in patients with type 2 diabetes.

    Directory of Open Access Journals (Sweden)

    Marco C Amato

    Full Text Available AIMS: Although there is still no clear definition of "adipose tissue dysfunction" or ATD, the identification of a clinical marker of altered fat distribution and function may provide the needed tools for early identification of a condition of cardiometabolic risk. Our aim was to evaluate the correlations among various anthropometric indices [BMI, Waist Circumference (WC, Hip Circumference (HC, Waist/Hip ratio (WHR, Body Adiposity Index (BAI and Visceral adiposity Index (VAI] and several adipocytokines [Visfatin, Resistin, Leptin, Soluble leptin receptors (sOB-R, Adiponectin, Ghrelin, Adipsin, PAI-1, vascular endothelial growth factor (VEGF, Hepatocyte growth factor (HGF TNF-α, hs-CRP, IL-6, IL-18] in patients with type 2 diabetes (DM2. MATERIALS AND METHODS: Ninety-one DM2 patients (age: 65.25 ± 6.38 years; 42 men and 49 women in stable treatment for the last six months with metformin in monotherapy (1.5-2 g/day were cross-sectionally studied. Clinical, anthropometric, and metabolic parameters were evaluated. Serum adipocytokine levels were assayed with Luminex based kits. RESULTS: At the Pearson's correlation, among all the indices investigated, VAI showed a significant correlation with almost all adipocytokines analyzed [Visfatin, Resistin and hsCRP (all p<0.001; Adiponectin, sOb-R, IL-6, IL-18, HGF (all p<0.010; Ghrelin and VEGF (both p<0.05]. Through a two-step cluster analysis, 55 patients were identified with the most altered adipocytokine profile (patients with ATD. At a ROC analysis, VAI showed the highest C-statistic [0.767 (95% CI 0.66-0.84] of all the indices. CONCLUSIONS: Our study suggests that the VAI, among the most common indexes of adiposity assessment, shows the best correlation with the best known adipocytokines and cardiometabolic risk serum markers. Although to date we are still far from clearly identifying an ATD, the VAI would be an easy tool for clearly mirroring a condition of cardiometabolic risk, in the absence of an overt metabolic syndrome.

  20. Elevated C-Peptides, Abdominal Obesity, and Abnormal Adipokine Profile are Associated With Higher Gleason Scores in Prostate Cancer.

    Science.gov (United States)

    Di Sebastiano, Katie M; Pinthus, Jehonathan H; Duivenvoorden, Wilhelmina C M; Patterson, Laurel; Dubin, Joel A; Mourtzakis, Marina

    2017-02-01

    Prostate cancer development is associated with numerous lifestyle factors (i.e., physical activity, nutrition intake) and metabolic perturbations. These factors have been studied independently; here, we used an integrative approach to characterize these lifestyle and metabolic parameters in men undergoing diagnostic prostate biopsies. We prospectively evaluated 51 consecutive men for body composition, metabolic factors including glucose- and lipid-related measures, as well as lifestyle factors prior to prostate biopsy. Evaluations were performed in a blinded manner and were subsequently related to biopsy outcomes for: (i) presence or absence of cancer; and (ii) where cancer was present, Gleason score. Serum C-peptide concentrations were significantly greater in participants with Gleason scores ≥4 + 3 (2.8 ± 1.1 ng/ml) compared to those with Gleason 3 + 3 (1.4 ± 0.6 ng/ml) or Gleason 3 + 4 (1.3 ± 0.8 ng/ml, P = 0.002), suggesting greater insulin secretion despite lack of differences in fasting glucose concentrations. Central adiposity, measured by waist circumference, was significantly greater in participants with Gleason ≥4 + 3 (110.1 ± 7.4 cm) compared to those with Gleason 3 + 4 (102.0 ± 9.5 cm, P = 0.028). Men with Gleason ≥4 + 3 also had significantly greater leptin concentrations than those with lower Gleason scores (Gleason ≥4 + 3: 15.6 ± 3.3 ng/ml vs. Gleason 3 + 4: 8.1 ± 8.1 ng/ml, P obesity-related metabolic perturbations (C-peptide, central adiposity, leptin, and leptin:adiponectin ratios) which may associate with more aggressive prostate cancer histology. Prostate 77:211-221, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  1. Nrg4 promotes fuel oxidation and a healthy adipokine profile to ameliorate diet-induced metabolic disorders

    Directory of Open Access Journals (Sweden)

    Zhimin Chen

    2017-08-01

    Conclusions: Nrg4 exerts pleiotropic beneficial effects on energy balance and glucose and lipid metabolism to ameliorate obesity-associated metabolic disorders. Biologic therapeutics based on Nrg4 may improve both type 2 diabetes and non-alcoholic fatty liver disease (NAFLD in patients.

  2. Quinoa extract enriched in 20-hydroxyecdysone protects mice from diet-induced obesity and modulates adipokines expression.

    Science.gov (United States)

    Foucault, Anne-Sophie; Mathé, Véronique; Lafont, René; Even, Patrick; Dioh, Waly; Veillet, Stanislas; Tomé, Daniel; Huneau, Jean-François; Hermier, Dominique; Quignard-Boulangé, Annie

    2012-02-01

    Besides their well-known effect in the molting control in insects, ecdysteroids are steroid hormones that display potential pharmacologic and metabolic properties in mammals. The most common ecdysteroid, 20-hydroxyecdysone (20E) is found in many plants such as quinoa. The aim of the present study was to investigate the ability of quinoa extract (Q) enriched in 20E supplementation to prevent the onset of diet-induced obesity and to regulate the expression of adipocyte-specific genes in mice. Mice were fed a standard low-fat (LF) or a high-fat (HF) diet with or without supplementation by 20E-enriched Q or pure 20E for 3 weeks. Supplementation with Q reduced adipose tissue development in HF mice without modification of their body weight gain. This adipose tissue-specific effect was mainly associated with a reduced adipocyte size and a decrease in the expression of several genes involved in lipid storage, including lipoprotein lipase and phosphoenolpyruvate carboxykinase. Furthermore, Q-treated mice exhibited marked attenuation of mRNA levels of several inflammation markers (monocyte chemotactic protein-1, CD68) and insulin resistance (osteopontin, plasminogen activator inhibitor-1 (PAI-1)) as compared to HF mice. Q supplementation also reversed the effects of HF-induced downregulation of the uncoupling protein(s) (UCP(s)) mRNA levels in muscle. Similar results were obtained in mice fed a HF diet supplemented with similar amounts of pure 20E, suggesting that the latter accounted for most of the Q effects. Our study indicates that Q has an antiobesity activity in vivo and could be used as a nutritional supplement for the prevention and treatment of obesity and obesity-associated disorders.

  3. The association of bone turnover markers with pro- and anti-inflammatory adipokines in patients with gestational diabetes

    Directory of Open Access Journals (Sweden)

    Beata Telejko

    2015-05-01

    Full Text Available Objective. The aim of the study was to assess differences in circulating osteocalcin (OC and osteoprotegerin (OPG, as well as in their expression in subcutaneous adipose tissue (SAT, visceral adipose tissue (VAT and placental tissue obtained from patients with gestational diabetes mellitus (GDM and normal glucose tolerance (NGT. Materials and method. Serum levels of OC, OPG and soluble nuclear factor-kB ligand (sRANKL were measured in 49 women with GDM and 30 subjects with NGT between weeks 24–32 of gestation, and three months after childbirth. OC and OPG mRNA expression was measured in 23 patients with GDM and 23 women with NGT at term, using quantitative real-time RT-PCR. Results. The patients with GDM had decreased OC mRNA expression in SAT (p=0.015, lower adiponectin mRNA expression in VAT (p=0.039, and a lower circulating adiponectin level (p=0.04. Multiple regression analysis revealed that serum adiponectin was significantly associated with OC mRNA expression in SAT (b=0.49, p=0.03. Three months postpartum, the OPG/sRANKL ratio was markedly higher in the subjects with prior GDM (p=0.03 and correlated positively with HbA1c (R=0.33; p=0.04, fasting insulin (R=0.35; p=0.03 and HOMA-IR (R=0.34; p=0.04. Conclusions. In the patients with GDM decreased OC mRNA expression in SAT might be associated with a reduced stimulatory effect on adiponectin expression in adipose tissue. On the other hand, higher OPG/sRANKL ratio suggests a better protection against bone loss in the subjects with prior GDM.

  4. The Pathophysiology of HIV-/HAART-Related Metabolic Syndrome Leading to Cardiovascular Disorders: The Emerging Role of Adipokines

    OpenAIRE

    John Palios; Kadoglou, Nikolaos P. E.; Stylianos Lampropoulos

    2012-01-01

    Individuals infected with human immunodeficiency virus (HIV) frequently demonstrate metabolic syndrome (MS) associated with increased incidence of cardiovascular disorders. Characteristics of HIV infection, such as immunodeficiency, viral load, and duration of the disease, in addition to the highly active antiretroviral therapy (HAART) have been suggested to induce MS in these patients. It is well documented that MS involves a number of traditional cardiovascular risk factors, like glucose, l...

  5. Serum Level of the Adipokine “Vaspin” in Relation to Metabolic Parameters: Short – Term Effect of Specific Dietary Therapy

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    Maha I. A. Moaty

    2014-06-01

    CONCLUSION: The effect of the dietary supplements may play a role in alleviating the impact of the components of the MetS and may also sustain the level of the vaspin in the sensitization of the C-peptide in order to attain glucose homeostasis.

  6. Expression of CTRP3, a Novel Adipokine, in Rats at Different Pathogenic Stages of Type 2 Diabetes Mellitus and the Impacts of GLP-1 Receptor Agonist on It

    Directory of Open Access Journals (Sweden)

    Xin Li

    2014-01-01

    Full Text Available This study aimed to investigate the expression of C1q/TNF-related protein-3 (CTRP3 in rats at different pathogenic stages of type 2 diabetes mellitus (T2DM and the impacts of glucagon-like peptide-1 (GLP-1 receptor agonist on it. Male wistar rats were fed with high-fat diet for 10 weeks to induce insulin resistance (IR and then were given low-dose streptozotocin (STZ intraperitoneal injection to induce T2DM. Exendin-4 (Ex-4, a GLP-1 receptor agonist, was subcutaneous injected to the IR rats and T2DM rats for 4 weeks. The expression of CTRP3 mRNA and protein in epididymis adipose tissue of rats at the stage of IR was lower significantly than that of normal control (NC rats and decreased more when they were at the stage of overt T2DM (all P<0.05 or P<0.01. After the treatment with Ex-4, the mRNA and protein expressions of CTRP3 were increased by 15.5% (P<0.01 and 14.8% (P<0.05, respectively, in IR rats and increased by 20.6% (P<0.01 and 16.5% (P<0.05, respectively, in T2DM rats. Overall, this study found that the expression of CTRP3 in visceral adipose tissue was progressively decreased in a T2DM rat model from the pathogenic stage of IR to overt diabetes, while Ex-4 treatment increased its expression in such animals.

  7. Effect of obesity intervention programs on adipokines, insulin resistance, lipid profile, and low-grade inflammation in 3- to 5-y-old children

    NARCIS (Netherlands)

    Bocca, Gianni; Corpeleijn, Eva; Stolk, Ronald P.; Wolffenbuttel, Bruce H.; Sauer, Pieter J.

    2014-01-01

    BACKGROUND: Childhood obesity can cause the development of cardiovascular risk factors. We assessed the effect of a multidisciplinary intervention program on cardiovascular risk factors and compared this effect with a usual-care program in 3- to 5-y-old overweight or obese children. METHODS: Seventy

  8. Effect of obesity intervention programs on adipokines, insulin resistance, lipid profile, and low-grade inflammation in 3- to 5-y-old children

    NARCIS (Netherlands)

    Bocca, Gianni; Corpeleijn, Eva; Stolk, Ronald P.; Wolffenbuttel, Bruce H.; Sauer, Pieter J.

    BACKGROUND: Childhood obesity can cause the development of cardiovascular risk factors. We assessed the effect of a multidisciplinary intervention program on cardiovascular risk factors and compared this effect with a usual-care program in 3- to 5-y-old overweight or obese children. METHODS:

  9. Early changes in adipokine levels and baseline limb fat may predict HIV lipoatrophy over 2 years following initiation of antiretroviral therapy

    DEFF Research Database (Denmark)

    Calmy, A; Carey, D; Mallon, P W G

    2008-01-01

    BACKGROUND: No biological marker has been identified that predicts the development of lipodystrophy (LD). We investigated whether metabolic and body composition parameters could predict the development of LD over 2 years in adults initiating antiretroviral therapy (ART). METHODS: We used stored...... levels during the first 6 months of ART, independently predicted a peripheral fat loss of > or = 2 kg [odds ratio (OR) 2.58, 95% confidence interval (CI) 1.04-6.41; OR 3.15, 95% CI 1.34-7.35, respectively). VAT changes showed a borderline association with high baseline tumour necrosis factor-alpha levels...... and hip circumference (OR 1.04, 95% CI 1.00-1.07; OR 1.44, 95% CI 1.07-1.95, respectively). CONCLUSIONS: In ART-naïve men, higher baseline limb fat and an early increase in leptin concentrations may predict the subsequent development of lipoatrophy. We did not find the same risk factors in the two...

  10. Caloric restriction and the adipokine leptin alter the SDF-1 signaling axis in bone marrow and in bone marrow derived mesenchymal stem cells.

    Science.gov (United States)

    Periyasamy-Thandavan, Sudharsan; Herberg, Samuel; Arounleut, Phonepasong; Upadhyay, Sunil; Dukes, Amy; Davis, Colleen; Johnson, Maribeth; McGee-Lawrence, Meghan; Hamrick, Mark W; Isales, Carlos M; Hill, William D

    2015-07-15

    Growing evidence suggests that the chemokine stromal cell-derived factor-1 (SDF-1) is essential in regulating bone marrow (BM) derived mesenchymal stromal/stem cell (BMSC) survival, and differentiation to either a pro-osteogenic or pro-adipogenic fate. This study investigates the effects of caloric restriction (CR) and leptin on the SDF-1/CXCR4 axis in bone and BM tissues in the context of age-associated bone loss. For in vivo studies, we collected bone, BM cells and BM interstitial fluid from 12 and 20 month-old C57Bl6 mice fed ad-libitum (AL), and 20-month-old mice on long-term CR with, or without, intraperitoneal injection of leptin for 10 days (10 mg/kg). To mimic conditions of CR in vitro, 18 month murine BMSCs were treated with (1) control (Ctrl): normal proliferation medium, (2) nutrient restriction (NR): low glucose, low serum medium, or (3) NR + leptin: NR medium + 100 ng/ml leptin for 6-48 h. In BMSCs both protein and mRNA expression of SDF-1 and CXCR4 were increased by CR and CR + leptin. In contrast, the alternate SDF-1 receptor CXCR7 was decreased, suggesting a nutrient signaling mediated change in SDF-1 axis signaling in BMSCs. However, in bone SDF-1, CXCR4 and 7 gene expression increase with age and this is reversed with CR, while addition of leptin returns this to the "aged" level. Histologically bone formation was lower in the calorically restricted mice and BM adipogenesis increased, both effects were reversed with the 10 day leptin treatment. This suggests that in bone CR and leptin alter the nutrient signaling pathways in different ways to affect the local action of the osteogenic cytokine SDF-1. Studies focusing on the molecular interaction between nutrient signaling by CR, leptin and SDF-1 axis may help to address age-related musculoskeletal changes.

  11. Preventive effect of a melon extract rich in superoxide scavenging activity on abdominal and liver fat and adipokine imbalance in high-fat-fed hamsters.

    Science.gov (United States)

    Décordé, Kelly; Agne, Anta; Lacan, Dominique; Ramos, Jeanne; Fouret, Gilles; Ventura, Emilie; Feillet-Coudray, Christine; Cristol, Jean-Paul; Rouanet, Jean-Max

    2009-07-22

    Studies showed that dietary antioxidants could be a therapy against obesity that is associated with a state of oxidative stress. Thus, this paper investigates whether a dietary ingredient, a melon juice extract rich in superoxide dismutase, would prevent the development of such obesity in hamsters. Five groups received a standard diet or a high-fat diet (HF) plus a daily gavage with water (control) or extract at 0.7, 2.8, or 5.6 mg/day. After 84 days, the higher dose lowered triglyceridemia (68%), production of liver superoxide anion (12%), mitochondrial cytochrome c oxidase activity (40%), lipid and protein oxidation products (35 and 35%, respectively), and leptinemia (99%) and increased adiponectinemia (29%), leading to a concomitant reduction in insulinemia (39%), insulin resistance (41%), and abdominal lipids (25%). The extract triggered a remarkable decrease of liver lipids (73%) and fully prevented the steatohepatitis induced by the HF diet. Chronic consumption of this melon extract may represent a new alternative to reduce obesity induced by a high-fat diet.

  12. Expression of CTRP3, a novel adipokine, in rats at different pathogenic stages of type 2 diabetes mellitus and the impacts of GLP-1 receptor agonist on it.

    Science.gov (United States)

    Li, Xin; Jiang, Li; Yang, Miao; Wu, Yu-wen; Sun, Su-xin; Sun, Jia-zhong

    2014-01-01

    This study aimed to investigate the expression of C1q/TNF-related protein-3 (CTRP3) in rats at different pathogenic stages of type 2 diabetes mellitus (T2DM) and the impacts of glucagon-like peptide-1 (GLP-1) receptor agonist on it. Male wistar rats were fed with high-fat diet for 10 weeks to induce insulin resistance (IR) and then were given low-dose streptozotocin (STZ) intraperitoneal injection to induce T2DM. Exendin-4 (Ex-4), a GLP-1 receptor agonist, was subcutaneous injected to the IR rats and T2DM rats for 4 weeks. The expression of CTRP3 mRNA and protein in epididymis adipose tissue of rats at the stage of IR was lower significantly than that of normal control (NC) rats and decreased more when they were at the stage of overt T2DM (all P diabetes, while Ex-4 treatment increased its expression in such animals.

  13. Fibroblast growth factor 21 is elevated in metabolically unhealthy obesity and affects lipid deposition, adipogenesis, and adipokine secretion of human abdominal subcutaneous adipocytes

    Directory of Open Access Journals (Sweden)

    Lucia Berti

    2015-07-01

    Conclusions: The hepatokine FGF21 exerts weak lipogenic and anti-adipogenic actions and marked adiponectin-suppressive and leptin and interleukin-6 release-promoting effects in human differentiating preadipocytes. Together with the higher serum concentrations in MUHO subjects, our findings reveal FGF21 as a circulating factor promoting the development of metabolically unhealthy adipocytes.

  14. Adipokines, Oxidized Low-Density Lipoprotein, and C-Reactive Protein Levels in Lean, Overweight, and Obese Portuguese Patients with Type 2 Diabetes

    Science.gov (United States)

    Neuparth, Maria João; Proença, Jorge Brandão; Santos-Silva, Alice; Coimbra, Susana

    2013-01-01

    Aim. Our aim was to study how different BMI scores may influence the levels of inflammation, oxidative stress, adipogenesis, glucose, and lipid metabolism, in lean, overweight, and obese Portuguese patients with type 2 diabetes mellitus (T2DM). Methods. We studied 28 lean, 38 overweight, and 17 obese patients with T2DM and 20 controls (gender and age matched). The circulating levels of oxLDL, CRP, and some adipokines—adiponectin, leptin, and chemerin—and the lipid profile were evaluated. Results. Obese patients presented significantly lower levels of adiponectin and higher leptin, oxLDL, and chemerin levels, as compared to the overweight, lean, and control groups. Overweight, compared to lean and control, subjects showed significantly lower adiponectin and higher leptin and chemerin levels; oxLDL values were significantly higher in overweight than in lean patients. Lean patients presented significantly higher chemerin values than the control. Obese patients presented significantly higher CRP values, as compared to lean patients and the control group. Obese and overweight patients presented significantly higher triglycerides values than lean patients. Except for CRP, all the observed significant changes between control and patients remained significant after statistical adjustment for the body mass index (BMI). Conclusion. The levels of leptin, adiponectin, oxLDL, CRP, and triglycerides in patients with T2DM seem to be more associated with obesity and less with diabetes. Chemerin levels were raised in lean, overweight, and obese patients, suggesting that, independently of BMI, an adipocyte dysfunction occurs. Moreover, chemerin may provide an important early biomarker of adipocyte dysfunction and a link between obesity and type 2 diabetes mellitus. PMID:24634792

  15. Overexpressing the novel autocrine/endocrine adipokine WISP2 induces hyperplasia of the heart, white and brown adipose tissues and prevents insulin resistance

    DEFF Research Database (Denmark)

    Grünberg, John R; Hoffmann, Jenny M; Hedjazifar, Shahram

    2017-01-01

    undifferentiated. To examine effects of increased WISP2 in vivo, we generated an aP2-WISP2 transgenic (Tg) mouse. These mice had increased serum levels of WISP2, increased lean body mass and whole body energy expenditure, hyperplastic brown/white adipose tissues and larger hyperplastic hearts. Obese Tg mice...

  16. The Roles of Adipokines in the Antidepressant Actions of Exercise%脂肪细胞因子与运动的抗抑郁作用

    Institute of Scientific and Technical Information of China (English)

    薛香莉; 刘微娜; 漆正堂; 季浏

    2016-01-01

    Adipose tissue is recognized as a key regulator of metabolism and energy balance ,and its endocrine function has attracted more and more attention in recent years .Adipocytokines are expressed in the brain or central nervous system ,and brain dysfunction is associated with the adipocytokines disorders in depressed patients .Moreover ,the abnormal expression levels of blood adipocytokines in patients with depression suggests that adipocytokines may be consid‐ered as biomarkers in depression .Regular exercise can regulate the expression and secretion of most adipocytokines (such as leptin ,adiponectin ,irisin ,apelin ,resistin ,nesfatin ,et al .);more‐over ,exercise can improve the depression‐like behaviors by regulating the expression levels of monoamine neurotransmitters ,HPA axis activity ,central inflammation ,hippocampal neurogene‐sis and neurotrophic factor expression ,and nerve poison metabolism .We hope to find some pe‐ripheral adipocytokines as depression biomarkers used for biopsy and further clarify the antide‐pressant effects of exercise .The findings are supposed to better understand the beneficial effects of exercise on brain function (brain‐adipose tissue "crosstalk") ,and suggest new targets for novel antidepressants research and personalized exercise intervention of depression .%脂肪组织被公认为是代谢和能量平衡的关键调节者,近年来,其内分泌功能备受关注。脂肪组织产生或分泌的脂肪细胞因子在脑部或中枢神经系统表达或富集,而抑郁症患者大脑高级神经功能紊乱伴随着许多脂肪细胞因子表达失衡,且许多抑郁症患者的血液脂肪细胞因子水平异常,提示,其可能成为抑郁症新型的生物标志物。规律的运动可调节大部分脂肪细胞因子(瘦素、脂联素、鸢尾素、爱帕琳肽、抵抗素、nesfatin等)的表达和分泌,进而调节中枢单胺类神经递质表达水平、HPA轴活性、中枢炎症反应、海马神经发生及神经营养因子表达、神经毒害物质代谢等,发挥其抗抑郁效应。进一步揭示脂肪细胞因子介导脂肪组织‐脑组织“crosstalk”的多条路径并为运动防控抑郁症等精神疾病提供新视角。

  17. Association of 1-y changes in diet pattern with cardiovascular disease risk factors and adipokines: results from the 1-y randomized Oslo Diet and Exercise Study

    NARCIS (Netherlands)

    Jacobs, D.R.; Sluik, D.; Rokling-Andersen, M.H.; Anderssen, S.A.; Drevon, C.A.

    2009-01-01

    Background: We hypothesized that favorable changes in dietary patterns would lead to a reduction in body size and an improvement in metabolic status. Objective: The objective was to study changes in diet patterns relative to changes in body size, blood pressure, and circulating concentrations of lip

  18. Absence of an adipogenic effect of rosiglitazone on mature 3T3-L1 adipocytes: increase of lipid catabolism and reduction of adipokine expression

    NARCIS (Netherlands)

    Wang, P.; Renes, J.; Bouwman, F.; Bunschoten, A.; Mariman, E.; Keijer, J.

    2007-01-01

    Aims/hypothesis: The thiazolidinedione (TZD) rosiglitazone is a peroxisome proliferator-activated receptor-¿ agonist that induces adipocyte differentiation and, hence, lipid accumulation. This is in apparent contrast to the long-term glucose-lowering, insulin-sensitising effect of rosiglitazone. We

  19. Inflammatory Adipokines Decrease Expression of Two High Molecular Weight Isoforms of Tropomyosin Similar to the Change in Type 2 Diabetic Patients

    Science.gov (United States)

    Leitch, Helen F.; Harvey, John N.; Thomas, Trevor H.

    2016-01-01

    Cardiovascular disease and cancer are increased in Type 2 diabetes. TPM1 and TPM4 genes encode proteins associated with cardiovascular and neoplastic disease. High (HMW) and low (LMW) molecular weight isoforms from TPM1 and TPM4 are altered in several cancer cells and the 3'UTR of TPM1 mRNA is tumour suppressive. Leukocytes influence cardiovascular and neoplastic disease by immunosurveillance for cancer and by chronic inflammation in Type 2 diabetes and cardiovascular disease. The aim was to determine changes in expression of isoforms from TPM1 and TPM4 genes in leukocytes from Type 2 diabetic patients and to use the leukocyte cell line THP1 to identify possible mediators of changes in the patients. Gene expression was determined by RT-qPCR. In diabetes, expression of HMW isoforms from TPM1 were markedly decreased (0.55 v 1.00; p = 0.019) but HMW isoforms from TPM4 were not significantly different (0.76 v 1.00; p = 0.205). Within individual variance in expression of HMW isoforms was very high. The change in expression in HMW isoforms from TPM1 and TPM4 was replicated in THP1 cells treated with 1 ng/ml TNFα (0.10 and 0.12 v 1.00 respectively) or 10 ng/ml IL-1α (0.17 and 0.14 v 1.00 respectively). Increased insulin or glucose concentrations had no substantial effects on TPM1 or TPM4 expression. Decreased TPM1 mRNA resulted in decreases in HMW protein levels. Expression of HMW isoforms from TPM1 is decreased in Type 2 diabetes. This is probably due to increased levels of inflammatory cytokines TNFα and IL-1α in Type 2 diabetes. Lower levels of TPM1 mRNA reduce tumour suppression and could contribute to increased cancer risk in Type 2 diabetes. Decreased HMW tropomyosin isoforms are associated with cancer. Decreased HMW isoforms give rise to cells that are more plastic, motile, invasive and prone to dedifferentiation resulting in leukocytes that are more invasive but less functionally effective. PMID:27649540

  20. Obesity and Its Metabolic Complications: The Role of Adipokines and the Relationship between Obesity, Inflammation, Insulin Resistance, Dyslipidemia and Nonalcoholic Fatty Liver Disease

    OpenAIRE

    2014-01-01

    Accumulating evidence indicates that obesity is closely associated with an increased risk of metabolic diseases such as insulin resistance, type 2 diabetes, dyslipidemia and nonalcoholic fatty liver disease. Obesity results from an imbalance between food intake and energy expenditure, which leads to an excessive accumulation of adipose tissue. Adipose tissue is now recognized not only as a main site of storage of excess energy derived from food intake but also as an endocrine organ. The expan...

  1. [Roles of rs 6923761 gene variant in glucagon-like peptide 1 receptor on weight, cardiovascular risk factor and serum adipokine levels in morbid obese patients].

    Science.gov (United States)

    de Luis, Daniel Antonio; Pacheco, David; Aller, Rocío; Izaola, Olatz; Bachiller, Rosario

    2014-04-01

    Antecedentes: Los estudios de receptor de GLP-1 se han dirigido a la identificación de polimorfismos en el gen receptor de GLP- 1 que pueden ser un factor que contribuye en la patogénesis de la diabetes mellitus y factores de riesgo cardiovascular. Sin embargo, el papel de las variantes del receptor de GLP-1 variantes en el peso corporal, factores de riesgo cardiovasculares y adipocitoquinas sigue estando poco estudiado en pacientes con obesidad morbida. Objetivo: Nuestro objetivo fue analizar los efectos del polimorfismo del receptor de GLP-1 rs6923761 sobre el peso corporal, factores de riesgo cardiovascular y los niveles de adipocitoquinas séricas en pacientes con obesidad mórbida. Diseño: Se estudió una muestra de 175 obesos mórbidos. La glucosa en ayunas, proteína C reactiva (PCR), insulina, resistencia a la insulina ( HOMA), colesterol total, LDL- colesterol, HDL- colesterol, triglicéridos y la concentración de adipoquinas se midieron. También se determinaron el peso, índice de masa corporal, circunferencia de la cintura, masa grasa a través de bioimpedancia y la presión arterial. Resultados: Un total de 87 obesos (49,7%) tenían el genotipo GG y 88 (50,3%) de los sujetos del estudio tenían los siguientes genotipos; GA (71 obesos, el 40,6%) o AA (17 sujetos del estudio, el 9,7%) ( segundo grupo) . En el grupo con genotipo GG, los niveles de glucosa (4,4 ± 2,3 mg/dl, p < 0,05), triglicéridos (6,8 ± 4,3 mg/dl , p < 0,05), insulina (4,5 ± 2,3 UI/l , p < 0,05) y HOMA (1,5 ± 0,9 unidades, p < 0,05 ) fueron mayores que en el grupo mutante. No se detectaron diferencias en el resto de parámetros analizados Conclusión: Existe una asociación entre los parámetros metabólicos y el alelo mutante (A) del polimorfismo rs6923761 del receptor de GLP- 1 en pacientes con obesidad mórbida. Los niveles de triglicéridos, insulina y resistencia a la insulina son más elevados en los sujetos portadores del alelo A.

  2. Maternal Plasma Concentration of the Pro-Inflammatory Adipokine Pre-B-Cell Enhancing Factor (PBEF)/ Visfatin Is Elevated In Pregnant Patients with Acute Pyelonephritis

    Science.gov (United States)

    Mazaki-Tovi, Shali; Vaisbuch, Edi; Romero, Roberto; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Kim, Sun Kwon; Nhan-Chang, Chia-Ling; Gomez, Ricardo; Yoon, Bo H.; Yeo, Lami; Mittal, Pooja; Ogge, Giovanna; Gonzalez, Juan M.; Hassan, Sonia S.

    2012-01-01

    Problem Visfatin/pre-B-cell enhancing factor (PBEF) has been implicated in the regulation of the innate immune system, as well as in glucose metabolism. Specifically, visfatin plays a requisite role in delayed neutrophil apoptosis in patients with sepsis. The aim of this study was to determine whether pyelonephritis during pregnancy is associated with changes in maternal plasma visfatin concentration in normal weight and overweight/obese patients. Methods of Study This cross-sectional study included the following groups: 1) normal pregnant women (n=200); and 2) pregnant women with pyelonephritis (n=40). Maternal plasma visfatin concentrations were determined by ELISA. Non-parametric statistics were used for analyses. Results 1) The median maternal plasma visfatin concentration was significantly higher in patients with pyelonephritis than in those with a normal pregnancy; 2) among overweight/obese pregnant women, those with pyelonephritis had a significantly higher median plasma visfatin concentration than women with a normal pregnancy; and 3) pyelonephritis was independently associated with higher maternal plasma visfatin concentrations after adjustment for maternal age, pre-gestational BMI, smoking status, gestational age at sampling, and birthweight. Conclusions Acute pyelonephritis during pregnancy is associated with a high circulating maternal visfatin concentration. These findings suggest that visfatin/PBEF may play a role in the regulation of the complex and dynamic crosstalk between inflammation and metabolism during pregnancy. PMID:20085562

  3. Adiponectin levels correlate with the severity of hypertriglyceridaemia in glycogen storage disease Ia

    NARCIS (Netherlands)

    Bandsma, R. H. J.; Smit, G. P. A.; Reijngoud, D. -J.; Kuipers, F.

    2009-01-01

    Glycogen storage disease type Ia (GSD Ia) is characterized by severe hypercholesterolaemia and hypertriglyceridaemia. Little is known about the aetiology of the hyperlipidaemia in GSD Ia. Adipokines play an important regulatory role in lipid metabolism. We investigated whether adipokine concentratio

  4. Curcuma longa polyphenols improve insulin-mediated lipid accumulation and attenuate proinflammatory response of 3T3-L1 adipose cells during oxidative stress through regulation of key adipokines and antioxidant enzymes.

    Science.gov (United States)

    Septembre-Malaterre, Axelle; Le Sage, Fanny; Hatia, Sarah; Catan, Aurélie; Janci, Laurent; Gonthier, Marie-Paule

    2016-07-08

    Plant polyphenols may exert beneficial action against obesity-related oxidative stress and inflammation which promote insulin resistance. This study evaluated the effect of polyphenols extracted from French Curcuma longa on 3T3-L1 adipose cells exposed to H2 O2 -mediated oxidative stress. We found that Curcuma longa extract exhibited high amounts of curcuminoids identified as curcumin, demethoxycurcumin, and bisdemethoxycurcumin, which exerted free radical-scavenging activities. Curcuma longa polyphenols improved insulin-mediated lipid accumulation and upregulated peroxisome proliferator-activated receptor-gamma gene expression and adiponectin secretion which decreased in H2 O2 -treated cells. Curcuminoids attenuated H2 O2 -enhanced production of pro-inflammatory molecules such as interleukin-6, tumor necrosis factor-alpha, monocyte chemoattractant protein-1, and nuclear factor κappa B. Moreover, they reduced intracellular levels of reactive oxygen species elevated by H2 O2 and modulated the expression of genes encoding superoxide dismutase and catalase antioxidant enzymes. Collectively, these findings highlight that Curcuma longa polyphenols protect adipose cells against oxidative stress and may improve obesity-related metabolic disorders. © 2016 BioFactors, 42(4):418-430, 2016. © 2016 International Union of Biochemistry and Molecular Biology.

  5. Possível papel das adipocinas no lúpus eritematoso sistêmico e na artrite reumatoide Possible role of adipokines in systemic lupus erythematosus and rheumatoid arthritis

    OpenAIRE

    Vitalina de Souza Barbosa; Jozelia Rêgo; Nílzio Antônio da Silva

    2012-01-01

    Nos últimos anos têm sido descritos mediadores sintetizados no tecido adiposo, chamados adipocinas. Eles apresentam ação hormonal, regulando o apetite e o metabolismo da glicose, mas também atuam como citocinas, com efeitos sobre o sistema imune, incluindo efeitos na autoimunidade. As adipocinas mais importantes são: leptina, adiponectina, visfatina e resistina. Algumas delas vêm sendo estudadas nas doenças autoimunes reumáticas, particularmente no lúpus eritematoso sistêmico (LES) e na artri...

  6. 脂肪因子vaspin血清水平与代谢和肾脏参数的关系%Serum levels of the adipokine vaspin in relation to metabolic and renal parameters

    Institute of Scientific and Technical Information of China (English)

    周丽斌; 陈名道

    2008-01-01

    近来研究发现,脂肪细胞分泌的脂肪因子与代谢综合征各组分密切相关,其分泌异常可导致肥胖患者心血管疾病的风险增加。2005年Hida等首先在OLETF(Otsuka Long-Evans Tokushima Fatty)2型糖尿病肥胖大鼠的内脏脂肪组织中发现的vaspin是一种具有胰岛素增敏作用的脂肪因子,属于丝氨酸蛋白酶抑制剂超家族。肥胖小鼠给予vaspin可改善糖耐量,增加胰岛素敏感性,

  7. Lack of Effects of a Single High-Fat Meal Enriched with Vegetable n-3 or a Combination of Vegetable and Marine n-3 Fatty Acids on Intestinal Peptide Release and Adipokines in Healthy Female Subjects.

    Science.gov (United States)

    Narverud, Ingunn; Myhrstad, Mari C W; Herzig, Karl-Heinz; Karhu, Toni; Dahl, Tuva B; Halvorsen, Bente; Ulven, Stine M; Holven, Kirsten B

    2016-01-01

    Peptides released from the small intestine and colon regulate short-term food intake by suppressing appetite and inducing satiety. Intake of marine omega-3 (n-3) fatty acids (FAs) from fish and fish oils is associated with beneficial health effects, whereas the relation between intake of the vegetable n-3 fatty acid α-linolenic acid and diseases is less clear. The aim of the present study was to investigate the postprandial effects of a single high-fat meal enriched with vegetable n-3 or a combination of vegetable and marine n-3 FAs with their different unsaturated fatty acid composition on intestinal peptide release and the adipose tissue. Fourteen healthy lean females consumed three test meals with different fat quality in a fixed order. The test meal consisted of three cakes enriched with coconut fat, linseed oil, and a combination of linseed and cod liver oil. The test days were separated by 2 weeks. Fasting and postprandial blood samples at 3 and 6 h after intake were analyzed. A significant postprandial effect was observed for cholecystokinin, peptide YY, glucose-dependent insulinotropic polypeptide, amylin and insulin, which increased, while leptin decreased postprandially independent of the fat composition in the high-fat meal. In conclusion, in healthy, young, lean females, an intake of a high-fat meal enriched with n-3 FAs from different origin stimulates intestinal peptide release without any difference between the different fat compositions.

  8. Lack of Effects of a Single High-Fat Meal Enriched with Vegetable n-3 or a Combination of Vegetable and Marine n-3 Fatty Acids on Intestinal Peptide Release and Adipokines in Healthy Female Subjects

    Science.gov (United States)

    Narverud, Ingunn; Myhrstad, Mari C. W.; Herzig, Karl-Heinz; Karhu, Toni; Dahl, Tuva B.; Halvorsen, Bente; Ulven, Stine M.; Holven, Kirsten B.

    2016-01-01

    Peptides released from the small intestine and colon regulate short-term food intake by suppressing appetite and inducing satiety. Intake of marine omega-3 (n-3) fatty acids (FAs) from fish and fish oils is associated with beneficial health effects, whereas the relation between intake of the vegetable n-3 fatty acid α-linolenic acid and diseases is less clear. The aim of the present study was to investigate the postprandial effects of a single high-fat meal enriched with vegetable n-3 or a combination of vegetable and marine n-3 FAs with their different unsaturated fatty acid composition on intestinal peptide release and the adipose tissue. Fourteen healthy lean females consumed three test meals with different fat quality in a fixed order. The test meal consisted of three cakes enriched with coconut fat, linseed oil, and a combination of linseed and cod liver oil. The test days were separated by 2 weeks. Fasting and postprandial blood samples at 3 and 6 h after intake were analyzed. A significant postprandial effect was observed for cholecystokinin, peptide YY, glucose-dependent insulinotropic polypeptide, amylin and insulin, which increased, while leptin decreased postprandially independent of the fat composition in the high-fat meal. In conclusion, in healthy, young, lean females, an intake of a high-fat meal enriched with n-3 FAs from different origin stimulates intestinal peptide release without any difference between the different fat compositions. PMID:27630989

  9. L-4F Inhibits Oxidized Low-density Lipoprotein-induced Inflammatory Adipokine Secretion via Cyclic AMP/Protein Kinase A-CCAAT/Enhancer Binding Protein β Signaling Pathway in 3T3-L1 Adipocytes

    Directory of Open Access Journals (Sweden)

    Xiang-Zhu Xie

    2016-01-01

    Conclusions: OxLDL induces C/EBPβ protein synthesis in a time-dependent manner and enhances MCP-1 secretion and expression in 3T3-L1 adipocytes. L-4F dose-dependently counterbalances the pro-inflammatory effect of oxLDL, and cyclic AMP/PKA-C/EBPβ signaling pathway may participate in it.

  10. A Placebo-Controlled Study on the Effects of the Glucagon-Like Peptide-1 Mimetic, Exenatide, on Insulin Secretion, Body Composition and Adipokines in Obese, Client-Owned Cats

    DEFF Research Database (Denmark)

    Hoelmkjaer, Kirsten M.; Albrechtsen, Nicolai J. Wewer; Holst, Jens J.;

    2016-01-01

    Glucagon-like Peptide-1 mimetics increase insulin secretion and reduces body weight in humans. In lean, healthy cats, short-term treatment has produced similar results, whereas the effect in obese cats or with extended duration of treatment is unknown. Here, prolonged (12 weeks) treatment...... with the Glucagon-like Peptide-1 mimetic, exenatide, was evaluated in 12 obese, but otherwise healthy, client-owned cats. Cats were randomized to exenatide (1.0 μg/kg) or placebo treatment twice daily for 12 weeks. The primary endpoint was changes in insulin concentration; the secondary endpoints were glucose...... by exenatide (P>0.05). Twelve weeks of exenatide was well-tolerated, with only two cases of mild, self-limiting gastrointestinal signs and a single case of mild hypoglycemia. The long-term insulinotropic effect of exenatide appeared less pronounced in obese cats compared to previous short-term studies in lean...

  11. 非酒精性脂肪肝患者脂肪因子与Ghrelin血清学检测及临床意义%Serum Adipokines and Ghrelin in non-alcoholic fatty liver

    Institute of Scientific and Technical Information of China (English)

    徐青

    2008-01-01

    目的 检测非酒精性脂肪肝(NAFLD)患者血清脂肪因子与Ghrelin,探讨这些因子与NAFLD发病的关系.方法 NAFLD患者和健康对照各40例,Ghrelin、Leptin、Adiponectin与胰岛素用放免法测定,TNFα用ELISA法测定.计算胰岛素抵抗指数(HOMA-IR),并分析与脂肪因子、Ghrelin的相关性.结果 NAFLD组ALT、AST、BMI、FINS、HOMA-IR、Leptin和TNFα均高于健康对照组,Ghrelin与Adiponectin水平低于健康对照组,而血糖水平无明显差异.其中胰岛素抵抗指数与Leptin、TNFα呈正相关,与Adiponectin、Ghrelin(r=-0.23,P<0.01)呈负相关.结论 在NAFLD发病过程中,Adipokines与Ghrelin均起到很重要的作用,并与胰岛素抵抗有关.

  12. Lack of effects of a single high-fat meal enriched with vegetable n-3 or a combination of vegetable and marine n-3 fatty acids on intestinal peptide release and adipokines in healthy female subjects

    Directory of Open Access Journals (Sweden)

    Ingunn Naverud

    2016-08-01

    Full Text Available Peptides released from the small intestine and colon regulate short-term food intake by suppressing appetite and inducing satiety. Intake of marine omega-3 (n-3 fatty acids from fish and fish oils is associated with beneficial health effects, whereas the relation between intake of the vegetable n-3 fatty acid α-linolenic acid and diseases is less clear. The aim of the present study was to investigate the postprandial effects of a single high-fat meal enriched with vegetable n-3 or a combination of vegetable and marine n-3 fatty acids with their different unsaturated fatty acid composition on intestinal peptide release and the adipose tissue. Fourteen healthy lean females consumed three test meals with different fat quality in a fixed order. The test meal consisted of three cakes enriched with coconut fat, linseed oil and a combination of linseed and cod liver oil. The test days were separated by two weeks. Fasting and postprandial blood samples at three and six hours after intake were analysed. A significant postprandial effect was observed for cholecystokinin, peptide YY, glucose-dependent insulinotropic polypeptide, amylin and insulin which increased, while leptin decreased postprandially independent of the fat composition in the high-fat meal. In conclusion, in healthy, young, lean females, an intake of a high-fat meal enriched with n-3 fatty acids from different origin stimulates intestinal peptide release without any difference between the different fat compositions.

  13. A Placebo-Controlled Study on the Effects of the Glucagon-Like Peptide-1 Mimetic, Exenatide, on Insulin Secretion, Body Composition and Adipokines in Obese, Client-Owned Cats

    DEFF Research Database (Denmark)

    Hoelmkjaer, Kirsten M.; Albrechtsen, Nicolai Jacob Wewer; Holst, Jens Juul

    2016-01-01

    Glucagon-like Peptide-1 mimetics increase insulin secretion and reduces body weight in humans. In lean, healthy cats, short-term treatment has produced similar results, whereas the effect in obese cats or with extended duration of treatment is unknown. Here, prolonged (12 weeks) treatment...... with the Glucagon-like Peptide-1 mimetic, exenatide, was evaluated in 12 obese, but otherwise healthy, client-owned cats. Cats were randomized to exenatide (1.0 μg/kg) or placebo treatment twice daily for 12 weeks. The primary endpoint was changes in insulin concentration; the secondary endpoints were glucose...... by exenatide (P>0.05). Twelve weeks of exenatide was well-tolerated, with only two cases of mild, self-limiting gastrointestinal signs and a single case of mild hypoglycemia. The long-term insulinotropic effect of exenatide appeared less pronounced in obese cats compared to previous short-term studies in lean...

  14. 3,4-Oxo-isopropylidene-shikimic acid promotes adiopkine expression during murine 3T3-L1 fibroblast differentiation into adipocytes

    Directory of Open Access Journals (Sweden)

    Shifen Dong

    2014-10-01

    Conclusions: These findings demonstrated that ISA promoted adipogenesis by up-regulating expressions of C/EBP β, PPAR γ, C/EBP α, aP2 and FAS, and also stimulated adipokines during adipocyte differentiation. Further study should clarify the relationship between stimulation of adipokines and cognitive enhancing effect of ISA.

  15. Physiological concentrations of leptin do not affect human neutrophils.

    NARCIS (Netherlands)

    Kamp, V.M.; Langereis, J.D.; Aalst, C.W. van; Linden, J. van der; Ulfman, L.H.; Koenderman, L.

    2013-01-01

    Leptin is an adipokine that is thought to be important in many inflammatory diseases, and is known to influence the function of several leukocyte types. However, no clear consensus is present regarding the responsiveness of neutrophils for this adipokine. In this study a 2D DIGE proteomics approach

  16. Physiological concentrations of leptin do not affect human neutrophils.

    NARCIS (Netherlands)

    Kamp, V.M.; Langereis, J.D.; Aalst, C.W. van; Linden, J. van der; Ulfman, L.H.; Koenderman, L.

    2013-01-01

    Leptin is an adipokine that is thought to be important in many inflammatory diseases, and is known to influence the function of several leukocyte types. However, no clear consensus is present regarding the responsiveness of neutrophils for this adipokine. In this study a 2D DIGE proteomics approach

  17. Obesity-Induced Changes in Adipose Tissue Microenvironment and Their Impact on Cardiovascular Disease.

    Science.gov (United States)

    Fuster, José J; Ouchi, Noriyuki; Gokce, Noyan; Walsh, Kenneth

    2016-05-27

    Obesity is causally linked with the development of cardiovascular disorders. Accumulating evidence indicates that cardiovascular disease is the collateral damage of obesity-driven adipose tissue dysfunction that promotes a chronic inflammatory state within the organism. Adipose tissues secrete bioactive substances, referred to as adipokines, which largely function as modulators of inflammation. The microenvironment of adipose tissue will affect the adipokine secretome, having actions on remote tissues. Obesity typically leads to the upregulation of proinflammatory adipokines and the downregulation of anti-inflammatory adipokines, thereby contributing to the pathogenesis of cardiovascular diseases. In this review, we focus on the microenvironment of adipose tissue and how it influences cardiovascular disorders, including atherosclerosis and ischemic heart diseases, through the systemic actions of adipokines. © 2016 American Heart Association, Inc.

  18. Influence of G1359A polimorphysm of the cannabinoid receptor gene (CNR1 on insulin resistance and adipokines in patients with non alcoholic fatty liver disease Influencia del polimorfismo G1359a del gen del receptor cannabinoide (CNR1 sobre la resistencia a la insulina y adipocinas en pacientes con enfermedad hepática no alcohólica

    Directory of Open Access Journals (Sweden)

    R. Aller

    2012-10-01

    Full Text Available Background: Considering the evidence that endogenous cannabinoid system plays a role in metabolic aspects of body weight and metabolic syndrome components such as non alcoholic fatty liver disease (NAFLD. The aim of our study was to investigate the influence of this polymorphism on insulin resistance, liver histological changes, anthropometric parameters and adipocytokines in patients with NAFLD. Material and methods: A population of 71 patients with NAFLD was recruited in a cross sectional study. A biochemical analysis of serum was measured. Genotype of G1359A polymorphism of CB1 receptor gene CB1 receptor was studied. Forty one patients (36.9% had the genotype G1359G (wild type group and twenty nine (26.1% patients G1359A or A1359A (mutant type group. Results: Twenty four 24 patients (32,3% had a Brunt grade > 4 and 12 patients (17% had a significative fibrosis (F > = 2. HOMA values were higher in wild type group than mutant type group. Adiponectin and visfatin levels were higher in mutant type group. Moreover, TNF-alpha and resistin levels were higher in wild type group than mutant type group. Patients with mutant genotype showed less frequently elevated levels of AST. AST > 40 UI/L was detected in 28.5% of patients in the mutant vs. 53% of patients with wild genotype, p = 4 less frequently than patients with wild type group (28.5%vs 7.1%. Conclusion: A variant of the polymorphism G1359A CBR1 is associated with lower levels of HOMA, TNF-alpha, resistin and higher levels of adiponectin than patients with the wild variant of this polymorphism. Besides, patients with A allele variant shown lower Brunt grade in liver biopsy.Antecedentes: Teniendo en cuenta la evidencia de que el sistema cannabinoide endógeno juega un papel importante en aspectos metabólicos, peso corporal y componentes del síndrome metabólico como la enfermedad hepática NO alcohólica (EHNA. El objetivo de nuestro estudio fue investigar la influencia de este polimorfismo en la resistencia a la insulina, cambios en la histología hepática, parámetros antropométricos y adipocitoquinas en pacientes con hígado graso no alcohólico. Material y métodos: Una población de 71 pacientes con hígado graso no alcohólico fue reclutado en un estudio de corte transversal. Se realizó un análisis bioquímico de suero. El genotipo del polimorfismo G1359A del gen del receptor CB1 se ha estudiado en todos los pacientes. Cuarenta y un pacientes (36,9% tenían el genotipo G1359G (grupo de tipo salvaje y veintinueve (26,1% de los pacientes o G1359A A1359A (grupo mutante. Resultados: Veinticuatro 24 pacientes (32,3% tenían un grado de Brunt > 4 y 12 pacientes (17% tenían una fibrosis significativa (F > = 2. Los valores de HOMA fueron mayores en el grupo con genotipo salvaje que el grupo mutante. Los niveles de adiponectina y visfatina fueron mayores en el grupo con genotipo mutante. Por otra parte, el TNF-alfa y los niveles de resistina fueron más altos en el grupo con genotipo salvaje que el grupo mutante. Los pacientes con genotipo mutante mostraron niveles elevados de menor frecuencia de AST. AST > 40 UI/L se detectó en el 28,5% de los pacientes con el genotipo mutante frente a 53% de los pacientes con genotipo salvaje, p = 4 con menos frecuencia que los pacientes con genotipo salvaje (28,5%vs 7,1%. Conclusión: Una variante del polimorfismo G1359A CBR1 se asocia con menores niveles de HOMA, TNF-alfa, resistina y mayores niveles de adiponectina que los pacientes con la variante salvaje de este polimorfismo. Además, los pacientes con una variante del alelo muestra menor grado de Brunt en la biopsia hepática.

  19. Adipokines and highly active antiretroviral therapy related lipodystrophy: clinical study of 52 cases%脂肪因子与高效抗逆转录病毒治疗相关脂肪营养不良的临床研究

    Institute of Scientific and Technical Information of China (English)

    陶梅梅; 张璐; 邱志峰; 谢静; 韩扬; 余卫; 黎明; 李太生

    2009-01-01

    目的 调查接受高效抗逆转录病毒治疗(HAART)的AIDS患者糖脂代谢异常的发生率及其在HIV相关脂肪营养不良综合征(HIV related lipodystrophy,HIV-LD)组和非HIV-LD)组中的差异;比较两组的脂联素(adiponectin,APN)、瘦素(leptin,LEP)水平及其与糖脂代谢、脂肪异常分布的关系.方法 募集2007年3至5月期间在北京协和医院门诊随诊的成年HIV/AIDS患者52例,根据患者报告和医师评估结果,将上述患者分成HIV-LD组与非HIV-LD组,并对其进行全身双能X射线扫描(DEXA)检查和血浆胆固醇(CHO)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)和胰岛索测定,应用ELISA法测定血浆APN和LEP水平,调查血脂异常和高胰岛素血症的发生情况及两组之间差异,并分析APN和LEP水平及其与血脂、胰岛素水平和各部位体脂含量的相关性.结果 ①52例HIV/AIDS患者中,至少一项血脂指标异常者59.6%,合并CHO、TG及HDL-C异常血症者分别为17.3%、50.0%和17.3%,空腹高胰岛素血症发生率25.0%.②LD组的TG水平显著高于非HIV-LD组,LD组的HDL-C水平和APN水平显著低于非HIV-LD组.HIV-LD患者的APN水平降低是HDL-C和胰岛素水平异常的独立预测指标,与四肢/全身脂肪总含量正相关,与躯干/全身脂肪总含量负相关.两组的血浆LEP水平均与全身脂肪总含量、四肢和躯干脂肪含量正相关.结论 血脂异常和胰岛素抵抗在接受HAART的AIDS患者中有较高发生率,HIV-LD组比非HIV-LD组更为明显.血浆APN水平下降在HIV-LD组中是HDL-C和胰岛素水平异常的独立预测指标,与脂肪异常分布密切相关;血浆LEP水平则是反映人体内脂肪总最的生物学标志之一.%Objective To investigate the prevalence of glucose and lipid abnormalities in AIDS patients treated with highly active antiretroviral therapy (HAART) and difference thereof between the HIV-lipedystrophy (LD) and non-HIV-LD groups, and to compare the plasma levels of adiponectin (APN) and leptin (LEP) and their relationship to metabolic disturbance and fat redistribution in these 2 groups Methods Fifty-two HIV-infected patients were divided into HIV-LD group and non-HIV-LD group according to the patients' reports and doctors' evaluation. Body composition was assessed by whole body dual-energy X-ray absorptiometry Plasma samples were analyzed for cholesterol, triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), insulin, APN, and LEP. The prevalence of dyslipidemia and hyperinsulinemia, the difference of adipocytokine levels, and the relationship of adiponectin, leptin with lipids, insulin as well as fat mass in different body regions were analyzed between the groups. Results The prevalence rates of hypercholesterolaemia, hypertriglyceridaemia, and low HDL-C level were 17.3%, 50, 0%, and 17.3% respectively. The rate of hyperinsulinemia and any kind of dyslipidemia were 25.0% and 59.6%. Compared with non- HIV-LD patients, HIV-LD patients had higher TG level, and lower HDL-C and APN levels. In the HIV-LD group, the APN level was correlated positively with limb/total body fat, but negatively with trunk/total body fat, and was an independent predictor of HDL-C and insulin level. However, LEP was positively correlated with the levels of total body fat, limb fat, and trunk fat in both groups. Conclusion The prevalence rates of dyslipidemia and insulin resistance are high in Chinese HIV/AIDS patients receiving HAART, especially in the HIV-LD group. The APN concentration in the HIV-LD patients is closely related to fat redistribution and independently predicts the levels of HDL-C and insulin. LEP can serve as a biomarker of total body fat mass.

  20. Regulation of vascular tone by adipocytes

    Directory of Open Access Journals (Sweden)

    Van de Voorde Johan

    2011-03-01

    Full Text Available Abstract Recent studies have shown that adipose tissue is an active endocrine and paracrine organ secreting several mediators called adipokines. Adipokines include hormones, inflammatory cytokines and other proteins. In obesity, adipose tissue becomes dysfunctional, resulting in an overproduction of proinflammatory adipokines and a lower production of anti-inflammatory adipokines. The pathological accumulation of dysfunctional adipose tissue that characterizes obesity is a major risk factor for many other diseases, including type 2 diabetes, cardiovascular disease and hypertension. Multiple physiological roles have been assigned to adipokines, including the regulation of vascular tone. For example, the unidentified adipocyte-derived relaxing factor (ADRF released from adipose tissue has been shown to relax arteries. Besides ADRF, other adipokines such as adiponectin, omentin and visfatin are vasorelaxants. On the other hand, angiotensin II and resistin are vasoconstrictors released by adipocytes. Reactive oxygen species, leptin, tumour necrosis factor α, interleukin-6 and apelin share both vasorelaxing and constricting properties. Dysregulated synthesis of the vasoactive and proinflammatory adipokines may underlie the compromised vascular reactivity in obesity and obesity-related disorders.

  1. Adipose tissue and its role in organ crosstalk.

    Science.gov (United States)

    Romacho, T; Elsen, M; Röhrborn, D; Eckel, J

    2014-04-01

    The discovery of adipokines has revealed adipose tissue as a central node in the interorgan crosstalk network, which mediates the regulation of multiple organs and tissues. Adipose tissue is a true endocrine organ that produces and secretes a wide range of mediators regulating adipose tissue function in an auto-/paracrine manner and important distant targets, such as the liver, skeletal muscle, the pancreas and the cardiovascular system. In metabolic disorders such as obesity, enlargement of adipocytes leads to adipose tissue dysfunction and a shift in the secretory profile with an increased release of pro-inflammatory adipokines. Adipose tissue dysfunction has a central role in the development of insulin resistance, type 2 diabetes, and cardiovascular diseases. Besides the well-acknowledged role of adipokines in metabolic diseases, and the increasing number of adipokines being discovered in the last years, the mechanisms underlying the release of many adipokines from adipose tissue remain largely unknown. To combat metabolic diseases, it is crucial to better understand how adipokines can modulate adipose tissue growth and function. Therefore, we will focus on adipokines with a prominent role in auto-/paracrine crosstalk within the adipose tissue such as RBP4, HO-1, WISP2, SFRPs and chemerin. To depict the endocrine crosstalk between adipose tissue with skeletal muscle, the cardiovascular system and the pancreas, we will report the main findings regarding the direct effects of adiponectin, leptin, DPP4 and visfatin on skeletal muscle insulin resistance, cardiovascular function and β-cell growth and function.

  2. Perivascular Adipose Tissue and Cardiometabolic Disease

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2013-04-01

    Full Text Available BACKGROUND: Obesity is associated with insulin resistance, hypertension, and cardiovascular disease, but the mechanisms underlying these associations are incompletely understood. Microvascular dysfunction may play an important role in the pathogenesis of both insulin resistance and hypertension in obesity. CONTENT: Perivascular adipose tissue (PVAT is a local deposit of adipose tissue surrounding the vasculature. PVAT is present throughout the body and has been shown to have a local effect on blood vessels. The influence of PVAT on the vasculature changes with increasing adiposity. PVAT similarly to other fat depots, is metabolically active, secreting a wide array of bioactive substances, termed ‘adipokines’. Adipokines include cytokines, chemokines and hormones that can act in a paracrine, autocrine or endocrine fashion. Many of the proinflammatory adipokines upregulated in obesity are known to influence vascular function, including endothelial function, oxidative stress, vascular stiffness and smooth muscle migration. Adipokines also stimulate immune cell migration into the vascular wall, potentially contributing to the inflammation found in atherosclerosis. Finally, adipokines modulate the effect of insulin on the vasculature, thereby decreasing insulin-mediated muscle glucose uptake. This leads to alterations in nitric oxide signaling, insulin resistance and potentially atherogenesis. SUMMARY: PVAT surrounds blood vessels. PVAT and the adventitial layer of blood vessels are in direct contact with each other. Healthy PVAT secretes adipokines and regulates vascular function. Obesity is associated with changes in adipokine secretion and the resultant inflammation of PVAT. The dysregulation of adipokines changes the effect of PVAT on the vasculature. Changes in perivascular adipokines secretion in obesity appear to contribute to the development of obesity-mediated vascular disease. KEYWORDS: obesity, perivascular adipose tissue, PVAT

  3. Direct effects of leptin and adiponectin on peripheral reproductive tissues: a critical review.

    Science.gov (United States)

    Kawwass, Jennifer F; Summer, Ross; Kallen, Caleb B

    2015-08-01

    Obesity is a risk factor for infertility and adverse reproductive outcomes. Adipose tissue is an important endocrine gland that secretes a host of endocrine factors, called adipokines, which modulate diverse physiologic processes including appetite, metabolism, cardiovascular function, immunity and reproduction. Altered adipokine expression in obese individuals has been implicated in the pathogenesis of a host of health disorders including diabetes and cardiovascular disease. It remains unclear whether adipokines play a significant role in the pathogenesis of adverse reproductive outcomes in obese individuals and, if so, whether the adipokines are acting directly or indirectly on the peripheral reproductive tissues. Many groups have demonstrated that receptors for the adipokines leptin and adiponectin are expressed in peripheral reproductive tissues and that these adipokines are likely, therefore, to exert direct effects on these tissues. Many groups have tested for direct effects of leptin and adiponectin on reproductive tissues including the testis, ovary, uterus, placenta and egg/embryo. The hypothesis that decreased fertility potential or adverse reproductive outcomes may result, at least in part, from defects in adipokine signaling within reproductive tissues has also been tested. Here, we present a critical analysis of published studies with respect to two adipokines, leptin and adiponectin, for which significant data have been generated. Our evaluation reveals significant inconsistencies and methodological limitations regarding the direct effects of these adipokines on peripheral reproductive tissues. We also observe a pervasive failure to account for in vivo data that challenge observations made in vitro. Overall, while leptin and adiponectin may directly modulate peripheral reproductive tissues, existing data suggest that these effects are minor and non-essential to human or mouse reproductive function. Current evidence suggests that direct effects of

  4. The impact of adipose tissue-derived factors on the hypothalamic-pituitary-gonadal (HPG) axis.

    Science.gov (United States)

    Tsatsanis, Christos; Dermitzaki, Eirini; Avgoustinaki, Pavlina; Malliaraki, Niki; Mytaras, Vasilis; Margioris, Andrew N

    2015-01-01

    Adipose tissue produces factors, including adipokines, cytokines and chemokines which, when released, systemically exert endocrine effects on multiple tissues thereby affecting their physiology. Adipokines also affect the hypothalamic-pituitary-gonadal (HPG) axis both centrally, at the hypothalamic-pituitary level, and peripherally acting on the gonads themselves. Among the adipokines, leptin, adiponectin, resistin, chemerin and the peptide kisspeptin have pleiotropic actions on the HPG axis affecting male and female fertility. Furthermore, adipokines and adipose tissue-produced factors readily affect the immune system resulting in inflammation, which in turn impact the HPG axis, thus evidencing a link between metabolic inflammation and fertility. In this review we provide an overview of the existing extensive bibliography on the crosstalk between adipose tissue-derived factors and the HPG axis, with particular focus on the impact of obesity and the metabolic syndrome on gonadal function and fertility.

  5. Concise Review: The Obesity Cancer Paradigm: Exploration of the Interactions and Crosstalk with Adipose Stem Cells

    National Research Council Canada - National Science Library

    Strong, Amy L; Burow, Matthew E; Gimble, Jeffrey M; Bunnell, Bruce A

    2015-01-01

    ..., and postmenopausal breast cancers. The increased morbidity and mortality of obesity‐associated cancers have been attributed to higher levels of hormones, adipokines, and cytokines secreted by the adipose tissue...

  6. Adipose tissue was traditionally been viewed as an inert storage depot

    African Journals Online (AJOL)

    Animal Science

    these genomic regions, random genetic drift or sampling bias could also have ... The project focused on genetic variation in genes that encode adipokines, .... are described according to guidelines of the Human Genome Variation Society ...

  7. Adipose tissue dysfunction and hypertriglyceridemia : mechanisms and management

    NARCIS (Netherlands)

    van de Woestijne, A. P.; Monajemi, H.; Kalkhoven, E.; Visseren, F. L. J.

    2011-01-01

    Elevated plasma triglyceride levels, as often seen in obese subjects, are independently associated with an increased risk of cardiovascular diseases. By secreting adipokines (such as adiponectin and leptin) and other proteins (such as lipoprotein lipase and cholesteryl ester transferase protein),

  8. Effects and Molecular Mechanism of GST-Irisin on Lipolysis and Autocrine Function in 3T3-L1 Adipocytes

    National Research Council Canada - National Science Library

    Gao, Shanshan; Li, Fangmin; Li, Huimin; Huang, Yibing; Liu, Yu; Chen, Yuxin

    2016-01-01

    Irisin, which was recently identified as a myokine and an adipokine, transforms white adipose tissue to brown adipose tissue and has increasingly caught the attention of the medical and scientific community...

  9. The association of asthma, nasal allergies, and positive skin prick tests with obesity, leptin, and adiponectin

    OpenAIRE

    Newson, RB; M. Jones; Forsberg, B; Janson, C; Bossios, A; Dahlen, S-E; Toskala, EM; Al-Kalemji, A; Kowalski, ML; Rymarcsyk, B; Salagean, EM; van Drunen, CM; Bachert, C; Wehrend, T; Krämer, User

    2014-01-01

    Background Cross-sectional and longitudinal reports show that obese adults have more asthma than non-obese adults. A proposed mechanism is via effects of adipokines (leptin and adiponectin) on the immune system. Objective We wished to measure the associations of asthma and other atopic diseases with serum adipokine levels and to find whether the associations with asthma were strong enough to rule out the possibility that they are secondary to the association of fatness measures with ast...

  10. [Sleep disorder and lifestyle-related disease].

    Science.gov (United States)

    Shibata, Rei; Murohara, Toyoaki

    2015-06-01

    Sleep disorder is associated with the lifestyle-related diseases including obesity, insulin resistance and atherosclerosis. Adipose tissue functions as an endocrine organ by producing bioactive secretory proteins, also known as adipokines, that can directly act on nearby or remote organs. Recently, the associations between these adipokines and sleep disorders such as obstructive sleep apnea have been reported. In this review, we focus on the relationship between sleep disorder and lifestyle-related diseases.

  11. Towards the elucidation of the true impact of adipocytokines on cardiovascular risk in rheumatoid arthritis

    OpenAIRE

    Dessein, Patrick H.; Solomon, Ahmed

    2013-01-01

    Adipo(cyto)kines are mostly produced by adipose tissue and orchestrate the adverse impact of excess adiposity on cardiovascular risk. Adipokines also contribute importantly to the pathophysiology of rheumatoid arthritis. Congruent with data reported in previous investigations, Kang and colleagues report in this issue of Arthritis Research & Therapy that adipokine concentrations are further associated with metabolic risk and inflammation and that the leptin–adiponectin ratio associates with th...

  12. Pharmacologic concentrations of linezolid modify oxidative phosphorylation function and adipocyte secretome

    Directory of Open Access Journals (Sweden)

    Laura Llobet

    2017-10-01

    Full Text Available The oxidative phosphorylation system is important for adipocyte differentiation. Therefore, xenobiotics inhibitors of the oxidative phosphorylation system could affect adipocyte differentiation and adipokine secretion. As adipokines impact the overall health status, these xenobiotics may have wide effects on human health. Some of these xenobiotics are widely used therapeutic drugs, such as ribosomal antibiotics. Because of its similarity to the bacterial one, mitochondrial translation system is an off-target for these compounds. To study the influence of the ribosomal antibiotic linezolid on adipokine production, we analyzed its effects on adipocyte secretome. Linezolid, at therapeutic concentrations, modifies the levels of apolipoprotein E and several adipokines and proteins related with the extracellular matrix. This antibiotic also alters the global methylation status of human adipose tissue-derived stem cells and, therefore, its effects are not limited to the exposure period. Besides their consequences on other tissues, xenobiotics acting on the adipocyte oxidative phosphorylation system alter apolipoprotein E and adipokine production, secondarily contributing to their systemic effects.

  13. Adiponectin, Leptin, and Resistin in Asthma: Basic Mechanisms through Population Studies

    Directory of Open Access Journals (Sweden)

    Akshay Sood

    2013-01-01

    Full Text Available Adipokines, factors produced by adipose tissue, may be proinflammatory (such as leptin and resistin or anti-inflammatory (such as adiponectin. Effects of these adipokines on the lungs have the potential to evoke or exacerbate asthma. This review summarizes basic mechanistic data through population-based and clinical studies addressing the potential role of adipokines in asthma. Augmenting circulating concentrations of adiponectin attenuates allergic airway inflammation and airway hyperresponsiveness in mice. Murine data is supported by human data that suggest that low serum adiponectin is associated with greater risk for asthma among women and peripubertal girls. Further, higher serum total adiponectin may be associated with lower clinical asthma severity among children and women with asthma. In contrast, exogenous administration of leptin results in augmented allergic airway hyperresponsiveness in mice. Alveolar macrophages obtained from obese asthmatics are uniquely sensitive to leptin in terms of their potential to augment inflammation. Consistent with this basic mechanistic data, epidemiologic studies demonstrate that higher serum leptin is associated with greater asthma prevalence and/or severity and that these associations may be stronger among women, postpubertal girls, and prepubertal boys. The role of adipokines in asthma is still evolving, and it is not currently known whether modulation of adipokines may be helpful in asthma prevention or treatment.

  14. The Impact of Organokines on Insulin Resistance, Inflammation, and Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Kyung Mook Choi

    2016-03-01

    Full Text Available Immoderate energy intake, a sedentary lifestyle, and aging have contributed to the increased prevalence of obesity, sarcopenia, metabolic syndrome, type 2 diabetes, and cardiovascular disease. There is an urgent need for the development of novel pharmacological interventions that can target excessive fat accumulation and decreased muscle mass and/or strength. Adipokines, bioactive molecules derived from adipose tissue, are involved in the regulation of appetite and satiety, inflammation, energy expenditure, insulin resistance and secretion, glucose and lipid metabolism, and atherosclerosis. Recently, there is emerging evidence that skeletal muscle and the liver also function as endocrine organs that secrete myokines and hepatokines, respectively. Novel discoveries and research into these organokines (adipokines, myokines, and hepatokines may lead to the development of promising biomarkers and therapeutics for cardiometabolic disease. In this review, I summarize recent data on these organokines and focus on the role of adipokines, myokines, and hepatokines in the regulation of insulin resistance, inflammation, and atherosclerosis.

  15. The association of asthma, nasal allergies, and positive skin prick tests with obesity, leptin, and adiponectin

    DEFF Research Database (Denmark)

    Newson, R. B.; Jones, M.; Forsberg, B.;

    2014-01-01

    BackgroundCross-sectional and longitudinal reports show that obese adults have more asthma than non-obese adults. A proposed mechanism is via effects of adipokines (leptin and adiponectin) on the immune system. ObjectiveWe wished to measure the associations of asthma and other atopic diseases...... with serum adipokine levels and to find whether the associations with asthma were strong enough to rule out the possibility that they are secondary to the association of fatness measures with asthma. MethodsThe Global Asthma and Allergy Network of Excellence (GA(2)LEN) clinical follow-up survey is a clinical...... measures of fatness including body mass index and waist/hip ratio, current asthma, and specific skin prick and IgE sensitisation. We used inverse sampling-probability-weighted rank and regression statistics to measure population associations of disease outcomes with adipokines in males and females...

  16. Epicardial Fat: Physiological, Pathological, and Therapeutic Implications

    Science.gov (United States)

    Salazar, Juan; Luzardo, Eliana; Mejías, José Carlos; Ferreira, Antonio; Rivas-Ríos, José Ramón; Bermúdez, Valmore

    2016-01-01

    Epicardial fat is closely related to blood supply vessels, both anatomically and functionally, which is why any change in this adipose tissue's behavior is considered a potential risk factor for cardiovascular disease development. When proinflammatory adipokines are released from the epicardial fat, this can lead to a decrease in insulin sensitivity, low adiponectin production, and an increased proliferation of vascular smooth muscle cells. These adipokines move from one compartment to another by either transcellular passing or diffusion, thus having the ability to regulate cardiac muscle activity, a phenomenon called vasocrine regulation. The participation of these adipokines generates a state of persistent vasoconstriction, increased stiffness, and weakening of the coronary wall, consequently contributing to the formation of atherosclerotic plaques. Therefore, epicardial adipose tissue thickening should be considered a risk factor in the development of cardiovascular disease, a potential therapeutic target for cardiovascular pathology and a molecular point of contact for “endocrine-cardiology.” PMID:27213076

  17. Weight cycling enhances adipose tissue inflammatory responses in male mice.

    Directory of Open Access Journals (Sweden)

    Sandra Barbosa-da-Silva

    Full Text Available BACKGROUND: Obesity is associated with low-grade chronic inflammation attributed to dysregulated production, release of cytokines and adipokines and to dysregulated glucose-insulin homeostasis and dyslipidemia. Nutritional interventions such as dieting are often accompanied by repeated bouts of weight loss and regain, a phenomenon known as weight cycling (WC. METHODS: In this work we studied the effects of WC on the feed efficiency, blood lipids, carbohydrate metabolism, adiposity and inflammatory markers in C57BL/6 male mice that WC two or three consecutive times by alternation of a high-fat (HF diet with standard chow (SC. RESULTS: The body mass (BM grew up in each cycle of HF feeding, and decreased after each cycle of SC feeding. The alterations observed in the animals feeding HF diet in the oral glucose tolerance test, in blood lipids, and in serum and adipose tissue expression of adipokines were not recuperated after WC. Moreover, the longer the HF feeding was (two, four and six months, more severe the adiposity was. After three consecutive WC, less marked was the BM reduction during SC feeding, while more severe was the BM increase during HF feeding. CONCLUSION: In conclusion, the results of the present study showed that both the HF diet and WC are relevant to BM evolution and fat pad remodeling in mice, with repercussion in blood lipids, homeostasis of glucose-insulin and adipokine levels. The simple reduction of the BM during a WC is not able to recover the high levels of adipokines in the serum and adipose tissue as well as the pro-inflammatory cytokines enhanced during a cycle of HF diet. These findings are significant because a milieu with altered adipokines in association with WC potentially aggravates the chronic inflammation attributed to dysregulated production and release of adipokines in mice.

  18. Metabolic and Vascular Consequences of Adipose Tissue Dysfunction

    NARCIS (Netherlands)

    Westerink, J.|info:eu-repo/dai/nl/343038617

    2012-01-01

    Adipose Tissue Dysfunction (ATD) has been proposed as the pathophysiological route by which obesity confers its associated increased risk for cardiovascular disease and is characterized by an increased secretion of pro-inflammatory cytokines and adipokines and reduced secretion of anti-inflammatory

  19. Adipose Tissue Dysfunction in Nascent Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Andrew A. Bremer

    2013-01-01

    Full Text Available The metabolic syndrome (MetS confers an increased risk for both type 2 diabetes mellitus (T2DM and cardiovascular disease (CVD. Moreover, studies on adipose tissue biology in nascent MetS uncomplicated by T2DM and/or CVD are scanty. Recently, we demonstrated that adipose tissue dysregulation and aberrant adipokine secretion contribute towards the syndrome’s low-grade chronic proinflammatory state and insulin resistance. Specifically, we have made the novel observation that subcutaneous adipose tissue (SAT in subjects with nascent MetS has increased macrophage recruitment with cardinal crown-like structures. We have also shown that subjects with nascent MetS have increased the levels of SAT-secreted adipokines (IL-1, IL-6, IL-8, leptin, RBP-4, CRP, SAA, PAI-1, MCP-1, and chemerin and plasma adipokines (IL-1, IL-6, leptin, RBP-4, CRP, SAA, and chemerin, as well as decreased levels of plasma adiponectin and both plasma and SAT omentin-1. The majority of these abnormalities persisted following correction for increased adiposity. Our data, as well as data from other investigators, thus, highlight the importance of subcutaneous adipose tissue dysfunction in subjects with MetS and its contribution to the proinflammatory state and insulin resistance. This adipokine profile may contribute to increased insulin resistance and low-grade inflammation, promoting the increased risk of T2DM and CVD.

  20. Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis

    OpenAIRE

    Bozec, Aline; Hannemann, Nicole

    2016-01-01

    Considering that adipose tissue (AT) is an endocrine organ, it can influence whole body metabolism. Excessive energy storage leads to the dysregulation of adipocytes, which in turn induces abnormal secretion of adipokines, triggering metabolic syndromes such as obesity, dyslipidemia, hyperglycemia, hyperinsulinemia, insulin resistance and type 2 diabetes. Therefore, investigating the molecular mechanisms behind adipocyte dysregulation could help to develop novel therapeutic strategies. Our pr...

  1. Plasma resistin, adiponectin, and risk of incident atrial fibrillation : The Framingham Offspring Study

    NARCIS (Netherlands)

    Rienstra, Michel; Sun, Jenny X.; Lubitz, Steven A.; Frankel, David S.; Vasan, Ramachandran S.; Levy, Daniel; Magnani, Jared W.; Sullivan, Lisa M.; Meigs, James B.; Ellinor, Patrick T.; Benjamin, Emelia J.

    2012-01-01

    BACKGROUND: We sought to investigate whether higher concentrations of resistin and lower concentrations of adiponectin relate to incident atrial fibrillation (AF) and whether this association is mediated by AF risk factors and inflammation. Resistin and adiponectin are adipokines that have been asso

  2. Nutritional disorder

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    2009157 Adipokines and highly active antiretroviral therapy related lipodystrophy:clinical study of 52 cases.TAO Meimei(陶梅梅),et al.Dept infect Dis,PUMC Hosp,PUMC & CAMS,Beijing 100730.Natl Med J China,2009;89(13):867-871.

  3. Ubiquitin specific protease 2 acts as a key modulator for the regulation of cell cycle by adiponectin and leptin in cancer cells.

    Science.gov (United States)

    Nepal, Saroj; Shrestha, Anup; Park, Pil-Hoon

    2015-09-05

    Adiponectin and leptin, both produced from adipose tissue, cause cell cycle arrest and progression, respectively in cancer cells. Ubiquitin specific protease-2 (USP-2), a deubiquitinating enzyme, is known to impair proteasome-induced degradation of cyclin D1, a critical cell cycle regulator. Herein, we investigated the effects of these adipokines on USP-2 expression and its potential role in the modulation of cell cycle. Treatment with globular adiponectin (gAcrp) decreased, whereas leptin increased USP-2 expression both in human hepatoma and breast cancer cells. In addition, overexpression or gene silencing of USP-2 affected cyclin D1 expression and cell cycle progression/arrest by adipokines. Adiponectin and leptin also modulated in vitro proteasomal activity, which was partially dependent on USP-2 expression. Taken together, our results reveal that modulation of USP-2 expression plays a crucial role in cell cycle regulation by adipokines. Thus, USP-2 would be a promising therapeutic target for the modulation of cancer cell growth by adipokines.

  4. Adipose tissue dysfunction and hypertriglyceridemia : mechanisms and management

    NARCIS (Netherlands)

    van de Woestijne, A. P.; Monajemi, H.; Kalkhoven, E.; Visseren, F. L. J.

    2011-01-01

    Elevated plasma triglyceride levels, as often seen in obese subjects, are independently associated with an increased risk of cardiovascular diseases. By secreting adipokines (such as adiponectin and leptin) and other proteins (such as lipoprotein lipase and cholesteryl ester transferase protein), ad

  5. Adipose Tissue Dysfunction : Clinical Relevance and Diagnostic Possibilities

    NARCIS (Netherlands)

    Schrover, I. M.; Spiering, W.; Leiner, T.; Visseren, F. L J

    2016-01-01

    Adipose tissue dysfunction is defined as an imbalance between pro- and anti-inflammatory adipokines, causing insulin resistance, systemic low-grade inflammation, hypercoagulability, and elevated blood pressure. These can lead to cardiovascular disease and diabetes mellitus type 2. Although quantity

  6. Local and systemic effects of visceral and perivascular adipose tissue

    NARCIS (Netherlands)

    Verhagen, S.N.

    2012-01-01

    Rather than being solely a storage depot for triglycerides, adipose tissue is able to secrete pro- and anti-inflammatory cytokines and adipokines. A state of low grade inflammation associated with excess adipose tissue is involved in the increase in the incidences of atherosclerotic diseases and

  7. Idiopathic intracranial hypertension, hormones, and 11β-hydroxysteroid dehydrogenases

    DEFF Research Database (Denmark)

    Markey, Keira A; Uldall, Maria; Botfield, Hannah;

    2016-01-01

    Idiopathic intracranial hypertension (IIH) results in raised intracranial pressure (ICP) leading to papilledema, visual dysfunction, and headaches. Obese females of reproductive age are predominantly affected, but the underlying pathological mechanisms behind IIH remain unknown. This review...... such as adipokines, steroid hormones, and ICP regulation may be key to the understanding and future management of IIH....

  8. Endotrophin triggers adipose tissue fibrosis and metabolic dysfunction

    DEFF Research Database (Denmark)

    Sun, Kai; Park, Jiyoung; Gupta, Olga T

    2014-01-01

    We recently identified endotrophin as an adipokine with potent tumour-promoting effects. However, the direct effects of local accumulation of endotrophin in adipose tissue have not yet been studied. Here we use a doxycycline-inducible adipocyte-specific endotrophin overexpression model to demonst...

  9. Adipose Tissue Dysfunction : Clinical Relevance and Diagnostic Possibilities

    NARCIS (Netherlands)

    Schrover, I. M.; Spiering, W.; Leiner, T.; Visseren, F. L J

    2016-01-01

    Adipose tissue dysfunction is defined as an imbalance between pro- and anti-inflammatory adipokines, causing insulin resistance, systemic low-grade inflammation, hypercoagulability, and elevated blood pressure. These can lead to cardiovascular disease and diabetes mellitus type 2. Although quantity

  10. Carotid intima media thickness is associated with plasma adiponectin but not with the leptin : adiponectin ratio independently of metabolic syndrome

    NARCIS (Netherlands)

    Dullaart, Robin P. F.; Kappelle, Paul J.W.H.; Dallinga-Thie, Geesje M.

    2010-01-01

    Purpose: A recent report showed no benefit of the leptin: adiponectin ratio (L: A ratio) over individual adipokine levels in CHD prediction [ 8]. We determined associations of carotid intima media thickness (IMT) with the L: A ratio taking account of cardiovascular risk factors in a high risk popula

  11. Carotid intima media thickness is associated with plasma adiponectin but not with the leptin : adiponectin ratio independently of metabolic syndrome

    NARCIS (Netherlands)

    Dullaart, Robin P. F.; Kappelle, Paul J.W.H.; Dallinga-Thie, Geesje M.

    Purpose: A recent report showed no benefit of the leptin: adiponectin ratio (L: A ratio) over individual adipokine levels in CHD prediction [ 8]. We determined associations of carotid intima media thickness (IMT) with the L: A ratio taking account of cardiovascular risk factors in a high risk

  12. Branched Chain Amino Acids Are Associated with Insulin Resistance Independent of Leptin and Adiponectin in Subjects with Varying Degrees of Glucose Tolerance

    NARCIS (Netherlands)

    Connelly, Margery A.; Wolak-Dinsmore, Justyna; Dullaart, Robin P. F.

    Background: Branched chain amino acids (BCAA) may be involved in the pathogenesis of insulin resistance and are associated with type 2 diabetes mellitus (T2DM) development. Adipokines such as leptin and adiponectin influence insulin resistance and reflect adipocyte dysfunction. We examined the

  13. Adiponectin and leptin induce VCAM-1 expression in human and murine chondrocytes.

    Directory of Open Access Journals (Sweden)

    Javier Conde

    Full Text Available BACKGROUND: Osteoarthritis (OA and rheumatoid arthritis (RA, the most common rheumatic diseases, are characterized by irreversible degeneration of the joint tissues. There are several factors involved in the pathogenesis of these diseases including pro-inflammatory cytokines, adipokines and adhesion molecules. OBJECTIVE: Up to now, the relationship between adipokines and adhesion molecules at cartilage level was not explored. Thus, the aim of this article was to study the effect of leptin and adiponectin on the expression of VCAM-1 in human and murine chondrocytes. For completeness, intracellular signal transduction pathway was also explored. METHODS: VCAM-1 expression was assessed by quantitative RT-PCR and western blot analysis upon treatment with leptin, adiponectin and other pertinent reagents in cultured human primary chondrocytes. Signal transduction pathways have been explored by using specific pharmacological inhibitors in the adipokine-stimulated human primary chondrocytes and ATDC5 murine chondrocyte cell line. RESULTS: Herein, we demonstrate, for the first time, that leptin and adiponectin increase VCAM-1 expression in human and murine chondrocytes. In addition, both adipokines have additive effect with IL-1β. Finally, we demonstrate that several kinases, including JAK2, PI3K and AMPK are at a play in the intracellular signalling of VCAM-1 induction. CONCLUSIONS: Taken together, our results suggest that leptin and adiponectin could perpetuate cartilage-degrading processes by inducing also factors responsible of leukocyte and monocyte infiltration at inflamed joints.

  14. Cross-talk between the heart and adipose tissue in cachectic heart failure patients with respect to alterations in body composition: a prospective study

    DEFF Research Database (Denmark)

    Christensen, Heidi Marie; Kistorp, Caroline Michaela Nervil; Schou, Morten;

    2014-01-01

    Cardiac cachexia (CC) is associated with changes in body composition. Lipolysis and increased energy expenditure caused by A- and B natriuretic peptides (NPs) have been suggested to play a role in CC. We tested the hypothesis that neurohormones and adipokines are associated with body composition...

  15. Low adiponectin levels at baseline and decreasing adiponectin levels over 10 years of follow-up predict risk of the metabolic syndrome

    DEFF Research Database (Denmark)

    Lindberg, S; Jensen, J S; Bjerre, Mette

    2017-01-01

    AIM: Adiponectin is the most abundant adipokine and may play a key role in the interplay between obesity, inflammation, insulin resistance and the metabolic syndrome (MetS). Thus, this large population-based cohort investigated whether adiponectin at baseline and/or a decrease in adiponectin during...

  16. Adipose tissue dysfunction and hypertriglyceridemia : mechanisms and management

    NARCIS (Netherlands)

    van de Woestijne, A. P.; Monajemi, H.; Kalkhoven, E.; Visseren, F. L. J.

    2011-01-01

    Elevated plasma triglyceride levels, as often seen in obese subjects, are independently associated with an increased risk of cardiovascular diseases. By secreting adipokines (such as adiponectin and leptin) and other proteins (such as lipoprotein lipase and cholesteryl ester transferase protein), ad

  17. Adipose tissue as an immunological organ : implications for childhood obesity

    NARCIS (Netherlands)

    Schipper, H.S.

    2013-01-01

    Obesity is increasingly considered as an inflammatory disorder. In adults, obesity induces inflammation of adipose tissue (AT). Through the release of inflammatory lipids and immune mediating proteins called adipokines, AT inflammation spreads to other tissues ranging from liver and muscle to the

  18. Adiponectin concentration is associated with muscle insulin sensitivity, AMPK phosphorylation and ceramide content in skeletal muslce of men, but not women

    DEFF Research Database (Denmark)

    Høeg, Louise Dalgas; Sjøberg, Kim Anker; Lundsgaard, Annemarie

    2013-01-01

    Adiponectin is an adipokine that regulates metabolism and increases insulin sensitivity. Mechanisms behind this insulin sensitizing effect have been investigated in rodents, but little is known in humans especially in skeletal muscle. Women have higher serum concentrations of adiponectin than men...

  19. Aerobic Exercise Modulates the Free Fatty Acids and Inflammatory Response During Obesity and Cancer Cachexia.

    Science.gov (United States)

    Teixeira, Alexandre Abilio de Souza; Lira, Fábio Santos; Pimentel, Gustavo D; Oliveira de Souza, Camila; Batatinha, Helena; Biondo, Luana A; Yamashita, Alex S; Junior, Edson A Lima; Neto, José Cesar Rosa

    2016-01-01

    White adipose tissue (WAT) is no longer considered a tissue whose main function is the storage of TAG. Since the discovery of leptin in 1994, several studies have elucidated the important role of WAT as an endocrine organ, the source of the adipokines. The low-grade inflammation observed in obese and cancer cachexia patients is explained, at least partially, by the exacerbated release of proinflammatory adipokines. Despite of the recent progress in the characterization of the various adipokines and lipokines produced by WAT, little is known about the mechanisms regulating the secretion of these molecules in different physiological and pathological circumstances. Chronic exercise is a nonpharmacological therapy employed in several chronic diseases and shows an anti-inflammatory effect through the regulation of the cytokine network. In this review, we address the potential mechanisms by which the aerobic physical exercise modulate the production and release of inflammatory adipokines, as well as the inflammation-lipolysis axis in WAT, with special focus in the therapeutic role of exercise in obesity-associated insulin resistance and cancer cachexia.

  20. Molecular mechanisms of the anti-obesity potential effect of Moringa oleifera in the experimental model

    Directory of Open Access Journals (Sweden)

    Fateheya Mohamed Metwally

    2017-03-01

    Conclusions: It is reasonable to assume that the anti-obesity, anti-atherogenic and anti-diabetic properties of M. oleifera are mechanistically achieved via working directly on the adipokines of the visceral adipose tissue. Therefore, M. oleifera may be a good therapeutic candidate for the symptoms of metabolic syndrome.

  1. Chemokine-like receptor 1 deficiency does not affect the development of insulin resistance and nonalcoholic fatty liver disease in mice

    NARCIS (Netherlands)

    Gruben, Nanda; Vergara, Marcela Aparicio; Kloosterhuis, Niels J.; van der Molen, Henk; Stoelwinder, Stefan; Youssef, Sameh; de Bruin, Alain; Delsing, Dianne J.; Kuivenhoven, Jan Albert; van de Sluis, Bart; Hofker, Marten H.; Koonen, Debby P. Y.

    2014-01-01

    The adipokine chemerin and its receptor, chemokine-like receptor 1 (Cmklr1), are associated with insulin resistance and nonalcoholic fatty liver disease (NAFLD), which covers a broad spectrum of liver diseases, ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). It is possible that

  2. Characterization of the human visceral adipose tissue secretome

    NARCIS (Netherlands)

    Alvarez Llamas, Gloria; Szalowska, Ewa; de Vries, Marcel P.; Weening, Desiree; Landman, Karloes; Hoek, Annemieke; Wolffenbuttel, Bruce H. R.; Roelofsen, Johan; Vonk, Roel J.

    2007-01-01

    Adipose tissue is an endocrine organ involved in storage and release of energy but also in regulation of energy metabolism in other organs via secretion of peptide and protein hormones (adipokines). Especially visceral adipose tissue has been implicated in the development of metabolic syndrome and t

  3. Human serum levels of fetal antigen 1 (FA1/Dlk1) increase with obesity, are negatively associated with insulin sensitivity and modulate inflammation in vitro

    DEFF Research Database (Denmark)

    Chacón, M R; Miranda, M; Jensen, C H

    2008-01-01

    of Insulin Resistance), cytokines (sIL-6), adipokines (adiponectin) and circulating soluble fractions of tumor necrosis factor-alpha receptors 1 and 2 (sTNFR1 and sTNFR2). RESULTS: IN the obesity study, levels of FA1 in serum were found to increase with obesity. The S(i) index was negatively dependent on FA1...

  4. CST, an Herbal Formula, Exerts Anti-Obesity Effects through Brain-Gut-Adipose Tissue Axis Modulation in High-Fat Diet Fed Mice.

    Science.gov (United States)

    Ansari, AbuZar; Bose, Shambhunath; Yadav, Mukesh Kumar; Wang, Jing-Hua; Song, Yun-Kyung; Ko, Seong-Gyu; Kim, Hojun

    2016-11-11

    The brain, gut, and adipose tissue interact to control metabolic pathways, and impairment in the brain-gut-adipose axis can lead to metabolic disorders, including obesity. Chowiseungcheng-tang (CST), a herbal formulation, is frequently used to treat metabolic disorders. Here, we investigated the anti-obesity effect of CST and its link with brain-gut-adipose axis using C57BL/6J mice as a model. The animals were provided with a normal research diet (NRD) or high-fat diet (HFD) in absence or presence of CST or orlistat (ORL) for 12 weeks. CST had a significant anti-obesity effect on a number of vital metabolic and obesity-related parameters in HFD-fed mice. CST significantly decreased the expression levels of genes encoding obesity-promoting neuropeptides (agouti-related peptide, neuropeptide Y), and increased the mRNA levels of obesity-suppressing neuropeptides (proopiomelanocortin, cocaine-and amphetamine-regulated transcript) in the hypothalamus. CST also effectively decreased the expression level of gene encoding obesity-promoting adipokine (retinol-binding protein-4) and increased the mRNA level of obesity-suppressing adipokine (adiponectin) in visceral adipose tissue (VAT). Additionally, CST altered the gut microbial composition in HFD groups, a phenomenon strongly associated with key metabolic parameters, neuropeptides, and adipokines. Our findings reveal that the anti-obesity impact of CST is mediated through modulation of metabolism-related neuropeptides, adipokines, and gut microbial composition.

  5. Comparison of Isotope-labeled Amino Acid Incorporation Rates (CILAIR) Provides a Quantitative Method to Study Tissue Secretomes

    NARCIS (Netherlands)

    Roelofsen, Johan; Dijkstra, Martijn; Weening, Desiree; de Vries, Marcel; Hoek, Annemieke; Vonk, Roel J.

    2009-01-01

    Adipose tissue is an endocrine organ involved in regulation of whole-body energy metabolism via storage of lipids and secretion of various peptide hormones (adipokines). We previously characterized the adipose tissue secretome and showed that [(13)C]lysine incorporation into secreted proteins can be

  6. Local and systemic effects of visceral and perivascular adipose tissue

    NARCIS (Netherlands)

    Verhagen, S.N.

    2012-01-01

    Rather than being solely a storage depot for triglycerides, adipose tissue is able to secrete pro- and anti-inflammatory cytokines and adipokines. A state of low grade inflammation associated with excess adipose tissue is involved in the increase in the incidences of atherosclerotic diseases and typ

  7. The role of Tip60 in adipogenesis

    NARCIS (Netherlands)

    Gao, Y.

    2013-01-01

    Besides providing insulation and protection against mechanical stress, white adipose tissue (WAT) has long been recognized as a storage depot for excess energy. WAT also releases a wide range of adipokines, which for example regulate immune responses, blood pressure and reproduction. Expansion of WA

  8. Characterization of the human visceral adipose tissue secretome

    NARCIS (Netherlands)

    Alvarez Llamas, Gloria; Szalowska, Ewa; de Vries, Marcel P.; Weening, Desiree; Landman, Karloes; Hoek, Annemieke; Wolffenbuttel, Bruce H. R.; Roelofsen, Johan; Vonk, Roel J.

    2007-01-01

    Adipose tissue is an endocrine organ involved in storage and release of energy but also in regulation of energy metabolism in other organs via secretion of peptide and protein hormones (adipokines). Especially visceral adipose tissue has been implicated in the development of metabolic syndrome and t

  9. Comparison of Isotope-labeled Amino Acid Incorporation Rates (CILAIR) Provides a Quantitative Method to Study Tissue Secretomes

    NARCIS (Netherlands)

    Roelofsen, Johan; Dijkstra, Martijn; Weening, Desiree; de Vries, Marcel; Hoek, Annemieke; Vonk, Roel J.

    2009-01-01

    Adipose tissue is an endocrine organ involved in regulation of whole-body energy metabolism via storage of lipids and secretion of various peptide hormones (adipokines). We previously characterized the adipose tissue secretome and showed that [(13)C]lysine incorporation into secreted proteins can be

  10. High-fat diet enhances and monocyte chemoattractant protein-1 deficiency reduces bone loss in mice with pulmonary metastases of Lewis lung carcinoma

    Science.gov (United States)

    Bone is adversely affected by metastasis and metastasis-associated complications. Obesity is a risk factor for both bone and cancer. Adipose tissue is an endocrine organ that produces pro-inflammatory adipokines, such as monocyte chemotactic protein-1 (MCP-1), that contribute to obesity and obesit...

  11. Cinnamon extract regulates plasma levels of adipose-derived factors and expression of multiple genes related to carbohydrate metabolism and lipogenesis in adipose tissue of fructose-fed rats

    Science.gov (United States)

    We reported previously that a dietary cinnamon extract (CE) improves systemic insulin sensitivity and dyslipidemia by enhancing insulin signaling. In the present study, we examined the effects of CE on several biomarkers including plasma levels of adipose-derived adipokines, and the potential molec...

  12. The association between the metabolic syndrome and alanine amino transferase is mediated by insulin resistance via related metabolic intermediates (the Cohort on diabetes and atherosclerosis Maastricht (CODAM) study)

    NARCIS (Netherlands)

    Jacobs, M.; Greevenbroek, van M.M.J.; Kallen, van der C.J.H.; Ferreira, I.; Feskens, E.J.M.; Jansen, E.H.J.M.; Schalkwijk, C.G.; Stehouwer, C.D.A.

    2011-01-01

    The metabolic syndrome is associated with nonalcoholic fatty liver disease (NAFLD) as well as with insulin resistance, inflammatory adipokines, endothelial dysfunction, and higher plasma levels of nonesterified fatty acids (NEFA), all of which may also affect the development of NAFLD. Therefore, we

  13. Serum Resistin Level and Progression of Atherosclerosis during Glucocorticoid Therapy for Systemic Autoimmune Diseases.

    Science.gov (United States)

    Tanaka, Nahoko; Masuoka, Shotaro; Kusunoki, Natsuko; Nanki, Toshihiro; Kawai, Shinichi

    2016-09-16

    Adipokines are important regulators of several processes, including inflammation and atherosclerosis. In patients with systemic autoimmune diseases, atherosclerosis is accelerated with higher cardiovascular morbidity and mortality. We prospectively investigated the association of adipokines and glucocorticoid therapy with progression of premature atherosclerosis in 38 patients starting glucocorticoid therapy for systemic autoimmune diseases. To detect premature atherosclerosis, carotid ultrasonography was performed at initiation of glucocorticoid therapy and after a mean three-year follow-up period. The ankle-brachial pressure index and cardio-ankle vascular index (CAVI) were measured. Serum adipokine levels were determined with enzyme-linked immunosorbent assay kits. Twenty-three patients (60.5%) had carotid artery plaque at baseline. The carotid artery intima-media thickness (IMT) increased significantly during follow-up. Glucocorticoids reduced the serum resistin level, while increasing serum leptin and high molecular weight-adiponectin. There was slower progression of atherosclerosis (carotid IMT and CAVI) at follow-up in patients with greater reduction of serum resistin and with higher cumulative prednisolone dose. In conclusion, progression of premature atherosclerosis occurred at an early stage of systemic autoimmune diseases before initiation of glucocorticoid therapy. Since resistin, an inflammation and atherosclerosis related adipokine, is reduced by glucocorticoids, glucocortidoid therapy may not accelerate atherosclerosis in patients with systemic autoimmune diseases.

  14. Dietary t10,c12-CLA but not c9,t11 CLA reduces adipocyte size in the absence of changes in the adipose renin-angiotensin system in fa/fa Zucker rats.

    Science.gov (United States)

    DeClercq, Vanessa; Zahradka, Peter; Taylor, Carla G

    2010-11-01

    In obesity, increased activity of the local renin-angiotensin system (RAS) and enlarged adipocytes with altered adipokine production are linked to the development of obesity-related health problems and cardiovascular disease. Mixtures of conjugated linoleic acid (CLA) isomers have been shown to reduce adipocyte size and alter the production of adipokines. The objective of this study was to investigate the effects of feeding individual CLA isomers on adipocyte size and adipokines associated with the local adipose RAS. Male fa/fa Zucker rats received either (a) control, (b) cis(c)9,trans(t)11-CLA, or (c) t10,c12-CLA diet for 8 weeks. The t10,c12-CLA isomer reduced adipocyte size and increased cell number in epididymal adipose tissue. RT-PCR and Western blot analysis revealed that neither CLA isomer altered mRNA or protein levels of angiotensinogen or AngII receptors in adipose tissue. Likewise, levels of the pro-inflammatory cytokines TNF-α and IL-6 or the anti-inflammatory cytokine IL-10 were unchanged in adipose tissue. Similarly, neither CLA isomer had any effect on phosphorylation nor DNA binding of NF-κB. Our results suggest that although the t10,c12-CLA isomer had beneficial effects on reducing adipocyte size in obese rats, this did not translate into changes in the local adipose RAS or associated adipokines.

  15. Branched Chain Amino Acids Are Associated with Insulin Resistance Independent of Leptin and Adiponectin in Subjects with Varying Degrees of Glucose Tolerance

    NARCIS (Netherlands)

    Connelly, Margery A.; Wolak-Dinsmore, Justyna; Dullaart, Robin P. F.

    2017-01-01

    Background: Branched chain amino acids (BCAA) may be involved in the pathogenesis of insulin resistance and are associated with type 2 diabetes mellitus (T2DM) development. Adipokines such as leptin and adiponectin influence insulin resistance and reflect adipocyte dysfunction. We examined the exten

  16. An RBP4 promoter polymorphism increases risk of type 2 diabetes

    NARCIS (Netherlands)

    M. van Hoek (Mandy); A. Dehghan (Abbas); M.C. Zillikens (Carola); A. Hofman (Albert); J.C.M. Witteman (Jacqueline); E.J.G. Sijbrands (Eric)

    2008-01-01

    textabstractAims/hypothesis: Retinol-binding protein 4 (RBP4), originally known for retinol transport, was recently identified as an adipokine affecting insulin resistance. The RBP4 -803GA promoter polymorphism influences binding of hepatic nuclear factor 1α and is associated with type 2 diabetes in

  17. Evaluation of insulin resistance degree of diabetes patients complicated with obesity and its correlation with serum indexes

    Institute of Scientific and Technical Information of China (English)

    Wan-Ju Fang; Gang Wei

    2015-01-01

    Objective:To study the insulin resistance degree of diabetes patients complicated with obesity and its correlation with serum indexes.Methods: 120 cases of patients diagnosed of type 2 diabetes in our hospital from May 2012 to August 2014 were chosen for study and divided into obese group and non-obese group according to BMI index. Then insulin resistance index as well as contents of serum adipokines and inflammatory cytokines of both groups was compared.Results: (1) insulin resistance related indexes: compared with insulin resistance indexes of non-obese group, HOMA-IR, HOMO-β, HbA1c and FINS of obese group were higher; ISI was lower; (2) adipokines: compared with adipokine contents of non-obese group, serum CTRP3 and Akt contents of obese group were lower while serum Nesfatin-1, Apelin, Chemerin and CMKLR1 contents were higher; (3) inflammatory cytokines: compared with contents of inflammation related cytokines of non-obese group, SFRP5 andβ2-arrestin contents of obese group were lower; Wnt5a, JNK-1, PGRN and SPARC contents were higher. Conclusion:Diabetes patients complicated with obesity show obvious insulin resistance and secretion of serum adipokines and inflammatory cytokines is abnormal.

  18. An RBP4 promoter polymorphism increases risk of type 2 diabetes

    NARCIS (Netherlands)

    M. van Hoek (Mandy); A. Dehghan (Abbas); M.C. Zillikens (Carola); A. Hofman (Albert); J.C.M. Witteman (Jacqueline); E.J.G. Sijbrands (Eric)

    2008-01-01

    textabstractAims/hypothesis: Retinol-binding protein 4 (RBP4), originally known for retinol transport, was recently identified as an adipokine affecting insulin resistance. The RBP4 -803GA promoter polymorphism influences binding of hepatic nuclear factor 1α and is associated with type 2 diabetes in

  19. Central insulin and leptin-mediated autonomic control of glucose homeostasis

    Science.gov (United States)

    Largely as a result of rising obesity rates, the incidence of type 2 diabetes is escalating rapidly. Type 2 diabetes results from multi-organ dysfunctional glucose metabolism. Recent publications have highlighted hypothalamic insulin- and adipokine-sensing as a major determinant of peripheral glucos...

  20. Monocyte chemotactic protein-1 deficiency reduces spontaneous metastasis of Lewis lung carcinoma in mice fed a high-fat diet

    Science.gov (United States)

    Obesity is a risk factor for cancer. Adipose tissue produces pro-inflammatory adipokines that contribute obesity-related malignant progression. This study investigated the effects of monocyte chemotactic protein-1 (MCP-1) deficiency on pulmonary metastasis of Lewis lung carcinoma (LLC) in male C57...

  1. MR spectroscopy of hepatic fat and adiponectin and leptin levels during testosterone therapy in type 2 diabetes: a randomized, double-blinded, placebo-controlled trial

    DEFF Research Database (Denmark)

    Magnussen, L V; Andersen, P E; Diaz, Alejandro Rafael

    2017-01-01

    Men with type 2 diabetes mellitus (T2D) often have lowered testosterone levels and an increased risk of cardiovascular disease (CVD). Ectopic fat increases the risk of CVD, whereas subcutaneous gluteofemoral fat protects against CVD and has a beneficial adipokine-secreting profile. Testosterone r...

  2. Comparison of Isotope-labeled Amino Acid Incorporation Rates (CILAIR) Provides a Quantitative Method to Study Tissue Secretomes

    NARCIS (Netherlands)

    Roelofsen, Johan; Dijkstra, Martijn; Weening, Desiree; de Vries, Marcel; Hoek, Annemieke; Vonk, Roel J.

    Adipose tissue is an endocrine organ involved in regulation of whole-body energy metabolism via storage of lipids and secretion of various peptide hormones (adipokines). We previously characterized the adipose tissue secretome and showed that [(13)C]lysine incorporation into secreted proteins can be

  3. Viscous dietary fiber reduces adiposity and plasma leptin and increases muscle expression of fat oxidation genes in rats

    National Research Council Canada - National Science Library

    Islam, Ajmila; Civitarese, Anthony E; Hesslink, Robert L; Gallaher, Daniel D

    2012-01-01

    .... Body composition was measured by dual-energy X-ray absorptiometry (DXA) and fat pad weight. Plasma adipokines, AMP kinase activation, and enzyme and mRNA analysis of key regulators of energetics in liver and soleus muscle were measured...

  4. Resistin Regulates Pituitary Lipid Metabolism and Inflammation In Vivo and In Vitro

    Directory of Open Access Journals (Sweden)

    F. Rodriguez-Pacheco

    2013-01-01

    Full Text Available The adipokine resistin is an insulin-antagonizing factor that also plays a regulatory role in inflammation, immunity, food intake, and gonadal function and also regulates growth hormone (GH secretion in rat adenopituitary cells cultures with the adipokine. Although adipose tissue is the primary source of resistin, it is also expressed in other tissues, including the pituitary. The aim of this study is to investigate the possible action of resistin on the lipid metabolism in the pituitary gland in vivo (rats in two different nutritional status, fed and fast, treated with resistin on acute and a chronic way and in vitro (adenopituitary cell cultures treated with the adipokine. Here, by a combination of in vivo and in vitro experimental models, we demonstrated that central acute and chronic administration of resistin enhance mRNA levels of the lipid metabolic enzymes which participated on lipolysis and moreover inhibiting mRNA levels of the lipid metabolic enzymes involved in lipogenesis. Taken together, our results demonstrate for the first time that resistin has a regulatory role on lipid metabolism in the pituitary gland providing a novel insight in relation to the mechanism by which this adipokine can participate in the integrated control of lipid metabolism.

  5. Weight loss after gastric bypass surgery in women is followed by a metabolically favorable decrease in 11beta-hydroxysteroid dehydrogenase 1 expression in subcutaneous adipose tissue

    DEFF Research Database (Denmark)

    Simonyte, Kotryna; Olsson, Tommy; Näslund, Ingmar;

    2010-01-01

    The role of 11beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1) in the pathogenesis of obesity has been elucidated in humans and in various rodent models. Obesity is accompanied by disturbances in glucocorticoid metabolism, circulating adipokine levels, and fatty acid (FA) reesterification. This ...

  6. Human Adipose Tissue Conditioned Media from Lean Subjects Is Protective against H2O2 Induced Neurotoxicity in Human SH-SY5Y Neuronal Cells

    Directory of Open Access Journals (Sweden)

    Zhongxiao Wan

    2015-01-01

    Full Text Available Adipose tissue secretes numerous hormone-like factors, which are known as adipokines. Adipokine receptors have been identified in the central nervous system but the potential role of adipokine signaling in neuroprotection is unclear. The aim of this study is to determine (1 Whether adipokines secreted from cultured adipose tissue of lean humans is protective against oxidative stress-induced neurotoxicity in human SH-SY5Y neuronal cells; and (2 To explore potential signaling pathways involved in these processes. Adipose tissue conditioned media (ATCM from healthy lean subjects completely prevented H2O2 induced neurotoxicity, while this effect is lost after heating ATCM. ATCM activated the phosphorylation of ERK1/2, JNK and Akt at serine 308 in SH-SY5Y cells. PD98059 (25 µM, SP600125 (5 µM and LY29400 (20 µM partially blocked the protective effects of ATCM against H2O2 induced neurotoxicity. Findings demonstrate that heat-sensitive factors secreted from human adipose tissue of lean subjects are protective against H2O2 induced neurotoxicity and ERK1/2, JNK, and PI3K signaling pathways are involved in these processes. In conclusion, this study demonstrates preliminary but encouraging data to further support that adipose tissue secreted factors from lean human subjects might possess neuroprotective properties and unravel the specific roles of ERK1/2, JNK and PI3K in these processes.

  7. CST, an Herbal Formula, Exerts Anti-Obesity Effects through Brain-Gut-Adipose Tissue Axis Modulation in High-Fat Diet Fed Mice

    Directory of Open Access Journals (Sweden)

    AbuZar Ansari

    2016-11-01

    Full Text Available The brain, gut, and adipose tissue interact to control metabolic pathways, and impairment in the brain-gut-adipose axis can lead to metabolic disorders, including obesity. Chowiseungcheng-tang (CST, a herbal formulation, is frequently used to treat metabolic disorders. Here, we investigated the anti-obesity effect of CST and its link with brain-gut-adipose axis using C57BL/6J mice as a model. The animals were provided with a normal research diet (NRD or high-fat diet (HFD in absence or presence of CST or orlistat (ORL for 12 weeks. CST had a significant anti-obesity effect on a number of vital metabolic and obesity-related parameters in HFD-fed mice. CST significantly decreased the expression levels of genes encoding obesity-promoting neuropeptides (agouti-related peptide, neuropeptide Y, and increased the mRNA levels of obesity-suppressing neuropeptides (proopiomelanocortin, cocaine-and amphetamine-regulated transcript in the hypothalamus. CST also effectively decreased the expression level of gene encoding obesity-promoting adipokine (retinol-binding protein-4 and increased the mRNA level of obesity-suppressing adipokine (adiponectin in visceral adipose tissue (VAT. Additionally, CST altered the gut microbial composition in HFD groups, a phenomenon strongly associated with key metabolic parameters, neuropeptides, and adipokines. Our findings reveal that the anti-obesity impact of CST is mediated through modulation of metabolism-related neuropeptides, adipokines, and gut microbial composition.

  8. Potential Mechanisms of Exercise in Gestational Diabetes

    Directory of Open Access Journals (Sweden)

    Saeid Golbidi

    2013-01-01

    Full Text Available Gestational diabetes mellitus (GDM is defined as glucose intolerance first diagnosed during pregnancy. This condition shares same array of underlying abnormalities as occurs in diabetes outside of pregnancy, for example, genetic and environmental causes. However, the role of a sedentary lifestyle and/or excess energy intake is more prominent in GDM. Physically active women are less likely to develop GDM and other pregnancy-related diseases. Weight gain in pregnancy causes increased release of adipokines from adipose tissue; many adipokines increase oxidative stress and insulin resistance. Increased intramyocellular lipids also increase cellular oxidative stress with subsequent generation of reactive oxygen species. A well-planned program of exercise is an important component of a healthy lifestyle and, in spite of old myths, is also recommended during pregnancy. This paper briefly reviews the role of adipokines in gestational diabetes and attempts to shed some light on the mechanisms by which exercise can be beneficial as an adjuvant therapy in GDM. In this regard, we discuss the mechanisms by which exercise increases insulin sensitivity, changes adipokine profile levels, and boosts antioxidant mechanisms.

  9. Hypoxia induces apelin expression in human adipocytes.

    Science.gov (United States)

    Geiger, K; Muendlein, A; Stark, N; Saely, C H; Wabitsch, M; Fraunberger, P; Drexel, H

    2011-06-01

    Adipokines play a central role in the development of diseases associated with insulin resistance and obesity. Hypoxia in adipose tissue leads to a dysregulation of the expression of adipokines. The effect of hypoxia on the more recently identified adipokine apelin in human adipocytes is unclear. Therefore, we aimed at investigating the role of hypoxia on the expression of the adipokine apelin. Differentiated human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes were cultured under hypoxic conditions for varying time periods. A modular incubator chamber was used to create a hypoxic tissue culture environment (defined as 1% O(2), 94% N, and 5% CO(2)). In addition, hypoxic conditions were mimicked by using CoCl(2). The effect of hypoxia on the expression of the investigated adipokines was measured by real-time PCR and the secretion of apelin was quantified by ELISA. Induction of hypoxia significantly induced mRNA expression of leptin and apelin in differentiated SGBS adipocytes compared with the normoxic control condition. Expression of adiponectin was significantly decreased by hypoxia. In addition, the amount of secreted apelin protein in response to hypoxia was elevated compared to untreated cells. Furthermore, we could demonstrate that the observed hypoxia-induced induction of apelin mRNA expression is in the first phase dependent on HIF-1α. In our study, we could demonstrate for the first time that apelin expression and secretion by human adipocytes are strongly induced under hypoxic conditions and that the early response on hypoxia with apelin induction is dependent on HIF-1α. © Georg Thieme Verlag KG Stuttgart · New York.

  10. The adipocyte as an endocrine organ in the regulation of metabolic homeostasis.

    Science.gov (United States)

    Harwood, H James

    2012-07-01

    Over the past decade and a half it has become increasingly clear that adipose tissue is a much more complex organ than was initially considered and that its metabolic functions extend well beyond the classical actions of thermoregulation and of storage and release of fatty acids. In fact, it is now well established that adipose tissue plays a critical role in maintenance of energy homeostasis through secretion of a large number of adipokines that interact with central as well as peripheral organs such as the brain, liver, pancreas, and skeletal muscle to control diverse processes, such as food intake, energy expenditure, carbohydrate and lipid metabolism, blood pressure, blood coagulation, and inflammation. While many of these adipokines are adipocyte-derived and have a variety of endocrine functions, others are produced by resident macrophages and interact in a paracrine fashion to control adipocyte metabolism. It is also abundantly clear that the dysregulation of adipokine secretion and action that occurs in obesity plays a fundamental role in the development of a variety of cardiometabolic disorders, including the metabolic syndrome, type 2 diabetes, inflammatory disorders, and vascular disorders, that ultimately lead to coronary heart disease. Described herein are the traditional as well as endocrine roles of adipose tissue in controlling energy metabolism and their dysregulation in obesity that leads to development of cardiometabolic disorders, with a focus on what is currently known regarding the characteristics and roles in both health and disease of the adipocyte-derived adipokines, adiponectin, leptin, resistin, and retinol binding protein 4, and the resident macrophage-derived adipokines, tumor necrosis factor-α and interleukin-6. This article is part of a Special Issue entitled 'Central Control of Food Intake'. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Inflammation, Oxidative Stress, and Obesity

    Directory of Open Access Journals (Sweden)

    José A. Morales-González

    2011-05-01

    Full Text Available Obesity is a chronic disease of multifactorial origin and can be defined as an increase in the accumulation of body fat. Adipose tissue is not only a triglyceride storage organ, but studies have shown the role of white adipose tissue as a producer of certain bioactive substances called adipokines. Among adipokines, we find some inflammatory functions, such as Interleukin-6 (IL-6; other adipokines entail the functions of regulating food intake, therefore exerting a direct effect on weight control. This is the case of leptin, which acts on the limbic system by stimulating dopamine uptake, creating a feeling of fullness. However, these adipokines induce the production of reactive oxygen species (ROS, generating a process known as oxidative stress (OS. Because adipose tissue is the organ that secretes adipokines and these in turn generate ROS, adipose tissue is considered an independent factor for the generation of systemic OS. There are several mechanisms by which obesity produces OS. The first of these is the mitochondrial and peroxisomal oxidation of fatty acids, which can produce ROS in oxidation reactions, while another mechanism is over-consumption of oxygen, which generates free radicals in the mitochondrial respiratory chain that is found coupled with oxidative phosphorylation in mitochondria. Lipid-rich diets are also capable of generating ROS because they can alter oxygen metabolism. Upon the increase of adipose tissue, the activity of antioxidant enzymes such as superoxide dismutase (SOD, catalase (CAT, and glutathione peroxidase (GPx, was found to be significantly diminished. Finally, high ROS production and the decrease in antioxidant capacity leads to various abnormalities, among which we find endothelial dysfunction, which is characterized by a reduction in the bioavailability of vasodilators, particularly nitric oxide (NO, and an increase in endothelium-derived contractile factors, favoring atherosclerotic disease.

  12. Adiponectin induced AMP-activated protein kinase impairment mediates insulin resistance in Bama mini-pig fed high-fat and high-sucrose diet

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    Miaomiao Niu

    2017-08-01

    Full Text Available Objective Adipose tissue is no longer considered as an inert storage organ for lipid, but instead is thought to play an active role in regulating insulin effects via secretion adipokines. However, conflicting reports have emerged regarding the effects of adipokines. In this study, we investigated the role of adipokines in glucose metabolism and insulin sensitivity in obese Bama mini-pigs. Methods An obesity model was established in Bama mini-pigs, by feeding with high-fat and high-sucrose diet for 30 weeks. Plasma glucose and blood biochemistry levels were measured, and intravenous glucose tolerance test was performed. Adipokines, including adiponectin, interleukin-6 (IL-6, resistin and tumor necrosis factor alpha (TNF-α, and glucose-induced insulin secretion were also examined by radioimmunoassay. AMP-activated protein kinase (AMPK phosphorylation in skeletal muscle, which is a useful insulin resistance marker, was examined by immunoblotting. Additionally, associations of AMPK phosphorylation with plasma adipokines and homeostasis model assessment of insulin resistance (HOMA-IR index were assessed by Pearce’s correlation analysis. Results Obese pigs showed hyperglycemia, high triglycerides, and insulin resistance. Adiponectin levels were significantly decreased (p<0.05 and IL-6 amounts dramatically increased (p<0.05 in obese pigs both in serum and adipose tissue, corroborating data from obese mice and humans. However, circulating resistin and TNF-α showed no difference, while the values of TNF-α in adipose tissue were significantly higher in obese pigs, also in agreement with data from obese humans but not rodent models. Moreover, strong associations of skeletal muscle AMPK phosphorylation with plasma adiponectin and HOMA-IR index were obtained. Conclusion AMPK impairment induced by adiponectin decrease mediates insulin resistance in high-fat and high-sucrose diet induction. In addition, Bama mini-pig has the possibility of a conformable

  13. Thyroid status influence on adiponectin, acylation stimulating protein (ASP and complement C3 in hyperthyroid and hypothyroid subjects

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    Zhang Jianhua

    2006-02-01

    Full Text Available Abstract Background Thyroid abnormalities (hyperthyroid and hypothyroid are accompanied by changes in intermediary metabolism including alterations in body weight, insulin resistance and lipid profile. The aims of this study were to examine plasma ASP, its precursor C3 and adiponectin in hyperthyroid and hypothyroid subjects as compared to controls. Methods A total of 99 subjects were recruited from endocrinology/out-patient clinics: 46 hyperthyroid subjects, 23 hypothyroid subjects and 30 control subjects. Subjects were evaluated for FT4, FT3, TSH, glucose, insulin, complete lipid profile and the adipokines: adiponectin, acylation stimulating protein (ASP and complement C3. Results Hyperthyroidism was associated with a 95% increase in adiponectin (p = 0.0002, a 47% decrease in C3 (p Conclusion These changes suggest that thyroid disease may be accompanied by changes in adipokines, which may contribute to the phenotype expressed.

  14. [Leptin: a link between obesity and osteoarthritis?].

    Science.gov (United States)

    Terlain, Bernard; Presle, Nathalie; Pottie, Pascale; Mainard, Didier; Netter, Patrick

    2006-10-01

    In addition to aging, obesity is one of the most common underlying causes of osteoarthritis (OA). Mechanical loading, together with biochemical and systemic factors linked to altered lipid metabolism, are thought to contribute to the onset of OA. It has been suggested that OA is a systemic metabolic disease associated with lipid disorders affecting joint homeostasis. These gradual changes may be due to the local effect of adipokines, and especially leptin. Indeed, their relative levels in joints differ from that found in plasma. In particular, leptin levels are increased and adiponectin and resistin levels are reduced This hypothesis is supported by--leptin overexpression in OA cartilage and its correlation with the degree of cartilage destruction,--abundant leptin synthesis by osteophytes, and--the high leptin levels found in OA joints from female patients. This link between OA and adipokines provides new leads regarding the prevention of OA and the identification of new drug targets.

  15. Elevated body mass index as a risk factor for chronic kidney disease: current perspectives

    Directory of Open Access Journals (Sweden)

    Garl

    2014-07-01

    Full Text Available Jocelyn S Garland Department of Medicine, Queen's University, Kingston, ON, Canada Abstract: Chronic kidney disease (CKD is defined by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative as the presence of reduced kidney function or kidney damage for a period of 3 months or greater. Obesity is considered a risk factor for CKD development, but its precise role in contributing to CKD and end stage kidney disease is not fully elucidated. In this narrative review, the objectives are to describe the pathogenesis of CKD in obesity, including the impact of altered adipokine secretion in obesity and CKD, and to provide an overview of the clinical studies assessing the risk of obesity and CKD development. Keywords: obesity, chronic renal disease, adipokine

  16. Adiponectin: an attractive marker for metabolic disorders in Chronic Obstructive Pulmonary Disease (COPD).

    Science.gov (United States)

    Bianco, Andrea; Mazzarella, Gennaro; Turchiarelli, Viviana; Nigro, Ersilia; Corbi, Graziamaria; Scudiero, Olga; Sofia, Matteo; Daniele, Aurora

    2013-10-14

    Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory lung disease which may be complicated by development of co-morbidities including metabolic disorders. Metabolic disorders commonly associated with this disease contribute to lung function impairment and mortality. Systemic inflammation appears to be a major factor linking COPD to metabolic alterations. Adipose tissue seems to interfere with systemic inflammation in COPD patients by producing a large number of proteins, known as "adipokines", involved in various processes such as metabolism, immunity and inflammation. There is evidence that adiponectin is an important modulator of inflammatory processes implicated in airway pathophysiology. Increased serum levels of adiponectin and expression of its receptors on lung tissues of COPD patients have recently highlighted the importance of the adiponectin pathway in this disease. Further, in vitro studies have demonstrated an anti-inflammatory activity for this adipokine at the level of lung epithelium. This review focuses on mechanisms by which adiponectin is implicated in linking COPD with metabolic disorders.

  17. Leptin as a link between the immune system and kidney-related diseases: leading actor or just a coadjuvant?

    Science.gov (United States)

    Moraes-Vieira, P M M; Bassi, E J; Araujo, R C; Câmara, N O S

    2012-08-01

    Food intake and nutritional status modify the physiological responses of the immune system to illness and infection and regulate the development of chronic inflammatory processes, such as kidney disease. Adipose tissue secretes immune-related proteins called adipokines that have pleiotropic effects on both the immune and neuroendocrine systems, linking metabolism and immune physiology. Leptin, an adipose tissue-derived adipokine, displays a variety of immune and physiological functions, and participates in several immune responses. Here, we review the current literature on the role of leptin in kidney diseases, linking adipose tissue and the immune system with kidney-related disorders. The modulation of this adipose hormone may have a major impact on the treatment of several immune- and metabolic-related kidney diseases.

  18. Obesity-Related Metabolic Syndrome: Mechanisms of Sympathetic Overactivity

    Directory of Open Access Journals (Sweden)

    Maria Paola Canale

    2013-01-01

    Full Text Available The prevalence of the metabolic syndrome has increased worldwide over the past few years. Sympathetic nervous system overactivity is a key mechanism leading to hypertension in patients with the metabolic syndrome. Sympathetic activation can be triggered by reflex mechanisms as arterial baroreceptor impairment, by metabolic factors as insulin resistance, and by dysregulated adipokine production and secretion from visceral fat with a mainly permissive role of leptin and antagonist role of adiponectin. Chronic sympathetic nervous system overactivity contributes to a further decline of insulin sensitivity and creates a vicious circle that may contribute to the development of hypertension and of the metabolic syndrome and favor cardiovascular and kidney disease. Selective renal denervation is an emerging area of interest in the clinical management of obesity-related hypertension. This review focuses on current understanding of some mechanisms through which sympathetic overactivity may be interlaced to the metabolic syndrome, with particular regard to the role of insulin resistance and of some adipokines.

  19. Characteristics of resistin in rheumatoid arthritis angiogenesis.

    Science.gov (United States)

    Su, Chen-Ming; Huang, Chun-Yin; Tang, Chih-Hsin

    2016-06-01

    Adipokines have been reported to be involved in the regulation of various physiological processes, including the immune response. Rheumatoid arthritis (RA) is an example of a systemic immune disease that causes chronic inflammation of the synovium and bone destruction in the joint. Recent therapeutic strategies based on the understanding of the role of cytokines and cellular mechanisms in RA have improved our understanding of angiogenesis. On the other hand, endogenous endothelial progenitor cells, which are a population isolated from peripheral blood monocytes have recently been identified as a homing target for pro-angiogeneic factor and vessel formation. In this review, we summarize the effects of common adipokines, such as adiponectin, leptin and resistin in RA pathogenesis and discuss other potential mechanisms of relevance for the therapeutic treatment of RA.

  20. High serum resistin is associated with an increase in adiposity but not a worsening of insulin resistance in Pima Indians

    DEFF Research Database (Denmark)

    de Courten, Barbora; Degawa-Yamauchi, Mikako; Considine, Robert V

    2004-01-01

    ) and hepatic glucose output during low-dosage insulin infusion of a hyperinsulinemic clamp (HGO; a measure of hepatic insulin resistance), and acute insulin secretory response (AIR; assessed by 25-g intravenous glucose tolerance test). Follow-up measurements of M, BHGO, HGO, and AIR were available for 34......Resistin is an adipokine with putative prodiabetogenic properties. Like other hormones secreted by adipose tissue, resistin is being investigated as a possible etiologic link between excessive adiposity and insulin resistance. Although there is growing evidence that circulating levels...... of this adipokine are proportional to the degree of adiposity, an effect on insulin resistance in humans remains unproven. To evaluate the relations among resistin, obesity, and insulin resistance, we measured fasting serum resistin levels in 113 nondiabetic (75-g oral glucose tolerance test) Pima Indians (ages 29...

  1. Effects of bariatric surgery on the level of hormones that regulate body weight. What is the basis of success?

    Directory of Open Access Journals (Sweden)

    Alina Yur'evna Babenko

    2014-06-01

    Full Text Available The growth of obesity and type 2 diabetes incidence has made bariatric surgery a widespread method of treatment. The effectiveness of bariatricoperations in the treatment of obesity and related metabolic diseases is thoroughly highlighted in medical literature. However, the resultsof surgery do not always correlate with type of operation. As before, the mechanisms have not been fully studied of how the bariatric surgeryinfluence on insulinresistance, entero-insulin axes, adipokines. Understanding such mechanisms will allow us to determine more precisely theindications relating to surgical treatment, and enhance the effectiveness of surgery in specific patient. The review is focusing on the influence ofvarious types of bariatric surgery on the level of adipokines and incretines that participate in regulation of appetite and of fat and carbohydratemetabolism. The article elaborates modern concepts related to the impact of bariatric operations on metabolic disorders in obesity.

  2. Targeting the Peroxisome Proliferator-Activated Receptor-γ to Counter the Inflammatory Milieu in Obesity

    Directory of Open Access Journals (Sweden)

    Cesar Corzo

    2013-12-01

    Full Text Available Adipose tissue, which was once viewed as a simple organ for storage of triglycerides, is now considered an important endocrine organ. Abnormal adipose tissue mass is associated with defects in endocrine and metabolic functions which are the underlying causes of the metabolic syndrome. Many adipokines, hormones secreted by adipose tissue, regulate cells from the immune system. Interestingly, most of these adipokines are proinflammatory mediators, which increase dramatically in the obese state and are believed to be involved in the pathogenesis of insulin resistance. Drugs that target peroxisome proliferator-activated receptor-γ have been shown to possess anti-inflammatory effects in animal models of diabetes. These findings, and the link between inflammation and the metabolic syndrome, will be reviewed here.

  3. Dose-dependent effects of atorvastatin on myocardial infarction

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    Barbarash O

    2015-06-01

    Full Text Available Olga Barbarash, Olga Gruzdeva, Evgenya Uchasova, Ekaterina Belik, Yulia Dyleva, Victoria KaretnikovaFederal State Budgetary Institution, Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo, the Russian Federation Background: Dyslipidemia is a key factor determining the development of both myocardial infarction (MI and its subsequent complications. Dyslipidemia is associated with endothelial dysfunction, activation of inflammation, thrombogenesis, and formation of insulin resistance. Statin therapy is thought to be effective for primary and secondary prevention of complications associated with atherosclerosis.Methods: This study examined 210 patients with Segment elevated MI (ST elevated MI who were treated with atorvastatin from the first 24 hours after MI. Group 1 (n=110 were given atorvastatin 20 mg/day. Group 2 (n=100 were given atorvastatin 40 mg/day. At days 1 and 12 after MI onset, insulin resistance levels determined by the homeostasis model assessment of insulin resistance index, lipid profiles, and serum glucose, insulin, adipokine, and ghrelin levels were measured.Results: Free fatty acid levels showed a sharp increase during the acute phase of MI. Treatment with atorvastatin 20 mg/day, and especially with 40 mg/day, resulted in a decrease in free fatty acid levels. The positive effect of low-dose atorvastatin (20 mg/day is normalization of the adipokine status. Administration of atorvastatin 20 mg/day was accompanied with a statistically significant reduction in glucose levels (by 14% and C-peptide levels (by 38%, and a decrease in the homeostasis model assessment of insulin resistance index on day 12.Conclusion: Determination of atorvastatin dose and its use during the in-hospital period and subsequent periods should take into account changes in biochemical markers of insulin resistance and adipokine status in patients with MI.Keywords: myocardial infarction, statin, insulin resistance, adipokines

  4. Insight into the effects of adipose tissue inflammation factors on miR-378 expression and the underlying mechanism.

    Science.gov (United States)

    Jiang, Xinye; Xue, Mei; Fu, Ziyi; Ji, Chenbo; Guo, Xirong; Zhu, Lu; Xu, Lulian; Pang, Lingxia; Xu, Meiyu; Qu, Hongming

    2014-01-01

    Obesity and the related metabolic syndrome have emerged as major public health issues in modern society. miRNAs have been shown to play key roles in regulating obesity-related metabolic syndrome, and some miRNAs regulated by adiponectin were identified as novel targets for controlling adipose tissue inflammation. miR-378 is a candidate target that was shown to be involved in adipose differentiation, mitochondrial metabolism and systemic energy homeostasis. However, little is known about the regulatory mechanisms of miR-378 expression. To better understand the physiological role of miR-378 in obesity and metabolic syndrome, it is crucial that we understand the regulation of miR-378 gene expression in human adipocytes. In this study, we investigated the effects of adipokines and inflammatory cytokines on miR-378 expression using Real-time PCR and the potential regulatory mechanisms using luciferase reporter assays and electrophoretic mobility shift assay (EMSA). Results : We found that adipokines and cytokines upregulated miR-378 expression primarily through SREBP and C/EBP binding sites in the miR-378 promoter region. Our findings showed that adipokines induced miR-378 expression and revealed the most likely mechanism of adipokine-induced miR-378 dysregulation in human adipocytes. miRNAs have been shown to function in regulating obesity-related metabolic syndrome, and miR-378 may be a novel target for controlling adipose tissue inflammation. This study offers a theoretical basis for understanding systemic adipose tissue inflammation and may provide new strategies for clinical treatment. © 2014 S. Karger AG, Basel.

  5. Metabolic alterations following visceral fat removal and expansion

    OpenAIRE

    Foster, Michelle T.; Pagliassotti, Michael J

    2012-01-01

    Increased visceral adiposity is a risk factor for metabolic disorders such as dyslipidemia, hypertension, insulin resistance and type 2 diabetes, whereas peripheral (subcutaneous) obesity is not. Though the specific mechanisms which contribute to these adipose depot differences are unknown, visceral fat accumulation is proposed to result in metabolic dysregulation because of increased effluent, e.g., fatty acids and/or adipokines/cytokines, to the liver via the hepatic portal vein. Pathologic...

  6. TNF-α and adipocyte biology

    OpenAIRE

    Cawthorn, William P.; Sethi, Jaswinder K.

    2007-01-01

    Dyslipidemia and insulin resistance are commonly associated with catabolic or lipodystrophic conditions (such as cancer and sepsis) and with pathological states of nutritional overload (such as obesity-related type 2 diabetes). Two common features of these metabolic disorders are adipose tissue dysfunction and elevated levels of tumour necrosis factor-alpha (TNF-α). Herein, we review the multiple actions of this pro-inflammatory adipokine on adipose tissue biology. These include inhibition of...

  7. The cell biology of fat expansion

    OpenAIRE

    Rutkowski, Joseph M.; Stern, Jennifer H.; Scherer, Philipp E.

    2015-01-01

    Adipose tissue is a complex, multicellular organ that profoundly influences the function of nearly all other organ systems through its diverse metabolite and adipokine secretome. Adipocytes are the primary cell type of adipose tissue and play a key role in maintaining energy homeostasis. The efficiency with which adipose tissue responds to whole-body energetic demands reflects the ability of adipocytes to adapt to an altered nutrient environment, and has profound systemic implications. Deciph...

  8. Adipose Tissue Dysregulation and Reduced Insulin Sensitivity in Non-Obese Individuals with Enlarged Abdominal Adipose Cells

    OpenAIRE

    Hammarstedt Ann; Graham Timothy E; Kahn Barbara B

    2012-01-01

    Abstract Background Obesity contributes to Type 2 diabetes by promoting systemic insulin resistance. Obesity causes features of metabolic dysfunction in the adipose tissue that may contribute to later impairments of insulin action in skeletal muscle and liver; these include reduced insulin-stimulated glucose transport, reduced expression of GLUT4, altered expression of adipokines, and adipocyte hypertrophy. Animal studies have shown that expansion of adipose tissue alone is not sufficient to ...

  9. The association of asthma, nasal allergies, and positive skin prick tests with obesity, leptin, and adiponectin.

    Science.gov (United States)

    Newson, R B; Jones, M; Forsberg, B; Janson, C; Bossios, A; Dahlen, S-E; Toskala, E M; Al-Kalemji, A; Kowalski, M L; Rymarczyk, B; Salagean, E M; van Drunen, C M; Bachert, C; Wehrend, T; Krämer, U; Mota-Pinto, A; Burney, P; Leynaert, B; Jarvis, D

    2014-02-01

    Cross-sectional and longitudinal reports show that obese adults have more asthma than non-obese adults. A proposed mechanism is via effects of adipokines (leptin and adiponectin) on the immune system. We wished to measure the associations of asthma and other atopic diseases with serum adipokine levels and to find whether the associations with asthma were strong enough to rule out the possibility that they are secondary to the association of fatness measures with asthma. The Global Asthma and Allergy Network of Excellence (GA(2) LEN) clinical follow-up survey is a clinical survey, embedded in a larger multi-centre cross-sectional postal survey, involving, with a case/control design, enrichment of the sample with subjects with asthma and chronic rhinosinusitis (CRS). We recorded serum leptin or adiponectin in 845 men and 1110 women in 15 centres and also anthropometric measures of fatness including body mass index and waist/hip ratio, current asthma, and specific skin prick and IgE sensitisation. We used inverse sampling-probability-weighted rank and regression statistics to measure population associations of disease outcomes with adipokines in males and females, adjusting for confounders (area, age, smoking history, and number of elder siblings) and also mutually adjusting associations with adipokines and fatness measures. One thousand nine hundred and fifty-five subjects aged 16-77 years had information on leptin or adiponectin levels. Leptin and leptin/adiponectin ratio were positively associated with the level of asthma, especially in females (Somers' D of leptin by asthma score, 0.20; 95% CI, 0.08-0.30; P = 0.00079). These associations were attenuated after adjusting for confounders and became non-significant after additionally adjusting for fatness measures and multiple comparisons. Asthma levels are positively associated with serum leptin. However, we cannot rule out the possibility that this association is secondary to associations of both with fatness

  10. Role of Obesity in Asthma Control, the Obesity-Asthma Phenotype

    OpenAIRE

    2013-01-01

    Asthma is a disease with distinct phenotypes that have implications for both prognosis and therapy. Epidemiologic studies have demonstrated an association between asthma and obesity. Further studies have shown that obese asthmatics have poor asthma control and more severe asthma. This obese-asthma group may represent a unique phenotype. The mechanisms behind poor asthma control in obese subjects remain unclear, but recent research has focused on adipokines and their effects on the airways as ...

  11. Adipose tissue and adipocytes supports tumorigenesis and metastasis#

    OpenAIRE

    Nieman, Kristin M; Romero, Iris L.; Van Houten, Bennett; Lengyel, Ernst

    2013-01-01

    Adipose tissue influences tumor development in two major ways. First, obese individuals have a higher risk of developing certain cancers (endometrial, esophageal, and renal cell cancer). However, the risk of developing other cancers (melanoma, rectal, and ovarian) is not altered by body mass. In obesity, hypertrophied adipose tissue depots are characterized by a state of low grade inflammation. In this activated state, adipocytes and inflammatory cells secrete adipokines and cytokines which a...

  12. Diet-Induced Obesity Is Associated with an Impaired NK Cell Function and an Increased Colon Cancer Incidence

    OpenAIRE

    Ina Bähr; Vincent Goritz; Henriette Doberstein; Grit Gesine Ruth Hiller; Philip Rosenstock; Janine Jahn; Ole Pörtner; Tobias Berreis; Thomas Mueller; Julia Spielmann; Heike Kielstein

    2017-01-01

    Obesity is associated with an increased colon cancer incidence, but underlying mechanisms remained unclear. Previous studies showed altered Natural killer (NK) cell functions in obese individuals. Therefore, we studied the impact of an impaired NK cell functionality on the increased colon cancer risk in obesity. In vitro investigations demonstrated a decreased IFN-γ secretion and cytotoxicity of human NK cells against colon tumor cells after NK cell preincubation with the adipokine leptin. In...

  13. Cadmium modulates adipocyte functions in metallothionein-null mice

    Energy Technology Data Exchange (ETDEWEB)

    Kawakami, Takashige; Nishiyama, Kaori; Kadota, Yoshito; Sato, Masao; Inoue, Masahisa; Suzuki, Shinya, E-mail: suzukis@ph.bunri-u.ac.jp

    2013-11-01

    Our previous study has demonstrated that exposure to cadmium (Cd), a toxic heavy metal, causes a reduction of adipocyte size and the modulation of adipokine expression. To further investigate the significance of the Cd action, we studied the effect of Cd on the white adipose tissue (WAT) of metallothionein null (MT{sup −/−}) mice, which cannot form atoxic Cd–MT complexes and are used for evaluating Cd as free ions, and wild type (MT{sup +/+}) mice. Cd administration more significantly reduced the adipocyte size of MT{sup −/−} mice than that of MT{sup +/+} mice. Cd exposure also induced macrophage recruitment to WAT with an increase in the expression level of Ccl2 (MCP-1) in the MT{sup −/−} mice. The in vitro exposure of Cd to adipocytes induce triglyceride release into culture medium, decrease in the expression levels of genes involved in fatty acid synthesis and lipid hydrolysis at 24 h, and at 48 h increase in phosphorylation of the lipid-droplet-associated protein perilipin, which facilitates the degradation of stored lipids in adipocytes. Therefore, the reduction in adipocyte size by Cd may arise from an imbalance between lipid synthesis and lipolysis. In addition, the expression levels of leptin, adiponectin and resistin decreased in adipocytes. Taken together, exposure to Cd may induce unusually small adipocytes and modulate the expression of adipokines differently from the case of physiologically small adipocytes, and may accelerate the risk of developing insulin resistance and type 2 diabetes. - Highlights: • Cd causes a marked reduction in adipocyte size in MT-null mice. • Cd enhances macrophage migration into adipose tissue and disrupt adipokine secretion. • MT gene alleviates Cd-induced adipocyte dysfunctions. • Cd enhances the degradation of stored lipids in adipocytes, mediated by perilipin. • Cd induces unusually small adipocytes and the abnormal expression of adipokines.

  14. Drosophila adiponectin receptor in insulin producing cells regulates glucose and lipid metabolism by controlling insulin secretion.

    Directory of Open Access Journals (Sweden)

    Su-Jin Kwak

    Full Text Available Adipokines secreted from adipose tissue are key regulators of metabolism in animals. Adiponectin, one of the adipokines, modulates pancreatic beta cell function to maintain energy homeostasis. Recently, significant conservation between Drosophila melanogaster and mammalian metabolism has been discovered. Drosophila insulin like peptides (Dilps regulate energy metabolism similarly to mammalian insulin. However, in Drosophila, the regulatory mechanism of insulin producing cells (IPCs by adipokine signaling is largely unknown. Here, we describe the discovery of the Drosophila adiponectin receptor and its function in IPCs. Drosophila adiponectin receptor (dAdipoR has high homology with the human adiponectin receptor 1. The dAdipoR antibody staining revealed that dAdipoR was expressed in IPCs of larval and adult brains. IPC- specific dAdipoR inhibition (Dilp2>dAdipoR-Ri showed the increased sugar level in the hemolymph and the elevated triglyceride level in whole body. Dilps mRNA levels in the Dilp2>dAdipoR-Ri flies were similar with those of controls. However, in the Dilp2>dAdipoR-Ri flies, Dilp2 protein was accumulated in IPCs, the level of circulating Dilp2 was decreased, and insulin signaling was reduced in the fat body. In ex vivo fly brain culture with the human adiponectin, Dilp2 was secreted from IPCs. These results indicate that adiponectin receptor in insulin producing cells regulates insulin secretion and controls glucose and lipid metabolism in Drosophila melanogaster. This study demonstrates a new adipokine signaling in Drosophila and provides insights for the mammalian adiponectin receptor function in pancreatic beta cells, which could be useful for therapeutic application.

  15. The association between obesity and gynecological cancer

    OpenAIRE

    Yin-Hsun Feng

    2015-01-01

    Obesity is a growing problem and has significant implications for a variety of diseases, including human cancers. A positive association between obesity and incidence of many gynecological cancers, including endometrial cancer, ovarian cancer, and breast cancer has been observed. The mechanism proposed to connect obesity and these cancers was sex hormone, insulin resistance, and certain adipokines. Obesity adversely affects survival in most studies. For endometrial cancer, the obesity was ass...

  16. Effects of Obesity on Transcriptomic Changes and Cancer Hallmarks in Estrogen Receptor–Positive Breast Cancer

    Science.gov (United States)

    Fuentes-Mattei, Enrique; Velazquez-Torres, Guermarie; Phan, Liem; Zhang, Fanmao; Chou, Ping-Chieh; Shin, Ji-Hyun; Choi, Hyun Ho; Chen, Jiun-Sheng; Zhao, Ruiying; Chen, Jian; Gully, Chris; Carlock, Colin; Qi, Yuan; Zhang, Ya; Wu, Yun; Esteva, Francisco J.; Luo, Yongde; McKeehan, Wallace L.; Ensor, Joe; Hortobagyi, Gabriel N.; Pusztai, Lajos; Fraser Symmans, W.; Lee, Mong-Hong

    2014-01-01

    Background Obesity increases the risk of cancer death among postmenopausal women with estrogen receptor–positive (ER+) breast cancer, but the direct evidence for the mechanisms is lacking. The purpose of this study is to demonstrate direct evidence for the mechanisms mediating this epidemiologic phenomenon. Methods We analyzed transcriptomic profiles of pretreatment biopsies from a prospective cohort of 137 ER+ breast cancer patients. We generated transgenic (MMTV-TGFα;A y /a) and orthotopic/syngeneic (A y /a) obese mouse models to investigate the effect of obesity on tumorigenesis and tumor progression and to determine biological mechanisms using whole-genome transcriptome microarrays and protein analyses. We used a coculture system to examine the impact of adipocytes/adipokines on breast cancer cell proliferation. All statistical tests were two-sided. Results Functional transcriptomic analysis of patients revealed the association of obesity with 59 biological functional changes (P cancer hallmarks. Gene enrichment analysis revealed enrichment of AKT-target genes (P = .04) and epithelial–mesenchymal transition genes (P = .03) in patients. Our obese mouse models demonstrated activation of the AKT/mTOR pathway in obesity-accelerated mammary tumor growth (3.7- to 7.0-fold; P obesity-induced secretion of adipokines and breast tumor formation and growth (0.5-fold, P = .04; 0.3-fold, P breast cancer cell proliferation and invasion. Metformin suppress adipocyte-induced cell proliferation and adipocyte-secreted adipokines in vitro. Conclusions Adipokine secretion and AKT/mTOR activation play important roles in obesity-accelerated breast cancer aggressiveness in addition to hyperinsulinemia, estrogen signaling, and inflammation. Metformin and everolimus have potential for therapeutic interventions of ER+ breast cancer patients with obesity. PMID:24957076

  17. Effects of obesity on transcriptomic changes and cancer hallmarks in estrogen receptor-positive breast cancer.

    Science.gov (United States)

    Fuentes-Mattei, Enrique; Velazquez-Torres, Guermarie; Phan, Liem; Zhang, Fanmao; Chou, Ping-Chieh; Shin, Ji-Hyun; Choi, Hyun Ho; Chen, Jiun-Sheng; Zhao, Ruiying; Chen, Jian; Gully, Chris; Carlock, Colin; Qi, Yuan; Zhang, Ya; Wu, Yun; Esteva, Francisco J; Luo, Yongde; McKeehan, Wallace L; Ensor, Joe; Hortobagyi, Gabriel N; Pusztai, Lajos; Fraser Symmans, W; Lee, Mong-Hong; Yeung, Sai-Ching Jim

    2014-07-01

    Obesity increases the risk of cancer death among postmenopausal women with estrogen receptor-positive (ER+) breast cancer, but the direct evidence for the mechanisms is lacking. The purpose of this study is to demonstrate direct evidence for the mechanisms mediating this epidemiologic phenomenon. We analyzed transcriptomic profiles of pretreatment biopsies from a prospective cohort of 137 ER+ breast cancer patients. We generated transgenic (MMTV-TGFα;A (y) /a) and orthotopic/syngeneic (A (y) /a) obese mouse models to investigate the effect of obesity on tumorigenesis and tumor progression and to determine biological mechanisms using whole-genome transcriptome microarrays and protein analyses. We used a coculture system to examine the impact of adipocytes/adipokines on breast cancer cell proliferation. All statistical tests were two-sided. Functional transcriptomic analysis of patients revealed the association of obesity with 59 biological functional changes (P cancer hallmarks. Gene enrichment analysis revealed enrichment of AKT-target genes (P = .04) and epithelial-mesenchymal transition genes (P = .03) in patients. Our obese mouse models demonstrated activation of the AKT/mTOR pathway in obesity-accelerated mammary tumor growth (3.7- to 7.0-fold; P obesity-induced secretion of adipokines and breast tumor formation and growth (0.5-fold, P = .04; 0.3-fold, P breast cancer cell proliferation and invasion. Metformin suppress adipocyte-induced cell proliferation and adipocyte-secreted adipokines in vitro. Adipokine secretion and AKT/mTOR activation play important roles in obesity-accelerated breast cancer aggressiveness in addition to hyperinsulinemia, estrogen signaling, and inflammation. Metformin and everolimus have potential for therapeutic interventions of ER+ breast cancer patients with obesity. © The Author 2014. Published by Oxford University Press.

  18. Drosophila adiponectin receptor in insulin producing cells regulates glucose and lipid metabolism by controlling insulin secretion.

    Science.gov (United States)

    Kwak, Su-Jin; Hong, Seung-Hyun; Bajracharya, Rijan; Yang, Se-Yeol; Lee, Kyu-Sun; Yu, Kweon

    2013-01-01

    Adipokines secreted from adipose tissue are key regulators of metabolism in animals. Adiponectin, one of the adipokines, modulates pancreatic beta cell function to maintain energy homeostasis. Recently, significant conservation between Drosophila melanogaster and mammalian metabolism has been discovered. Drosophila insulin like peptides (Dilps) regulate energy metabolism similarly to mammalian insulin. However, in Drosophila, the regulatory mechanism of insulin producing cells (IPCs) by adipokine signaling is largely unknown. Here, we describe the discovery of the Drosophila adiponectin receptor and its function in IPCs. Drosophila adiponectin receptor (dAdipoR) has high homology with the human adiponectin receptor 1. The dAdipoR antibody staining revealed that dAdipoR was expressed in IPCs of larval and adult brains. IPC- specific dAdipoR inhibition (Dilp2>dAdipoR-Ri) showed the increased sugar level in the hemolymph and the elevated triglyceride level in whole body. Dilps mRNA levels in the Dilp2>dAdipoR-Ri flies were similar with those of controls. However, in the Dilp2>dAdipoR-Ri flies, Dilp2 protein was accumulated in IPCs, the level of circulating Dilp2 was decreased, and insulin signaling was reduced in the fat body. In ex vivo fly brain culture with the human adiponectin, Dilp2 was secreted from IPCs. These results indicate that adiponectin receptor in insulin producing cells regulates insulin secretion and controls glucose and lipid metabolism in Drosophila melanogaster. This study demonstrates a new adipokine signaling in Drosophila and provides insights for the mammalian adiponectin receptor function in pancreatic beta cells, which could be useful for therapeutic application.

  19. Effect of Obesity and Chronic Inflammation on TRAIL-Based Immunotherapy for Advanced Breast Cancer

    Science.gov (United States)

    2015-04-01

    Results pertaining to Task 1. Altered serum cytokine profile in female BALB/c diet -induced obese (DIO) mice The majority of prior studies on murine DIO...stromal cell composition . As visceral adipose tissue increases in obese mice and obesity triggers increased production of adipokines like IL-6 and...percentages and/or phenotypes of DC in mice with 4T1 tumors in the absence of any therapy. Diet -induced obese mice were generated by feeding cohorts of

  20. Leptin Is Associated With Persistence of Hyperglycemia in Acute Pancreatitis: A Prospective Clinical Study.

    Science.gov (United States)

    Kennedy, James I C; Askelund, Kathryn J; Premkumar, Rakesh; Phillips, Anthony R J; Murphy, Rinki; Windsor, John A; Petrov, Maxim S

    2016-02-01

    Adipokines have many homeostatic roles, including modulation of glucose metabolism, but their role in the pathophysiology of hyperglycemia associated with acute and critical illnesses in general, and acute pancreatitis (AP) in particular, is largely unknown. This study aimed to investigate the relationship between a panel of adipokines and hyperglycemia in the early course of AP, as well as the role of adipokines as predictors of AP severity.Adiponectin, leptin, omentin, resistin, and visfatin were measured on a daily basis in the first 72 hours after hospital admission. A first set of analyses was undertaken with admission glycemia stratified by severity, and a second set of analyses was undertaken based on persistence of early hyperglycemia. All of the analyses were adjusted for confounders.A total of 32 patients with AP were included in this study. None of the studied adipokines was significantly associated with glucose level on admission. Leptin was significantly (P = 0.003) increased in patients with persistent hyperglycemia. Adiponectin was significantly associated with the Acute Physiology and Chronic Health Evaluation II (APACHE II) score in patients with persistent hyperglycemia (P = 0.015), visfatin with APACHE II score in patients with persistent hyperglycemia (P = 0.014), and omentin with APACHE II score in all of the patients regardless of the presence or absence of hyperglycemia (P = 0.021).Leptin is significantly associated with persistent hyperglycemia in the early course of AP. Omentin has a potential to become an accurate predictor of AP severity.

  1. [Persistence of chronic inflammatory responses, role in the development of chronic pancreatitis, obesity and pancreatic cancer].

    Science.gov (United States)

    Khristich, T N

    2014-11-01

    The purpose of the review--to analyze the basic data of the role of chronic low-intensity inflammatory response as general biological process in the development and progression of chronic pancreatitis, obesity, and pancreatic cancer. Highlighted evidence from epidemiological studies showing that chronic pancreatitis and obesity are independent risk factors for pancreatic cancer, regardless of diabetes. Studied role of adipokines as Cytokines regulating of immune inflammatory response. Draws attention to the staging of pancreatic cancer in obesity.

  2. The Newest Hypothesis about Vitiligo: Most of the Suggested Pathogeneses of Vitiligo Can Be Attributed to Lack of One Factor, Zinc-α2-Glycoprotein

    OpenAIRE

    Bagherani, Nooshin

    2012-01-01

    Zinc- α 2-glycoprotein (ZAG) is a recently identified adipokine, assigned to the chromosome 7q22.1. It is a multidisciplinary protein, which is secreted in various body fluids. The ZAG plays roles in lipolysis, regulation of metabolism, cell proliferation and differentiation, regulation of melanin synthesis, cell adhesion, immunoregulation, and so forth. Vitiligo is the most common depigmenting skin disorder, characterized by acquired, progressive, and circumscribed amelanosis of the skin and...

  3. Decreased adipose tissue zinc content is associated with metabolic parameters in high fat fed Wistar rats

    OpenAIRE

    Alexey A. Tinkov; Elizaveta V. Popova; Evgenia R. Gatiatulina; Anastasia A. Skalnaya; Elena N. Yakovenko; Irina B. Alchinova; Mikhail Y. Karganov; Anatoly V. Skalny; Nikonorov, Alexandr A.

    2016-01-01

    Background. Limited data on adipose tissue zinc content in obesity exist. At the same time, the association between adipose tissue zinc content and metabolic parameters in dietary-induced obesity is poorly studied. Therefore, the primary objective of this study is to assess adipose tissue zinc content and its association  with morphometric parameters, adipokine spectrum, proinflammatory cytokines, and apolipoprotein profile in high fat fed Wistar rats. Material and method...

  4. Metabolic alterations following visceral fat removal and expansion

    OpenAIRE

    Foster, Michelle T.; Pagliassotti, Michael J.

    2012-01-01

    Increased visceral adiposity is a risk factor for metabolic disorders such as dyslipidemia, hypertension, insulin resistance and type 2 diabetes, whereas peripheral (subcutaneous) obesity is not. Though the specific mechanisms which contribute to these adipose depot differences are unknown, visceral fat accumulation is proposed to result in metabolic dysregulation because of increased effluent, e.g., fatty acids and/or adipokines/cytokines, to the liver via the hepatic portal vein. Pathologic...

  5. The Liposuction-Induced Effects on Adiponectin and Selected Cytokines Are Not Affected by Exercise Training in Women

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    Marina Yazigi Solis

    2014-01-01

    Full Text Available It has been suggested that the abrupt liposuction-induced decrease in adipose tissue could affect adipokine secretion pattern. We hypothesized that exercise training could positively impact adipokine metabolism following liposuction. The aim of this study was to investigate the effects of liposuction on inflammation-related adipokines in women who were either exercise-trained or remained sedentary after surgery. Thirty-six healthy normal-weight women underwent an abdominal liposuction and two months after surgery were randomly allocated into two groups: trained (TR, n=18, four-month exercise program and nontrained (NT, n=18. Inflammation-related adipokine serum levels (TNF-α, IL-6, IL-10, and adiponectin and abdominal and thigh subcutaneous adipose tissue (scAT mRNA levels were assessed before (PRE and six months after surgery (POST6. TNF-α, IL-6, and IL-10 serum levels were unchanged in both groups. In contrast, TNF-α, IL-6, and IL-10 mRNA levels in scAT were increased, whereas adiponectin scAT mRNA and serum levels were decreased at POST6 (P<0.05, main effect for time. No changes were observed in mRNA levels of MCP-1, CD14, and CD68 in any of the groups. In conclusion, liposuction downregulates adiponectin scAT gene expression and serum levels and upregulates scAT gene expression of inflammation-related genes six months after surgery in normal-weight women, irrespective of exercise training.

  6. Efeitos da perda de peso sobre o metabolismo ósseo de pacientes submetidos à cirurgia bariátrica de Bypass Gástrico em Y de Roux: efeitos da cirurgia bariátrica sobre o metabolismo

    OpenAIRE

    Biagioni, Maria Fernanda Giovanetti [UNESP

    2015-01-01

    Introduction: despite the success at weight loss and control of comorbidities, bariatric surgeries such as gastric bypass Roux-Y (RYGB), promote changes in hormone metabolism and adipose tissue, which may be associated with increased remodeling and bone loss. Among the possible mechanisms involved are the adipokines influence on the modulation of the expression of the receptor activator of nuclear factor kappa β ligand (RANKL), and osteoprotegerin (OPG), and increased expression of sclerostin...

  7. Bone Marrow Leptin Signaling Mediates Obesity-Associated Adipose Tissue Inflammation in Male Mice

    OpenAIRE

    Dib, Lea H.; Ortega, M. Teresa; Fleming, Sherry D.; Chapes, Stephen K.; Melgarejo, Tonatiuh

    2013-01-01

    Obesity is characterized by an increased recruitment of proinflammatory macrophages to the adipose tissue (AT), leading to systemic inflammation and metabolic disease. The pathogenesis of this AT inflammation, however, remains to be elucidated. The circulating adipokine leptin is increased in obesity and is involved in immune cell function and activation. In the present study, we investigated the role of leptin in the induction of obesity-associated inflammation. We generated radiation chimer...

  8. Serum Vaspin Levels Are Associated with the Development of Clinically Manifest Arthritis in Autoantibody-Positive Individuals.

    Directory of Open Access Journals (Sweden)

    Karen I Maijer

    Full Text Available We have previously shown that overweight may increase the risk of developing rheumatoid arthritis (RA in autoantibody positive individuals. Adipose tissue could contribute to the development of RA by production of various bioactive peptides. Therefore, we examined levels of adipokines in serum and synovial tissue of subjects at risk of RA.Fifty-one individuals positive for immunoglobulin M rheumatoid factor (IgM-RF and/or anti-citrullinated protein antibodies (ACPA, without arthritis, were included in this prospective study. Levels of adiponectin, vaspin, resistin, leptin, chemerin and omentin were determined in baseline fasting serum samples (n = 27. Synovial tissue was obtained by arthroscopy at baseline and we examined the expression of adiponectin, resistin and visfatin by immunohistochemistry.The development of clinically manifest arthritis after follow-up was associated with baseline serum vaspin levels (HR1.5 (95% CI 1.1 to 2.2; p = 0.020, also after adjustment for overweight (HR1.7 (95% CI 1.1 to 2.5; p = 0.016. This association was not seen for other adipokines. Various serum adipokine levels correlated with BMI (adiponectin r = -0.538, leptin r = 0.664; chemerin r = 0.529 and systemic markers of inflammation such as CRP levels at baseline (adiponectin r = -0.449, omentin r = -0.557, leptin r = 0.635, chemerin r = 0.619, resistin r = 0.520 and ESR (leptin r = 0.512, chemerin r = 0.708, p-value<0.05. Synovial expression of adiponectin, resistin and visfatin was not associated with development of clinically manifest arthritis.In this exploratory study, serum adipokines were associated with an increased inflammatory state in autoantibody-positive individuals at risk of developing RA. Furthermore, serum vaspin levels may assist in predicting the development of arthritis in these individuals.

  9. Exercise Effects on White Adipose Tissue: Beiging and Metabolic Adaptations.

    Science.gov (United States)

    Stanford, Kristin I; Middelbeek, Roeland J W; Goodyear, Laurie J

    2015-07-01

    Regular physical activity and exercise training have long been known to cause adaptations to white adipose tissue (WAT), including decreases in cell size and lipid content and increases in mitochondrial proteins. In this article, we discuss recent studies that have investigated the effects of exercise training on mitochondrial function, the "beiging" of WAT, regulation of adipokines, metabolic effects of trained adipose tissue on systemic metabolism, and depot-specific responses to exercise training. The major WAT depots in the body are found in the visceral cavity (vWAT) and subcutaneously (scWAT). In rodent models, exercise training increases mitochondrial biogenesis and activity in both these adipose tissue depots. Exercise training also increases expression of the brown adipocyte marker uncoupling protein 1 (UCP1) in both adipose tissue depots, although these effects are much more pronounced in scWAT. Consistent with the increase in UCP1, exercise training increases the presence of brown-like adipocytes in scWAT, also known as browning or beiging. Training results in changes in the gene expression of thousands of scWAT genes and an altered adipokine profile in both scWAT and vWAT. Transplantation of trained scWAT in sedentary recipient mice results in striking improvements in skeletal muscle glucose uptake and whole-body metabolic homeostasis. Human and rodent exercise studies have indicated that exercise training can alter circulating adipokine concentration as well as adipokine expression in adipose tissue. Thus, the profound changes to WAT in response to exercise training may be part of the mechanism by which exercise improves whole-body metabolic health.

  10. BMI and BMD: The Potential Interplay between Obesity and Bone Fragility

    OpenAIRE

    Andrea Palermo; Dario Tuccinardi; Giuseppe Defeudis; Mikiko Watanabe; Luca D’Onofrio; Angelo Lauria Pantano; Nicola Napoli; Paolo Pozzilli; Silvia Manfrini

    2016-01-01

    Recent evidence demonstrating an increased fracture risk among obese individuals suggests that adipose tissue may negatively impact bone health, challenging the traditional paradigm of fat mass playing a protective role towards bone health. White adipose tissue, far from being a mere energy depot, is a dynamic tissue actively implicated in metabolic reactions, and in fact secretes several hormones called adipokines and inflammatory factors that may in turn promote bone resorption. More specif...

  11. Regulation of pituitary cell function by adiponectin.

    Science.gov (United States)

    Rodriguez-Pacheco, Francisca; Martinez-Fuentes, Antonio J; Tovar, Sulay; Pinilla, Leonor; Tena-Sempere, Manuel; Dieguez, Carlos; Castaño, Justo P; Malagon, María M

    2007-01-01

    Adiponectin is a member of the family of adipose tissue-related hormones known as adipokines, which exerts antidiabetic, antiatherogenic, antiinflammatory, and antiangiogenic properties. Adiponectin actions are primarily mediated through binding to two receptors expressed in several tissues, AdipoR1 and AdipoR2. Likewise, adiponectin expression has been detected in adipocytes as well as in a variety of extra-adipose tissues, including the chicken pituitary. Interestingly, adiponectin secretion and adiponectin receptor expression in adipocytes have been shown to be regulated by pituitary hormones. These observations led us to investigate whether adiponectin, like the adipokine leptin, regulates pituitary hormone production. Specifically, we focused our analysis on somatotrophs and gonadotrophs because of the relationship between the control of energy metabolism, growth and reproduction. To this end, the effects of adiponectin on both GH and LH secretion as well as its interaction with major stimulatory regulators of somatotrophs (ghrelin and GHRH) and gonadotrophs (GnRH) and with their corresponding receptors (GHS-R, GHRH-R, and GnRH-R), were evaluated in rat pituitary cell cultures. Results show that adiponectin inhibits GH and LH release as well as both ghrelin-induced GH release and GnRH-stimulated LH secretion in short-term (4 h) treated cell cultures, wherein the adipokine also increases GHRH-R and GHS-R mRNA content while decreasing that of GnRH-R. Additionally, we demonstrate that the pituitary expresses both adiponectin and adiponectin receptors under the regulation of the adipokine. In sum, our data indicate that adiponectin, either locally produced or from other sources, may play a neuroendocrine role in the control of both somatotrophs and gonadotrophs.

  12. The endocrine function of adipose tissue

    Directory of Open Access Journals (Sweden)

    Wagner de Jesus Pinto

    2014-09-01

    Full Text Available Currently it is considered the adipose tissue as a dynamic structure involved in many physiological and metabolic processes, produces and releases a variety of active peptides known by the generic name of adipokines that act performing endocrine, paracrine and autocrine. Furthermore, numbers expressed receptors that respond allows the afferent signals from endocrine organs, and also central nervous system. In 1987, the adipose tissue has been identified as the major site of metabolism of steroid hormones, thereafter, in 1994, it was recognized as an endocrine organ and the leptin being an early secretory products identified. In addition other biologically active substances were being isolated, such as adiponectin, resistin, TNF-a, interleukin-6 and others. The adipokines derived from adipose tissue modulate many metabolic parameters such as control of food intake, energy balance and peripheral insulin sensitivity, for example. Thus, the altered secretion of adipokines by adipose tissue may have metabolic effects may present complex relations with the pathophysiological process of obesity, endothelial dysfunction, inflammation, atherosclerosis and Diabetes mellitus. The understanding of the molecular processes occurring in the adipocytes may provide new tools for the treatment of pathophysiological conditions such as, for example, metabolic syndrome, obesity and diabetes mellitus.

  13. Proteomic characterization of adipose tissue constituents, a necessary step for understanding adipose tissue complexity.

    Science.gov (United States)

    Peinado, Juan R; Pardo, María; de la Rosa, Olga; Malagón, Maria M

    2012-02-01

    The original concept of adipose tissue as an inert storage depot for the excess of energy has evolved over the last years and it is now considered as one of the most important organs regulating body homeostasis. This conceptual change has been supported by the demonstration that adipose tissue serves as a major endocrine organ, producing a wide variety of bioactive molecules, collectively termed adipokines, with endocrine, paracrine and autocrine activities. Adipose tissue is indeed a complex organ wherein mature adipocytes coexist with the various cell types comprising the stromal-vascular fraction (SVF), including preadipocytes, adipose-derived stem cells, perivascular cells, and blood cells. It is known that not only mature adipocytes but also the components of SVF produce adipokines. Furthermore, adipokine production, proliferative and metabolic activities and response to regulatory signals (i.e. insulin, catecholamines) differ between the different fat depots, which have been proposed to underlie their distinct association to specific diseases. Herein, we discuss the recent proteomic studies on adipose tissue focused on the analysis of the separate cellular components and their secretory products, with the aim of identifying the basic features and the contribution of each component to different adipose tissue-associated pathologies.

  14. Effect of Weight Reduction Following Bariatric Surgery on Serum Visfatin and Adiponectin Levels in Morbidly Obese Subjects

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    Mohammad Javad Hosseinzadeh-Attar

    2013-04-01

    Full Text Available Objective: Adipokines are signaling and mediator proteins secreted from adipose tissue. A novel adipokine, visfatin, was reported as a protein which was mainly expressed in visceral adipose tissue. Controversial results have been shown regarding the changes of adipokines following weight reduction. So we investigated the effects of weight reduction on serum concentrations of adiponectin and visfatin in morbidly obese subjects. Methods: 35 severely obese patients (26 females and 9 males, aged 15-58 years, were studied. Anthropometric parameters and biochemical parameters as well as adiponectin and visfatin were analyzed before and 6 weeks after weight reduction. Results: Anthropometric indices decreased significantly. Blood levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride were reduced significantly. The reduction of visfatin and the elevation of adiponectin were significant as well. However, other parameters like fasting glucose and insulin did not change. Moreover, we could not find any significant correlation between the change of serum visfatin and that of adiponectin. Conclusions: 6-week weight reduction after bariatric surgery resulted in decreased serum visfatin and increased adiponectin levels. However, we cannot find any significant correlation between changes of adiponectin, visfatin, BMI, waist circumference, and insulin resistance. Further studies with different design are suggested to clarify these associations.

  15. Review article: Relationships between adipose tissue and psoriasis, with or without arthritis.

    Directory of Open Access Journals (Sweden)

    ERIC eTOUSSIROT

    2014-08-01

    Full Text Available Psoriasis (Pso is a common chronic cutaneous inflammatory disease involving the skin that is associated with serious comorbidities. Comorbidities in Pso include psoriatic arthritis (PsA, reduced quality of life, malignancy, depression, but also a constellation of associated conditions that enhance the cardiovascular (CV risk. Indeed, obesity is common in patients with Pso or PsA and is considered to be a risk factor for the onset of these diseases. Patients with Pso and PsA share common obesity-related complications such as metabolic syndrome, dyslipidemia, diabetes or insulin resistance and CV diseases. Chronic inflammation in Pso and PsA partially explains the development of atherosclerosis and CV diseases. In parallel, body composition is disturbed in patients with Pso or PsA, as suggested by anthropometric measurements, while an excess of abdominal adiposity is observed in PsA, enhancing the risk of metabolic syndrome and CV diseases. Adipokines may link the adipose tissue to the obesity-related complications of Pso and PsA. Indeed, altered circulating levels of the adipokines leptin, adiponectin, visfatine, and resistin have been found in patients with Pso or PsA. In addition, an excess of adipose tissue may compromise the therapeutic response to traditional drugs or biological agents in Pso and PsA. This paper reviews the comorbidities that contribute to enhanced CV risk, the body composition results, and the potential role of adipokines in systemic inflammation and energetic balance in Pso and PsA.

  16. Pulmonary hypertension and metabolic syndrome: Possible connection, PPARγ and Caveolin-1.

    Science.gov (United States)

    Mathew, Rajamma

    2014-08-26

    A number of disparate diseases can lead to pulmonary hypertension (PH), a serious disorder with a high morbidity and mortality rate. Recent studies suggest that the associated metabolic dysregulation may be an important factor adversely impacting the prognosis of PH. Furthermore, metabolic syndrome is associated with vascular diseases including PH. Inflammation plays a significant role both in PH and metabolic syndrome. Adipose tissue modulates lipid and glucose metabolism, and also produces pro- and anti-inflammatory adipokines that modulate vascular function and angiogenesis, suggesting a close functional relationship between the adipose tissue and the vasculature. Both caveolin-1, a cell membrane scaffolding protein and peroxisome proliferator-activated receptor (PPAR) γ, a ligand-activated transcription factor are abundantly expressed in the endothelial cells and adipocytes. Both caveolin-1 and PPARγ modulate proliferative and anti-apoptotic pathways, cell migration, inflammation, vascular homeostasis, and participate in lipid transport, triacylglyceride synthesis and glucose metabolism. Caveolin-1 and PPARγ regulate the production of adipokines and in turn are modulated by them. This review article summarizes the roles and inter-relationships of caveolin-1, PPARγ and adipokines in PH and metabolic syndrome.

  17. Implication of low level inflammation in the insulin resistance of adipose tissue at late pregnancy.

    Science.gov (United States)

    de Castro, J; Sevillano, J; Marciniak, J; Rodriguez, R; González-Martín, C; Viana, M; Eun-suk, O H; de Mouzon, S Hauguel; Herrera, E; Ramos, M P

    2011-11-01

    Insulin resistance is a characteristic of late pregnancy, and adipose tissue is one of the tissues that most actively contributes to the reduced maternal insulin sensitivity. There is evidence that pregnancy is a condition of moderate inflammation, although the physiological role of this low-grade inflammation remains unclear. The present study was designed to validate whether low-grade inflammation plays a role in the development of insulin resistance in adipose tissue during late pregnancy. To this end, we analyzed proinflammatory adipokines and kinases in lumbar adipose tissue of nonpregnant and late pregnant rats at d 18 and 20 of gestation. We found that circulating and tissue levels of adipokines, such as IL-1β, plasminogen activator inhibitor-1, and TNF-α, were increased at late pregnancy, which correlated with insulin resistance. The observed increase in adipokines coincided with an enhanced activation of p38 MAPK in adipose tissue. Treatment of pregnant rats with the p38 MAPK inhibitor SB 202190 increased insulin-stimulated tyrosine phosphorylation of the insulin receptor (IR) and IR substrate-1 in adipose tissue, which was paralleled by a reduction of IR substrate-1 serine phosphorylation and an enhancement of the metabolic actions of insulin. These results indicate that activation of p38 MAPK in adipose tissue contributes to adipose tissue insulin resistance at late pregnancy. Furthermore, the results of the present study support the hypothesis that physiological low-grade inflammation in the maternal organism is relevant to the development of pregnancy-associated insulin resistance.

  18. Elevated Serum Levels of Cysteine and Tyrosine: Early Biomarkers in Asymptomatic Adults at Increased Risk of Developing Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Nina Mohorko

    2015-01-01

    Full Text Available As there is effective intervention for delaying or preventing metabolic diseases, which are often present for years before becoming clinically apparent, novel biomarkers that would mark metabolic complications before the onset of metabolic disease should be identified. We investigated the role of fasting serum amino acids and their associations with inflammatory markers, adipokines, and metabolic syndrome (MetS components in subjects prior to the onset of insulin resistance (IR. Anthropometric measurements, food records, adipokines, biochemical markers, and serum levels of amino acids were determined in 96 asymptomatic subjects aged 25–49 years divided into three groups according to the number of MetS components present. Cysteine and tyrosine were significantly higher already in group with one component of MetS present compared to subjects without MetS components. Serum amino acid levels correlated with markers of inflammation and adipokines. Alanine and glycine explained 10% of insulin resistance variability. The role of tyrosine and cysteine, that were higher already with 1 component of MetS present, should be further investigated as they might point to future insulin disturbances.

  19. Therapies for Prevention and Treatment of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    J. Mendiola-Precoma

    2016-01-01

    Full Text Available Alzheimer’s disease (AD is the most common cause of dementia associated with a progressive neurodegenerative disorder, with a prevalence of 44 million people throughout the world in 2015, and this figure is estimated to double by 2050. This disease is characterized by blood-brain barrier disruption, oxidative stress, mitochondrial impairment, neuroinflammation, and hypometabolism; it is related to amyloid-β peptide accumulation and tau hyperphosphorylation as well as a decrease in acetylcholine levels and a reduction of cerebral blood flow. Obesity is a major risk factor for AD, because it induces adipokine dysregulation, which consists of the release of the proinflammatory adipokines and decreased anti-inflammatory adipokines, among other processes. The pharmacological treatments for AD can be divided into two categories: symptomatic treatments such as acetylcholinesterase inhibitors and N-methyl-D-aspartate (NMDA receptor antagonists and etiology-based treatments such as secretase inhibitors, amyloid binders, and tau therapies. Strategies for prevention of AD through nonpharmacological treatments are associated with lifestyle interventions such as exercise, mental challenges, and socialization as well as caloric restriction and a healthy diet. AD is an important health issue on which all people should be informed so that prevention strategies that minimize the risk of its development may be implemented.

  20. Therapies for Prevention and Treatment of Alzheimer's Disease.

    Science.gov (United States)

    Mendiola-Precoma, J; Berumen, L C; Padilla, K; Garcia-Alcocer, G

    2016-01-01

    Alzheimer's disease (AD) is the most common cause of dementia associated with a progressive neurodegenerative disorder, with a prevalence of 44 million people throughout the world in 2015, and this figure is estimated to double by 2050. This disease is characterized by blood-brain barrier disruption, oxidative stress, mitochondrial impairment, neuroinflammation, and hypometabolism; it is related to amyloid-β peptide accumulation and tau hyperphosphorylation as well as a decrease in acetylcholine levels and a reduction of cerebral blood flow. Obesity is a major risk factor for AD, because it induces adipokine dysregulation, which consists of the release of the proinflammatory adipokines and decreased anti-inflammatory adipokines, among other processes. The pharmacological treatments for AD can be divided into two categories: symptomatic treatments such as acetylcholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists and etiology-based treatments such as secretase inhibitors, amyloid binders, and tau therapies. Strategies for prevention of AD through nonpharmacological treatments are associated with lifestyle interventions such as exercise, mental challenges, and socialization as well as caloric restriction and a healthy diet. AD is an important health issue on which all people should be informed so that prevention strategies that minimize the risk of its development may be implemented.

  1. Adiponectin, Resistin, and Visfatin in Childhood Obesity and Exercise.

    Science.gov (United States)

    Jamurtas, Athanasios Z; Stavropoulos-Kalinoglou, Antonios; Koutsias, Stilianos; Koutedakis, Yiannis; Fatouros, Ioannis

    2015-11-01

    Childhood obesity is increasing alarmingly, and a strong association with chronic diseases has been established. Specific adipokines are released from the adipose tissue and relate with chronic diseases even in the pediatric population. Adiponectin levels are lower in obesity and increase with decreasing body weight. A few pediatric studies examining a possible relationship between resistin and obesity do not provide a clear picture. Most studies agree that visfatin levels appear elevated in childhood obesity. Exercise seems to increase adiponectin levels whereas resistin levels are reduced. The lack of data on the effects of acute and chronic exercise on visfatin levels precludes us from making safe conclusions as to what the effects of exercise (acute or chronic) would be on visfatin levels in children. Clearly, exercise has an impact on the adipose tissue and the release of adiponectin, resistin, and visfatin. However, other factors affect the secretion rate of these adipokines from the adipose tissue; these factors should also be taken into consideration when examining the effects of exercise on adipokines. Gender, age, body composition, physical activity levels, mode and intensity of exercise are some of the factors that should be looked into in future studies.

  2. Type 2 diabetes and cardiovascular disease: getting to the fat of the matter.

    Science.gov (United States)

    Goralski, Kerry B; Sinal, Christopher J

    2007-01-01

    The increasing national prevalence of obesity is a major public health concern and a substantial burden on the health care resources of Canada. In addition to the direct health impact of obesity, this condition is a well-established risk factor for the development of various prevalent comorbidities including type 2 diabetes, hypertension, and cardiovascular disease. Historically, adipose tissue has been regarded primarily as an organ for energy storage. However, the discovery of leptin in the mid 1990's revolutionized our understanding of this tissue and has focused attention on the endocrine function of adipose tissue as a source of secreted bioactive peptides. These compounds, collectively termed adipokines, regulate a number of biological functions including appetite and energy balance, insulin sensitivity, lipid metabolism, blood pressure, and inflammation. The physiological importance of adipokines has led to the hypothesis that changes in the synthesis and secretion of these compounds in the obese are a causative factor contributing to the development of obesity and obesity-related diseases in these individuals. Following from this it has been proposed that pharmacologic manipulation of adipokine levels may provide novel effective therapeutic strategies to treat and prevent obesity, type 2 diabetes, and cardiovascular disease.

  3. Bacterial Translocation – Impact on the Adipocyte Compartment

    Science.gov (United States)

    Kruis, Tassilo; Batra, Arvind; Siegmund, Britta

    2013-01-01

    Over the last decade it became broadly recognized that adipokines and thus the fat tissue compartment exert a regulatory function on the immune system. Our own group described the pro-inflammatory function of the adipokine leptin within intestinal inflammation in a variety of animal models. Following-up on this initial work, the aim was to reveal stimuli and mechanisms involved in the activation of the fat tissue compartment and the subsequent release of adipokines and other mediators paralleled by the infiltration of immune cells. This review will summarize the current literature on the possible role of the mesenteric fat tissue in intestinal inflammation with a focus on Crohn’s disease (CD). CD is of particular interest in this context since the transmural intestinal inflammation has been associated with a characteristic hypertrophy of the mesenteric fat, a phenomenon called “creeping fat.” The review will address three consecutive questions: (i) What is inducing adipocyte activation, (ii) which factors are released after activation and what are the consequences for the local fat tissue compartment and infiltrating cells; (iii) do the answers generated before allow for an explanation of the role of the mesenteric fat tissue within intestinal inflammation? With this review we will provide a working model indicating a close interaction in between bacterial translocation, activation of the adipocytes, and subsequent direction of the infiltrating immune cells. In summary, the models system mesenteric fat indicates a unique way how adipocytes can directly interact with the immune system. PMID:24432024

  4. Aucubin, a naturally occurring iridoid glycoside inhibits TNF-α-induced inflammatory responses through suppression of NF-κB activation in 3T3-L1 adipocytes.

    Science.gov (United States)

    Park, Kyoung Sik

    2013-06-01

    Obesity is closely associated with a state of chronic, low-grade inflammation characterized by abnormal cytokine production and activation of inflammatory signaling pathways in adipose tissue. Tumor necrosis factor (TNF)-α is chronically elevated in adipose tissues of obese rodents and humans. Increased levels of TNF-α are implicated in the induction of atherogenic adipokines, such as plasminogen activator inhibitor (PAI)-1, adipose-tissue-derived monocyte chemoattractant protein (MCP)-1, and interleukin (IL)-6. Aucubin, an iridoid glycoside existing in medicinal plants, has been reported to show an anti-inflammatory activity by suppression of TNF-α production in murine macrophages. The present study is aimed to investigate the effects of aucubin on TNF-α-induced atherogenic changes of the adipokines in differentiated 3T3-L1 cells. Aucubin significantly inhibited TNF-α-induced secretion and mRNA synthesis of the atherogenic adipokines including PAI-1, MCP-1, and IL-6. Further investigation of the molecular mechanism revealed that pretreatment with aucubin suppressed extracellular signal-regulated kinase (ERK) activation, inhibitory kappa Bα (IκBα) degradation, and subsequent nuclear factor kappa B (NF-κB) activation. These findings suggest that aucubin may improve obesity-induced atherosclerosis by attenuating TNF-α-induced inflammatory responses.

  5. Hypoxia and adipose tissue function and dysfunction in obesity.

    Science.gov (United States)

    Trayhurn, Paul

    2013-01-01

    The rise in the incidence of obesity has led to a major interest in the biology of white adipose tissue. The tissue is a major endocrine and signaling organ, with adipocytes, the characteristic cell type, secreting a multiplicity of protein factors, the adipokines. Increases in the secretion of a number of adipokines occur in obesity, underpinning inflammation in white adipose tissue and the development of obesity-associated diseases. There is substantial evidence, particularly from animal studies, that hypoxia develops in adipose tissue as the tissue mass expands, and the reduction in Po(2) is considered to underlie the inflammatory response. Exposure of white adipocytes to hypoxic conditions in culture induces changes in the expression of >1,000 genes. The secretion of a number of inflammation-related adipokines is upregulated by hypoxia, and there is a switch from oxidative metabolism to anaerobic glycolysis. Glucose utilization is increased in hypoxic adipocytes with corresponding increases in lactate production. Importantly, hypoxia induces insulin resistance in fat cells and leads to the development of adipose tissue fibrosis. Many of the responses of adipocytes to hypoxia are initiated at Po(2) levels above the normal physiological range for adipose tissue. The other cell types within the tissue also respond to hypoxia, with the differentiation of preadipocytes to adipocytes being inhibited and preadipocytes being transformed into leptin-secreting cells. Overall, hypoxia has pervasive effects on the function of adipocytes and appears to be a key factor in adipose tissue dysfunction in obesity.

  6. The role of chemerin in human disease

    Directory of Open Access Journals (Sweden)

    Magdalena Stojek

    2017-02-01

    Full Text Available Adipose tissue is not merely a storage depot of triacylglycerols but also a major endocrine organ. Its cells, including adipocytes, synthesize and secrete a range of biologically active molecules termed adipokines. Adipokines that display the properties of cytokines are often called adipocytokines. In recent years there has been increasing interest in a new adipokine called chemerin. Chemerin is a protein synthesized mostly by the adipose tissue and the liver as inactive pre-pro-chemerin. After the intracellular hydrolytic cutting off of the 20-amino-acid N-terminal polypeptide, it is secreted into the bloodstream as inactive pro-chemerin. Biologically active chemerin is then derived from pro-chemerin after cleavage of the C-terminal fragment by serum proteases involved in inflammation, coagulation and fibrinolysis. Proteolytic cleavage leads to formation of several chemerin-derived peptides, both biologically active (often with opposing functions and inactive.Within the last decade, there has been a growing number of publications regarding the role of chemerin in human disease. It seems to be implicated in the inflammatory response, metabolic syndrome, cardiovascular disease and alimentary tract disorders. The article presents the most recent information on the role of chemerin in human disease, and specifically alimentary tract disorders. The available evidence suggests that chemerin is an important link between adipose tissue mass, metabolic processes, the immune system and inflammation, and therefore plays a major role in human pathophysiology.

  7. 3T3-L1 preadipocytes exhibit heightened monocyte-chemoattractant protein-1 response to acute fatty acid exposure.

    Science.gov (United States)

    Dordevic, Aimee L; Konstantopoulos, Nicky; Cameron-Smith, David

    2014-01-01

    Preadipocytes contribute to the inflammatory responses within adipose tissue. Whilst fatty acids are known to elicit an inflammatory response within adipose tissue, the relative contribution of preadipocytes and mature adipocytes to this is yet to be determined. We aimed to examine the actions of common dietary fatty acids on the acute inflammatory and adipokine response in 3T3-L1 preadipocytes and differentiated mature adipocytes. Gene expression levels of key adipokines in 3T3-L1 preadipocytes and adipocytes were determined following incubation with palmitic acid, myristic acid or oleic acid and positive inflammatory control, lipopolysaccharide for 2 and 4 h. Inflammatory kinase signalling was assessed by analysis of nuclear factor-κB, p38-mitogen-activated protein kinase and c-jun amino-terminal kinase phosphorylation. Under basal conditions, intracellular monocyte chemoattractant protein-1 and interleukin-6 gene expression levels were increased in preadipocytes, whereas mature adipocytes expressed increased gene expression levels of leptin and adiponectin. Fatty acid exposure at 2 and 4 h increased both monocyte chemoattractant protein-1 and interleukin-6 gene expression levels in preadipocytes to greater levels than in mature adipocytes. There was an accompanying increase of inhibitor of κB-α degradation and nuclear factor-κB (p65) (Ser536) phosphorylation with fatty acid exposure in the preadipocytes only. The current study points to preadipocytes rather than the adipocytes as the contributors to both immune cell recruitment and inflammatory adipokine secretion with acute increases in fatty acids.

  8. Bacterial translocation - impact on the adipocyte compartment.

    Science.gov (United States)

    Kruis, Tassilo; Batra, Arvind; Siegmund, Britta

    2014-01-01

    Over the last decade it became broadly recognized that adipokines and thus the fat tissue compartment exert a regulatory function on the immune system. Our own group described the pro-inflammatory function of the adipokine leptin within intestinal inflammation in a variety of animal models. Following-up on this initial work, the aim was to reveal stimuli and mechanisms involved in the activation of the fat tissue compartment and the subsequent release of adipokines and other mediators paralleled by the infiltration of immune cells. This review will summarize the current literature on the possible role of the mesenteric fat tissue in intestinal inflammation with a focus on Crohn's disease (CD). CD is of particular interest in this context since the transmural intestinal inflammation has been associated with a characteristic hypertrophy of the mesenteric fat, a phenomenon called "creeping fat." The review will address three consecutive questions: (i) What is inducing adipocyte activation, (ii) which factors are released after activation and what are the consequences for the local fat tissue compartment and infiltrating cells; (iii) do the answers generated before allow for an explanation of the role of the mesenteric fat tissue within intestinal inflammation? With this review we will provide a working model indicating a close interaction in between bacterial translocation, activation of the adipocytes, and subsequent direction of the infiltrating immune cells. In summary, the models system mesenteric fat indicates a unique way how adipocytes can directly interact with the immune system.

  9. Role of omentin and chemerin in metabolic syndrome and tumor diseases

    Directory of Open Access Journals (Sweden)

    Błażej Szydło

    2016-08-01

    Full Text Available For the past few years adipokines have been a center of appreciation and interest. They are biologically active molecules causing pleiotropic effects. They assist in angiogenesis, adipose tissue metabolism and inflammation, and modulate tissue sensitivity for insulin. Adipokines are produced in adipose tissue, so an abnormal quantity of this tissue leads to impaired levels of these factors. Because of their different concentrations in various conditions, it would be plausible to use them as markers for individual conditions, such as obesity, type 2 diabetes mellitus, pancreatitis, gastric cancer, lung cancer or colon cancer. Such adipokines as leptin, resistin, visfatin, adiponectin, and apelin are subjects of research. In our study we focused on the function and significance of chemerin and omentin in metabolic syndrome and cancers. In type 2 diabetes mellitus, both chemerin and omentin enhance the body sensitivity to insulin, which results in increased glucose uptake. However, in diabetic patients, serum concentration of omentin decreases, while that of chemerin increases. A similar trend was observed in obese patients. As a cancer marker, chemerin turned out to be helpful in diagnosis of gastric cancer, mesothelioma, and polycystic ovary syndrome, which can lead to endometrial cancer. An elevated concentration of omentin was noted in colon cancer, and increased expression of the omentin gene was reported in nasal polyps and mesothelioma.

  10. Adiponectin and its receptors in the ovary: further evidence for a link between obesity and hyperandrogenism in polycystic ovary syndrome.

    Science.gov (United States)

    Comim, Fabio V; Hardy, Kate; Franks, Stephen

    2013-01-01

    Polycystic ovary syndrome (PCOS), characterized by ovarian androgen excess, is the commonest endocrine disorder in women. Obesity increases androgen synthesis, a phenomenon attributed to the accompanying hyperinsulinemia. Our hypothesis was that adipokines, fat cell-derived hormones, play a direct role in modulating ovarian androgen secretion. Therefore, the aims of this study were to explore the effects of adipokines (in particular, adiponectin) on ovarian steroidogenesis and compare the expression of adiponectin receptors in ovaries from women with and without PCO. Sections of archived human ovaries (nine from women with normal ovaries and 16 with PCOS, classified histologically, with reference to menstrual history and ultrasound) were analysed by quantitative morphometry and the proportion of positive-labelling cells compared. In addition, studies of androgen production in relation to adipokine function in primary bovine theca cell culture were also performed. A significantly lower proportion of theca cells expressed adiponectin receptors 1 and 2 (AdipoR1, AdipoR2) in polycystic ovaries than in normal ovaries. In cultured theca cells, adiponectin suppressed androstenedione production and gene expression of LH receptor and key enzymes in the androgen synthesis pathway. Moreover, knockdown of genes for AdipoR1 and AdipoR2 was associated with increased androstenedione secretion by bovine theca cells. These results provide evidence for a direct link between fat cell metabolism and ovarian steroidogenesis, suggesting that disruption of adiponectin and/or its receptors plays a key role in pathogenesis of hyperandrogenism in PCOS.

  11. Reproducibility of Retinol Binding Protein 4 and Omentin-1 Measurements over a Four Months Period: A Reliability Study in a Cohort of 207 Apparently Healthy Participants.

    Directory of Open Access Journals (Sweden)

    Clemens Wittenbecher

    Full Text Available The reliability of single time point measurements of the novel adipokines retinol-binding protein 4 and omentin-1 in the blood has not been evaluated in large samples yet. The present study aimed to assess the amount of biological variation of these two adipokines within individuals. The study sample comprised 207 participants (124 women and 83 men from Potsdam (Germany and surrounding areas, with an average age of 56.5 years (SD 4.2. Blood samples were collected from each participant twice, approximately four months apart. Using enzyme linked immunosorbent assays, the concentrations of retinol-binding protein 4 and omentin-1 were determined in EDTA plasma. As indicators of reliability, intraclass correlation coefficients (ICCs were calculated from the repeated biomarker measurements. The ICCs for repeated retinol-binding protein 4 and omentin-1 measurements were 0.77 (95% CI 0.71, 0.82 and 0.83 (95% CI 0.78, 0.87, respectively, indicating for both adipokines excellent reliability. ICCs were stable across strata according to sex, age, BMI, and blood pressure. Thus, for epidemiological studies it seems reasonable to rely on concentrations of retinol-binding protein 4 and omentin-1 in samples from a single time point if repeated measurements are not available.

  12. Serum and synovial fluid lipidomic profiles predict obesity-associated osteoarthritis, synovitis, and wound repair

    Science.gov (United States)

    Wu, Chia-Lung; Kimmerling, Kelly A.; Little, Dianne; Guilak, Farshid

    2017-01-01

    High-fat diet-induced obesity is a major risk factor for osteoarthritis (OA) and diminished wound healing. The objective of this study was to determine the associations among serum and synovial fluid lipid levels with OA, synovitis, adipokine levels, and wound healing in a pre-clinical obese mouse model of OA. Male C57BL/6 J mice were fed either a low-fat (10% kcal) or one of three high-fat (HF, 60% kcal) diets rich in saturated fatty acids (SFAs), ω-6 or ω-3 polyunsaturated FAs (PUFAs). OA was induced by destabilization of the medial meniscus. Mice also received an ear punch for evaluating wound healing. Serum and synovial fluid were collected for lipidomic and adipokine analyses. We demonstrated that the serum levels of ω-3 PUFAs were negatively correlated with OA and wound size, but positively correlated with adiponectin levels. In contrast, most ω-6 PUFAs exhibited positive correlations with OA, impaired healing, and inflammatory adipokines. Interestingly, levels of pentadecylic acid (C15:0, an odd-chain SFA) and palmitoleic acid were inversely correlated with joint degradation. This study extends our understanding of the links of FAs with OA, synovitis and wound healing, and reports newly identified serum and synovial fluid FAs as predictive biomarkers of OA in obesity. PMID:28317846

  13. Lycopene supplementation modulates plasma concentrations and epididymal adipose tissue mRNA of leptin, resistin and IL-6 in diet-induced obese rats.

    Science.gov (United States)

    Luvizotto, Renata de Azevedo Melo; Nascimento, Andre F; Imaizumi, Erika; Pierine, Damiana T; Conde, Sandro J; Correa, Camila R; Yeum, Kyung-Jin; Ferreira, Ana Lucia A

    2013-11-01

    Obesity is characterised by chronic low-grade inflammation, and lycopene has been reported to display anti-inflammatory effects. However, it is not clear whether lycopene supplementation modulates adipokine levels in vivo in obesity. To determine whether lycopene supplementation can regulate adipokine expression in obesity, male Wistar rats were randomly assigned to receive a control diet (C, n 6) ora hyperenergetic diet (DIO, n 12) for 6 weeks. After this period, the DIO animals were randomised into two groups: DIO (n 6) and DIO supplemented with lycopene (DIO + L, n 6). The animals received maize oil (C and DIO) or lycopene (DIO + L, 10 mg/kg body weight(BW) per d) by oral administration for a 6-week period. The animals were then killed by decapitation, and blood samples and epididymal adipose tissue were collected for hormonal determination and gene expression evaluation (IL-6, monocyte chemoattractant protein-1(MCP-1), TNF-α, leptin and resistin). There was no detectable lycopene in the plasma of the C and DIO groups. However, the mean lycopene plasma concentration was 24 nmol in the DIO + L group. Although lycopene supplementation did not affect BW or adiposity, it significantly decreased leptin, resistin and IL-6 gene expression in epididymal adipose tissue and plasma concentrations. Also, it significantly reduced the gene expression of MCP-1 in epididymal adipose tissue. Lycopene affects adipokines by reducing leptin, resistin and plasma IL-6 levels. These data suggest that lycopene may be an effective strategy in reducing inflammation in obesity.

  14. Increased peroxisome proliferator-activated receptor γ expression levels in visceral adipose tissue, and serum CCL2 and interleukin-6 levels during visceral adipose tissue accumulation.

    Science.gov (United States)

    Yogarajah, Thaneswary; Bee, Yvonne-Tee Get; Noordin, Rahmah; Yin, Khoo Boon

    2015-01-01

    This study was conducted to determine the mRNA and protein expression levels of peroxisome proliferator-activated receptors (PPARs) in visceral adipose tissue, as well as serum adipokine levels, in Sprague Dawley rats. The rats were fed either a normal (control rats) or excessive (experimental rats) intake of food for 8 or 16 weeks, then sacrificed, at which time visceral and subcutaneous adipose tissues, as well as blood samples, were collected. The mRNA and protein expression levels of PPARs in the visceral adipose tissues were determined using reverse transcription-polymerase chain reaction and Western blotting, respectively. In addition, the levels of adipokines in the serum samples were determined using commercial ELISA kits. The results revealed that at 8 weeks, the mass of subcutaneous adipose tissue was higher than that of the visceral adipose tissue in the experimental rats, but the reverse occurred at 16 weeks. Furthermore, at 16 weeks the experimental rats exhibited an upregulation of PPARγ mRNA and protein expression levels in the visceral adipose tissues, and significant increases in the serum levels of CCL2 and interleukin (IL)-6 were observed, compared with those measured at 8 weeks. In conclusion, this study demonstrated that the PPARγ expression level was likely correlated with serum levels of CCL2 and IL-6, molecules that may facilitate visceral adipose tissue accumulation. In addition, the levels of the two adipokines in the serum may be useful as surrogate biomarkers for the expression levels of PPARγ in accumulated visceral adipose tissues.

  15. [Epicardial adipose tissue and its role in cardiac physiology and disease].

    Science.gov (United States)

    Toczyłowski, Kacper; Gruca, Michał; Baranowski, Marcin

    2013-06-20

    Adipose tissue secretes a number of cytokines, referred to as adipokines. Intensive studies conducted over the last two decades showed that adipokines exert broad effects on cardiac metabolism and function. In addition, the available data strongly suggests that these cytokines play an important role in development of cardiovascular diseases. Epicardial adipose tissue (EAT) has special properties that distinguish it from other deposits of visceral fat. Overall, there appears to be a close functional and anatomic relationship between the EAT and the cardiac muscle. They share the same coronary blood supply, and there is no structure separating the adipose tissue from the myocardium or coronary arteries. The role of EAT in osierdziocardiac physiology remains unclear. Its putative functions include buffering coronary arteries against the torsion induced by the arterial pulse wave and cardiac contraction, regulating fatty acid homeostasis in the coronary microcirculation, thermogenesis, and neuroprotection of the cardiac autonomic ganglia and nerves. Obesity (particularly the abdominal phenotype) leads to elevated EAT content, and the available data suggests that high amount of this fat depot is associated with increased risk of ischemic heart disease, cardiac hypertrophy and diastolic dysfunction. The mass of EAT is small compared to other fat deposits in the body. Nevertheless, its close anatomic relationship to the heart suggests that this organ is highly exposed to EAT-derived adipokines which makes this tissue a very promising area of research. In this paper we review the current knowledge on the role of EAT in cardiac physiology and development of heart disease.

  16. Pulmonary hypertension and metabolic syndrome: Possible connection, PPARγ and Caveolin-1

    Institute of Scientific and Technical Information of China (English)

    Rajamma; Mathew

    2014-01-01

    A number of disparate diseases can lead to pulmonary hypertension(PH), a serious disorder with a high morbidity and mortality rate. Recent studies suggest that the associated metabolic dysregulation may be an important factor adversely impacting the prognosis of PH. Furthermore, metabolic syndrome is associated with vascular diseases including PH. Inflammation plays a significant role both in PH and metabolic syndrome. Adipose tissue modulates lipid and glucose metabolism, and also produces pro-and anti-inflammatory adipokines that modulate vascular function and angiogenesis, suggesting a close functional relationship between the adipose tissue and the vasculature. Both caveolin-1, a cell membrane scaffolding protein and peroxisome proliferator-activated receptor(PPAR) γ, a ligandactivated transcription factor are abundantly expressed in the endothelial cells and adipocytes. Both caveolin-1 and PPARγ modulate proliferative and anti-apoptotic pathways, cell migration, inflammation, vascular homeostasis, and participate in lipid transport, triacylglyceride synthesis and glucose metabolism. Caveolin-1 and PPARγ regulate the production of adipokines and in turn are modulated by them. This review article summarizes the roles and inter-relationships of caveolin-1,PPARγ and adipokines in PH and metabolic syndrome.

  17. Transcriptomic Profiling of Adipose Tissue in Obese Women in Response to Acupuncture Catgut Embedding Therapy with Moxibustion.

    Science.gov (United States)

    Garcia-Vivas, Jessica M; Galaviz-Hernandez, Carlos; Fernandez-Retana, Jorge; Pedroza-Torres, Abraham; Perez-Plasencia, Carlos; Lopez-Camarillo, Cesar; Marchat, Laurence A

    2016-08-01

    Complementary and alternative medicine, such as Traditional Chinese Medicine, represents an efficient therapeutic option for obesity control. It was previously reported that acupuncture catgut embedding therapy (ACET) with moxibustion reduces body weight and reverts insulin resistance in obese women. This study aimed to evidence changes in adipokines and gene expression in adipose tissue that could explain the effects of ACET with moxibustion. Overweight/obese women were treated with ACET with moxibustion or sham acupuncture as control. Peripheral blood samples and fat biopsies were taken before and after intervention. Circulating adipokines (leptin, adiponectin, tumor necrosis factor alpha, and resistin) were quantified by enzyme-linked immunosorbent assay. Gene expression in adipose tissue was determined by cDNA microarray assays and assessed by quantitative reverse transcription real-time polymerase chain reaction. ACET with moxibustion did not modify circulating adipokines levels. However, correlations with anthropometric and biochemical parameters were affected. Interestingly, transcriptional changes in adipose tissue revealed the modulation of genes participating in homeostasis control, lipid metabolism, olfactory transduction, and gamma-aminobutyric acid signaling pathway. The effects of ACET with moxibustion on body weight and insulin resistance were associated with the regulation of biochemical events that are altered in obesity.

  18. In Utero Nutritional Manipulation Provokes Dysregulated Adipocytokines Production in F1 Offspring in Rats

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    Mervat Y. Hanafi

    2016-01-01

    Full Text Available Background. Intrauterine environment plays a pivotal role in the origin of fatal diseases such as diabetes. Diabetes and obesity are associated with low-grade inflammatory state and dysregulated adipokines production. This study aims to investigate the effect of maternal obesity and malnutrition on adipokines production (adiponectin, leptin, and TNF-α in F1 offspring in rats. Materials and Methods. Wistar rats were allocated in groups: F1 offspring of control mothers under control diet (CF1-CD and under high-fat diet (CF1-HCD, F1 offspring of obese mothers under CD (OF1-CD and under HCD (OF1-HCD, and F1 offspring of malnourished mothers under CD (MF1-CD and under HCD (MF1-HCD. Every 5 weeks postnatally, blood samples were obtained for biochemical analysis. Results. At the end of the 30-week follow-up, OF1-HCD and MF1-HCD exhibited hyperinsulinemia, moderate dyslipidemia, insulin resistance, and impaired glucose homeostasis compared to CF1-CD and CF1-HCD. OF1-HCD and MF1-HCD demonstrated low serum levels of adiponectin and high levels of leptin compared to CF1-CD and CF1-HCD. OF1-CD, OF1-HCD, and MF1-HCD had elevated serum levels of TNF-α compared to CF1-CD and CF1-HCD (p<0.05. Conclusion. Maternal nutritional manipulation predisposes the offspring to development of insulin resistance in their adult life, probably via instigating dysregulated adipokines production.

  19. Sarcopenia, obesity, and natural killer cell immune senescence in aging: altered cytokine levels as a common mechanism.

    Science.gov (United States)

    Lutz, Charles T; Quinn, LeBris S

    2012-08-01

    Human aging is characterized by both physical and physiological frailty. A key feature of frailty, sarcopenia is the age-associated decline in skeletal muscle mass, strength, and endurance that characterize even the healthy elderly. Increases in adiposity, particularly in visceral adipose tissue, are almost universal in aging individuals and can contribute to sarcopenia and insulin resistance by increasing levels of inflammatory cytokines known collectively as adipokines. Aging also is associated with declines in adaptive and innate immunity, known as immune senescence, which are risk factors for cancer and all-cause mortality. The cytokine interleukin-15 (IL-15) is highly expressed in skeletal muscle tissue and declines in aging rodent models. IL-15 inhibits fat deposition and insulin resistance, is anabolic for skeletal muscle in certain situations, and is required for the development and survival of natural killer (NK) lymphocytes. We review the effect that adipokines and myokines have on NK cells, with special emphasis on IL-15. We posit that increased adipokine and decreased IL-15 levels during aging constitute a common mechanism for sarcopenia, obesity, and immune senescence.

  20. Benefits of healthy adipose tissue in the treatment of diabetes.

    Science.gov (United States)

    Gunawardana, Subhadra C

    2014-08-15

    The major malfunction in diabetes mellitus is severe perturbation of glucose homeostasis caused by deficiency of insulin. Insulin deficiency is either absolute due to destruction or failure of pancreatic β cells, or relative due to decreased sensitivity of peripheral tissues to insulin. The primary lesion being related to insulin, treatments for diabetes focus on insulin replacement and/or increasing sensitivity to insulin. These therapies have their own limitations and complications, some of which can be life-threatening. For example, exogenous insulin administration can lead to fatal hypoglycemic episodes; islet/pancreas transplantation requires life-long immunosuppressive therapy; and anti-diabetic drugs have dangerous side effects including edema, heart failure and lactic acidosis. Thus the need remains for better safer long term treatments for diabetes. The ultimate goal in treating diabetes is to re-establish glucose homeostasis, preferably through endogenously generated hormones. Recent studies increasingly show that extra-pancreatic hormones, particularly those arising from adipose tissue, can compensate for insulin, or entirely replace the function of insulin under appropriate circumstances. Adipose tissue is a versatile endocrine organ that secretes a variety of hormones with far-reaching effects on overall metabolism. While unhealthy adipose tissue can exacerbate diabetes through limiting circulation and secreting of pro-inflammatory cytokines, healthy uninflamed adipose tissue secretes beneficial adipokines with hypoglycemic and anti-inflammatory properties, which can complement and/or compensate for the function of insulin. Administration of specific adipokines is known to alleviate both type 1 and 2 diabetes, and leptin mono-therapy is reported to reverse type 1 diabetes independent of insulin. Although specific adipokines may correct diabetes, administration of individual adipokines still carries risks similar to those of insulin monotherapy. Thus a

  1. WJD 5th Anniversary Special Issues(1): Insulin Benefits of healthy adipose tissue in the treatment of diabetes

    Institute of Scientific and Technical Information of China (English)

    Subhadra; C; Gunawardana

    2014-01-01

    The major malfunction in diabetes mellitus is severe perturbation of glucose homeostasis caused by deficiency of insulin.Insulin deficiency is either absolute due to destruction or failure of pancreaticβcells,or relative due to decreased sensitivity of peripheral tissues to insulin.The primary lesion being related to insulin,treatments for diabetes focus on insulin replacement and/or increasing sensitivity to insulin.These therapies have their own limitations and complications,some of which can be life-threatening.For example,exogenous insulin administration can lead to fatal hypoglycemic episodes;islet/pancreas transplantation requires life-long immunosuppressive therapy;and anti-diabetic drugs have dangerous side effects including edema,heart failure and lactic acidosis.Thus the need remains for better safer long term treatments for diabetes.The ultimate goal in treating diabetes is to re-establish glucose homeostasis,preferably through endogenously generated hormones.Recent studies increasingly show that extra-pancreatic hormones,particularly those arising from adipose tissue,can compensate for insulin,or entirely replace the function of insulin under appropriate circumstances.Adipose tissue is a versatile endocrine organ that secretes a variety of hormones with far-reaching effects on overall metabolism.While unhealthy adipose tissue can exacerbate diabetes through limiting circulation and secreting of pro-inflammatory cytokines,healthy uninflamed adipose tissue secretes beneficial adipokines with hypoglycemic and anti-inflammatory properties,which can complement and/or compensate for the function of insulin.Administration of specific adipokines is known to alleviate both type 1 and 2 diabetes,and leptin mono-therapy is reported to reverse type 1 diabetes independent of insulin.Although specific adipokines may correct diabetes,administration of individual adipokines still carries risks similar to those of insulin monotherapy.Thus a better approach is to

  2. Perivascular adipose tissue-secreted angiopoietin-like protein 2 (Angptl2) accelerates neointimal hyperplasia after endovascular injury.

    Science.gov (United States)

    Tian, Zhe; Miyata, Keishi; Tazume, Hirokazu; Sakaguchi, Hisashi; Kadomatsu, Tsuyoshi; Horio, Eiji; Takahashi, Otowa; Komohara, Yoshihiro; Araki, Kimi; Hirata, Yoichiro; Tabata, Minoru; Takanashi, Shuichiro; Takeya, Motohiro; Hao, Hiroyuki; Shimabukuro, Michio; Sata, Masataka; Kawasuji, Michio; Oike, Yuichi

    2013-04-01

    Much attention is currently focused on the role of perivascular adipose tissue in development of cardiovascular disease (CVD). Some researchers view it as promoting CVD through secretion of cytokines and growth factors called adipokines, while recent reports reveal that perivascular adipose tissue can exert a protective effect on CVD development. Furthermore, adiponectin, an anti-inflammatory adipokine, reportedly suppresses neointimal hyperplasia after endovascular injury, whereas such vascular remodeling is enhanced by pro-inflammatory adipokines secreted by perivascular adipose, such as tumor necrosis factor-α (TNF-α). These findings suggest that extent of vascular remodeling, a pathological process associated with CVD development, depends on the balance between pro- and anti-inflammatory adipokines secreted from perivascular adipose tissue. We previously demonstrated that angiopoietin-like protein 2 (Angptl2), a pro-inflammatory factor secreted by adipose tissue, promotes adipose tissue inflammation and subsequent systemic insulin resistance in obesity. Here, we examined whether Angptl2 secreted by perivascular adipose tissue contributes to vascular remodeling after endovascular injury in studies of transgenic mice expressing Angptl2 in adipose tissue (aP2-Angptl2 transgenic mice) and Angptl2 knockout mice (Angptl2(-/-) mice). To assess the role of Angptl2 secreted by perivascular adipose tissue on vascular remodeling after endovascular injury, we performed adipose tissue transplantation experiments using these mice. Wild-type mice with perivascular adipose tissue derived from aP2-Angptl2 mice exhibited accelerated neointimal hyperplasia after endovascular injury compared to wild-type mice transplanted with wild-type tissue. Conversely, vascular inflammation and neointimal hyperplasia after endovascular injury were significantly attenuated in wild-type mice transplanted with Angptl2(-/-) mouse-derived perivascular adipose tissue compared to wild-type mice

  3. Epicardial adipose tissue and its role in cardiac physiology and disease 

    Directory of Open Access Journals (Sweden)

    Kacper Toczyłowski

    2013-06-01

    Full Text Available Adipose tissue secretes a number of cytokines, referred to as adipokines. Intensive studies conducted over the last two decades showed that adipokines exert broad effects on cardiac metabolism and function. In addition, the available data strongly suggests that these cytokines play an important role in development of cardiovascular diseases. Epicardial adipose tissue (EAT has special properties that distinguish it from other deposits of visceral fat. Overall, there appears to be a close functional and anatomic relationship between the EAT and the cardiac muscle. They share the same coronary blood supply, and there is no structure separating the adipose tissue from the myocardium or coronary arteries. The role of EAT in osierdziocardiac physiology remains unclear. Its putative functions include buffering coronary arteries against the torsion induced by the arterial pulse wave and cardiac contraction, regulating fatty acid homeostasis in the coronary microcirculation, thermogenesis, and neuroprotection of the cardiac autonomic ganglia and nerves. Obesity (particularly the abdominal phenotype leads to elevated EAT content, and the available data suggests that high amount of this fat depot is associated with increased risk of ischemic heart disease, cardiac hypertrophy and diastolic dysfunction. The mass of EAT is small compared to other fat deposits in the body. Nevertheless, its close anatomic relationship to the heart suggests that this organ is highly exposed to EAT-derived adipokines which makes this tissue a very promising area of research. In this paper we review the current knowledge on the role of EAT in cardiac physiology and development of heart disease.

  4. Hypoxia in adipose tissue: a basis for the dysregulation of tissue function in obesity?

    Science.gov (United States)

    Trayhurn, Paul; Wang, Bohan; Wood, I Stuart

    2008-08-01

    White adipose tissue is a key endocrine and secretory organ, releasing multiple adipokines, many of which are linked to inflammation and immunity. During the expansion of adipose tissue mass in obesity there is a major inflammatory response in the tissue with increased expression and release of inflammation-related adipokines, including IL-6, leptin, monocyte chemoattractant protein-1 and TNF-alpha, together with decreased adiponectin production. We proposed in 2004 (Trayhurn & Wood, Br J Nutr 92, 347-355) that inflammation in adipose tissue in obesity is a response to hypoxia in enlarged adipocytes distant from the vasculature. Hypoxia has now been directly demonstrated in adipose tissue of several obese mouse models (ob/ob, KKAy, diet-induced) and molecular studies indicate that the level of the hypoxia-inducible transcription factor, hypoxia-inducible factor-1 alpha, is increased, as is expression of the hypoxia-sensitive marker gene, GLUT1. Cell- culture studies on murine and human adipocytes show that hypoxia (induced by low O2 or chemically) leads to stimulation of the expression and secretion of a number of inflammation-related adipokines, including angiopoietin-like protein 4, IL-6, leptin, macrophage migration inhibitory factor and vascular endothelial growth factor. Hypoxia also stimulates the inflammatory response of macrophages and inhibits adipocyte differentiation from preadipocytes. GLUT1 gene expression, protein level and glucose transport by human adipocytes are markedly increased by hypoxia, indicating that low O2 tension stimulates glucose utilisation. It is suggested that hypoxia has a pervasive effect on adipocyte metabolism and on overall adipose tissue function, underpinning the inflammatory response in the tissue in obesity and the subsequent development of obesity-associated diseases, particularly type 2 diabetes and the metabolic syndrome.

  5. Differentiation of human adipocytes at physiological oxygen levels results in increased adiponectin secretion and isoproterenol-stimulated lipolysis.

    Science.gov (United States)

    Famulla, Susanne; Schlich, Raphaela; Sell, Henrike; Eckel, Jürgen

    2012-07-01

    Adipose tissue (AT) hypoxia occurs in obese humans and mice. Acute hypoxia in adipocytes causes dysregulation of adipokine secretion with an increase in inflammatory factors and diminished adiponectin release. O2 levels in humans range between 3 and 11% revealing that conventional in vitro culturing at ambient air and acute hypoxia treatment (1% O2) are performed under non-physiological conditions. In this study, we mimicked physiological conditions by differentiating human primary adipocytes under 10% or 5% O2 in comparison to 21% O2. Induction of differentiation markers was comparable between all three conditions. Adipokine release by adipocytes differentiated at lower oxygen levels was altered, with a marked upregulation of adiponectin, IL-6 and DPP4 secretion, and reduced leptin levels compared with adipocytes differentiated at 21% O2. Isoproterenol-induced lipolysis was significantly elevated in adipocytes differentiated at 10% and 5% compared with 21% O2. This effect was accompanied by increased protein expression of β-1 and -2 adrenergic receptor, HSL and perilipin. Conditioned medium (CM) of adipocytes differentiated at the three different conditions was generated for stimulation of human skeletal muscle cells (SkMC) or smooth muscle cells (SMC). CM-induced insulin resistance in SkMC was comparable for the different CMs. However, the SMC proliferative effect of CM from adipocytes differentiated at 10% O2 was significantly reduced compared with 21% O2. This study demonstrates that oxygen levels during adipogenesis are important factors altering adipocyte functionality such as adipokine release, in particular adiponectin secretion, as well as the hormone-induced lipolytic pathway.

  6. The differential anti-inflammatory effects of exercise modalities and their association with early carotid atherosclerosis progression in patients with type 2 diabetes.

    Science.gov (United States)

    Kadoglou, N P E; Fotiadis, G; Kapelouzou, A; Kostakis, A; Liapis, C D; Vrabas, I S

    2013-02-01

    Adipokines, visfatin, apelin, vaspin and ghrelin have emerged as novel cardiovascular risk factors. We aimed to evaluate the effects of different exercise modalities on the aforementioned novel adipokines and carotid intima-media thickness in patients with Type 2 diabetes mellitus. One hundred patients with Type 2 diabetes were equivalently (n = 25) randomized into four groups: (1) a control group with patients encouraged to perform self-controlled exercise; (2) a supervised aerobic exercise group (exercise four times/week, 60 min/session, 60-75% of maximum heart rate); (3) a resistance training group (60-80% baseline maximum load achieved in one repetition); and (4) a combined aerobic exercise plus resistance training group, as in groups 2 and 3. All participants had HbA(1c) levels ≥ 48 mmol/mol (≥ 6.5%), without overt diabetic vascular complications. Blood samples, clinical characteristics, peak oxygen uptake and carotid intima-media thickness measurements were obtained at baseline and at the end of the study, after 6 months. At baseline, there were non-significant differences between groups. All active groups significantly ameliorated glycaemic profile, insulin sensitivity and triglycerides levels compared with the control group (P exercise capacity compared with the resistance training and the control groups (P exercise group and the aerobic exercise plus resistance training group, and compared with the other groups (P exercise modalities. Finally, aerobic training attenuated the carotid intima-media thickness progression (0.017 ± 0.006 mm) compared with the control subjects (0.129 ± 0.042 mm, P Type 2 diabetes, all exercise training modalities improved metabolic profile. Importantly, aerobic training predominantly ameliorated adipokines concentrations and carotid intima-media thickness progression. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

  7. Quantitative analysis of secretome from adipocytes regulated by insulin

    Institute of Scientific and Technical Information of China (English)

    Hu Zhou; Yuanyuan Xiao; Rongxia Li; Shangyu Hong; Sujun Li; Lianshui Wang; Rong Zeng; Kan Liao

    2009-01-01

    Adipocyte is not only a central player involved in storage and release of energy, but also in regulation of energy metabolism in other organs via secretion of pep-tides and proteins. During the pathogenesis of insulin resistance and type 2 diabetes, adipocytes are subjected to the increased levels of insulin, which may have a major impact on the secretion of adipokines. We have undertaken cleavable isotope-coded affinity tag (clCAT) and label-free quantitation approaches to identify and quantify secretory factors that are differen-tially secreted by 3T3-LI adipocytes with or without insulin treatment. Combination of clCAT and label-free results, there are 317 proteins predicted or annotated as secretory proteins. Among these secretory proteins, 179 proteins and 53 proteins were significantly up-regulated and down-regulated, respectively. A total of 77 reported adipokines were quantified