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Sample records for adipokines

  1. Clinical Relevance of Adipokines

    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.

  2. Adipokines and Insulin Resistance

    Rabe, Katja; Lehrke, Michael; Parhofer, Klaus G; Broedl, Uli C.

    2008-01-01

    Obesity is associated with an array of health problems in adult and pediatric populations. Understanding the pathogenesis of obesity and its metabolic sequelae has advanced rapidly over the past decades. Adipose tissue represents an active endocrine organ that, in addition to regulating fat mass and nutrient homeostasis, releases a large number of bioactive mediators (adipokines) that signal to organs of metabolic importance including brain, liver, skeletal muscle, and the immune system—there...

  3. Adipokines and Hepatic Insulin Resistance

    Yu Li; Lin Ding; Waseem Hassan; Daoud Abdelkader; Jing Shang

    2013-01-01

    Obesity is a major risk factor for insulin resistance and type 2 diabetes. Adipose tissue is now considered to be an active endocrine organ that secretes various adipokines such as adiponectin, leptin, resistin, tumour necrosis factor-α, and interleukin-6. Recent studies have shown that these factors might provide a molecular link between increased adiposity and impaired insulin sensitivity. Since hepatic insulin resistance plays the key role in the whole body insulin resistance, clarificatio...

  4. CARDIOVASCULAR DISORDERS WITH HYPOTHYROIDISM AND ADIPOKINES

    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.

  5. Adipokines mediate inflammation and insulin resistance

    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.

  6. Adipokines and the Female Reproductive Tract

    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.

  7. The Importance of Adipokines in Alzheimer's Disease

    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

  8. The role of adipokines in monoclonal gammopathies

    Oliveira, Luís Alberto Resendes de

    2015-01-01

    In the pathogenesis of monoclonal gammopathies (MG), namely in multiple myeloma (MM), the bone marrow microenvironment displays a critical role. As there is accumulating evidence supporting a link between obesity and MM, it is possible that this association is made through altered adipokines secretion levels. Whereas these hormones are important in several physiologic functions, there are studies showing that they also participate in the carcinogenesis process of some solid tumors. However, a...

  9. Ethnic Differences in Maternal Adipokines during Normal Pregnancy

    Xinhua Chen; Scholl, Theresa O.

    2015-01-01

    Two adipokines (adiponectin and resistin) have opposite relations with insulin resistance and inflammation. Our major focus was to determine whether there were detectable ethnic differences in maternal adipokines during pregnancy. We also explored the correlation of the adipokines with maternal glucose homeostasis, blood pressure and anthropometric parameters. Pregnant women (n = 1634) were from a large prospective cohort study in Camden NJ (African-American 36.8%; Hispanic 47.6%; Caucasian 1...

  10. Serum Levels of the Adipokine Progranulin Depend on Renal Function

    Richter, Judit; Focke, Denise; Ebert, Thomas; Kovacs, Peter; Bachmann, Anette; Lössner, Ulrike; Kralisch, Susan; Kratzsch, Jürgen; Beige, Joachim; Anders, Matthias; Bast, Ingolf; Blüher, Matthias; Stumvoll, Michael; Fasshauer, Mathias

    2013-01-01

    OBJECTIVE Progranulin has recently been introduced as a novel adipokine inducing insulin resistance and obesity. In the current study, we investigated renal elimination, as well as association of the adipokine with markers of the metabolic syndrome. RESEARCH DESIGN AND METHODS Progranulin serum levels were quantified by enzyme-linked immunosorbent assay and correlated to anthropometric and biochemical parameters of renal function and glucose and lipid metabolism, as well as inflammation, in 5...

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

    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. Anticoagulants used in plasma collection affect adipokine multiplexed measurements.

    Allione, Alessandra; Di Gaetano, Cornelia; Dani, Nadia; Barberio, Davide; Sieri, Sabina; Krogh, Vittorio; Matullo, Giuseppe

    2016-04-01

    Obesity is an important health problem worldwide. Adipose tissue acts as an endocrine organ that secretes various bioactive substances, called adipokines, including pro-inflammatory biomarkers such as TNF-α, IL-6, leptin and C-reactive protein (CRP) and anti-inflammatory molecules such as adiponectin. The deregulated production of adipokines in obesity is linked to the pathogenesis of various disease processes and monitoring their variation is critical to understand metabolic diseases. The aim of this study was to determine the plasma concentration of adipokines in healthy subjects by multiplexed measurements and the effect of anticoagulants on their levels. Plasma samples from 10 healthy donors were collected in two different anticoagulants (sodium citrate or heparin). All markers, excluding TNF-α, showed significantly higher concentrations in heparinized compared to citrate plasma. However, levels of adipokines in different plasma samples were highly correlated for most of these markers. We reported that different anticoagulants used in the preparation of the plasma samples affected the measurements of some adipokines. The importance of the present results in epidemiology is relevant when comparing different studies in which blood samples were collected with different anticoagulants. PMID:26945995

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

    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. PMID:24002404

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

    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.

  15. Ethnic Differences in Maternal Adipokines during Normal Pregnancy

    Xinhua Chen

    2015-12-01

    Full Text Available Two adipokines (adiponectin and resistin have opposite relations with insulin resistance and inflammation. Our major focus was to determine whether there were detectable ethnic differences in maternal adipokines during pregnancy. We also explored the correlation of the adipokines with maternal glucose homeostasis, blood pressure and anthropometric parameters. Pregnant women (n = 1634 were from a large prospective cohort study in Camden NJ (African-American 36.8%; Hispanic 47.6%; Caucasian 15.6%. Serum adiponectin and resistin were measured at entry (week 16.8 and the 3rd trimester (week 30.7 using the Luminex xMapTechnology. Significant differences were observed among ethnic groups, controlling for confounding variables. African American women were exceptional in that they had decreased adiponectin and increased resistin throughout the course of pregnancy (p < 0.05 to p < 0.0001 and a greater than two fold risk of simultaneously exhibiting low adiponectin (lowest tertile and high resistin (highest tertile compared to Caucasians and/or Hispanics. The cohort as a whole and each ethnic group showed similar negative correlations between adiponectin, and glucose homeostasis, blood pressure and anthropometric parameters but there was lesser correspondence with resistin. Our data underscore the need for further research on ethnic variation in adipokines and other physiologic biomarkers during complicated and uncomplicated pregnancy.

  16. Ethnic Differences in Maternal Adipokines during Normal Pregnancy.

    Chen, Xinhua; Scholl, Theresa O

    2016-01-01

    Two adipokines (adiponectin and resistin) have opposite relations with insulin resistance and inflammation. Our major focus was to determine whether there were detectable ethnic differences in maternal adipokines during pregnancy. We also explored the correlation of the adipokines with maternal glucose homeostasis, blood pressure and anthropometric parameters. Pregnant women (n = 1634) were from a large prospective cohort study in Camden NJ (African-American 36.8%; Hispanic 47.6%; Caucasian 15.6%). Serum adiponectin and resistin were measured at entry (week 16.8) and the 3rd trimester (week 30.7) using the Luminex xMapTechnology. Significant differences were observed among ethnic groups, controlling for confounding variables. African American women were exceptional in that they had decreased adiponectin and increased resistin throughout the course of pregnancy (p Hispanics. The cohort as a whole and each ethnic group showed similar negative correlations between adiponectin, and glucose homeostasis, blood pressure and anthropometric parameters but there was lesser correspondence with resistin. Our data underscore the need for further research on ethnic variation in adipokines and other physiologic biomarkers during complicated and uncomplicated pregnancy. PMID:26703679

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

    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.

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

    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

  19. Adipokines and the Peripheral and Neural Control of Energy Balance

    Ahima, Rexford S.; Lazar, Mitchell A.

    2008-01-01

    Adipokines are secreted by adipose tissue and control various physiological systems. Low leptin levels during fasting stimulate feeding, reduce energy expenditure, and modulate neuroendocrine and immune function to conserve energy stores. On the other hand, rising leptin levels in the overfed state prevent weight gain by inhibiting food intake and increasing energy expenditure. These actions are mediated by neuronal circuits in the hypothalamus and brainstem. Leptin also controls glucose and ...

  20. Human NK Cell Subset Functions Are Differentially Affected by Adipokines

    Huebner, Lena; Engeli, Stefan; Christiane D Wrann; Goudeva, Lilia; Laue, Tobias; Kielstein, Heike

    2013-01-01

    Background: Obesity is a risk factor for various types of infectious diseases and cancer. The increase in adipose tissue causes alterations in both adipogenesis and the production of adipocyte-secreted proteins (adipokines). Since natural killer (NK) cells are the host’s primary defense against virus-infected and tumor cells, we investigated how adipocyte-conditioned medium (ACM) affects functions of two distinct human NK cell subsets. Methods: Isolated human peripheral blood mononuclear cell...

  1. Clinical significance of serum adipokines levels in lung cancer.

    Kerenidi, Theodora; Lada, Martha; Tsaroucha, Agori; Georgoulias, Panagiotis; Mystridou, Parthena; Gourgoulianis, Konstantinos I

    2013-06-01

    Adipokines have a significant effect on metabolism, immunoinflammatory responses as well as on carcinogenesis; therefore, we aimed at evaluating their potential predictive and prognostic significance in lung cancer. Eighty patients--mean age 62.9 ± 9.2 years--with previously untreated lung cancer (61 NSCLC and 19 SCLC) of all stages and 40 healthy individuals were enrolled in this study. Serum levels of leptin, adiponectin and ghrelin were measured using human Radioimmunoassay kits. Serum leptin levels in lung cancer patients were lower compared to control (p < 0.0001), while adiponectin and ghrelin levels were significantly increased in patients (p = 0.0003 and p = 0.0043, respectively). Additionally, the leptin/adiponectin ratio was significantly lower in the patients group compared to controls (p < 0.0001]. There was no association between serum levels of adipokines and any of the patient clinicopathological characteristics or response to therapy. Nevertheless, patients with lower values of serum leptin had shorter overall survival (p = 0.014), whereas multivariate analysis revealed leptin levels as an independent prognostic factor for survival (p = 0.024, HR 0.452, CI 95 % 0.232-0.899). These results suggest that adipokines may play a role in the pathogenesis of lung cancer, while leptin serum levels might provide useful prognostic information. PMID:23430445

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

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

    2015-01-01

    Background 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. Methods The subjects were 509 employees (296 men and 213 women), aged 20 to 6...

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

    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.

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

    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.

  5. Human NK cell subset functions are differentially affected by adipokines.

    Lena Huebner

    Full Text Available BACKGROUND: Obesity is a risk factor for various types of infectious diseases and cancer. The increase in adipose tissue causes alterations in both adipogenesis and the production of adipocyte-secreted proteins (adipokines. Since natural killer (NK cells are the host's primary defense against virus-infected and tumor cells, we investigated how adipocyte-conditioned medium (ACM affects functions of two distinct human NK cell subsets. METHODS: Isolated human peripheral blood mononuclear cells (PBMCs were cultured with various concentrations of human and murine ACM harvested on two different days during adipogenesis and analyzed by fluorescent-activated cell sorting (FACS. RESULTS: FACS analyses showed that the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL, granzyme A (GzmA and interferon (IFN-γ in NK cells was regulated in a subset-specific manner. ACM treatment altered IFN-γ expression in CD56(dim NK cells. The production of GzmA in CD56(bright NK cells was differentially affected by the distinct adipokine compositions harvested at different states of adipogenesis. Comparison of the treatment with either human or murine ACM revealed that adipokine-induced effects on NK cell expression of the leptin receptor (Ob-R, TRAIL and IFN-γ were species-specific. CONCLUSION: Considering the growing prevalence of obesity and the various disorders related to it, the present study provides further insights into the roles human NK cell subsets play in the obesity-associated state of chronic low-grade inflammation.

  6. Physiological Roles of Adipokines, Hepatokines, and Myokines in Ruminants.

    Roh, Sang-Gun; Suzuki, Yutaka; Gotoh, Takafumi; Tatsumi, Ryuichi; Katoh, Kazuo

    2016-01-01

    Since the discovery of leptin secreted from adipocytes, specialized tissues and cells have been found that secrete the several peptides (or cytokines) that are characterized to negatively and positively regulate the metabolic process. Different types of adipokines, hepatokines, and myokines, which act as cytokines, are secreted from adipose, liver, and muscle tissue, respectively, and have been identified and examined for their physiological roles in humans and disease in animal models. Recently, various studies of these cytokines have been conducted in ruminants, including dairy cattle, beef cattle, sheep, and goat. Interestingly, a few cytokines from these tissues in ruminants play an important role in the post-parturition, lactation, and fattening (marbling) periods. Thus, understanding these hormones is important for improving nutritional management in dairy cows and beef cattle. However, to our knowledge, there have been no reviews of the characteristics of these cytokines in beef and dairy products in ruminants. In particular, lipid and glucose metabolism in adipose tissue, liver tissue, and muscle tissue are very important for energy storage, production, and synthesis, which are regulated by these cytokines in ruminant production. In this review, we summarize the physiological roles of adipokines, hepatokines, and myokines in ruminants. This discussion provides a foundation for understanding the role of cytokines in animal production of ruminants. PMID:26732322

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

    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. PMID:27326465

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

    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.

  9. Impact of runting on adipokine gene expression in neonatal pig adipose tissue

    This study examined the effects of runting on adipokines in neonatal adipose tissue. Pigs were selected as runts (R) by birth weight adipose tissues were collected at d1 (n = 5), d7 (n = 7) or d21 (n...

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

    MacQueen, Glenda M.; Taylor, Valerie H

    2010-01-01

    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 MED...

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

    Hidekuni Inadera

    2008-01-01

    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...

  12. Circuit Resistance Exercise Improves Glycemic Control and Adipokines in Females with Type 2 Diabetes Mellitus

    Nam Hwoeh Yeo; Young Jun Kim; Hye-Jeong Lee 167; Dukkuy Kim; Ki Ok Shin; Jin Hee Woo; Sunghwun Kang

    2009-01-01

    The aim of study was to evaluate whether circuit resistance exercise (CE) improves glycemic control and adipokine levels in comparison with walking exercise (WE) in 15 adult postmenopausal Korean females with type 2 diabetes mellitus (T2DM). The participants were randomly assigned to either the CE or WE group. Subjects exercised for 1 h, three times per week for 12 weeks. The parameters measured were body composition, respiratory rate, blood glucose, insulin and adipokines. The body compositi...

  13. ADIPOKINES CONTENT AND ECHOCARDIOGRAPHY INDICATORS OF WOMEN WITH HYPOTHYROIDISM

    I. Yu. Kapralova

    2015-01-01

    Full Text Available Study objective: to study the adipokines content and echocardiography indicators of women with hypothyroidism.Materials and methods. 30 women with hypothyroidism were included into the study with the average age of 55.2 ± 2.2 years old and the duration of disease of 8.53 ± 0.84 years. Anthropometric parameters of all patients were measured. Levels of leptin, resistin, adiponectin were investigated with enzyme multiplied immunoassay. Morphometric parameters of the left ventricle (LV were assessed with echocardiography.Results. The examined patients with hypothyroidism displayed increased concentration of leptin and resistin, as well as decreased concentration of adiponectin. Concentric and eccentric hypertrophy of the left ventricle is revealed in more than half of cases with patients with the hypofunction of the thyroid gland.Conclusion. Evident decreasing of the level of adiponektin and increasing of the level of leptin and resistin was revealed with examined patients on the background of the excessive body weight. Hypertrophy of the left ventricle and diastolic dysfunction of the myocard with its relatively preserved contractile ability was revealed with women that suffer from hypothyroidism. Age, excessive body weight, increasing of arterial blood pressure, and hypoadiponectinemia play a significant role in the left ventricle myocardial remodeling.

  14. Adipokine resistin predicts anti-inflammatory effect of glucocorticoids in asthma

    Nieminen Riina

    2011-05-01

    Full Text Available Abstract Background Adipokines are protein mediators secreted by adipose tissue. Recently, adipokines have also been involved in the regulation of inflammation and allergic responses, and suggested to affect the risk of asthma especially in obese female patients. We assessed if adipokines predict responsiveness to glucocorticoids and if plasma adipokine levels are associated with lung function or inflammatory activity also in non-obese (body mass index (BMI ≤ 30 kg/m2 women with newly-diagnosed steroid-naïve asthma. Methods Lung function, exhaled NO, plasma levels of adipokines leptin, resistin, adiponectin and adipsin, and inflammatory markers were measured in 35 steroid-naïve female asthmatics and in healthy controls. The measurements were repeated in a subgroup of asthmatics after 8 weeks of treatment with inhaled fluticasone. Adipokine concentrations in plasma were adjusted for BMI. Results High baseline resistin concentrations were associated with a more pronounced decrease in serum levels of eosinophil cationic protein (ECP (r = -0.745, p = 0.013, eosinophil protein X (EPX (r = -0.733, p = 0.016 and myeloperoxidase (MPO (r = -0.721, p = 0.019 during fluticasone treatment. In asthmatics, leptin correlated positively with asthma symptom score and negatively with lung function. However, no significant differences in plasma adipokine levels between non-obese asthmatics and healthy controls were found. The effects of resistin were also investigated in human macrophages in cell culture. Interestingly, resistin increased the production of proinflammatory factors IL-6 and TNF-α and that was inhibited by fluticasone. Conclusions High resistin levels predicted favourable anti-inflammatory effect of inhaled glucocorticoids suggesting that resistin may be a marker of steroid-sensitive phenotype in asthma. High leptin levels were associated with a more severe disease suggesting that the link between leptin and asthma is not restricted to obesity.

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

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

    2009-01-01

    Adipokines play important regulatory roles in the pathophysiology of obesity and insulin resistance. We measured plasma and interstitial concentrations of the adipokines adiponectin, resistin, leptin, monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6) and interleukin-8 (IL-8) 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<0.05), but no regional differences were...... 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, P<0.05), whereas MCP-1, IL-6 and IL-8 concentrations were higher in subcutaneous adipose tissue than...

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

    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. Proinflammatory tissue response and recovery of adipokines during 4 days of subcutaneous large-pore microdialysis

    Clausen, Trine Schnedler; Kaastrup, Peter; Stallknecht, Bente

    2009-01-01

    INTRODUCTION: Subcutaneous adipose tissue (SAT) is increasingly being recognized as a highly active tissue secreting adipokines involved in many physiological and pathophysiological processes. Microdialysis is a technique used for in vivo sampling of interstitial fluid from e.g. SAT. The technique...

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

    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.

  19. Fat cell size and adipokine expression in relation to gender, depot and metabolic risk factors in morbidly obese adolescents

    Zhang, Yiying; Zitsman, Jeffrey L.; Hou, Jue; Fennoy, Ilene; Guo, Kaiying; Feinberg, Joshua; Leibel, Rudolph L

    2013-01-01

    Objective To understand the regulation of adipocyte size and adipokine expression in relation to gender, anatomic location, adiposity, and metabolic risk factors in adolescents with morbid obesity. Design and Methods Adipocyte size and adipokine expression in paired abdominal subcutaneous (SAT) and omental (VAT) surgical adipose tissues were related to gender, anatomic location, adiposity, and metabolic risk factors in a group of morbidly obese adolescents. Results Significant depot- and/or g...

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

    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.

  1. Roles of FGFs as adipokines in adipose tissue development, remodeling, and metabolism

    NobuyukiItoh

    2014-01-01

    White and brown adipose tissues, 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 twenty-two FGFs, FGF1, FGF10, and FGF21 play roles as adipokines, adipocyte-secreted proteins, in the development and function of white and brown adipose tissues. FGF1 is a critical transducer in white adipose tissue remodeling. The PPARγ–F...

  2. Betaine reduces the expression of inflammatory adipokines caused by hypoxia in human adipocytes.

    Olli, K; Lahtinen, S; Rautonen, N; Tiihonen, K

    2013-01-14

    Obesity is characterised by a state of chronic low-grade inflammation and the elevated circulating and tissue levels of inflammatory markers, including inflammation-related adipokines, released from white adipose tissue. The expression and release of these adipokines generally rises as the adipose tissue expands and hypoxic conditions start to develop within the tissue. Here, the effect of betaine, a trimethylglycine having a biological role as an osmolyte and a methyl donor, on the expression of inflammation-related markers was tested in human adipocytes under hypoxia. Differentiated adipocytes were cultivated under low (1 %) oxygen tension for 8-20 h. The expression of different adipokines, including IL-6, leptin, PPARγ, TNF-α and adiponectin, was measured by quantitative PCR by determining the relative mRNA level from the adipocytes. Hypoxia, in general, led to a decrease in the expression of PPARγ mRNA in human adipocytes, whereas the expression levels of leptin and IL-6 mRNA were substantially increased by hypoxia. The cultivation of adipocytes under hypoxia also led to a reduction in the expression of TNF-α mRNA. The results showed that hypoxia increased the relative quantification of leptin gene transcription, and that betaine (250 μmol/l) reduced this effect, caused by low oxygen conditions. Under hypoxia, betaine also reduced the mRNA level of the pro-inflammatory markers IL-6 and TNF-α. These results demonstrate that the extensive changes in the expression of inflammation-related adipokines in human adipocytes caused by hypoxia can be diminished by the presence of physiologically relevant concentrations of betaine. PMID:22424556

  3. Role of Adipokines and Other Inflammatory Mediators in Gestational Diabetes Mellitus and Previous Gestational Diabetes Mellitus

    Zoe Iliodromiti; Kalliopi I. Pappa; Charalambos Siristatidis; Konstantinos Dafopoulos; Stavros Sifakis; Nikolaos Vrachnis; Panagiotis Belitsos

    2012-01-01

    Previous Gestational Diabetes Mellitus (pGDM) is a common condition and has been associated with future development of Type 2 Diabetes Mellitus (T2DM) and Metabolic Syndrome (MS) in women affected. The pathogenesis and risk factors implicated in the development of these conditions later in the lives of women with pGDM are not as yet fully understood. Research has recently focused on a group of substances produced mainly by adipose tissue called adipokines, this group including, among others, ...

  4. Up-regulation of the anti-inflammatory adipokine adiponectin in acute liver failure in mice

    Wolf, A.M.; Wolf, D; M.A. Avila; Moschen, A R; Berasain, C; Enrich, B. (Barbara); Rumpold, H. (Holger); Tilg, H

    2006-01-01

    BACKGROUND/AIMS: Recent reports suggest that the adipose tissue and adipokines are potent modulators of inflammation. However, there is only scarce knowledge on the functional role and regulation of endogenous adiponectin in non-fat tissues such as the liver under conditions of acute inflammation. METHODS: In the present study, we investigated adiponectin expression in healthy murine liver tissue and under inflammatory conditions in vivo. RESULTS: Adiponectin mRNA was readily detectable...

  5. CIRCUIT RESISTANCE EXERCISE IMPROVES GLYCEMIC CONTROL AND ADIPOKINES IN FEMALES WITH TYPE 2 DIABETES MELLITUS

    Nam Hwoeh Yeo

    2009-12-01

    Full Text Available The aim of study was to evaluate whether circuit resistance exercise (CE improves glycemic control and adipokine levels in comparison with walking exercise (WE in 15 adult postmenopausal Korean females with type 2 diabetes mellitus (T2DM. The participants were randomly assigned to either the CE or WE group. Subjects exercised for 1 h, three times per week for 12 weeks. The parameters measured were body composition, respiratory rate, blood glucose, insulin and adipokines. The body composition of the CE group showed a significant reduction (all p < 0.05 in body weight, body mass index (BMI, and percentage of body fat and a significant increase in muscle mass. Respiratory function was also significantly increased in the CE group. Additionally, hemoglobin A1c (HbA1c changed favorably in the CE group, as were the concentrations of adipokines such as retinol binding protein 4 (RBP-4 (p < 0.05, adiponectin (p < 0.01, and monocyte chemoattractant protein-1 (MCP-1 (p < 0.01. In addition, significant correlations with CE were evident for homeostatic model assessment insulin resistance (HOMA-IR and glucose (r = 0.69, p < 0.001, muscle mass and glucose (r = 0.45, p < 0.05, and muscle mass and HbA1c (r = 0.39, p < 0.05. The beneficial effects of CE include the development of muscle mass, which effectively increases glucose use and reduces the amount of insulin required. Thus, our results suggest that CE improves glycemic control and adipokines resulting from incrementally increased muscle mass and reductions of body weight, BMI and percentage of body fat for T2DM postmenopausal Korean women

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

    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. PMID:18583460

  7. Adipokines and Insulin Resistance in Young Adult Survivors of Childhood Cancer

    Latoch, Eryk; Muszynska-Roslan, Katarzyna; Panas, Agata; Panasiuk, Anna; Sawicka-Zukowska, Malgorzata; Zelazowska-Rutkowska, Beata; Zabrocka, Ewa; Krawczuk-Rybak, Maryna

    2016-01-01

    We examined the association between adipokines (leptin, adiponectin, and resistin), radiotherapy, measurement of body fat, and insulin resistance among young adult survivors of childhood cancer (CCS). Materials and Methods. Seventy-six survivors were included (mean age 24.1 ± 3.5 years). Insulin resistance (IR) was calculated using the homeostasis model assessment (HOMA-IR). The serum levels of adipokines were assayed by immunoassays. Fat mass was evaluated by DXA. Results. Mean adiponectin level and mean body FAT were higher in the examined females than in males (10009 ± 6367 ng/mL versus 6433 ± 4136 ng/mL, p < 0.01; 35.98 ± 9.61% versus 22.7 ± 7.46%, p < 0.001). Among CCS, one of 75 patients met the criteria of insulin resistance, and in 14 patients there was impaired fasting glucose. The multiple regression model for females showed that leptin/adiponectin ratio (LA ratio) significantly affected HOMA-IR (increase of 0.024 per each unit of LA ratio; p < 0.05). Radiotherapy had no effect on serum adipokines and IR. Conclusion. The observed results support the hypothesis that adiponectin might be associated with insulin resistance and it can not be ruled out that changes in the mean level of adiponectin per FAT mass or leptin/adiponectin ratio may precede the occurrence of insulin resistance in the future.

  8. Changes in profile of lipids and adipokines in patients with newly diagnosed hypothyroidism and hyperthyroidism.

    Chen, Yanyan; Wu, Xiafang; Wu, Ruirui; Sun, Xiance; Yang, Boyi; Wang, Yi; Xu, Yuanyuan

    2016-01-01

    Changes in profile of lipids and adipokines have been reported in patients with thyroid dysfunction. But the evidence is controversial. The present study aimed to explore the relationships between thyroid function and the profile of lipids and adipokines. A cross-sectional study was conducted in 197 newly diagnosed hypothyroid patients, 230 newly diagnosed hyperthyroid patients and 355 control subjects. Hypothyroid patients presented with significantly higher serum levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDLC), fasting insulin, resistin and leptin than control (p Hyperthyroid patients presented with significantly lower serum levels of high-density lipoprotein cholesterol, LDLC and leptin, as well as higher levels of fasting insulin, resistin, adiponectin and homeostasis model insulin resistance index (HOMA-IR) than control (p < 0.05). Nonlinear regression and multivariable linear regression models all showed significant associations of resistin or adiponectin with free thyroxine and association of leptin with thyroid-stimulating hormone (p < 0.001). Furthermore, significant correlation between resistin and HOMA-IR was observed in the patients (p < 0.001). Thus, thyroid dysfunction affects the profile of lipids and adipokines. Resistin may serve as a link between thyroid dysfunction and insulin resistance. PMID:27193069

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

    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

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

    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.

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

    Luo, Xiao; Jia, Ru; Zhang, Qiangling; Sun, Bo; Yan, Jianqun

    2016-01-01

    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. PMID:27223282

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

    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.

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

    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.

  14. Ex Vivo and In Vivo Regulation of Lipocalin-2, a Novel Adipokine, by Insulin

    Tan, Bee K.; Adya, Raghu; Shan, Xiaoye; Syed, Farhatullah; Lewandowski, Krzysztof C.; O'Hare, John P.; Randeva, Harpal S

    2009-01-01

    OBJECTIVE—Lipocalin-2, a novel adipokine, has been shown to be elevated in obese, insulin-resistant, and diabetic subjects. We therefore sought to study the ex vivo and in vivo effects of insulin on lipocalin-2 levels in humans. RESEARCH DESIGN AND METHODS—We investigated the in vivo effects of insulin (hyperinsulinemia) on circulating lipocalin-2 levels by enzyme-linked immunosorbent assay via a prolonged insulin-glucose infusion. The ex vivo effect of insulin on adipose tissue lipocalin-2 p...

  15. Activation of AMP-activated protein kinase attenuates hepatocellular carcinoma cell adhesion stimulated by adipokine resistin

    Yang, Chen-Chieh; Chang, Shun-Fu; Chao, Jian-Kang; Lai, Yi-Liang; Chang, Wei-En; Hsu, Wen-Hsiu; Kuo, Wu-Hsien

    2014-01-01

    Background Resistin, adipocyte-secreting adipokine, may play critical role in modulating cancer pathogenesis. The aim of this study was to investigate the effects of resistin on HCC adhesion to the endothelium, and the mechanism underlying these resistin effects. Methods Human SK-Hep1 cells were used to study the effect of resistin on intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expressions as well as NF-κB activation, and hence cell adhesion to hu...

  16. Adipokines and Insulin Resistance%脂肪因子与胰岛素抵抗

    陈卓

    2011-01-01

    Adipose tissue has been identified as an active endocrine organ that not only stores energy and regulates nutrient homeostasis but also releases a large nunber of protein hormones( adipokines ) ,which communicate with liver,skeletal muscle, and the brain thereby modulating hemostasis, blood pressure, lipid and glucose metabolism,inflammation, and atherosclerosis. It has been reported that sonde adipokines such as adiponectin, leptin, omentin, visfatin, vaspin associated with insulin sensitizer, however, other adipokines such as chenerin, resistin, retinol binding protein 4, tumor necrosis factor and interleukin-6 might induce insulin resistance. Increase or decreass in the expression of these adipokines would have effect on the biological effects of insulin at different levels. The interplay between adipose tissue-derived hormones as well as their effects on glucose homeostasis are becoming a new research focus.%脂肪组织除了调节能量储存和营养平衡,还是一个活跃的内分泌器官,它释放出大量的蛋白激素(脂肪因子)作用于肝脏、骨骼肌、大脑等部位,从而实现对止血、血压、糖脂代谢、炎症、动脉粥样硬化等生理活动的调节.已有报道脂联素、瘦素、网膜素、内脂素、丝氨酸蛋白酶抑制剂等具有胰岛素增敏剂的作用;然而,其他一些脂肪因子,如chemerin、抵抗素、视黄醇结合蛋白4、肿瘤坏死因子和白细胞介素6等则可能诱导胰岛素抵抗,这些因子表达的增强或减弱,可从不同层面影响胰岛素的生物学效应.脂肪组织源性激素之间的相互作用及其对血糖稳态的调节正成为一个新的研究热点.

  17. Serum adipokines might predict liver histology findings in non-alcoholic fatty liver disease

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

    2016-01-01

    AIM: To assess significance of serum adipokines to determine the histological severity of non-alcoholic fatty liver disease. METHODS: Patients with persistent elevation in serum aminotransferase levels and well-defined characteristics of fatty liver at ultrasound were enrolled. Individuals with a history of alcohol consumption, hepatotoxic medication, viral hepatitis or known liver disease were excluded. Liver biopsy was performed to confirm non-alcoholic liver disease (NAFLD). The degrees of liver steatosis, lobular inflammation and fibrosis were determined based on the non-alcoholic fatty liver activity score (NAS) by a single expert pathologist. Patients with a NAS of five or higher were considered to have steatohepatitis. Those with a NAS of two or lower were defined as simple fatty liver. Binary logistic regression was used to determine the independent association of adipokines with histological findings. Receiver operating characteristic (ROC) analysis was employed to determine cut-off values of serum adipokines to discriminate the grades of liver steatosis, lobular inflammation and fibrosis. RESULTS: Fifty-four participants aged 37.02 ± 9.82 were enrolled in the study. Higher serum levels of visfatin, IL-8, TNF-α levels were associated independently with steatosis grade of more than 33% [β = 1.08 (95%CI: 1.03-1.14), 1.04 (95%CI: 1.008-1.07), 1.04 (95%CI: 1.004-1.08), P < 0.05]. Elevated serum IL-6 and IL-8 levels were associated independently with advanced lobular inflammation [β = 1.4 (95%CI: 1.09-1.8), 1.07 (95%CI: 1.003-1.15), P < 0.05]. Similarly, higher TNF-α, resistin, and hepcidin levels were associated independently with advanced fibrosis stage [β = 1.06 (95%CI: 1.002-1.12), 19.86 (95%CI: 2.79-141.19), 560.72 (95%CI: 5.98-5255.33), P < 0.05]. Serum IL-8 and TNF-α values were associated independently with the NAS score, considering a NAS score of 5 as the reference value [β = 1.05 (95%CI: 1.01-1.1), 1.13 (95%CI: 1.04-1.22), P < 0

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

    Paweł Madej; Grzegorz Franik; Piotr Kurpas; Aleksander Owczarek; Jerzy Chudek; Magdalena Olszanecka-Glinianowicz

    2016-01-01

    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 anthropometr...

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

    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.

  20. Adipose tissue and adipokines--energy regulation from the human perspective.

    Trayhurn, Paul; Bing, Chen; Wood, I Stuart

    2006-07-01

    There has been a rapid rise in the incidence of obesity, primarily as a result of changes in lifestyle (diet and activity levels). Obesity has provided considerable impetus for the investigation of the fundamental mechanisms involved in the regulation of energy balance. Important developments include the identification of novel factors involved in the control of appetite, such as ghrelin, orexin A, and the endogenous cannabinoids, and the emergence of the concept of "nonexercise activity thermogenesis" (NEAT) provided new perspectives on energy expenditure. Studies on white adipose tissue have led to the recognition that it is an important endocrine organ, communicating with the brain and peripheral tissues through the secretion of leptin and other adipokines. There is a rapidly expanding list of protein factors released by white adipose tissue, including the key hormone, adiponectin. Of particular note is the range of cytokines, chemokines, and other inflammation-related proteins secreted by white fat as tissue mass rises; indeed, obesity is characterized by chronic mild inflammation. The adipokines provide an extensive network of communication both within adipose tissue and with other organs, and some are implicated directly in the pathologies associated with obesity, particularly the metabolic syndrome. Although the focus remains very much on obesity in humans, the disorder and its sequelae are also a growing concern in companion animals. PMID:16772463

  1. The role of adipokines and insulin resistance in the pathogenesis of nonalcoholic fatty liver disease

    Bartłomiej Orlik

    2010-05-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD develops in 17–33�0of the population of developed countries. The incidence of NAFLD is constantly growing due to the increasing prevalence of obesity. It is estimated that one third of subjects with NAFLD suffer from nonalcoholic steatohepatitis (NASH and 15�0of them develop liver cirrhosis within a five-year period. In recent years this important complication of obesity became the subject of numerous studies. It, the pathogenesis of NAFLD is still unclear. A key role in the development of this disease was attributed to insulin resistance. Hormones and cytokines produced by adipose tissue called adipokines may be a link between obesity, insulin resistance, and NAFLD. However, it is well known that increased levels of adipokines such as TNF-α, IL-6, and resistin and a decreased level of adiponectin augment inflammation in the liver. Further studies are necessary to explain the roles of leptin, visfatin, retinol binding protein-4, omentin, and vaspin in the pathogenesis of NAFLD. The aim this paper is to introduce new areas of study on the pathogenesis of NAFLD.

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

    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.

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

    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

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

    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

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

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

    2015-01-01

    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 ...

  6. Role of adipokines in the obesity-inflammation relationship: the effect of fat removal.

    Esposito, Katherine; Giugliano, Giovanni; Scuderi, Nicolò; Giugliano, Dario

    2006-09-15

    During the past 10 years, there has been a dramatic increase in the prevalence of obesity in the United States and other developed nations. Recent studies indicate that adipose tissue is an endocrine organ producing numerous proteins, collectively referred to as adipokines, with broad biological activity, that play an important autocrine role in obesity-associated complications. Adipose tissue in general and visceral fat in particular are thought to be key regulators of inflammation. Inflammation is heavily involved in the onset and development of atherothrombotic disease. Moreover, chronic inflammation may also represent a triggering factor in the origin of the metabolic syndrome and type 2 diabetes mellitus. According to a hypothesis, stimuli such as overnutrition, physical inactivity, and aging would result in cytokine hypersecretion and eventually lead to insulin resistance and diabetes in genetically or metabolically predisposed individuals. This article discusses the current understanding of important adipokines thought to be involved in the metabolic and cardiovascular risk associated with obesity. Available evidence linking fat removal by liposuction to modification of cardiovascular risk and vascular inflammatory markers in the obese patient is also presented. Most studies have shown that liposuction produces beneficial effects on insulin resistance and vascular inflammation in the obese patient, reducing its cardiovascular risk. Besides having a significant role in body contouring of the obese patient at the end of the lengthy process of bariatric surgery and massive weight loss, plastic surgery should be incorporated into a multifaceted program of lifestyle changes that allows the obese patient to obtain weight loss and, more importantly, to maintain the reduced weight in the long term. PMID:16980868

  7. Effects of Estrogens on Adipokines and Glucose Homeostasis in Female Aromatase Knockout Mice.

    Michelle L Van Sinderen

    Full Text Available The maintenance of glucose homeostasis within the body is crucial for constant and precise performance of energy balance and is sustained by a number of peripheral organs. Estrogens are known to play a role in the maintenance of glucose homeostasis. Aromatase knockout (ArKO mice are estrogen-deficient and display symptoms of dysregulated glucose metabolism. We aim to investigate the effects of estrogen ablation and exogenous estrogen administration on glucose homeostasis regulation. Six month-old female wildtype, ArKO, and 17β-estradiol (E2 treated ArKO mice were subjected to whole body tolerance tests, serum examination of estrogen, glucose and insulin, ex-vivo muscle glucose uptake, and insulin signaling pathway analyses. Female ArKO mice display increased body weight, gonadal (omental adiposity, hyperinsulinemia, and liver triglycerides, which were ameliorated upon estrogen treatment. Tolerance tests revealed that estrogen-deficient ArKO mice were pyruvate intolerant hence reflecting dysregulated hepatic gluconeogenesis. Analyses of skeletal muscle, liver, and adipose tissues supported a hepatic-based glucose dysregulation, with a down-regulation of Akt phosphorylation (a key insulin signaling pathway molecule in the ArKO liver, which was improved with E2 treatment. Concurrently, estrogen treatment lowered ArKO serum leptin and adiponectin levels and increased inflammatory adipokines such as tumour necrosis factor alpha (TNFα and interleukin 6 (IL6. Furthermore, estrogen deficiency resulted in the infiltration of CD45 macrophages into gonadal adipose tissues, which cannot be reversed by E2 treatment. This study describes the effects of estrogens on glucose homeostasis in female ArKO mice and highlights a primary phenotype of hepatic glucose dysregulation and a parallel estrogen modified adipokine profile.

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

    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

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

    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...

  10. Obesity indices and adipokines in non-diabetic obese patients with early stages of chronic kidney disease

    Stępień, Mariusz; Stępień, Anna; Wlazeł, Rafał Nikodem; Paradowski, Marek; Banach, Maciej; Rysz, Magdalena; Rysz, Jacek

    2013-01-01

    Background The aim of this study was to estimate obesity parameters: waist circumference (WC), waist-to-hip ratio (WHR), weight-to-height ratio (WHtR), visceral adiposity index (VAI), body adiposity index (BAI), and serum adipokines (leptin, adiponectin, resistin) and their associations with estimated glomerular filtration rate (eGFR), serum creatinine, and microalbuminuria (MA) in patients with early stages of CKD and in non-CKD obese patients. Material/Methods 67 non-diabetic obese (BMI ≥30...

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

    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. PMID:26692319

  12. Anterior pituitary influence on adipokine expression and secretion by porcine adipocytes.

    Saleri, R; Cavalli, V; Martelli, P; Borghetti, P

    2016-06-01

    Nutritional stressors may cause negative effects on animal health and growth and lead to significant economic impact. Adipose tissue is an endocrine organ producing, mediators and hormones, called adipokines. They play a dynamic role in body homeostasis and in the regulation of energy expenditure, interacting with feeding behavior, hormones and growth factors. This in vitro study aimed to investigate how nutritional conditions and growth hormone (GH) can influence nitric oxide (NO) production and the expression and secretion of three important adipokines, that is leptin, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), by swine adipocytes. In our experimental model, mesenchymal stem cells from omental adipose tissue were induced to adipogenic differentiation. After differentiation, adipocytes were incubated for 24 h (T0) with DMEM/Ham's F12 (group A) or DMEM/Ham's F12 salts (group B), a DMEM/Ham's F12 formulation deprived of nutritional components. Primary adipocyte cells were also co-cultured for 4 h (T+4) or 12 h (T+12) with or without anterior pituitary slices. To stimulate GH secretion by pituitary cells, growth hormone releasing hormone at 10-8 M was added at the start of the incubation times (4 or 12 h). At T0, T+4 and T+12, NO production, leptin, IL-6 and TNF-α expression and secretion were measured. NO increased (Pculture conditions. Deprived medium and coincubation with anterior pituitary positively influenced leptin secretion and expression. TNF-α was expressed and secreted only in deprived culture condition groups (B, B1 and B2). Nutrients availability and pituitary co-culture did not affect IL-6 expression and secretion. Our study shows an endocrine function for porcine adipocytes. In our model, adipocytes readily responded to nutritional inputs by secretion of molecules affecting energy balance. This secretion capacity was modulated by GH. Improving our knowledge of the role of adipocyte in the endocrine system, may lead to a more complete

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

    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.

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

    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.

  15. Pref-1 and adipokine expression in adipose tissues of GK and Zucker rats.

    Barbu, Andreea; Hedlund, Gabriella Persdotter; Lind, Jenny; Carlsson, Carina

    2009-02-27

    In view of the central role of preadipocyte factor-1, adiponectin and leptin in white adipose tissue function, the aim of the present study was to analyze the mRNA expression of these proteins and of the inflammatory markers interleukin-6 and tumor necrosis factor-alpha in visceral and subcutaneous fat pads of rats with different metabolic disorders. We demonstrated highly divergent expression of preadipocyte factor-1, upregulated expression of adiponectin, interleukin-6 and TNF-alpha mRNA in adipose tissues of the diabetic Goto Kakizaki rat compared to the obese Zucker rat. This was correlated to an increased number of large adipocytes and serum levels of adiponectin. Furthermore, in all four strains studied (as above plus Wistar Furth and Zucker Lean), significant heterogeneity was evident in adipokine expression within specific adipose tissues previously defined as belonging to the visceral or subcutaneous fat depots. These results suggest that significantly increased levels of inflammation and redistribution of adipocyte size are mechanisms contributing to the development of type 2 diabetes in the GK rat. PMID:19084046

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

    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.

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

    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 (Pthyroid 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 (Pdisruptor 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. PMID:24167152

  18. The adipokine Chemerin induces lipolysis and adipogenesis in bovine intramuscular adipocytes.

    Fu, Yuan-Yuan; Chen, Kun-Lin; Li, Hui-Xia; Zhou, Guang-Hong

    2016-07-01

    The adipokine Chemerin is reported to regulate adipogenesis and glucose homeostasis in vivo and in 3T3-L1 cells. Our team is focused on the role of Chemerin in metabolism and intramuscular adipocyte differentiation because intramuscular fat is the basic material for the formation of marbling in livestock and poultry meat. In this study, bovine intramuscular mature adipocytes were cultured in medium with Chemerin, and the process of lipolysis of mature adipocytes and the adipogenesis of de-differentiated preadipocytes were investigated. The results showed that Chemerin induced significant lipolytic metabolism in intramuscular mature adipocytes, indicated by increased levels of glycerol, FFA, and up-regulated expression of the lipolysis critical factors HSL, LPL, and leptin. Meanwhile, the expressions of adipogenic key factors PPARγ, C/EBPα, and A-FABP were decreased by Chemerin during lipolysis or dedifferentiation in mature adipocytes. The de-differentiated preadipocytes could re-differentiate into mature adipocytes. Intriguingly, the formation of cells' lipid droplets was promoted by Chemerin during preadipocyte differentiation. In addition, mRNA and protein expressions of PPARγ, C/EBPα, and A-FABP were up-regulated by Chemerin during preadipocytes differentiation. These results suggest that Chemerin promotes lipolysis in mature adipocytes and induces adipogenesis during preadipocyte re-differentiation, further indicating a dual role for Chemerin in the deposition of intramuscular fat in ruminant animals. PMID:27260300

  19. Evaluation of Melatonin, and Adipokines in Patients with Alzheimer’s Disease

    Entedhar Rifaat Sarhat

    2015-06-01

    Full Text Available Alzheimer’s disease (AD is one of the most common causes for the development of Dementia in the elderly. In past two decades there has been abundant research in pathogenesis of AD and possible prevention and treatment. The objective of this study is to evaluate the level of melatonin, and adipokines in patients with AD and control group. The study included 52 patients with AD and 52 healthy subject as control group. The results showed that serum melatonin, leptin, adiponectin, levels of patients with AD were significantly lower than the levels found for control participants (P < 0.0001. Patients with AD had significantly higher mean serum ghrelin, and resistin levels than the controls (P < 0.0001, there was positive correlation between adiponectin with leptin, and ghrelin. In conclusion, the results of this study showed that Circulating melatonin, leptin, and adiponectin were associated with a reduced incidence of AD, Resistin levels may be considered as a predictor of AD and it may predict activation of the immune system in AD pathophysiology.

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

    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.

  1. Association of adipokines and estradiol with bone and carotid calcifications in postmenopausal women.

    Värri, M; Niskanen, L; Tuomainen, Tp; Honkanen, R; Kröger, H; Tuppurainen, M T

    2016-04-01

    Objectives Carotid artery calcifications (CAC) and high carotid artery intima-media thickness (cIMT) are associated with low bone mineral density (BMD) by unknown mechanisms in postmenopausal women. Leptin, adiponectin and estradiol may mediate these associations. Our aim was to study the relationships of the aforementioned factors to bone health (BMD) and carotid atherosclerosis (CAC and cIMT). Method Participants (n = 290, mean age 73.6 years) for this cross-sectional OSTPRE-BBA study (Kuopio Osteoporosis Risk Factor and Prevention - Bone, Brain and Atherosclerosis) were randomly selected from the OSTPRE cohort in 2009. Femoral neck and total body BMDs, trunk and total body fat mass were measured with dual-energy X-ray absorptiometry, and cIMT (mm) and CAC (no/yes) were measured with B-type ultrasound. Free estradiol, adiponectin and leptin were measured from serum samples. Results Circulating estradiol levels were associated with leptin (β = 0.131, p  0.05), when adjusted for total body fat mass. There were no associations between estradiol tertiles and BMDs, or with cIMT or CAC. Adiponectin levels were inversely associated with femoral neck BMD (p = 0.019, β = -0.138) and total body BMD (p = 0.009, β = -0.142), adjusted for total body fat mass, age, current smoking and estradiol, but showed no relationship with CAC or cIMT. Leptin levels were not associated with BMDs or cIMT; but the odds ratio was 1.5 between the CAC and leptin quartiles (p = 0.014), adjusted for total body fat mass, age, statin use and calcium intake. Conclusion The adipokines are associated with vascular calcification and low BMD. Moreover, estradiol was not independently associated with BMD or CAC. PMID:26849745

  2. Activation of AMP-activated protein kinase attenuates hepatocellular carcinoma cell adhesion stimulated by adipokine resistin

    Resistin, adipocyte-secreting adipokine, may play critical role in modulating cancer pathogenesis. The aim of this study was to investigate the effects of resistin on HCC adhesion to the endothelium, and the mechanism underlying these resistin effects. Human SK-Hep1 cells were used to study the effect of resistin on intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expressions as well as NF-κB activation, and hence cell adhesion to human umbilical vein endothelial cells (HUVECs). 5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR), an AMP-activated protein kinase (AMPK) activator, was used to determine the regulatory role of AMPK on HCC adhesion to the endothelium in regard to the resistin effects. Treatment with resistin increased the adhesion of SK-Hep1 cells to HUVECs and concomitantly induced NF-κB activation, as well as ICAM-1 and VCAM-1 expressions in SK-Hep1 cells. Using specific blocking antibodies and siRNAs, we found that resistin-induced SK-Hep1 cell adhesion to HUVECs was through NF-κB-regulated ICAM-1 and VCAM-1 expressions. Moreover, treatment with AICAR demonstrated that AMPK activation in SK-Hep1 cells significantly attenuates the resistin effect on SK-Hep1 cell adhesion to HUVECs. These results clarify the role of resistin in inducing HCC adhesion to the endothelium and demonstrate the inhibitory effect of AMPK activation under the resistin stimulation. Our findings provide a notion that resistin play an important role to promote HCC metastasis and implicate AMPK may be a therapeutic target to against HCC metastasis

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

    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.

  4. Serum adipokines and adipose tissue distribution in rheumatoid arthritis and ankylosing spondylitis. A comparative study.

    ERIC eTOUSSIROT

    2013-12-01

    Full Text Available Rheumatoid arthritis (RA and ankylosing spondylitis (AS are inflammatory rheumatic diseases that may modify body composition. Adipose tissue has the ability to release a wide range of products involved in physiologic functions, but also in various pathological processes, including the inflammatory/immune response. RA and AS are both associated with the development of cardiovascular complications. It is has been established that central/abdominal and particularly intra-abdominal or visceral adiposity is closely linked to cardiovascular events. Thus, in this study, we aimed to evaluate the body composition of patients with RA or AS compared to healthy controls (HC with a special emphasis on the visceral region. In parallel, we measured adipose products or adipokines, namely leptin, adiponectin and its high molecular weight (HMW isoform, resistin, and ghrelin, a gastric peptide that plays a role in energetic balance. The homeostasis model assessment for insulin resistance (HOMA-IR and atherogenic index were used to evaluate cardiovascular risk. One hundred and twelve subjects were enrolled (30 patients with RA, 31 with AS and 51 HC. Body composition was measured using dual-energy X-ray absorptiometry (DXA to determine total fat mass and lean mass, adiposity, fat in the android and gynoid regions, and visceral fat. Patients and HC did not differ in terms of body mass index. On the contrary, adiposity was increased in RA (p= 0.01 while visceral fat was also increased, but only in women (p=0.01. Patients with AS tended to have lower total fat mass (p=0.07 and higher lean mass compared to HC (p = 0.07. Leptin and leptin/fat mass were decreased in male patients with AS (p

  5. Ox-LDL induces ER stress and promotes the adipokines secretion in 3T3-L1 adipocytes.

    Yaqin Chen

    Full Text Available Adipocytes behave as a rich source of adipokines, which may be the link between obesity and its complications. Endoplasmic reticulum (ER stress in adipocytes can modulate adipokines secretion. The aim of this study is to evaluate the effect of oxidized low density lipoprotein (ox-LDL treatment on ER stress and adipokines secretion in differentiated adipocytes. 3T3-L1 pre-adipocytes were cultured and differentiated into mature adipocytes in vitro. Differentiated adipocytes were incubated with various concentrations of ox-LDL (0-100 µg/ml for 48 hours; 50 µg/ml ox-LDL for various times (0-48 hours with or without tauroursodeoxycholic acid (TUDCA (0-400 µM pre-treatment. The protein expressions of ER stress markers, glucose regulated protein 78(GRP78 and CCAAT/enhancer binding protein [C/EBP] homologous protein (CHOP in adipocytes were detected by Western blot. The mRNA expressions of visfatin and resistin were measured by real-time PCR and the protein release of visfatin and resistin in supernatant were determined by ELISA. Treatment with ox-LDL could increase the cholesterol concentration in adipocytes. Ox-LDL induced the expressions of GRP78 and CHOP protein in adipocytes and promoted visfatin and resistin secretion in culture medium in dose and time-dependent manner. TUDCA could attenuate the effect of ox-LDL on GRP78 and CHOP expressions and reduce visfatin and resistin at mRNA and protein level in dose-dependent manner. In conclusion, ox-LDL promoted the expression and secretion of visfatin and resistin through its activation of ER stress, which may be related to the increase of cholesterol load in adipocytes.

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

    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

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

    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.

  8. Expression of miR-199a-3p in human adipocytes is regulated by free fatty acids and adipokines.

    Gu, Nan; You, Lianghui; Shi, Chunmei; Yang, Lei; Pang, Lingxia; Cui, Xianwei; Ji, Chenbo; Zheng, Wen; Guo, Xirong

    2016-08-01

    Obesity is associated with a notable risk for disease, including risk of cardiovascular disorders, type 2 diabetes mellitus (T2DM) and hypertension. Adipose tissue modulates the metabolism by releasing free fatty acids (FFAs) and adipokines, including leptin, resistin, tumor necrosis factor-α (TNF-α) and interleukin 6 (IL‑6). Altered secretion patterns of FFAs and adipokines have been demonstrated to result in obesity‑associated insulin resistance (IR) and inflammatory responses. MicroRNA-199a-3p (miR)-199a-3p expression is significantly induced in differentiated human adipose-derived mesenchymal stem cells and indicates the association with T2DM. However, the association between miR-199a-3p levels in adipocytes and obesity‑associated IR, as well as inflammatory responses remains to be elucidated. The present study observed an elevation of miR‑199a‑3p expression level in mature human adipocytes (visceral) compared with pre-adipocytes. In addition, miR‑199a‑3p expression was higher in visceral adipose deposits from obese subjects. FFA, TNF-α, IL‑6 and leptin significantly induced miR‑199a‑3p expression in mature human adipocytes, while resistin had the opposite effect. miR‑199a‑3p may represent a factor in the modulation of obesity‑associated IR and inflammatory responses. PMID:27279151

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

    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

  10. UV-induced inhibition of adipokine production in subcutaneous fat aggravates dermal matrix degradation in human skin

    Kim, Eun Ju; Kim, Yeon Kyung; Kim, Min-Kyoung; Kim, Sungsoo; Kim, Jin Yong; Lee, Dong Hun; Chung, Jin Ho

    2016-01-01

    Ultraviolet (UV) exposure to the human skin reduces triglycerides contents and lipid synthesis in the subcutaneous (SC) fat. Because adiponectin and leptin are the most abundant adipokines from the SC fat, we aim to investigate how they interact with UV exposure and skin aging. The expressions of adiponectin and leptin were significantly decreased in SC fat of sun-exposed forearm skin, in comparison with that of sun-protected buttock skin of the same elderly individuals, indicating that chronic UV exposure decreases both adipokines. Acute UV irradiation also decreased the expressions of adiponectin and leptin in SC fat. The expressions of adiponectin receptor 1/2 and leptin receptor were significantly decreased in the dermis as well as in SC fat. Moreover, while exogenous adiponectin and leptin administration prevented UV- and TNF-α induced matrix metalloproteinase (MMP)-1 expression, they also increased UV- and TNF-α induced reduction of type 1 procollagen production. Silencing of adiponectin, leptin or their receptors led to an increased MMP-1 and a decreased type 1 procollagen expression, which was reversed by treatment with recombinant human adiponectin or leptin. In conclusion, UV exposure decreases the expression of adiponectin and leptin, leading to the exacerbation of photoaging by stimulating MMP-1 expression and inhibiting procollagen synthesis. PMID:27161953

  11. Smoking Functions as a Negative Regulator of IGF1 and Impairs Adipokine Network in Patients with Rheumatoid Arthritis.

    Erlandsson, Malin C; Doria Medina, Roberto; Töyrä Silfverswärd, Sofia; Bokarewa, Maria I

    2016-01-01

    Objectives. Smoking is pathogenic for rheumatoid arthritis (RA) being tightly connected to the genetic and serological risk factors for this disease. This study aims to understand connections between cigarette smoking and serum levels of IGF1 and adipokines in RA. Methods. Serum levels of IGF1 and adipokines leptin, adiponectin, resistin, and visfatin were measured in two independent cohorts of RA patients from Gothenburg (n = 350) and Leiden (n = 193). An association of these parameters with smoking was tested in a direct comparison and proved by bivariate correlation analysis. The obtained associations were further tested in multivariate regression models where the confounders (age, gender, disease duration, and BMI) were controlled. Results. The smokers had significantly lower serum levels of IGF1, adiponectin, and leptin compared to never smokers. In regression analysis, smoking and low leptin, but not adiponectin, were associated and predicted low IGF1. Additionally, high disease activity and high BMI increased the probability of low leptin. Conclusions. The study indicates cigarette smoking as an important cause of a relative IGF1 and leptin deficiency in RA patients. This novel association between smoking and hypoleptinemia may be of importance for long-term prognosis of RA and for prediction of comorbidities. PMID:27041823

  12. Smoking Functions as a Negative Regulator of IGF1 and Impairs Adipokine Network in Patients with Rheumatoid Arthritis

    Erlandsson, Malin C.; Doria Medina, Roberto; Töyrä Silfverswärd, Sofia; Bokarewa, Maria I.

    2016-01-01

    Objectives. Smoking is pathogenic for rheumatoid arthritis (RA) being tightly connected to the genetic and serological risk factors for this disease. This study aims to understand connections between cigarette smoking and serum levels of IGF1 and adipokines in RA. Methods. Serum levels of IGF1 and adipokines leptin, adiponectin, resistin, and visfatin were measured in two independent cohorts of RA patients from Gothenburg (n = 350) and Leiden (n = 193). An association of these parameters with smoking was tested in a direct comparison and proved by bivariate correlation analysis. The obtained associations were further tested in multivariate regression models where the confounders (age, gender, disease duration, and BMI) were controlled. Results. The smokers had significantly lower serum levels of IGF1, adiponectin, and leptin compared to never smokers. In regression analysis, smoking and low leptin, but not adiponectin, were associated and predicted low IGF1. Additionally, high disease activity and high BMI increased the probability of low leptin. Conclusions. The study indicates cigarette smoking as an important cause of a relative IGF1 and leptin deficiency in RA patients. This novel association between smoking and hypoleptinemia may be of importance for long-term prognosis of RA and for prediction of comorbidities. PMID:27041823

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

    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

  14. Effect of telmisartan on selected adipokines, insulin sensitivity, and substrate utilization during insulin-stimulated conditions in patients with metabolic syndrome and impaired fasting glucose

    Wohl, P.; Krušinová, E.; Hill, M.; Kratochvílová, S.; Zídková, K.; Kopecký, J.; Neškudla, T.; Pravenec, Michal; Klementová, M.; Vrbíková, J.; Wohl, P.; Mlejnek, Petr; Pelikánová, T.

    2010-01-01

    Roč. 163, č. 4 (2010), s. 573-583. ISSN 0804-4643 R&D Projects: GA MZd(CZ) NR9359; GA MZd(CZ) NS10528 Institutional research plan: CEZ:AV0Z50110509 Keywords : telmisartan * insulin resistance * adipokines Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.482, year: 2010

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

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

    Highlights: ► CRP increases TNF-α and IL-6 genes expression in matured 3T3-L1 adipocytes. ► CRP suppresses adiponectin, leptin and PPAR-γ mRNA levels in matured 3T3-L1 cells. ► Wortmannin reverses effects of CRP on adiponectin, TNF-α and leptin mRNA levels. ► 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-γ) genes expression and raised tumor necrosis factor-α (TNF-α) 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-α and leptin genes expression. These results collectively suggest that CRP regulates adiponectin, TNF-α, leptin, IL-6 and PPAR-γ genes expression, and that might represent a mechanism by which CRP regulates insulin resistance, obesity and metabolic syndrome.

  17. THE ASSOCIATIONS OF ADIPOKINES WITH SELECTED MARKERS OF THE RENIN-ANGIOTENSINOGEN-ALDOSTERONE SYSTEM: THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS

    Allison, Matthew A.; Jenny, Nancy Swords; McClelland, Robyn L.; Cushman, Mary; Rifkin, Dena

    2014-01-01

    Among obese individuals, increased sympathetic nervous system activity results in increased renin and aldosterone production, as well as renal tubular sodium reabsorption. This study determined the associations between adipokines and selected measures of the reninangiotensinogen-aldosterone system (RAAS). The sample was 1,970 men and women from the Multi-Ethnic Study of Atherosclerosis who were free of clinical cardiovascular disease at baseline and had blood assayed for adiponectin, leptin, ...

  18. 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

    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.

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

    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

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

    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

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

    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

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

    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

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

    Park, Joong Shin; Norwitz, Errol R.; Panyavatthanasinh, Sitthysack; Kim, Sun Min; Lee, JoonHo; Park, Chan-Wook; Kim, Byoung Jae; Jun, Jong Kwan

    2016-01-01

    Objective To compare the concentrations of adipokines in amniotic fluid (AF) and cord blood collected from discordant dichorionic-diamniotic (DCDA) twin fetuses. Study Design 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. Results 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; ptwins. In Cohort 2, the concentration of serpin E1 (median, 246.0 ng/mL vs 182.8 ng/mL; ptwins, but no difference was noted in adiponectin and leptin concentrations. Levels of adiponectin (median, 10425.5 ng/mL vs 11552.0 ng/mL; ptwins whereas cord blood concentrations of serpin E1 (median, 15.5 ng/mL vs 13.3 ng/mL; ptwins. Conclusion 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. PMID:27135745

  4. Do adipokines underlie the association between known risk factors and breast cancer among a cohort of U.S. women?

    Gaudet, Mia M.; Falk, Roni T.; Gierach, Gretchen L.; Lacey, James V.; Graubard, Barry I.; Dorgan, Joanne F.; Brinton, Louise A.

    2010-01-01

    Obesity is a well-established risk factor for postmenopausal breast cancer, but mechanisms underlying the association are unclear. Adipocyte-derived, cytokine-like adipokines have been suggested as contributory factors. To evaluate their association with breast cancer risk factors and breast cancer risk, we conducted a nested case-control study of 234 postmenopausal breast cancer cases and 234 controls in a cohort of U.S. women with prospectively-collected serum samples obtained in the mid 1970’s and followed for up to 25 years. Adiponectin, absolute plasminogen activator inhibitor-1 (aPAI-1), and resistin were measured by a multiplex immunoassay. Sex hormones were available for 67 cases and 67 controls. Among controls, we found that lower levels of adiponectin and higher levels of aPAI-1 were correlated with increasing levels of estradiol (Spearman r=−0.26, p-value=0.033; r=0.42, p=0.0003), decreasing levels of sex hormone binding globulin (r=0.38, p=0.0013; r=−0.32, p=0.0076), and increasing body mass index (BMI) (r=−0.31, p=0.05). The lack of association with risk may be due to measurement error of the laboratory assays. In conclusion, lower levels of adiponectin and higher levels of aPAI-1 measured in prospectively-collected serum from postmenopausal women were associated with increasing BMI but not breast cancer risk. PMID:20579950

  5. Association of subcutaneous and visceral fat mass with serum concentrations of adipokines in subjects with type 2 diabetes mellitus

    The goal of the study was to examine the association of subcutaneous and visceral fat mass with serum concentrations of adipokines in 130 subjects with type 2 diabetes mellitus. The levels of serum high sensitivity C-reactive protein (HS-CRP), adiponectin, high-molecular-weight (HMW) adiponectin, interleukin-18, and retinol-binding protein 4 were measured. Percentage body fat was determined by dual energy X-ray absorptiometry, and subcutaneous and visceral fat areas were measured by abdominal CT. HS-CRP had significant positive correlations with percentage body fat and subcutaneous fat area, and a particularly significant positive correlation with visceral fat area. Serum adiponectin had a negative correlation with the subcutaneous and visceral fat areas, with the strongest correlation with the visceral fat area. Similar results were obtained for HMW adiponectin. Serum adiponectin had a negative correlation with visceral fat area in subjects with a visceral fat area 2, but not in those with a visceral fat area ≥100 cm2. In contrast, serum HS-CRP showed a positive correlation with visceral fat area in subjects with visceral fat area ≥100 cm2, but not in those with a visceral fat area 2. These findings indicate that an increased visceral fat area is associated with inflammatory changes, and that inflammatory reactions may alter the functional properties of visceral fat in type 2 diabetes mellitus. (author)

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

    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.

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

    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.

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

    Kim Aubin

    Full Text Available 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

  9. Soluble HMGB1 is a novel adipokine stimulating IL-6 secretion through RAGE receptor in SW872 preadipocyte cell line: contribution to chronic inflammation in fat tissue.

    Brice Nativel

    Full Text Available Low-grade inflammation (LGI is a central phenomenon in the genesis of obesity and insulin-resistance characterized by IL-6 in human serum. Whereas this LGI was initially thought to be mainly attributed to macrophage activation, it is now known that pre-adipocytes and adipocytes secrete several adipokines including IL-6 and participate to LGI and associated pathologies. In macrophages, HMGB1 is a nuclear yet secreted protein and acts as a cytokine to drive the production of inflammatory molecules through RAGE and TLR2/4. In this paper we tested the secretion of HMGB1 and the auto- and paracrine contribution to fat inflammation using the human preadipocyte cell line SW872 as a model. We showed that 1 human SW872 secreted actively HMGB1, 2 IL-6 production was positively linked to high levels of secreted HMGB1, 3 recombinant HMGB1 boosted IL-6 expression and this effect was mediated by the receptor RAGE and did not involve TLR2 or TLR4. These results suggest that HMGB1 is a major adipokine contributing to LGI implementation and maintenance, and can be considered as a target to develop news therapeutics in LGI associated pathologies such as obesity and type II diabetes.

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

    Research highlights: → Aging is associated with muscle atrophy and loss of muscle mass, known as the sarcopenia of aging. → We demonstrate that age-related muscle atrophy is associated with marked changes in miRNA expression in muscle. → Treating aged mice with the adipokine leptin significantly increased muscle mass and the expression of miRNAs involved in muscle repair. → 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-related hormones such as leptin

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

    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

  12. 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

    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...

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

    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

  14. Longitudinal changes in adipose tissue of dairy cows from late pregnancy to lactation. Part 1: The adipokines apelin and resistin and their relationship to receptors linked with lipolysis.

    Weber, M; Locher, L; Huber, K; Kenéz, Á; Rehage, J; Tienken, R; Meyer, U; Dänicke, S; Sauerwein, H; Mielenz, M

    2016-02-01

    The transition from pregnancy to lactation is characterized by major changes in glucose and adipose tissue metabolism. Anti- and prolipolytic pathways mediated via the hydroxycarboxylic acid receptors 1 (HCAR1) and 2 (HCAR2) and tumor necrosis factor-α receptor 1 (TNFR1), as well as the adipokines apelin and resistin, are likely involved in regulating these processes. This study aimed to determine the mRNA abundance of the aforementioned receptors in both subcutaneous and visceral adipose tissue, to characterize the adipokine concentrations in serum, and to test the effects of feeding diets with either high or low portions of concentrate and a concomitant niacin supplementation from late gestation to early lactation. Twenty pluriparous German Holstein cows were all kept on the same silage-based diet until d 42 antepartum, when they were allocated to 2 feeding groups: until d 1 antepartum, 10 animals each were assigned to either a high-concentrate (60:40 concentrate-to-roughage ratio) or a low-concentrate diet (30:70). Both groups were further subdivided into a control and a niacin group, the latter receiving 24 g/d of nicotinic acid from d -42 until 24. From d 1 to 24 postpartum, the concentrate portion was increased from 30 to 50% for all cows. Biopsies of subcutaneous (SCAT) and retroperitoneal adipose tissue (RPAT) were taken at d -42, 1, 21, and 100 relative to parturition. Blood samples were drawn along with the biopsies and on d -14, 3, 7, 14, and 42. The concentrations of the adipokines apelin and resistin in serum were measured via ELISA. The mRNA of the 3 receptors in AT was quantified as well as the protein abundance of HCAR2 by Western blot. The feeding regimen did not affect the variables examined. The concentrations of apelin remained fairly constant during the observation period, whereas the resistin concentrations increased toward parturition and decreased to precalving levels within 1 wk after calving. The mRNA abundance of HCAR1, HCAR2, and TNFR1

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

    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.

  16. 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

    Luciana Bahia; Luiz Guilherme Aguiar; Nivaldo Villela; Daniel Bottino; Amelio F. Godoy-Matos; Bruno Geloneze; Marcos Tambascia; Eliete Bouskela

    2006-01-01

    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 ...

  17. The associations of adipokines with selected markers of the renin-angiotensinogen-aldosterone system: the multi-ethnic study of atherosclerosis.

    Allison, M A; Jenny, N S; McClelland, R L; Cushman, M; Rifkin, D

    2015-02-01

    Among obese individuals, increased sympathetic nervous system (SNS) activity results in increased renin and aldosterone production, as well as renal tubular sodium reabsorption. This study determined the associations between adipokines and selected measures of the renin-angiotensinogen-aldosterone system (RAAS). The sample consisted of 1970 men and women from the Multi-Ethnic Study of Atherosclerosis who were free of clinical cardiovascular disease at baseline and had blood assayed for adiponectin, leptin, plasma renin activity (PRA) and aldosterone. The mean age was 64.7 years and 50% were female. The mean (s.d.) PRA and aldosterone were 1.45 (0.56) ng ml(-1) and 150.1 (130.5) pg ml(-1), respectively. After multivariable adjustment, a 1-s.d. increment of leptin was associated with a 0.55 ng ml(-1) higher PRA and 8.4 pg ml(-1) higher aldosterone (Pleptin and adiponectin were not materially changed with additional adjustment for PRA. Exclusion of those taking antihypertensive medications modestly attenuated the associations. The associations between leptin and both PRA and aldosterone were not different by gender but were significantly stronger among non-Hispanic Whites and Chinese Americans than African and Hispanic Americans (Pleptin may be relevant to blood pressure regulation via the RAAS, in that the associations appear to be robust to antihypertension medication use and that the associations are likely different by ethnicity. PMID:24919752

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

    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.

  19. Effects of Exenatide on Metabolic Changes, Sexual Hormones, Inflammatory Cytokines, Adipokines, and Weight Change in a DHEA-Treated Rat Model.

    Sun, Lingjun; Ji, Cheng; Jin, Lu; Bi, Yan; Feng, Wenhuan; Li, Ping; Shen, Shanmei; Zhu, Dalong

    2016-09-01

    Insulin resistance and hyperandrogenism are the main features of polycystic ovarian syndrome (PCOS). Low-grade inflammation is also involved in PCOS. This study was performed to evaluate the effect of exenatide on metabolic changes, sexual hormones, inflammatory cytokines, adipokines, and weight changes in a dehydroepiandrosterone (DHEA)-treated rat model. After the model was produced by daily subcutaneous injections of DHEA, rats were given metformin (265 mg/kg), exenatide (10 μg/kg), and saline (1 mL). One group served as a control group. Blood samples and ovarian tissues were removed and prepared for biochemical and hormonal analyses. Exenatide significantly reduced body weight and insulin, testosterone, interleukin 6 (IL-6), PEDF, and visfatin levels. Exenatide also ameliorated changes in ovarian morphology, as evidenced by decreased numbers of cystic follicles and various follicles and elevated numbers of granular cell layers. The effects observed with exenatide were comparable to those observed with metformin. This study has provided evidence that exenatide may be efficient in the treatment of PCOS. PMID:26917422

  20. Change of Body Composition and Adipokines and Their Relationship with Insulin Resistance across Pubertal Development in Obese and Nonobese Chinese Children: The BCAMS Study

    Lu Xu

    2012-01-01

    Full Text Available A transient increase in insulin resistance (IR is a component of puberty. We investigated the impact of body composition and adipokines on IR during puberty in Chinese children. This study included 3223 schoolchildren aged 6–18 years. IR was calculated using homeostasis model assessment (HOMA-IR. We revealed that body mass index (BMI and waist circumference increased gradually during puberty in both genders, while fat-mass percentage (FAT% increased steadily only in girls. Change of leptin showed striking sexual dimorphisms: in girls leptin increased steadily during puberty, whereas in boys, after a transient rise at the beginning of puberty, leptin declined by Tanner staging even in those overweight or obese. Inversely, adiponectin level decreased significantly during puberty. In both genders, HOMA-IR started to increase at the beginning of puberty, peaked in the middle, and revised at late puberty in overweight/obesity boys while it stayed high till the end of puberty in girls and normal weight boys. Multivariate regression analysis revealed that leptin presented a stronger indicator of HOMA-IR than anthropometric measures during puberty. Our results demonstrated that gender-specific FAT% and leptin changed with pubertal development. Leptin emerged as a stronger predictor of IR than traditional anthropometric indices, suggesting a prominent role in the development of pubertal IR.

  1. Effects of heat stress on serum insulin, adipokines, AMP-activated protein kinase, and heat shock signal molecules in dairy cows.

    Min, Li; Cheng, Jian-bo; Shi, Bao-lu; Yang, Hong-jian; Zheng, Nan; Wang, Jia-qi

    2015-06-01

    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 dairy cows were used. The treatments were: heat stress (HS, THI average=81.7, n=9) and cooling (CL, THI average=53.4, n=9). Samples of HS were obtained on August 16, 2013, and samples of CL were collected on April 7, 2014 in natural conditions. The second experiment: HS treatment cows (n=9) from the first experiment were fed for 8 weeks from August 16, 2013 to October 12, 2013. Samples for moderate heat stress, mild heat stress, and no heat stress were obtained, respectively, according to the physical alterations of the THI. Results showed that heat stress significantly increased the serum adiponectin, AMPK, HSF, HSP27, HSP70, and HSP90 (Pbiomarkers to supplement the THI and evaluate moderate heat stress in dairy cows in the future. PMID:26055916

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

    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.

  3. 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

    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

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

    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.

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

    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.

  6. Pioglitazone improves fat distribution, the adipokine profile and hepatic insulin sensitivity in non-diabetic end-stage renal disease subjects on maintenance dialysis: a randomized cross-over pilot study.

    Anne Zanchi

    Full Text Available BACKGROUND: Fat redistribution, increased inflammation and insulin resistance are prevalent in non-diabetic subjects treated with maintenance dialysis. The aim of this study was to test whether pioglitazone, a powerful insulin sensitizer, alters body fat distribution and adipokine secretion in these subjects and whether it is associated with improved insulin sensitivity. TRIAL DESIGN: This was a double blind cross-over study with 16 weeks of pioglitazone 45 mg vs placebo involving 12 subjects. METHODS: At the end of each phase, body composition (anthropometric measurements, dual energy X-ray absorptometry (DEXA, abdominal CT, hepatic and muscle insulin sensitivity (2-step hyperinsulinemic euglycemic clamp with 2H2-glucose were measured and fasting blood adipokines and cardiometabolic risk markers were monitored. RESULTS: Four months treatment with pioglitazone had no effect on total body weight or total fat but decreased the visceral/sub-cutaneous adipose tissue ratio by 16% and decreased the leptin/adiponectin (L/A ratio from 3.63 × 10(-3 to 0.76 × 10(-3. This was associated with a 20% increase in hepatic insulin sensitivity without changes in muscle insulin sensitivity, a 12% increase in HDL cholesterol and a 50% decrease in CRP. CONCLUSIONS/LIMITATIONS: Pioglitazone significantly changes the visceral-subcutaneous fat distribution and plasma L/A ratio in non diabetic subjects on maintenance dialysis. This was associated with improved hepatic insulin sensitivity and a reduction of cardio-metabolic risk markers. Whether these effects may improve the outcome of non diabetic end-stage renal disease subjects on maintenance dialysis still needs further evaluation. TRIAL REGISTRATION: ClinicalTrial.gov NCT01253928.

  7. Pioglitazone Improves Fat Distribution, the Adipokine Profile and Hepatic Insulin Sensitivity in Non-Diabetic End-Stage Renal Disease Subjects on Maintenance Dialysis: A Randomized Cross-Over Pilot Study

    Zanchi, Anne; Tappy, Luc; Lê, Kim-Anne; Bortolotti, Murielle; Theumann, Nicolas; Halabi, Georges; Gauthier, Thierry; Mathieu, Claudine; Tremblay, Sylvie; Bertrand, Pauline Coti; Burnier, Michel; Teta, Daniel

    2014-01-01

    Background Fat redistribution, increased inflammation and insulin resistance are prevalent in non-diabetic subjects treated with maintenance dialysis. The aim of this study was to test whether pioglitazone, a powerful insulin sensitizer, alters body fat distribution and adipokine secretion in these subjects and whether it is associated with improved insulin sensitivity. Trial Design This was a double blind cross-over study with 16 weeks of pioglitazone 45 mg vs placebo involving 12 subjects. Methods At the end of each phase, body composition (anthropometric measurements, dual energy X-ray absorptometry (DEXA), abdominal CT), hepatic and muscle insulin sensitivity (2-step hyperinsulinemic euglycemic clamp with 2H2-glucose) were measured and fasting blood adipokines and cardiometabolic risk markers were monitored. Results Four months treatment with pioglitazone had no effect on total body weight or total fat but decreased the visceral/sub-cutaneous adipose tissue ratio by 16% and decreased the leptin/adiponectin (L/A) ratio from 3.63×10−3 to 0.76×10−3. This was associated with a 20% increase in hepatic insulin sensitivity without changes in muscle insulin sensitivity, a 12% increase in HDL cholesterol and a 50% decrease in CRP. Conclusions/Limitations Pioglitazone significantly changes the visceral-subcutaneous fat distribution and plasma L/A ratio in non diabetic subjects on maintenance dialysis. This was associated with improved hepatic insulin sensitivity and a reduction of cardio-metabolic risk markers. Whether these effects may improve the outcome of non diabetic end-stage renal disease subjects on maintenance dialysis still needs further evaluation. Trial Registration ClinicalTrial.gov NCT01253928 PMID:25330088

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

    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.

  9. Effect of liposuction on adipokines, inflammatory markers and insulin resistance%脂肪抽吸术对脂源性激素、炎性标志物及胰岛素抵抗的影响

    马桂娥; 刘平; 雷华; 陈建; 刘珍君

    2010-01-01

    目的 探讨脂肪抽吸术对脂源性激素、炎性标志物与胰岛素抵抗的影响,并探讨其临床意义.方法 对16例接受腹部脂肪抽吸手术患者术前及术后3个月的血清脂联素、抵抗素、C反应蛋白、白细胞介素-6、肿瘤坏死因子-α及胰岛素敏感性进行检测并比较.结果 血清脂联素术后[(5.56±1.03)ng/ml]较术前[(6.54±1.27)ng/ml]明显升高(P0.05);CRP术后[(8.03±6.01)mg/L]与术前[(7.28±6.21)mg/L]比较,差异无统计学意义(P>0.05).结论 腹部脂肪抽吸术在去除大量皮下脂肪的同时,对脂源性激素及胰岛素抵抗等也有非常有益的影响.%Objective To study the effect of large-volume liposuction on adipokines,inflammatory markers and insulin resistance and its significance. Methods The levels of serum adiponectin, resistin,IL-6, ANF-α, CRP and insulin sensitivity were measured pre- and 3 months postoperatively in 16 consecutive patients undergoing liposuction. Results The adiponectin postoperative [ (5.56±1.03) ng/ml] was significantly higher than the preoperative [(6.54±1.27) ng/ml] (P0.05]; the posoperative CBP[(8.03±6.01) mg/L] was not significantly different with the preoperative [(7.28±6.21) mg/L,P >0.05]. Conclusions Large-volume liposuction has good effect on insulin resistance and adipokines.

  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

    Hoelmkjaer, Kirsten M.; Wewer Albrechtsen, Nicolai J.; Holst, Jens J.; Cronin, Anna M.; Nielsen, Dorte H.; Mandrup-Poulsen, Thomas; Bjornvad, Charlotte R.

    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 homeostasis, body weight, body composition as measured by dual-energy x-ray absorptiometry and overall safety. An intravenous glucose tolerance test (1 g/kg body weight) was conducted at week 0 and week 12. Exenatide did not change the insulin concentration, plasma glucose concentration or glucose tolerance (P>0.05 for all). Exenatide tended to reduce body weight on continued normal feeding. Median relative weight loss after 12 weeks was 5.1% (range 1.7 to 8.4%) in the exenatide group versus 3.2% (range -5.3 to 5.7%) in the placebo group (P = 0.10). Body composition and adipokine levels were unaffected 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 cats. Further investigations are required to fully elucidate the effect on insulin secretion, glucose tolerance and body weight in obese cats. PMID:27136422

  11. 糖尿病高危人群脂肪细胞因子与代谢综合征关系的研究%Relationship between metabolic syndrome and adipokines on diabetes among high-risk populations

    张秀娟; 黎明; 高珊; 王永慧; 刘书筠

    2012-01-01

    目的 研究脂肪细胞因子与代谢综合征(MS)的关系,探讨其对MS临床诊断的预测价值.方法 收集414名2型糖尿病(T2DM)一级亲属,根据2005年国际糖尿病联盟(IDF)共识诊断MS标准,分为MS0组(无MS组分)115例,MS1组(1种MS组分)118例,MS2组(2种MS组分)77例,MS3组(≥3种MS组分)104例,酶联免疫法测定上述人群的瘦素、内脂素、脂联素及抵抗素水平,放射免疫法测定血清视黄醇结合蛋白-4(RBP-4).结果 (1)随MS组分个数的聚集,血清脂联素水平逐渐降低,瘦素及女性RBP-4水平逐渐增加,三者均与MS组分聚集有较强的平行关系;而内脂素水平只在MS3组有明显降低;抵抗素水平则未见随MS组分聚集有变化趋势.(2)高瘦素水平Q4组(以四分位值分组)与低瘦素水平Q1组比较,MS的各组分(高血压、高血糖、血脂异常、胰岛素抵抗和肥胖)的检出率明显增加(Q4/Q1的OR值分别为1.3、1.8、1.6、5.2和3.0).(3)血清RBP-4水平增加不仅与糖调节异常相关(Q4/Q1,OR=2.6),且与高血压(Q4/Q1,OR=1.6)、血脂异常(Q4/Q1,OR=1.9)和肥胖(Q4/Q1,OR=1.5)及聚集即MS更相关(Q4/Q1,OR=2.7).在RBP-4水平高的Q4组,MS检出率为50%.(4)处于脂联素水平最低的Q1组与最高的Q4组相比,MS及其组分(血脂异常、肥胖、高血糖和胰岛素抵抗)的检出率显著增加(Q4/Q1,OR值为2.1~4.1),但高血压的检出率却呈下降趋势.结论 脂肪因子中以脂联素、瘦素和RBP-4与MS的关系最密切.提示三者可能也是参与MS形成的关键因子,可作为MS发病的早期预示标志物和治疗新靶点.%Objective To study the relationship between adipokines and metabolic syndrome (MS),and the predictive value of adipokines on diagnosis of MS.Methods According to the IDF consensus worldwide definition on MS in 2005,we divided the subjects into 4 groups:115 in MS0 (with none of MS component) ; 118 in MS1 (with one MS component) ; 77 in MS2 (with two MS components) and 104 in

  12. Adipokines and ghrelin in gastric cancer cachexia

    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.

  13. A role for adipokines in cranial development?

    2011-01-01

    During skeletal development, condensation of multipotential mesenchymal cells to differentiate towards the various cell types is an important process. Such processes include the formation of periodontal ligament cells (PDL cells), ameloblast and odontoblast cells. Even though the terminally differentiated cells differ in phenotype, they exhibit distinct similarities in the pattern of their secreted factors, which indicate a relationship between these cells. One of these common factors may be ...

  14. The Importance of Adipokines in Alzheimer's Disease

    Seyid Ahmet Ay; Ferhat Deniz; Kamil Baskoy; Arif Yonem

    2015-01-01

    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 var...

  15. 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

    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

  16. 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

    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

  17. 不同程度间歇低氧对3T3-L1脂肪细胞炎性细胞因子和脂肪因子的影响%Effects of Different Degrees of Intermittent Hypoxia on Inflammatory Cytokines and Adipokines in 3T3-L1 Adipocytes

    杨庆婵; 周芹; 王彦; 何庆; 冯靖; 陈宝元

    2013-01-01

    目的:测定不同程度间歇低氧(IH)处理的3T3-L1脂肪细胞中炎性细胞因子和脂肪因子水平的变化。方法建立阻塞性睡眠呼吸暂停(OSA)模式间歇低氧/再氧合(IH/ROX)细胞模型,将分化成熟的3T3-L1脂肪细胞分为5组,即3个不同程度IH组(5%O2,7.5%O2,10%O2,编号为IH-1,IH-2,IH-3)、持续低氧(10%O2,CH)组和正常氧对照(21%O2,IN)组。采用ELISA法测定脂肪细胞上清液中肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6、瘦素和脂联素的水平,Western blot测定脂肪细胞中低氧诱导因子(HIF)-1α、葡萄糖转运蛋白(Glut)-1水平,Real-time-PCR测定脂肪细胞中HIF-1α、Glut-1、TNF-α、IL-6、瘦素、脂联素的mRNA表达水平。结果 IH组和CH组TNF-α、IL-6和瘦素蛋白及其mRNA水平均高于IN组,IH-1组TNF-α、IL-6和瘦素蛋白及瘦素mRNA水平高于IH-2、IH-3组(均P<0.05);IH组和CH组脂联素蛋白及其mRNA水平均低于IN组,IH-1组低于IH-2、IH-3组(均P<0.05)。结论OSA模式IH与脂肪细胞炎性细胞因子和脂肪因子的表达和释放有关,IH可能是脂肪细胞炎症反应的基础,参与OSA患者胰岛素抵抗的发生。%Objective To study the effect of different degrees of intermittent hypoxia (IH) on inflammatory cytokines and adipokines in 3T3-L1 adipocytes. Methods An intermittent hypoxia/reoxygenation (IH/ROX) from obstructive sleep apnea (OSA) adipocyte model was established. 3T3-L1 adipocytes were divided into five groups, three IH groups (5% O2, 7.5%O2 and 10%O2, referred to as IH-1, IH-2 and IH-3), sustained hypoxia group (10%O2, CH) and the normal oxygen control group (21%O2, IN). ELISA method was used to detect values of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), leptin and adiponectin in cell supernatant. Western blot analysis was used to detect levels of hypoxia-inducible fac-tor-1α(HIF-1α) and glucose transporter-1 (Glut

  18. Age and Sex Mediated Changes in Epicardial Fat Adipokines

    Fei, Jia; Cook, Carla; BLOUGH, ERIC; Santanam, Nalini

    2010-01-01

    Aging, which is an independent risk factor for heart disease, alters body fat mass and its function. Epicardial fat plays an important physiological and pathophysiological role on cardiac structure and function. This study investigated if aging altered the abundance of epicardial (EF) and abdominal fat (AF) derived mediators in a sex dependent manner in female and male Fischer 344 × Brown Norway hybrid (FBN) rats. EF and AF were obtained from 48 female and male, young (6 months), aged (26/30 ...

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

    Manfredi Tesauro; Maria Paola Canale; Giuseppe Rodia; Nicola Di Daniele; Davide Lauro; Angelo Scuteri; Carmine Cardillo

    2011-01-01

    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 ...

  20. Slow growing pre weaning piglets have altered adipokine gene expression

    Pigs were selected from seven litters were monitored for growth rate from day 1 to 21. Samples of subcutaneous (SQ) and perirenal (PR) adipose tissues were collected at day 21 of age from the fastest and slowest growing piglets within the litter. Total RNA was extracted and reverse transcription a...

  1. Adiponectin: an adipokine with protective features against metabolic syndrome

    Maryam Esfahani

    2015-05-01

    Full Text Available Metabolic syndrome (MetS as a collection of obesity-associated disorders is associated with inflammation, oxidative stress, pro-thrombotic state, elevated risk of developing cardiovascular disease and type 2 diabetes. Adiponectin is one of the most abundant peptide hormones derived from adipose tissue. This protein plays a major role in glucose and lipid metabolism and prevents development of vascular changes. Anti-oxidative and anti-inflammatory effects are the other features of adiponectin. Hypoadiponectinemia is associated with hypertension and pro-thrombotic state. In this review, we discuss the crucial role of adiponectin in prevention of metabolic syndrome considering its effects on the components of this syndrome. Pharmacological interventions and lifestyle modification may increase plasma adiponectin level or tissue sensitivity which seems to be a promising target for prevention and therapeutic approaches of MetS and related diseases.

  2. Genetic variation in adipokine genes and risk of colorectal cancer

    Pechlivanis, S.; Bermejo, J. L.; Pardini, Barbara; Naccarati, Alessio; Vodičková, Ludmila; Novotný, J.; Hemminki, K.; Vodička, Pavel; Försti, A.

    2009-01-01

    Roč. 160, č. 6 (2009), s. 933-940. ISSN 0804-4643 R&D Projects: GA ČR GA310/07/1430; GA MZd NR8563 Grant ostatní: EU(SE) LSHC-CT-2004-503465 Institutional research plan: CEZ:AV0Z50390512 Keywords : colorectal cancer * diabetes Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.539, year: 2009

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

    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.

  4. 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

    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

  5. Polychlorinated Biphenyl-77 Induces Adipocyte Differentiation and Proinflammatory Adipokines and Promotes Obesity and Atherosclerosis

    Arsenescu, Violeta; Arsenescu, Razvan I; King, Victoria; Swanson, Hollie; Cassis, Lisa A.

    2008-01-01

    Background Obesity, an inflammatory condition linked to cardiovascular disease, is associated with expansion of adipose tissue. Highly prevalent coplanar polychlorinated biphenyls (PCBs) such as 3,3′,4,4′-tetrachlorobiphenyl (PCB-77) accumulate in adipose tissue because of their lipophilicity and increase with obesity. However, the effects of PCBs on adipocytes, obesity, and obesity-associated cardiovascular disease are unknown. Objectives In this study we examined in vitro and in vivo effect...

  6. Liver Function Parameters in Hip Fracture Patients: Relations to Age, Adipokines, Comorbidities and Outcomes

    Fisher, Leon; Srikusalanukul, Wichat; Fisher, Alexander; Smith, Paul

    2015-01-01

    Aim: To asses liver markers in older patients with hip fracture (HF) in relation to age, comorbidities, metabolic characteristics and short-term outcomes. Methods: In 294 patients with HF (mean age 82.0±7.9 years, 72.1% women) serum alanine aminotransferase (ALT), gammaglutamyltransferase (GGT), alkaline phosphatase (ALP), albumin, bilirubin, 25(OH)vitaminD, PTH, calcium, phosphate, magnesium, adiponectin, leptin, resistin, thyroid function and cardiac troponin I were measured. Results: Eleva...

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

    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.

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

    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.

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

    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

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

    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

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

    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...

  12. Intensity of Resistance Exercise Determines Adipokine and Resting Energy Expenditure Responses in Overweight Elderly Individuals

    Fatouros, Ioannis G.; Chatzinikolaou, Athanasios; Tournis, Symeon; Nikolaidis, Michalis G.; Jamurtas, Athanasios Z.; Douroudos, Ioannis I.; Papassotiriou, Ioannis; Thomakos, Petros M.; Taxildaris, Kyriakos; Mastorakos, George; Mitrakou, Asimina

    2009-01-01

    OBJECTIVE To evaluate the time course of leptin, adiponectin, and resting energy expenditure (REE) responses in overweight elderly males after acute resistance exercise protocols of various intensity configurations. RESEARCH DESIGN AND METHODS Forty inactive men (65–82 years) were randomly assigned to one of four groups (n = 10/group): control, low-intensity resistance exercise, moderate-intensity resistance exercise, and high-intensity resistance exercise. Exercise energy cost, REE, leptin, adiponectin, cortisol, insulin, lactate, glucose, nonesterified fatty acids (NEFAs), and glycerol were determined at baseline, immediately after exercise, and during a 72-h recovery period. RESULTS Exercise energy cost was lower in high-intensity than in low-intensity and moderate-intensity groups (221.6 ± 8.8 vs. 295.6 ± 10.7 and 281.6 ± 9.8 kcal, P < 0.001). Lactate, glucose, NEFAs, and glycerol concentrations increased (P < 0.001) after exercise and returned to baseline thereafter in all groups. REE increased (P < 0.001) in all groups at 12 h in an intensity-dependent manner (P < 0.05). REE reached baseline after 48 h in the low- and moderate-intensity groups and after 72 h in the high-intensity group. Cortisol peaked in all active groups after exercise (P < 0.001) and remained elevated (P < 0.001) for 12 h. After adjustment for plasma volume shifts, leptin remained unaltered. Adiponectin concentration increased after 12 h and remained elevated for 24 h only in the high-intensity group (P < 0.001). CONCLUSIONS Resistance exercise does not alter circulating leptin concentration but does increase REE and adiponectin in an intensity-dependent manner for as long as 48 and 24 h, respectively, in overweight elderly individuals. It appears that resistance exercise may represent an effective approach for weight management and metabolic control in overweight elderly individuals. PMID:19729520

  13. Intensity of Resistance Exercise Determines Adipokine and Resting Energy Expenditure Responses in Overweight Elderly Individuals

    Fatouros, Ioannis G.; Chatzinikolaou, Athanasios; Tournis, Symeon; Michalis G. Nikolaidis; Jamurtas, Athanasios Z.; Douroudos, Ioannis I.; Papassotiriou, Ioannis; Thomakos, Petros M.; Taxildaris, Kyriakos; Mastorakos, George; Mitrakou, Asimina

    2009-01-01

    OBJECTIVE To evaluate the time course of leptin, adiponectin, and resting energy expenditure (REE) responses in overweight elderly males after acute resistance exercise protocols of various intensity configurations. RESEARCH DESIGN AND METHODS Forty inactive men (65–82 years) were randomly assigned to one of four groups (n = 10/group): control, low-intensity resistance exercise, moderate-intensity resistance exercise, and high-intensity resistance exercise. Exercise energy cost, REE, leptin, ...

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

    Giuseppina Candore; Carmela Rita Balistreri; Calogero Caruso

    2010-01-01

    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 th...

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

    Lausten-Thomsen, Ulrik; Christiansen, Michael; Hedley, Paula Louise; Holm, Jens-Christian; Schmiegelow, Kjeld

    2016-01-01

    ]). Children exposed to maternal diabetes, chronic disease and preeclampsia were excluded. RESULTS: The LGA group exhibited significantly elevated concentrations of leptin (p<0.001) and of free leptin index (p<0.001) and decreased sOB-R concentrations (p=0.005) when compared to the AGA group, which persisted...

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

    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.

  17. Acute-Phase Serum Amyloid A: An Inflammatory Adipokine and Potential Link between Obesity and Its Metabolic Complications

    Rong-Ze Yang; Mi-Jeong Lee; Hong Hu; Pollin, Toni I.; Ryan, Alice S.; Nicklas, Barbara J.; Soren Snitker; Richard B Horenstein; Kristen Hull; Nelson H Goldberg; Goldberg, Andrew P.; Shuldiner, Alan R.; Fried, Susan K.; Da-Wei Gong

    2006-01-01

    Editors' Summary Background. Obesity often alters an individual's overall metabolism, which in turn leads to complications like diabetes, high blood pressure, and an increased risk of cardiovascular disease (disease of the heart and blood vessels, such as stroke or heart attacks). Having established a strong link between inflammation and cardiovascular disease, scientists now think that obesity might cause persistent low-level inflammation, and that this is the reason for the cardiovascular p...

  18. Adipokines resistin and lipokalin-2 and its role in the pathogenesis of polycystic ovary syndrome and metabolic syndrome

    Voronenko N.Yu.

    2013-10-01

    Full Text Available Adipose tissues hormones resistin and lipocalin -2 play an important role in the regulation of lipid and carbohydrate metabolism, inflammation and immune disorders, fertility and reproductive mechanisms. Obesity and overweight are significantly involved in the process of fertility decline. Women with obesity and metabolic syndrome have abnormal adypokine plasma levels. The aim of the study was to investigate the relationships between the women’s of the hypothalamic-pituitary-ovarian axis and energy metabolism. Methods: basal levels of resistin, lipocalin-2, follicular stimulating, luteinizing hormones, estradiol, total and free testosterone, dihydrotestosterone, dihydroepiandrosteron sulfate, androstenedione, cortisol, anti-mullerian hormone, prolactin, insulin, folistatin, homocysteine, interleukin-6 and sex-binding globulin were determined in the serum of 35 women of reproductive age with metabolic syndrome (MS, 33 patients of reproductive age with polycystic ovary syndrome (PCOS and in 54 healthy contols. It is found that despite the normal values of hormones lipocalin-2 and resistin even in patients with obesity, their concentrations significantly correlated with anthropometric, hormonal and metabolic parameters. We established statistically significant stimulatory effects of lipocalin-2 and resistin on the synthesis of ovarian steroids and the significant inhibitory effect of lipocalin-2 and resistin on ovarian and adrenal androgens synthesis in normal physical condition and reproductive health. In MS and PCOS these relationships are not established. The results obtained allow us to propose the assumption of the existence of metabolic changes of the sensitivity of the reproductive system and the adrenal gland to the effects of lipocalin -2 and resistin in women with PCOS and metabolic syndrome.

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

    Daniella Esteves Duque Guimarães; Fátima Lúcia de Carvalho Sardinha; Daniella de Moraes Mizurini; Maria das Graças Tavares do Carmo

    2007-01-01

    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 m...

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

    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.

  1. Removal of visceral fat prevents insulin resistance and glucose intolerance of aging: an adipokine-mediated process?

    Gabriely, Ilan; Ma, Xiao Hui; Yang, Xiao Man; Atzmon, Gil; Rajala, Michael W; Berg, Anders H; Scherer, Phillip; Rossetti, Luciano; Barzilai, Nir

    2002-10-01

    Age-dependent changes in insulin action and body fat distribution are risk factors for the development of type 2 diabetes. To examine whether the accumulation of visceral fat (VF) could play a direct role in the pathophysiology of insulin resistance and type 2 diabetes, we monitored insulin action, glucose tolerance, and the expression of adipo-derived peptides after surgical removal of VF in aging (20-month-old) F344/Brown Norway (FBN) and in Zucker Diabetic Fatty (ZDF) rats. As expected, peripheral and hepatic insulin action were markedly impaired in aging FBN rats, and extraction of VF (accounting for approximately 18% of their total body fat) was sufficient to restore peripheral and hepatic insulin action to the levels of young rats. When examined at the mechanistic level, removal of VF in ZDF rats prevented the progressive decrease in insulin action and delayed the onset of diabetes, but VF extraction did not alter plasma free fatty acid levels. However, the expression of tumor necrosis factor-alpha and leptin in subcutaneous (SC) adipose tissue were markedly decreased after VF removal (by approximately three- and twofold, respectively). Finally, extracted VF retained approximately 15-fold higher resistin mRNA compared with SC fat. Our data suggest that insulin resistance and the development of diabetes can be significantly reduced in aging rats by preventing the age-dependent accumulation of VF. This study documents a cause-and-effect relationship between VF and major components of the metabolic syndrome. PMID:12351432

  2. Selected adipokines – plasma concentrations and adipose tissue expressions during 24-hour lipid infusion in healthy men

    Kopecký, J.; Krušinová, E.; Klementová, M.; Kazdová, L.; Mlejnek, Petr; Pravenec, Michal; Hill, M.; Pelikánová, T.

    2010-01-01

    Roč. 59, č. 1 (2010), s. 89-96. ISSN 0862-8408 R&D Projects: GA MZd(CZ) NR9359 Institutional research plan: CEZ:AV0Z50110509 Keywords : TNFalpha * resistin * insulin resistance Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 1.646, year: 2010

  3. Adipokini u bolesnica sa sindromom policističnih jajnika [Adipokines in patients with polycystic ovary syndrome

    Zlopaša, Gordan

    2011-01-01

    Sindrom policističnih jajnika (PCOS) je multisistemski, endokrinološki, reprodukcijski i metabolički poremećaj, karakteriziran oligo/anovulacijama, hiperandrogenizmom i policističnim izgledom jajnika. Često je udružen s debljinom i inzulinskom rezistencijom. Žene s PCOS imaju povišen rizik za šećernu bolest tipa 2, dislipidemiju i kardiovaskularne bolesti. Sve je više studija koje govore u prilog da je lučenje hormona masnog tkiva – adipokina (leptina, adiponektina, grelina i rezistina) prom...

  4. Purple Sweet Potato Leaf Extract Induces Apoptosis and Reduces Inflammatory Adipokine Expression in 3T3-L1 Differentiated Adipocytes

    Shou-Lun Lee

    2015-01-01

    Full Text Available Background. Purple sweet potato leaves (PSPL are widely grown and are considered a healthy vegetable in Taiwan. PSPL contain a high content of flavonoids, and the boiling water-extracted PSPL (PSPLE is believed to prevent metabolic syndrome. However, its efficacy has not yet been verified. Therefore, we investigated the effect of PSPLE on adipocytes. Methods. The differentiated 3T3-L1 cells used in this study were derived from preadipocytes that were differentiated into adipocytes using an adipogenic agent (insulin, dexamethasone, and 3-isobutyl-1-methylxanthine; approximately 90% of the cells were differentiated using this method. Results. Treating the differentiated 3T3-L1 cells with PSPLE caused a dose-dependent decrease in the number of adipocytes rather than preadipocytes. In addition, treatment with PSPLE resulted in apoptosis of the differentiated 3T3-L1 cells as determined by DAPI analysis and flow cytometry. PSPLE also increased the expression of cleaved caspase-3 and poly ADP-ribose polymerase (PARP. Furthermore, PSPLE induced downregulation of interleukin-6 (IL-6 and tumor necrosis factor-α (TNF-α gene expression in the differentiated 3T3-L1 cells. Conclusions. These results suggest that PSPLE not only induced apoptosis but also downregulated inflammation-associated genes in the differentiated 3T3-L1 cells.

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

    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.

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

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

    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, featuri...

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

    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.

  8. The Drosophila TNF Eiger Is an Adipokine that Acts on Insulin-Producing Cells to Mediate Nutrient Response.

    Agrawal, Neha; Delanoue, Renald; Mauri, Alessandra; Basco, Davide; Pasco, Matthieu; Thorens, Bernard; Léopold, Pierre

    2016-04-12

    Adaptation of organisms to ever-changing nutritional environments relies on sensor tissues and systemic signals. Identification of these signals would help understand the physiological crosstalk between organs contributing to growth and metabolic homeostasis. Here we show that Eiger, the Drosophila TNF-α, is a metabolic hormone that mediates nutrient response by remotely acting on insulin-producing cells (IPCs). In the condition of nutrient shortage, a metalloprotease of the TNF-α converting enzyme (TACE) family is active in fat body (adipose-like) cells, allowing the cleavage and release of adipose Eiger in the hemolymph. In the brain IPCs, Eiger activates its receptor Grindelwald, leading to JNK-dependent inhibition of insulin production. Therefore, we have identified a humoral connexion between the fat body and the brain insulin-producing cells relying on TNF-α that mediates adaptive response to nutrient deprivation. PMID:27076079

  9. Thymidine kinase 2 deficiency-induced mitochondrial DNA depletion causes abnormal development of adipose tissues and adipokine levels in mice.

    Joan Villarroya

    Full Text Available Mammal adipose tissues require mitochondrial activity for proper development and differentiation. The components of the mitochondrial respiratory chain/oxidative phosphorylation system (OXPHOS are encoded by both mitochondrial and nuclear genomes. The maintenance of mitochondrial DNA (mtDNA is a key element for a functional mitochondrial oxidative activity in mammalian cells. To ascertain the role of mtDNA levels in adipose tissue, we have analyzed the alterations in white (WAT and brown (BAT adipose tissues in thymidine kinase 2 (Tk2 H126N knockin mice, a model of TK2 deficiency-induced mtDNA depletion. We observed respectively severe and moderate mtDNA depletion in TK2-deficient BAT and WAT, showing both tissues moderate hypotrophy and reduced fat accumulation. Electron microscopy revealed altered mitochondrial morphology in brown but not in white adipocytes from TK2-deficient mice. Although significant reduction in mtDNA-encoded transcripts was observed both in WAT and BAT, protein levels from distinct OXPHOS complexes were significantly reduced only in TK2-deficient BAT. Accordingly, the activity of cytochrome c oxidase was significantly lowered only in BAT from TK2-deficient mice. The analysis of transcripts encoding up to fourteen components of specific adipose tissue functions revealed that, in both TK2-deficient WAT and BAT, there was a consistent reduction of thermogenesis related gene expression and a severe reduction in leptin mRNA. Reduced levels of resistin mRNA were found in BAT from TK2-deficient mice. Analysis of serum indicated a dramatic reduction in circulating levels of leptin and resistin. In summary, our present study establishes that mtDNA depletion leads to a moderate impairment in mitochondrial respiratory function, especially in BAT, causes substantial alterations in WAT and BAT development, and has a profound impact in the endocrine properties of adipose tissues.

  10. Obesity-induced adipokine imbalance impairs mouse pulmonary vascular endothelial function and primes the lung for injury

    Shah, Dilip; Romero, Freddy; Duong, Michelle; Wang, Nadan; Paudyal, Bishnuhari; Benjamin T Suratt; Kallen, Caleb B.; Sun, Jianxin; Zhu, Ying; Walsh, Kenneth; Summer, Ross

    2015-01-01

    Obesity is a risk factor for the development of acute respiratory distress syndrome (ARDS) but mechanisms mediating this association are unknown. While obesity is known to impair systemic blood vessel function, and predisposes to systemic vascular diseases, its effects on the pulmonary circulation are largely unknown. We hypothesized that the chronic low grade inflammation of obesity impairs pulmonary vascular homeostasis and primes the lung for acute injury. The lung endothelium from obese m...

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

    Maha I.A. Moaty; Salwa M. El Shebini; Nihad H. Ahmed; Hussein, Ahmed M. S.; Magda S. Mohamed; Salwa T. Tapozada; Laila M. Hanna

    2014-01-01

    AIM: To investigate the association between the circulating vaspin concentration and both of glucose homeostasis and insulin resistance in metabolic syndrome (MetS) patients, and also to evaluate the metabolic impact of two different dietary therapies on such conditions. MATERIALS AND METHODS:  Fifty eight obese female volunteers suffering from MetS, followed a specially designed dietary therapy consists of a low caloric balanced diet, accompanied by either 30% doum biscuits (group A), or...

  12. Chronic elevation of systemic glucagon-like peptide-1 following surgical weight loss: association with nausea and vomiting and effects on adipokines.

    Al-Rasheid, Noora; Gray, Rosaire; Sufi, Pratik; Marina-Gonzalez, Nephtali; Al-Sayrafi, Mohammed; Atherton, Elizabeth; Mohamed-Ali, Vidya

    2015-02-01

    We determined whether persistent nausea and vomiting (N/V) symptoms following Roux-en-Y gastric bypass surgery is due to elevated systemic glucagon-like peptide-1 (GLP-1) and leptin in female non-diabetic subjects. Subjects with N/V post-Roux-en-Y gastric bypass (RYGB) surgery had significantly elevated fasting GLP-1 levels compared to that with post-operative asymptomatic subjects and to morbidly obese, obese and lean subjects not undergoing surgery. Weight loss, glycaemia, insulin and post-prandial GLP-1 levels were similar in all post-operative subjects. Despite comparable BMI, leptin was significantly lower in symptomatic subjects. Furthermore, leptin secretion from subcutaneous adipose tissue was inhibited by GLP-1 (0.1-1.0 nM; n = 6). Persistent N/V following RYGB surgery is associated with elevated fasting GLP-1, but lower leptin levels. The latter may be a consequence of the direct GLP-1 inhibition of leptin secretion from adipose tissue. PMID:25411121

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

    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.

  14. Effects of Electroacupuncture on Pro-/Anti-inflammatory Adipokines in Serum and Adipose Tissue in Lean and Diet-induced Obese Rats.

    Liaw, Jacqueline J T; Peplow, Philip V

    2016-04-01

    The effects of electroacupuncture (EA) on pro-/anti-inflammatory cytokines and blood glucose (BG) in lean and obese Long Evans rats were investigated. Group 1 and Group 3 had five lean and seven obese rats, respectively, and received EA at the Zhongwan/Guanyuan acupoints on Day 1, Day 3, Day 5, Day 8, Day 10, and Day 12. Group 2 and Group 4, with five lean and seven obese rats, respectively, did not undergo EA. After induction of anesthesia, BG was measured at 10 minutes and 20 minutes. EA was applied for 30 minutes, and BG was measured again. At the end of the study, blood and white adipose tissue were collected. Analyses showed that for all groups, the mean BG at 20 minutes (baseline) and 50 minutes were significantly greater on Day 1 than on any other day. Compared with Group 2, the baseline BG in Week 1 for Group 1 was significantly lower, but Groups 3 and 4 showed no difference. Group 1 had significantly higher serum interleukin-10 and tumor necrosis factor-α than Group 2, while Group 3's serum leptin was greater than Group 4's. White adipose tissue interleukin-10 and adiponectin:leptin ratio were higher for Group 1 than Group 2. EA affected no significant differences in any other components measured for lean and obese animals. PMID:27079227

  15. Body Composition, Lipid Profile, Adipokine Concentration, and Antioxidant Capacity Changes during Interventions to Treat Overweight with Exercise Programme and Whole-Body Cryostimulation

    Anna Lubkowska; Wioleta Dudzińska; Iwona Bryczkowska; Barbara Dołęgowska

    2015-01-01

    The aim of this study was to determine the effect of six-month-long physical exercise programme with a two-time exposure to whole-body cryostimulation (WBC) in 20 sessions on antioxidant enzyme activities, lipid profile, and body composition changes in obese people (30 adult subjects; BMI = 30.39 ± 4.31 kg/m2). Blood samples were taken before the programme, one month following the exercise programme, before and after the first WBC treatment, six months following the exercise programme, after ...

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

    Andries, Alin; Frystyk, Jan; Flyvbjerg, Allan;

    2015-01-01

    OBJECTIVE: Anorexia nervosa (AN) is characterised by complex neuroendocrine disturbances due to severe underweight, physical hyperactivity and purging behaviour. Cannabinoid agonists are used to palliate cachexia of various causes, but their interactions with the hormonal systems that are involved...

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

    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

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

    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.

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

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

    2008-01-01

    -ray absorptiometry) and an increase in visceral adipose tissue (VAT; an increase of at least 18 cm(2) from baseline to week 48 by abdominal computed tomography). Risk factors associated with limb fat loss and VAT gain were analysed by logistic regression. RESULTS: Fifty-four HIV-infected, treatment-naïve adults were...... different groups of patients with peripheral fat loss and central fat gain, suggesting a partially independent pathogenesis....

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

    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

  1. 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

    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.

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

    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...

  3. 饮食诱导肥胖及肥胖抵抗与脂肪细胞因子%The Relation of Diet-induced Obesity and Diet-induced Obesity Resistance to Adipokines

    刘蜜; 姜萍

    2009-01-01

    Levin提出饮食诱导肥胖(DIO)与饮食诱导肥胖抵抗(DIO-R)的概念后,其发生机制受到了广泛关注.现代研究认为脂肪组织除了能调节能量代谢外,还可以分泌多种细胞因子,如瘦素、脂联素、肿瘤坏死因子-α(TNF-α)和抵抗素等.在已发现的脂肪细胞因子中,瘦素、TNF-α和脂联素等与肥胖的发生密切关联.DIO大鼠血清瘦素水平比DIO-R大鼠高,DIO大鼠瘦素敏感性降低,发生了瘦素抵抗.DIO小鼠血浆脂联素水平比DIO-R小鼠低.DIO组TNF-α水平明显高于DIO-R组.

  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.

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

    2016-07-01

    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. PMID:27094023

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

    Wagner Luiz do Prado; Mara Cristina Lofrano; Lila Missae Oyama; Ana Raimunda Dâmaso

    2009-01-01

    A obesidade é uma doença complexa de etiologia multifacetada, com sua própria fisiopatologia, comorbidades e capacidades desabilitantes. Aceitar a obesidade como uma doença é fundamental para o seu tratamento. Atualmente, o tecido adiposo é um dos principais focos das pesquisas em obesidade, devido a uma revolução no entendimento da função biológica desse tecido desde a última década. Já está muito claro que o tecido adiposo branco secreta múltiplos peptídeos bioativos, denominados adipocinas...

  6. 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

    DeClercq, Vanessa; Zahradka, Peter; Taylor, Carla G.

    2010-01-01

    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 wi...

  7. Effect of CTRP3 on activation of adventitial fibroblasts induced by TGF-β1 from rat aorta in vitro

    Lin, Shaohui; Ma, Shaojun; Lu, Ping; Cai, Wenwei; Chen, Yi; Sheng, Jing

    2014-01-01

    CTRP3, discovered as novel adipokines, is a member of the C1q tumor necrosis factor (TNF) related protein (CTRP) super-family. CTRP3 is found to function as adipokines that display diverse biological activities in metabolic and cardiovascular diseases. Recent study demonstrated that CTRP3 was protective against pathological cardiac remodeling in mice. Nevertheless, the effect of CTRP3 on vascular remodeling remains undefined. Our present study aimed to explore the effects of adipokine CTRP3 o...

  8. The Liposuction-Induced Effects on Adiponectin and Selected Cytokines Are Not Affected by Exercise Training in Women

    Marina Yazigi Solis; Guilherme Giannini Artioli; Eduardo Montag; Vitor de Salles Painelli; Fábio Lopes Saito; Fernanda Rodrigues Lima; Hamilton Roschel; Bruno Gualano; Antonio Herbert Lancha Junior; Fabiana Braga Benatti

    2014-01-01

    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...

  9. Peptides from adipose tissue in mental disorders

    Wędrychowicz, Andrzej; Zając, Andrzej; Pilecki, Maciej; Kościelniak, Barbara; Tomasik, Przemysław J

    2014-01-01

    Adipose tissue is a dynamic endocrine organ that is essential to regulation of metabolism in humans. A new approach to mental disorders led to research on involvement of adipokines in the etiology of mental disorders and mood states and their impact on the health status of psychiatric patients, as well as the effects of treatment for mental health disorders on plasma levels of adipokines. There is evidence that disturbances in adipokine secretion are important in the pathogenesis, clinical pr...

  10. Associations among serum pro- and anti-inflammatory cytokines, metabolic mediators, body condition, and uterine disease in postpartum dairy cows

    Kasimanickam, Ramanathan K.; Kasimanickam, Vanmathy R; Olsen, Jesse R; Jeffress, Erin J; Moore, Dale A; Kastelic, John P.

    2013-01-01

    Background Adipose tissue is an active endocrine organ which secretes a wide range of hormones and protein factors, collectively termed adipokines. Adipokines affect appetite and satiety, glucose and lipid metabolism, inflammation and immune functions. The objectives were to evaluate serum concentrations of adipokines (adiponectin, leptin, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6) in lactating dairy cows with postpartum uterine inflammatory conditions (metritis, clin...

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

    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

  12. 3,4-Oxo-isopropylidene-shikimic acid promotes adiopkine expression during murine 3T3-L1 fibroblast differentiation into adipocytes

    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.

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

    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. PMID:27230642

  14. 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

    Isabel R. Madeira; Cecilia N. M. Carvalho; Fernanda M. Gazolla; Liana W. Pinto; Marcos A. Borges; Maria Alice N. Bordallo

    2009-01-01

    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...

  15. 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

    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.

  16. 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

    D. A. De Luis; R. Aller; Conde, R.; O. Izaola; B. de la Fuente; M. González Sagrado; D. Primo; M. Ruiz Mambrilla

    2012-01-01

    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 tra...

  17. PUTATIVE ROLE OF ADIPOSE TISSUE IN GROWTH AND METABOLISM OF COLON CANCER CELLS

    BettySchwartz

    2014-06-01

    Given that adipocytes are a major source of adipokines and energy for the cancer cell, understanding the mechanisms of metabolic symbiosis between cancer cells and adipocytes should reveal new therapeutic possibilities.

  18. Circulating Ghrelin, Leptin, and Soluble Leptin Receptor Concentrations and Cardiometabolic Risk Factors in a Community-Based Sample

    Ingelsson, Erik; Larson, Martin G.; Yin, Xiaoyan; Wang, Thomas J.; Meigs, James B; Lipinska, Izabella; Benjamin, Emelia J.; Keaney, John F.; Vasan, Ramachandran S.

    2008-01-01

    Context: The conjoint effects and relative importance of ghrelin, leptin, and soluble leptin receptor (sOB-R), adipokines involved in appetite control and energy expenditure in mediating cardiometabolic risk, is unknown.

  19. Adiponectin and Its Receptors in the Ovary: Further Evidence for a Link between Obesity and Hyperandrogenism in Polycystic Ovary Syndrome

    Fabio V Comim; Kate Hardy; Stephen Franks

    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 exp...

  20. Lower leptin/adiponectin ratio and risk of rapid lung function decline in chronic obstructive pulmonary disease

    Suzuki, Masaru; Makita, Hironi; Östling, Jörgen;

    2014-01-01

    compared with the Hokkaido COPD cohort study. There were no significant associations between lung function decline and adipokine levels in subjects without airflow limitation. CONCLUSIONS: A lower leptin/adiponectin ratio was associated with lung function decline in patients with COPD in two independent...... Japanese and Western cohort studies of populations of different ethnicity. Measure of systemic adipokines may provide utility in predicting patients with COPD at higher risk of lung function decline....

  1. Physiological Concentrations of Leptin Do Not Affect Human Neutrophils

    Kamp, V.M.; Langereis, J.D.; Aalst, C.W. van; Linden, J.; 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 was used as an unbiased approach to identify leptin-induced effects on neutrophils. Additionally chemotaxis and survival experiments were performed to reproduce results from literature showing puta...

  2. Leptin and resistin in overweight patients with and without asthma

    Muc, Magdalena; Todo-Bom, Ana; Mota-Pinto, Anabela; Vale-Pereira, Sofia; Loureiro, Carlos

    2014-01-01

    Background: Excess body mass increases the risk of development of asthmatic symptoms and their severity and decreases the treatment effectiveness. One of the hypotheses explaining the link between the two diseases concerns the adipokines, hormones produced by adipose tissue with a proinflammatory character. The aim of this study was to compare the levels of the adipokines (leptin and resistin) between overweight asthmatic patients, asthmatic patients with normal weight and overweight patients...

  3. Minireview: adiposity, inflammation, and atherogenesis.

    Lyon, Christopher J; Law, Ronald E; Hsueh, Willa A

    2003-06-01

    Adipose tissue is a dynamic endocrine organ that secretes a number of factors that are increasingly recognized to contribute to systemic and vascular inflammation. Several of these factors, collectively referred to as adipokines, have now been shown regulate, directly or indirectly, a number of the processes that contribute to the development of atherosclerosis, including hypertension, endothelial dysfunction, insulin resistance, and vascular remodeling. Several adipokines are preferentially expressed in visceral adipose tissue, and the secretion of proinflammatory adipokines is elevated with increasing adiposity. Not surprisingly, approaches that reduce adipose tissue depots, including surgical fat removal, exercise, and reduced caloric intake, improve proinflammatory adipokine levels and reduce the severity of their resultant pathologies. Systemic adipokine levels can also be favorably altered by treatment with several of the existing drug classes used to treat insulin resistance, hypertension, and hypercholesterolemia. Greater understanding of adipokine regulation, however, should result in the design of improved treatment strategies to control disease states associated with increase adiposity, an important outcome in view of the growing worldwide epidemic of obesity. PMID:12746274

  4. Secret talk between adipose tissue and central nervous system via secreted factors-an emerging frontier in the neurodegenerative research.

    Parimisetty, Avinash; Dorsemans, Anne-Claire; Awada, Rana; Ravanan, Palaniyandi; Diotel, Nicolas; Lefebvre d'Hellencourt, Christian

    2016-01-01

    First seen as a storage organ, the white adipose tissue (WAT) is now considered as an endocrine organ. WAT can produce an array of bioactive factors known as adipokines acting at physiological level and playing a vital role in energy metabolism as well as in immune response. The global effect of adipokines in metabolic activities is well established, but their impact on the physiology and the pathophysiology of the central nervous system (CNS) remains poorly defined. Adipokines are not only produced by the WAT but can also be expressed in the CNS where receptors for these factors are present. When produced in periphery and to affect the CNS, these factors may either cross the blood brain barrier (BBB) or modify the BBB physiology by acting on cells forming the BBB. Adipokines could regulate neuroinflammation and oxidative stress which are two major physiological processes involved in neurodegeneration and are associated with many chronic neurodegenerative diseases. In this review, we focus on four important adipokines (leptin, resistin, adiponectin, and TNFα) and one lipokine (lysophosphatidic acid-LPA) associated with autotaxin, its producing enzyme. Their potential effects on neurodegeneration and brain repair (neurogenesis) will be discussed. Understanding and regulating these adipokines could be an interesting lead to novel therapeutic strategy in order to counteract neurodegenerative disorders and/or promote brain repair. PMID:27012931

  5. Obesity, insulin resistance, adipocytokines and breast cancer: New biomarkers and attractive therapeutic targets.

    Dalamaga, Maria

    2013-08-20

    Worldwide, breast cancer (BC) represents the most common type of non-skin human malignancy and the second leading cause of cancer-related deaths amid women in Western countries. Obesity and its metabolic complications have rapidly become major global health issues and are associated with increased risk for cancer, especially BC in postmenopausal women. Adipose tissue is considered as a genuine endocrine organ secreting a variety of bioactive adipokines, such as leptin, adiponectin, resistin and nicotinamide phosphoribosyl-transferase/visfatin. Recent evidence has indicated that the constellation of obesity, insulin resistance and adipokines is associated with the risk and prognosis of postmenopausal BC. Direct evidence is growing rapidly supporting the stimulating and/or inhibiting role of adipokines in the process of development and progression of BC. Adipokines could exert their effects on the normal and neoplastic mammary tissue by endocrine, paracrine and autocrine mechanisms. Recent studies support a role of adipokines as novel risk factors and potential diagnostic and prognostic biomarkers in BC. This editorial aims at providing important insights into the potential pathophysiological mechanisms linking adipokines to the etiopathogenesis of BC in the context of a dysfunctional adipose tissue and insulin resistance in obesity. A better understanding of these mechanisms may be important for the development of attractive preventive and therapeutic strategies against obesity-related breast malignancy. PMID:24520544

  6. Epicardial Fat: Physiological, Pathological, and Therapeutic Implications

    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

  7. The Impact of Organokines on Insulin Resistance, Inflammation, and Atherosclerosis.

    Choi, Kyung Mook

    2016-03-01

    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. PMID:26996418

  8. Weight cycling enhances adipose tissue inflammatory responses in male mice.

    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.

  9. Identification, characterisation, and function of adipokinetic hormones and receptor in the African malaria mosquito, "Anopheles Gambiae" (Diptera)

    Kaufmann, Christian; Betschart, Bruno

    2007-01-01

    En utilisant la bioinformatique et la biologie moléculaire, nous avons pu identifier chez le principal vecteur africain de la malaria, le moustique, Anopheles gambiae deux hormones adipokinétiques (AKHs): l'octapeptide, Anoga-AKH-I (pQLTFTPAWa) et le décapeptide, Anoga-AKH-II, (pQVTFSRDWNAa). La fonction principale des AKHs est d’induire une hyperlipémie (effet d’adipokinétique), ainsi qu’une hypertrehalosémie et une hyperprolinémie. En tant que membres de la famille des AKH, les deux neurope...

  10. C1q/Tumor Necrosis Factor-Related Protein 9 Protects against Acute Myocardial Injury through an Adiponectin Receptor I-AMPK-Dependent Mechanism

    Kambara, Takahiro; Shibata, Rei; Ohashi, Koji; Matsuo, Kazuhiro; Hiramatsu-Ito, Mizuho; Enomoto, Takashi; Yuasa, Daisuke; Ito, Masanori; Hayakawa, Satoko; Ogawa, Hayato; Aprahamian, Tamar; Walsh, Kenneth; Murohara, Toyoaki; Ouchi, Noriyuki

    2015-01-01

    Obesity is a risk factor for cardiovascular disease. C1q/tumor necrosis factor-related protein 9 (CTRP9) is an adipokine that is downregulated by obesity. We investigated the role of CTRP9 in cardiac injury with loss-of-function genetic manipulations and defined the receptor-mediated signaling pathway downstream of this adipokine. CTRP9-knockout (CTRP9-KO) mice at the age of 12 weeks were indistinguishable from wild-type (WT) mice under basal conditions. CTRP9-KO mice had exacerbated contract...

  11. Endotrophin triggers adipose tissue fibrosis and metabolic dysfunction

    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......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...

  12. A randomized controlled intervention with fish oil versus sunflower oil from 9 to 18 months of age

    Andersen, Anders D; Michaelsen, Kim F; Hellgren, Lars; Trolle, Ellen; Lauritzen, Lotte

    2011-01-01

    intake affects adipose tissue growth, we randomly allocated 154 healthy infants to daily supplementation with FO or sunflower oil (SO) from 9 to 18 mo of age and measured z-score changes in various anthropometric assessments of body size and skinfold thicknesses and plasma adipokine concentrations. Among...

  13. Circulating Adipocytokines and Chronic Kidney Disease

    Mills, Katherine T.; L Lee Hamm; A Brent Alper; Chad Miller; Alhakam Hudaihed; Saravanan Balamuthusamy; Chung-Shiuan Chen; Yanxi Liu; Joseph Tarsia; Nader Rifai; Myra Kleinpeter; Jiang He; Jing Chen

    2013-01-01

    BACKGROUND: Adipokines have been associated with atherosclerotic heart disease, which shares many common risk factors with chronic kidney disease (CKD), but their relationship with CKD has not been well characterized. METHODS: We investigated the association of plasma leptin, resistin and adiponectin with CKD in 201 patients with CKD and 201 controls without. CKD was defined as estimated glomerular filtration rate (eGFR)

  14. Plasma cholesteryl ester transfer protein mass and phospholipid transfer protein activity are associated with leptin in type 2 diabetes mellitus

    Dullaart, R. P. F.; de Vries, R.; Dallinga-Thie, G. M.; van Tol, A.; Sluiter, W. J.

    2007-01-01

    Adipose tissue contributes to plasma levels of lipid transfer proteins and is also the major source of plasma adipokines. We hypothesized that plasma cholesteryl ester transfer protein (CETP) mass, phospholipid transfer protein (PLTP) activity and cholesteryl ester transfer (CET, a measure of CETP a

  15. 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

    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...

  16. Curcumin inhibition of angiogenesis and adipogenesis

    The growth of new blood vessels or angiogenesis is necessary for the growth of adipose tissue. Adipokines produced by fat cells stimulate this process. Some dietary polyphenols with antiangiogenic activity may suppress adipose tissue growth not only by inhibiting angiogenesis, but also by interferin...

  17. Visfatin mRNA expression in human subcutaneous adipose tissue is regulated by exercise

    Frydelund-Larsen, Lone; Åkerström, Thorbjörn; Nielsen, Søren; Keller, Pernille; Keller, Charlotte; Pedersen, Bente Klarlund

    2006-01-01

    Visfatin [pre-beta-cell colony-enhancing factor (PBEF)] is a novel adipokine that is produced by adipose tissue, skeletal muscle, and liver and has insulin-mimetic actions. Regular exercise enhances insulin sensitivity. In the present study, we therefore examined visfatin mRNA expression in...

  18. Adipose Tissue Dysfunction in Nascent Metabolic Syndrome

    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.

  19. Common variants in LEPR, IL6, AMD1, and NAMPT do not associate with risk of juvenile and childhood obesity in Danes

    Hollensted, Mette; Ahluwalia, Tarun Veer Singh; Have, Christian Theil;

    2015-01-01

    BACKGROUND: Childhood obesity is a highly heritable disorder, for which the underlying genetic architecture is largely unknown. Four common variants involved in inflammatory-adipokine triggering (IL6 rs2069845, LEPR rs1137100, NAMPT rs3801266, and AMD1 rs2796749) have recently been associated wit...

  20. Characterization of the human visceral adipose tissue secretome

    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

  1. Resistin Is More Abundant in Liver Than Adipose Tissue and Is Not Up-Regulated by Lipopolysaccharide

    Szalowska, Ewa; Elferink, Marieke G. L.; Hoek, Annemiek; Groothuis, Geny M. M.; Vonk, Roel J.

    2009-01-01

    Context: Resistin is an adipokine correlated with inflammatory markers and is predictive for cardiovascular diseases. There is evidence that serum resistin levels are elevated in obese patients; however, the role of resistin in insulin resistance and type 2 diabetes remains controversial. Objective:

  2. Comparison of Isotope-labeled Amino Acid Incorporation Rates (CILAIR) Provides a Quantitative Method to Study Tissue Secretomes

    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

  3. Adiponectin concentration is associated with muscle insulin sensitivity, AMPK phosphorylation and ceramide content in skeletal muslce of men, but not women

    Høeg, Louise Dalgas; Sjøberg, Kim Anker; Lundsgaard, Anne-Marie;

    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...

  4. Nutritional disorder

    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.

  5. Sex hormones and skeletal muscle weakness

    Sipilä, Sarianna; Narici, Marco; Kjaer, Michael;

    2013-01-01

    properties. HRT influences gene expression in e.g. cytoskeletal and cell-matrix proteins, has a stimulating effect upon IGF-I, and a role in IL-6 and adipokine regulation. Despite low circulating steroid-hormone level, postmenopausal women have a high local concentration of steroidogenic enzymes in skeletal...

  6. Direct comparison of health effects by dietary polyphenols at equimolar doses in wildtype moderate high-fat fed C57BL/6JOlaHsd mice

    van Schothorst, E. M.; Bunschoten, A.; Hoevenaars, F.P.M.; van der Stelt, I.; Janovská, Petra; Venema, D.; Kopecký, Jan; Hollman, P. C. H.; Keijer, J.

    2014-01-01

    Roč. 65, part A (2014), s. 95-102. ISSN 0963-9969 R&D Projects: GA ČR(CZ) GA13-00871S; GA MŠk(CZ) 7E10059 Institutional support: RVO:67985823 Keywords : polyphenols * intervention * adipokines * adipose tissue * transcriptomics Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 2.818, year: 2014

  7. Evaluation of insulin resistance degree of diabetes patients complicated with obesity and its correlation with serum indexes

    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.

  8. Paracrine-acting adiponectin promotes mammary epithelial differentiation and synergizes with genistein to enhance transcriptional response to estrogen receptor beta signaling

    Mammary stromal adipocytes constitute an active site for the synthesis of the adipokine adiponectin (APN) that may influence the mammary epithelial microenvironment. The relationship between 'local', mammary tissue-derived APN and breast cancer risk is poorly understood. Herein, we identify a novel ...

  9. Carotid intima media thickness is associated with plasma adiponectin but not with the leptin: adiponectin ratio independently of metabolic syndrome

    R.P.F. Dullaart; P.J.W.H. Kappelle; G.M. Dallinga-Thie

    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

  10. Metabolic Risk Susceptibility in Men Is Partially Related to Adiponectin/Leptin Ratio

    Gloria Lena Vega; Grundy, Scott M.

    2013-01-01

    Background. High adiponectin/leptin ratio may be protective from metabolic risks imparted by high triglyceride, low HDL, and insulin resistance. Methods. This cross-sectional study examines plasma adipokine levels in 428 adult men who were subgrouped according to low (

  11. Carotid intima media thickness is associated with plasma adiponectin but not with the leptin : adiponectin ratio independently of metabolic syndrome

    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

  12. The adiponectin receptor homologs in C. elegans promote energy utilization and homeostasis

    Svensson, Emma; Olsen, Louise Cathrine Braun; Mörck, Catarina;

    2011-01-01

    Adiponectin is an adipokine with insulin-sensitising actions in vertebrates. Its receptors, AdipoR1 and AdipoR2, are PAQR-type proteins with 7-transmembrane domains and topologies reversed that of GPCR's, i.e. their C-termini are extracellular. We identified three adiponectin receptor homologs in...

  13. Safflomide increases the expression of adiponectin in vitro and in vivo: Implication for hypoadiponectemia, visceral obesity, and insulin resistance

    Safflomide (N-caffeoyltryptamine) is a phenolic amide with serotonin-receptor antagonist and anti-oxidant activities. We investigated the effects of safflomide on the expression of adipokines in vitro and in vivo. Safflomide did not affect the expressions of TNF-a, IL-6, and MCP-1/CCL2 in hypertrop...

  14. Inflammation, Oxidative Stress, and Obesity

    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.

  15. Obesity-Related Metabolic Syndrome: Mechanisms of Sympathetic Overactivity

    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.

  16. Targeting the Peroxisome Proliferator-Activated Receptor-γ to Counter the Inflammatory Milieu in Obesity

    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.

  17. Idiopathic intracranial hypertension, hormones, and 11β-hydroxysteroid dehydrogenases

    Markey, Keira A; Uldall, Maria; Botfield, Hannah; Cato, Liam D; Miah, Mohammed A L; Hassan-Smith, Ghaniah; Jensen, Rigmor H; Gonzalez, Ana M; Sinclair, Alexandra J

    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 provides an overview of pathogenic factors that could result in IIH with particular focus on hormones and the impact of obesity, including its role in neuroendocrine signaling and driving inflammation. Despite occurring almost exclusively in obese women, there have been a few studies evaluating the mechanisms by which hormones and adipokines exert their effects on ICP regulation in IIH. Research involving 11β-hydroxysteroid dehydrogenase type 1, a modulator of glucocorticoids, suggests a potential role in IIH. Improved understanding of the complex interplay between adipose signaling factors such as adipokines, steroid hormones, and ICP regulation may be key to the understanding and future management of IIH.

  18. High serum resistin is associated with an increase in adiposity but not a worsening of insulin resistance in Pima Indians

    de Courten, Barbora; Degawa-Yamauchi, Mikako; Considine, Robert V;

    2004-01-01

    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......, circulating resistin levels are proportional to the degree of adiposity, but not the degree of insulin resistance. We unexpectedly found that high serum resistin levels do predict future increases in percent body fat. Our data suggest that resistin promotes obesity but not obesity-associated insulin...

  19. Elevated body mass index as a risk factor for chronic kidney disease: current perspectives

    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

  20. Thyroid status influence on adiponectin, acylation stimulating protein (ASP and complement C3 in hyperthyroid and hypothyroid subjects

    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.

  1. The association of asthma, nasal allergies, and positive skin prick tests with obesity, leptin, and adiponectin

    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...... 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......, adjusting for confounders (area, age, smoking history, and number of elder siblings) and also mutually adjusting associations with adipokines and fatness measures. ResultsOne thousand nine hundred and fifty-five subjects aged 16-77years had information on leptin or adiponectin levels. Leptin and leptin/adiponectin...

  2. The potential role of biomarkers in predicting gestational diabetes.

    Brink, Huguette S; van der Lely, Aart Jan; van der Linden, Joke

    2016-09-01

    Gestational diabetes (GD) is a frequent complication during pregnancy and is associated with maternal and neonatal complications. It is suggested that a disturbing environment for the foetus, such as impaired glucose metabolism during intrauterine life, may result in enduring epigenetic changes leading to increased disease risk in adult life. Hence, early prediction of GD is vital. Current risk prediction models are based on maternal and clinical parameters, lacking a strong predictive value. Adipokines are mainly produced by adipocytes and suggested to be a link between obesity and its cardiovascular complications. Various adipokines, including adiponectin, leptin and TNF&, have shown to be dysregulated in GD. This review aims to outline biomarkers potentially associated with the pathophysiology of GD and discuss the role of integrating predictive biomarkers in current clinical risk prediction models, in order to enhance the identification of those at risk. PMID:27492245

  3. Improved adipose tissue metabolism after 5-year growth hormone replacement therapy in growth hormone deficient adults: The role of zinc-α2-glycoprotein

    Balaž, Miroslav; Ukropcova, Barbara; Kurdiova, Timea; Vlcek, Miroslav; Surova, Martina; Krumpolec, Patrik; Vanuga, Peter; Gašperíková, Daniela; Klimeš, Iwar; Payer, Juraj; Wolfrum, Christian; Ukropec, Jozef

    2014-01-01

    Growth hormone (GH) supplementation therapy to adults with GH deficiency has beneficial effects on adipose tissue lipid metabolism, improving thus adipocyte functional morphology and insulin sensitivity. However, molecular nature of these effects remains unclear. We therefore tested the hypothesis that lipid-mobilizing adipokine zinc-α2-glycoprotein is causally linked to GH effects on adipose tissue lipid metabolism. Seventeen patients with severe GH deficiency examined before and after the 5...

  4. Differential Effect of Weight Loss on Adipocyte Size Subfractions in Patients With Type 2 Diabetes

    Pasarica, Magdalena; Tchoukalova, Yourka D.; Heilbronn, Leonie K.; Fang, Xiaobing; Albu, Jeanine B.; Kelley, David E.; Smith, Smith R.; Ravussin, Eric

    2009-01-01

    The size of adipocytes influences their function suggesting a differential responsiveness to intervention. We hypothesized that weight loss in patients with type 2 diabetes mellitus (T2DM) predominantly decreases the size of large and very-large adipocyte subfractions in parallel with beneficial changes in serum adipokines and improved insulin sensitivity. A total of 44 volunteers from the Look Action for Health in Diabetes trial, who lost weight after 1-year of intense lifestyle intervention...

  5. Impact of Doxorubicin Treatment on the Physiological Functions of White Adipose Tissue

    Luana Amorim Biondo; Edson Alves Lima Junior; Camila Oliveira de Souza; Maysa Mariana Cruz; Roberta D C Cunha; Maria Isabel Alonso-Vale; Lila Missae Oyama; Claudia M Oller Nascimento; Gustavo Duarte Pimentel; dos Santos, Ronaldo V. T.; Fabio Santos De Lira; José Cesar Rosa Neto

    2016-01-01

    White adipose tissue (WAT) plays a fundamental role in maintaining energy balance and important endocrine functions. The loss of WAT modifies adipokine secretion and disrupts homeostasis, potentially leading to severe metabolic effects and a reduced quality of life. Doxorubicin is a chemotherapeutic agent used clinically because of its good effectiveness against various types of cancer. However, doxorubicin has deleterious effects in many healthy tissues, including WAT, liver, and skeletal an...

  6. Obesity, insulin resistance, adipocytokines and breast cancer: New biomarkers and attractive therapeutic targets

    Dalamaga, Maria

    2013-01-01

    Worldwide, breast cancer (BC) represents the most common type of non-skin human malignancy and the second leading cause of cancer-related deaths amid women in Western countries. Obesity and its metabolic complications have rapidly become major global health issues and are associated with increased risk for cancer, especially BC in postmenopausal women. Adipose tissue is considered as a genuine endocrine organ secreting a variety of bioactive adipokines, such as leptin, adiponectin, resistin a...

  7. Leptin modulates electrophysiological characteristics and isoproterenol-induced arrhythmogenesis in atrial myocytes

    Lin, Yung-Kuo; Chen, Yao-Chang; Huang, Jen-Hung; Lin, Yenn-Jiang; Huang, Shiang-Suo; Chen, Shih-Ann; Chen, Yi-Jen

    2013-01-01

    Background Obesity is an important risk factor for atrial fibrillation (AF). Leptin is an important adipokine. However, it is not clear whether leptin directly modulates the electrophysiological characteristics of atrial myocytes. Results Whole cell patch clamp and indo-1 fluorescence were used to record the action potentials (APs) and ionic currents in isolated rabbit left atrial (LA) myocytes incubated with and without (control) leptin (100 nM) for 1 h to investigate the role of leptin on a...

  8. Effect of Leptin on In Vitro Nuclear Maturation and Apoptosis of Buffalo (Bubalus bubalis) Oocyte

    Amir Khaki; Rouzali Batavani; Gholamreza Najafi; Hamid Tahmasbian; Abolfazl Belbasi; Aram Mokarizadeh

    2014-01-01

    Background: Leptin, as a 16 kDa adipokine, is a pleiotropic cytokine-like hormone that primarily secreted from adipose tissue. It also involves in the regulation of energy homeostasis, neuroendocrine function, immunity, lipid and glucose homeostasis, fatty acid oxidation, angiogenesis, puberty and reproduction. The aim of this study was to investigate the effects of in vitro addition of leptin to in vitro maturation (IVM) medium on buffalo oocyte maturation and apoptosis. Materials and Method...

  9. Mechanisms mediating renal sympathetic nerve activation in obesity-related hypertension.

    Chen, W; Leo, S; Weng, C; Yang, X; Wu, Y; Tang, X

    2015-04-01

    Excessive renal sympathetic nerve activation may be one of the mechanisms underlying obesity-related hypertension. Impaired baroreflex sensitivity, adipokine disorders-such as leptin, adiponectin, and resistin-activation of the renin-angiotensin system, hyperinsulinemia, insulin resistance, and renal sodium retention present in obesity increase renal sympathetic nerve activity, thus contributing to the development of hypertension. Renal sympathetic denervation reduces both renal sympathetic activity and blood pressure in patients with obesity-related hypertension. PMID:24609799

  10. Leukocyte infiltration into spinal cord of EAE mice is attenuated by removal of endothelial leptin signaling

    Ouyang, Suidong; Hsuchou, Hung; Kastin, Abba J; Pramod K. Mishra; Wang, Yuping; Pan, Weihong

    2014-01-01

    Leptin, a pleiotropic adipokine, crosses the blood-brain barrier (BBB) and blood–spinal cord barrier (BSCB) from the periphery and facilitates experimental autoimmune encephalomyelitis (EAE). EAE induces dynamic changes of leptin receptors in enriched brain and spinal cord microvessels, leading to further questions about the potential roles of endothelial leptin signaling in EAE progression. In endothelial leptin receptor specific knockout (ELKO) mice, there were lower EAE behavioral scores i...

  11. The effect of aerobic exercise on serum adiponectin and leptin levels in postmenopausal females EFECTO DEL EJERCICIO FÍSICO AERÓBICO SOBRE LOS NIVELES SÉRICOS DE ADIPONECTINA Y LEPTINA EN MUJERES POSMENOPÁUSICAS

    Luz Helena Aranzález; Ismena Mockus; Doris Ramírez; Erica Mancera; Óscar García

    2011-01-01

    Background. Body weight variations are usually accompanied by modifications occurring in levels of circulating adipokines, such as adiponectin and leptin. Women tend to gain weight during the postmenopausal period. Physical exercise is part of the recommended treatment for being overweight and suffering from obesity as it has effects on adipose tissue and cardiovascular risk factors. Objective. Determining the effects of controlled aerobic exercise on normal weight, overweight and obese postm...

  12. Neonatal Exposure to Parathion Alters Lipid Metabolism in Adulthood: Interactions with Dietary Fat Intake and Implications for Neurodevelopmental Deficits

    Lassiter, T. Leon; Ryde, Ian T.; Levin, Edward D.; Seidler, Frederic J; Slotkin, Theodore A.

    2010-01-01

    Organophosphates are developmental neurotoxicants but recent evidence also points to metabolic dysfunction. We determined whether neonatal parathion exposure in rats has long-term effects on regulation of adipokines and lipid peroxidation. We also assessed the interaction of these effects with increased fat intake. Rats were given parathion on postnatal days 1–4 using doses (0.1 or 0.2 mg/kg/day) that straddle the threshold for barely detectable cholinesterase inhibition and the first signs o...

  13. Association of Increased Serum Leptin with Ameliorated Anemia and Malnutrition in Stage 5 Chronic Kidney Disease Patients after Parathyroidectomy

    Yao Jiang; Jingjing Zhang; Yanggang Yuan; Xiaoming Zha; Changying Xing; Chong Shen; Zhixiang Shen; Chao Qin; Ming Zeng; Guang Yang; Huijuan Mao; Bo Zhang; Xiangbao Yu; Bin Sun; Chun Ouyang

    2016-01-01

    Leptin is an adipokine that regulates various metabolism, but its association with secondary hyperparathyroidism (SHPT), a clinical manifestation of chronic kidney disease-mineral and bone disorder (CKD-MBD), remains obscure. Parathyroidectomy (PTX) is recommended for severe SHPT patients. Here, the associations between circulating leptin and clinical characteristics in CKD patients were investigated. Effects of PTX on leptin production were analyzed in vivo and in vitro. Controls and CKD pat...

  14. Obesity-Related Metabolic Syndrome: Mechanisms of Sympathetic Overactivity

    Maria Paola Canale; Simone Manca di Villahermosa; Giuliana Martino; Valentina Rovella; Annalisa Noce; Antonino De Lorenzo; Nicola Di Daniele

    2013-01-01

    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 adipo...

  15. The Role of Visfatin in Diabetic Nephropathy

    Kang, Young Sun; Cha, Dae Ryong

    2011-01-01

    As a result of the energy overload in obesity, insulin resistance, type 2 diabetes, dyslipidemia, hypertension, and atherosclerosis develop, which together comprise the metabolic syndrome. Although the kidney becomes a victim of hyperglycemia in diabetes mellitus, recent work has shown that the abnormalities of lipid and glucose metabolism in the kidney are similarly important to those in adipose tissue. Interestingly, obesity triggers the release of adipokines such as leptin, resistin, and v...

  16. Amelioration of diet-induced diabetes mellitus by removal of visceral fat.

    Pitombo, Cid; Araújo, Eliana P; De Souza, Cláudio T; Pareja, José C; Geloneze, Bruno; Velloso, Lício A

    2006-12-01

    The effect of visceral fat removal upon glucose homeostasis, insulin signal transduction, and serum adipokine levels in an animal model of diet-induced obesity and diabetes mellitus (DIO) was evaluated. Swiss mice were initially divided into two groups fed with regular rodent chow or with chow containing 24 g% saturated fat (DIO). DIO mice became obese and overtly diabetic after 8 weeks. DIO mice were then divided into three groups: control, sham, and visceral (epididymal and perinephric) fat removal. All groups were submitted to evaluation of basal glucose and insulin levels and i.p. insulin tolerance test. Insulin signal transduction in muscle was evaluated by immunoprecipitation and immunoblot, and serum adipokine levels were determined by ELISA. DIO mice became diabetic (228 versus 115 mg/dl), hyperinsulinemic (7.59 versus 3.15 ng/ml) and insulin resistant (K(itt) 2.88 versus 4.97%/min) as compared with control. Visceral fat removal partially reverted all parameters (147 mg/dl glucose; 3.82 ng/ml insulin; and 4.20%/min K(itt)). In addition, visceral fat removal completely reversed the impairment of insulin signal transduction through insulin receptor, insulin receptor substrate (IRS)-1, IRS-2 and Akt in muscle. Finally, serum levels of the pro-inflammatory cytokines tumour necrosis factor-alpha, interleukin (IL)-1beta and IL-6 were significantly increased, while adiponectin levels were significantly reduced in DIO mice. After visceral fat removal the levels of adipokines returned to near control levels. The present study shows that removal of visceral fat improves insulin signal transduction and glucose homeostasis in an animal model of diet-induced obesity and diabetes mellitus and these metabolic and molecular outcomes are accompanied by the restoration of adipokine levels. PMID:17170226

  17. The contribution of visceral fat to improved insulin signaling in Ames dwarf mice

    Menon, Vinal; Zhi, Xu; Hossain, Tanvir; Bartke, Andrzej; Spong, Adam; Gesing, Adam; Masternak, Michal M.

    2014-01-01

    Ames dwarf (Prop1 df, df/df) mice are characterized by growth hormone (GH), prolactin, and thyrotropin deficiency, remarkable extension of longevity and increased insulin sensitivity with low levels of fasting insulin and glucose. Plasma levels of anti-inflammatory adiponectin are increased in df/df mice, while pro-inflammatory IL-6 is decreased in plasma and epididymal fat. This represents an important shift in the balance between pro- and anti-inflammatory adipokines in adipose tissue, whic...

  18. Metabolic alterations following visceral fat removal and expansion

    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...

  19. Functional studies and expression regulation of two leptin isoforms in grass carp

    Chen, Ting; 陈廷

    2012-01-01

    Leptin, the protein product of obese gene, is a 16-kD adipokine with regulatory functions on food intake and energy metabolism. At present, limited information is available on leptin functions and regulation in lower vertebrates mainly due to the fact that the primary structure of leptin is highly diversified from fish to mammals. Leptin in teleost fish is even more complicated as leptin isoforms have been reported presumably as a result of whole-genome duplication that occurred during the ev...

  20. Different Adipose Depots: Their Role in the Development of Metabolic Syndrome and Mitochondrial Response to Hypolipidemic Agents

    Berge, Rolf K; Jon Skorve; Vidar Staalesen; Bodil Bjørndal; Lena Burri

    2011-01-01

    Adipose tissue metabolism is closely linked to insulin resistance, and differential fat distributions are associated with disorders like hypertension, diabetes, and cardiovascular disease. Adipose tissues vary in their impact on metabolic risk due to diverse gene expression profiles, leading to differences in lipolysis and in the production and release of adipokines and cytokines, thereby affecting the function of other tissues. In this paper, the roles of the various adipose tissues in obesi...

  1. Crosstalk between Adipocytes and Immune Cells in Adipose Tissue Inflammation and Metabolic Dysregulation in Obesity

    Huh, Jin Young; Park, Yoon Jeong; Ham, Mira; Kim, Jae Bum

    2014-01-01

    Recent findings, notably on adipokines and adipose tissue inflammation, have revised the concept of adipose tissues being a mere storage depot for body energy. Instead, adipose tissues are emerging as endocrine and immunologically active organs with multiple effects on the regulation of systemic energy homeostasis. Notably, compared with other metabolic organs such as liver and muscle, various inflammatory responses are dynamically regulated in adipose tissues and most of the immune cells in ...

  2. Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders

    Choe, Sung Sik; Huh, Jin Young; Hwang, In Jae; Kim, Jong In; Kim, Jae Bum

    2016-01-01

    The adipose tissue is a central metabolic organ in the regulation of whole-body energy homeostasis. The white adipose tissue functions as a key energy reservoir for other organs, whereas the brown adipose tissue accumulates lipids for cold-induced adaptive thermogenesis. Adipose tissues secrete various hormones, cytokines, and metabolites (termed as adipokines) that control systemic energy balance by regulating appetitive signals from the central nerve system as well as metabolic activity in ...

  3. The Effects of Leptin Replacement on Neural Plasticity

    Paz-Filho, Gilberto J.

    2016-01-01

    Leptin, an adipokine synthesized and secreted mainly by the adipose tissue, has multiple effects on the regulation of food intake, energy expenditure, and metabolism. Its recently-approved analogue, metreleptin, has been evaluated in clinical trials for the treatment of patients with leptin deficiency due to mutations in the leptin gene, lipodystrophy syndromes, and hypothalamic amenorrhea. In such patients, leptin replacement therapy has led to changes in brain structure and function in intr...

  4. Differentiation of human adipocytes at physiological oxygen levels results in increased adiponectin secretion and isoproterenol-stimulated lipolysis

    Famulla, Susanne; Schlich, Raphaela; Sell, Henrike; Eckel, Jürgen

    2012-01-01

    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...

  5. Serum Cytokines as Biomarkers in Islet Cell Transplantation for Type 1 Diabetes

    van der Torren, Cornelis R.; Verrijn Stuart, Annemarie A.; Lee, DaHae; Meerding, Jenny; van de Velde, Ursule; Pipeleers, Daniel; Gillard, Pieter; Keymeulen, Bart; de Jager, Wilco; Roep, Bart O.

    2016-01-01

    BACKGROUND: Islet cell transplantation holds a potential cure for type 1 diabetes, but many islet recipients do not reach long-lasting insulin independence. In this exploratory study, we investigated whether serum cytokines, chemokines and adipokines are associated with the clinical outcome of islet transplantation. METHODS: Thirteen islet transplant patients were selected on basis of good graft function (reaching insulin independence) or insufficient engraftment (insulin requiring) from our ...

  6. Preventive and improvement effects of exercise training and supplement intake in white adipose tissues on obesity and lifestyle-related diseases

    Sakurai, Takuya; Ogasawara, Junetsu; Kizaki, Takako; Ishibashi, Yoshinaga; Sumitani, Yoshikazu; Takahashi, Kazuto; Ishida, Hitoshi; Miyazaki, Hiromi; Saitoh, Daizoh; Haga, Shukoh; Izawa, Tetsuya; Ohno, Hideki

    2012-01-01

    Recent increases in the number of obese individuals and individuals suffering from lifestyle-related diseases, such as type 2 diabetes, that accompany obesity have become a serious social problem. White adipose tissue (WAT) is more than a mere organ for storage of energy; it is also a highly active metabolic and endocrine organ that secretes physiologically active substances collectively known as adipokines, including tumor necrosis factor-α and adiponectin. Dysregulated expression of adipoki...

  7. Childhood Obesity: Immune Response and Nutritional Approaches

    Magrone, Thea; Jirillo, Emilio

    2015-01-01

    Childhood obesity is characterized by a low-grade inflammation status depending on the multicellular release of cytokines, adipokines, and reactive oxygen species. In particular, the imbalance between anti-inflammatory T regulatory cells and inflammatory T helper 17 cells seems to sustain such a phlogistic condition. Alterations of gut microbiota since childhood also contribute to the maintenance of inflammation. Therefore, besides preventive measures and caloric restrictions, dietary intake ...

  8. Effects of gliclazide add on metformin on serum omentin-1 levels in patients with type 2 diabetes mellitus

    Al-Gareeb, Ali I.; Alrubai, Haidar F.; Sammar M Suliaman

    2016-01-01

    Background: Omentin is a newly identified adipokine that has beneficial influence against cardiovascular disorders. Hence, considering the impact of anti-diabetic drug on omentin levels may provide an adjuvant strategy to protect diabetic patients against valuable clinical hazards. Aim of the Study: To investigate the influence of metformin alone or in combination with gliclazide on the level of serum omentin among patients with type 2 diabetes mellitus (T2DM). Patients and Methods: A total o...

  9. The Liposuction-Induced Effects on Adiponectin and Selected Cytokines Are Not Affected by Exercise Training in Women

    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.

  10. Cellular and molecular basis of adipose tissue development: from stem cells to adipocyte physiology

    Louveau, Isabelle; Perruchot, Marie-Hélène; Gondret, Florence

    2014-01-01

    White adipose tissue plays a key role in the regulation of energy balance in vertebrates. Its primary function is to store and release energy. It is also recognized to secrete a variety of factors called adipokines that are involved in a wide range of physiological and metabolic functions. Unlike other tissues, adipose tissue mass has large capacity to expand and can be seen as a dynamic tissue able to adapt to a variety of environmental and genetic factors. The aim of this review...

  11. The Pathophysiology of Obesity and Its Clinical Manifestations

    Redinger, Richard N.

    2007-01-01

    Obesity is an exaggeration of normal adiposity and is a central player in the pathophysiology of diabetes mellitus, insulin resistance, dyslipidemia, hypertension, and atherosclerosis, largely due to its secretion of excessive adipokines. Obesity is a major contributor to the metabolic dysfunction involving lipid and glucose, but on a broader scale, it influences organ dysfunction involving cardiac, liver, intestinal, pulmonary, endocrine, and reproductive functions. Inflammatory, insulin-res...

  12. Central Leptin Regulation of Obesity and Fertility

    Tong, Qingchun; Xu, Yong

    2012-01-01

    The current obesity epidemic and lack of efficient therapeutics demand a clear understanding of the mechanism underlying body weight regulation. The cloning of leptin, a key body weight regulating adipokine released in proportion to the adipose tissue mass, has revolutionized our understanding of the mechanism by which the body weight is controlled. It is now well established that the brain, especially the hypothalamus, maintains body weight homeostasis by effectively adjusting food intake an...

  13. Association of circulating irisin levels with normal weight obesity, glycemic and lipid profile

    Mehrabian, Sarvenaz; Taheri, Ehsaneh; Karkhaneh, Maryam; Qorbani, Mostafa; Hosseini, Saeed

    2016-01-01

    Background Irisin, a recently identified myokine/adipokine, has potential role in type 2 diabetes and obesity. Normal weight obesity (NWO) is associated with a significantly higher risk of developing metabolic syndrome and cardiometabolic dysfunction. The aim of this study was to investigate association of irisin level with NWO, glycemicand lipid profile in women. Methods In this matchedcase-control study, 38 subjects with NWO (body mass index (BMI)  30) as case and 26 controls (BMI

  14. Relation of Absolute or Relative Adiposity to Insulin Resistance, Retinol Binding Protein-4, Leptin, and Adiponectin in Type 2 Diabetes

    You Lim Kim; Tae Kyun Kim; Eun Sun Cheong; Dong Geum Shin; Gyu Sik Choi; Jihye Jung; Kyung-Ah Han; Kyung Wan Min

    2012-01-01

    Background Central fat mass (CFM) correlates with insulin resistance and increases the risk of type 2 diabetes and cardiovascular complications; however, peripheral fat mass (PFM) is associated with insulin sensitivity. The aim of this study was to investigate the relation of absolute and relative regional adiposity to insulin resistance index and adipokines in type 2 diabetes. Methods Total of 83 overweighted-Korean women with type 2 diabetes were enrolled, and rate constants for plasma gluc...

  15. Serum Visfatin Levels, Adiposity and Glucose Metabolism in Obese Adolescents

    Taşkesen, Derya; Kirel, Birgül; Us, Tercan

    2012-01-01

    Objective: Visfatin, an adipokine, has insulin-mimetic effects. The main determinants of both the production and the physiologic role of visfatin are still unclear. The aim of this study is to determine the relation of serum visfatin to adiposity and glucose metabolism. Methods: 40 pubertal adolescents (20 females, 20 males; age range: 9-17 years) with exogenous obesity and 20 age- and sex-matched healthy adolescents (10 females, 10 males) were enrolled in the study. Oral glucose tolerance te...

  16. Angiotensinogen gene silencing reduces markers of inflammation and lipid accumulation in adipocytes

    NaimaMoustaid-Moussa; WentingXin; NishanKalupahana

    2013-01-01

    Inflammatory adipokines secreted from adipose tissue are major contributors to obesity-associated inflammation and other metabolic dysfunctions. We and others have recently documented the contribution of adipose tissue renin-angiotensin system (RAS) to the pathogenesis of obesity, inflammation and insulin resistance. We hypothesized that adipocyte-derived angiotensinogen (Agt) plays a critical role in adipogenesis and/or lipogenesis as well as inflammation. This was tested using 3T3-L1 adipo...

  17. Obesity and adipose tissue endocrine function

    Joshi, Anuradha Rajiv

    2013-01-01

    Many studies have profoundly changed the concept of adipose tissue from being an energy depot to an active endocrine organ. Adipose tissue secretes bioactive peptides, termed as ‘adipokines’.They act through autocrine, paracrine and endocrine pathways. In obesity, increased production of most adipokines affects multiple functions such as appetite and energy balance, immunity, insulin sensitivity, angiogenesis, blood pressure, lipid metabolism and haemostasis. Increased activity of the tumor n...

  18. IMMUNOLOGICAL FEATURES OF OBESITY AND THEIR INTERRELATION WITH VIOLATIONS OF A CARBOHYDRATE AND FATTY EXCHANGES

    A. F. Salikhova; L. M. Farkhutdinova

    2014-01-01

    Abstract. The article deals with biological issues of obesity, a global epidemic of XXI century. Adipose tissue is considered not only an energy-storage tissue, but as an endocrine organ as well which secretes a variety of bioactive substances (adipokines) including tumor necrosis factor (TNF)-α, interleukin-6 (IL-6). Cardiovascular diseases represent the main cause of morbidity and mortality in persons with excessive weight and obese patients. Atherosclerotic lesions represent a pathological...

  19. Enhanced ZAG production by subcutaneous adipose tissue is linked to weight loss in gastrointestinal cancer patients

    Mracek, T.; Stephens, N. A.; Gao, D.; Bao, Y.; Ross, J A; Rydén, M; Arner, P; Trayhurn, P.; Fearon, K C H; Bing, C

    2011-01-01

    Background: Profound loss of adipose tissue is a hallmark of cancer cachexia. Zinc-α2-glycoprotein (ZAG), a recently identified adipokine, is suggested as a candidate in lipid catabolism. Methods: In the first study, eight weight-stable and 17 cachectic cancer patients (weight loss ⩾5% in previous 6 months) were recruited. Zinc-α2-glycoprotein mRNA and protein expression were assessed in subcutaneous adipose tissue (SAT), subcutaneous adipose tissue morphology was examined and serum ZAG conce...

  20. Leptin, Adiponectin and Cognition in Middle-aged HIV-infected and Uninfected Women. The Brooklyn Women’s Interagency HIV Study

    Gustafson, Deborah R; Mielke, Michelle M; Keating, Sheila A; Holman, Susan; Minkoff, Howard; Crystal, Howard A

    2016-01-01

    Context Case-control study of women with and without HIV infection. Objective To explore the association of cognition and the adipokines, leptin and adiponectin (total; high molecular weight, HMW), in women with (HIV+) and without HIV (HIV−) infection. Design Cross-sectional analyses of adipokines and cognition using linear regression models of log-transformed adipokines, and Trails A, Trails B, Stroop interference time, Stroop word recall, Stroop color naming and reading, and Symbol Digit Modalities Test (SDMT) with consideration for age, HIV infection status, education, CD4 count, diabetes, body mass index (BMI), waist circumference (WC) and race/ethnicity. Setting Brooklyn, NY. Participants 354 participants (247 HIV+, 107 HIV−), in the Brooklyn Women’s Interagency HIV Study (WIHS), average age 38.9 years, with measured levels of leptin and adiponectin (total and high molecular weight, HMW). Main Outcome Measure Cognition Results Higher levels of leptin were positively associated with worse cognition on the basis of Trails A completion time and SDMT score. Among at risk HIV− women, leptin was associated with worse performance on Trails B. No associations were observed for total or HMW adiponectin. Conclusion Blood adipokine levels were measured to provide mechanistic insights regarding the association of adipose with cognitive function. These data suggest that higher levels of leptin, consistent with more adipose tissue, are associated with worse cognitive function in middle age. Monitoring leptin over time and with increasing age in relation to cognition and dementia, may lend insights to the role of adipose tissue in successful body and brain aging among women with HIV infection. PMID:27536467

  1. Vaspin attenuates the progression of atherosclerosis by inhibiting ER stress-induced macrophage apoptosis in apoE−/− mice

    Lin, Ying; Zhuang, Jianhui; Li, Hailing; Zhu, Guofu; ZHOU, SHUNPING; Li, Weiming; Peng, Wenhui; Xu, Yawei

    2015-01-01

    Visceral adipose tissue-derived serine protease inhibitor (vaspin) is a novel adipokine with potential insulin-sensitizing properties, which was initially detected in the visceral adipose tissue of genetically obese rats. Previous studies have demonstrated that vaspin exerts a protective effect on arteries undergoing atherosclerosis in vitro, and it has been shown to exert anti-inflammatory and antimigratory effects on vascular smooth muscle cells. Vaspin promotes proliferation and inhibits a...

  2. Macrophage-derived human resistin exacerbates adipose tissue inflammation and insulin resistance in mice

    Qatanani, Mohammed; Szwergold, Nava R.; Greaves, David R.; Ahima, Rexford S.; Lazar, Mitchell A.

    2009-01-01

    Resistin is an adipokine that contributes to insulin resistance in mice. In humans, however, studies investigating the link between resistin and metabolic disease are conflicting. Further complicating the matter, human resistin is produced mainly by macrophages rather than adipocytes. To address this important issue, we generated mice that lack adipocyte-derived mouse resistin but produce human resistin in a pattern similar to that found in humans, i.e., in macrophages (humanized resistin mic...

  3. Resistin in Rodents and Humans

    Hyeong Kyu Park; Ahima, Rexford S.

    2013-01-01

    Obesity is characterized by excess accumulation of lipids in adipose tissue and other organs, and chronic inflammation associated with insulin resistance and an increased risk of type 2 diabetes. Obesity, type 2 diabetes, and cardiovascular diseases are major health concerns. Resistin was first discovered as an adipose-secreted hormone (adipokine) linked to obesity and insulin resistance in rodents. Adipocyte-derived resistin is increased in obese rodents and strongly related to insulin resis...

  4. Dose-dependent effects of atorvastatin on myocardial infarction

    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

  5. Globular Adiponectin Causes Tolerance to LPS-Induced TNF-α Expression via Autophagy Induction in RAW 264.7 Macrophages: Involvement of SIRT1/FoxO3A Axis

    Tilija Pun, Nirmala; Subedi, Amit; Kim, Mi Jin; Park, Pil-Hoon

    2015-01-01

    Adiponectin, an adipokine predominantly produced from adipose tissue, exhibited potent anti-inflammatory properties. In particular, it inhibits production of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), in macrophages. Autophagy, an intracellular self-digestion process, has been recently shown to regulate inflammatory responses. In the present study, we investigated the role of autophagy induction in the suppression of Lipopolysaccharide (LPS) -induced TNF-α expressi...

  6. Relationship between Chemerin Levels and Cardiometabolic Parameters and Degree of Coronary Stenosis in Korean Patients with Coronary Artery Disease

    Yu-Jin Hah; Nam-Keong Kim; Mi-Kyung Kim; Hye-Soon Kim; Seung-Ho Hur; Hyuck-Jun Yoon; Yoon-Nyun Kim; Keun-Gyu Park

    2011-01-01

    Background Chemerin is a novel adipokine that is associated with inflammation and adipogenesis. However, it remains unclear whether chemerin is involved in patients with cardiovascular disease. We investigated whether the serum chemerin levels of Korean patients with coronary artery disease correlated with specific cardiometabolic parameters. Methods In total, 131 patients, all of whom had coronary artery stenosis exceeding 50%, participated in this study. Their serum chemerin levels and card...

  7. Possible modulation of FAS and PTP-1B signaling in ameliorative potential of Bombax ceiba against high fat diet induced obesity

    Gupta, Paras; Goyal, Rohit; Chauhan, Yamini; Sharma, Pyare Lal

    2013-01-01

    Background Bombax ceiba Linn., commonly called as Semal, is used in various gastro-intestinal disturbances. It contains Lupeol which inhibits PTP-1B, adipogenesis, TG synthesis and accumulation of lipids in adipocytes and adipokines whereas the flavonoids isolated from B. ceiba has FAS inhibitory activity. The present study was aimed to investigate ameliorative potential of Bombax ceiba to experimental obesity in Wistar rats, and its possible mechanism of action. Methods Male Wistar albino ra...

  8. Leptin fails to blunt the lipopolysaccharide-induced activation of the hypothalamic-pituitary-adrenal axis in rats

    Basharat, S.; Parker, JA; Murphy, KG; Bloom, SR; Buckingham, JC; John, CD

    2014-01-01

    Copyright @ 2013 The authors. This work is licensed under a Creative Commons Attribution 3.0 Unported License. Obesity is a risk factor for sepsis morbidity and mortality, whereas the hypothalamic-pituitary-adrenal (HPA) axis plays a protective role in the body's defence against sepsis. Sepsis induces a profound systemic immune response and cytokines serve as excellent markers for sepsis as they act as mediators of the immune response. Evidence suggests that the adipokine leptin may play a...

  9. Serum Vaspin Levels Are Associated with the Development of Clinically Manifest Arthritis in Autoantibody-Positive Individuals.

    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.

  10. Mammary Fat of Breast Cancer: Gene Expression Profiling and Functional Characterization

    Fengliang Wang; Sheng Gao; Fei Chen; Ziyi Fu; Hong Yin; Xun Lu; Jing Yu; Cheng Lu

    2014-01-01

    Mammary fat is the main composition of breast, and is the most probable candidate to affect tumor behavior because the fat produces hormones, growth factors and adipokines, a heterogeneous group of signaling molecules. Gene expression profiling and functional characterization of mammary fat in Chinese women has not been reported. Thus, we collected the mammary fat tissues adjacent to breast tumors from 60 subjects, among which 30 subjects had breast cancer and 30 had benign lesions. We isolat...

  11. Specific dietary patterns and concentrations of adiponectin

    Vajihe Izadi; Leila Azadbakht

    2015-01-01

    Background: One of the adipokines mostly secreted from adipose tissue is adiponectin. Adiponectin is well known as the anti-diabetic, anti-obesity and cardio-protective factor. Present study focused on the review the previous studies about relationship between adherence to healthy dietary pattern, independent of one or two special dietary components, and concentration of adiponectin. Materials and Methods: We searched in PubMed search engine from 2003 to July 2014 using the following key word...

  12. Adipose Tissue Overexpression of Vascular Endothelial Growth Factor Protects Against Diet-Induced Obesity and Insulin Resistance

    Elias, Ivet; Franckhauser, Sylvie; Ferré, Tura; Vilà, Laia; Tafuro, Sabrina; Muñoz, Sergio; Roca, Carles; Ramos, David; Pujol, Anna; Riu, Efren; Ruberte, Jesús; Bosch, Fatima

    2012-01-01

    During the expansion of fat mass in obesity, vascularization of adipose tissue is insufficient to maintain tissue normoxia. Local hypoxia develops and may result in altered adipokine expression, proinflammatory macrophage recruitment, and insulin resistance. We investigated whether an increase in adipose tissue angiogenesis could protect against obesity-induced hypoxia and, consequently, insulin resistance. Transgenic mice overexpressing vascular endothelial growth factor (VEGF) in brown adip...

  13. N-acetylcysteine and allopurinol synergistically enhance cardiac adiponectin content and reduce myocardial reperfusion injury in diabetic rats

    Tingting Wang; Shigang Qiao; Shaoqing Lei; Yanan Liu; Kwok F J Ng; Aimin Xu; Karen S L Lam; Irwin, Michael G; Zhengyuan Xia

    2011-01-01

    Background: Hyperglycemia-induced oxidative stress plays a central role in the development of diabetic myocardial complications. Adiponectin (APN), an adipokine with anti-diabetic and anti-ischemic effects, is decreased in diabetes. It is unknown whether or not antioxidant treatment with N-acetylcysteine (NAC) and/or allopurinol (ALP) can attenuate APN deficiency and myocardial ischemia reperfusion (MI/R) injury in the early stage of diabetes. Methodology/Principal Findings: Control or strept...

  14. Endocrine and Metabolic Effects of Adipose Tissue in Children and Adolescents

    Kotnik Primož; Fischer Posovszky Pamela; Wabitsch Martin

    2015-01-01

    Adipose tissue is implicated in many endocrine and metabolic processes. Leptin was among the first identified adipose-secreted factors, which act in an auto-, para- and endocrine manner. Since leptin, many other adipose tissue factors were determined, some primarily secreted from the adipocytes, some from other cells of the adipose tissue. So-called adipokines are not only involved in obesity and its complications, as are insulin resistance, type 2 diabetes and other components of the metabol...

  15. Role of Obesity in Asthma Control, the Obesity-Asthma Phenotype

    Shannon Novosad; Supriya Khan; Bruce Wolfe; Akram Khan

    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 ...

  16. Plasma adipocytokines and antioxidants-status in Korean overweight and obese females with dyslipidemia

    Ha, Ae Wha; Jeong, Su Youn; Kang, Nam E; Kim, Woo Kyoung

    2014-01-01

    BACKGROUD/OBEJECTIVES It is hypothesized that obese people with dyslipidemia is more likely to have increased oxidative stress and decreased antioxidant status, in comparison with the controls who were obese without dyslipidemia. Thus, the aims of the present study were to determine the dietary intakes, plasma adipokines, and antioxidative systems between obese with dyslipidemia and obese without dyslipidemia were investigated. SUBJECTS/METHODS Female subjects who were between 20 and 55 years...

  17. Palaeolithic diet decreases fasting plasma leptin concentrations more than a diabetes diet in patients with type 2 diabetes: a randomised cross-over trial

    Fontes-Villalba, Maelán; Lindeberg, Staffan; Granfeldt, Yvonne; Knop, Filip K.; Memon, Ashfaque A.; Carrera-Bastos, Pedro; Picazo, Óscar; Chanrai, Madhvi; Sunquist, Jan; Sundquist, Kristina; Jönsson, Tommy

    2016-01-01

    Background We have previously shown that a Palaeolithic diet consisting of the typical food groups that our ancestors ate during the Palaeolithic era, improves cardiovascular disease risk factors and glucose control compared to the currently recommended diabetes diet in patients with type 2 diabetes. To elucidate the mechanisms behind these effects, we evaluated fasting plasma concentrations of glucagon, insulin, incretins, ghrelin, C-peptide and adipokines from the same study. Methods In a r...

  18. Cadmium modulates adipocyte functions in metallothionein-null mice

    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−/−) mice, which cannot form atoxic Cd–MT complexes and are used for evaluating Cd as free ions, and wild type (MT+/+) mice. Cd administration more significantly reduced the adipocyte size of MT−/− mice than that of MT+/+ mice. Cd exposure also induced macrophage recruitment to WAT with an increase in the expression level of Ccl2 (MCP-1) in the MT−/− 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

  19. Effects of telmisartan vs olmesartan on metabolic parameters, insulin resistance and adipocytokines in hypertensive obese patients Efectos de telmisartan vs olmesartan sobre parámetros antropométricos, resistencia a la insulina y adipocitoquinas en pacientes hipertensos obesos

    D. A. De Luis; Conde, R.; M González-Sagrado; R. Aller; O. Izaola; A. Dueñas; J. L. Pérez Castrillón; Romero, E.

    2010-01-01

    Background: Angiotensin II regulates the production of adipokines. The objective was to study the effect of treatment with telmisartan versus olmesartan in hypertensiveobese and overweight patients. Subjects: A sample of 65 overweight and obese patients with mild to moderate hypertension was analyzed in a prospective way with a randomized trial. Patients were randomized to telmisartan (80 mg/day) or olmesartan (40 mg/day) for 3 months. Weight, body mass index, blood pressure, basal glucose, i...

  20. Interactions Between Housing Density and Ambient Temperature in the Cage Environment: Effects on Mouse Physiology and Behavior

    Toth, Linda A; Trammell, Rita A; Ilsley-Woods, Megan

    2015-01-01

    To determine how housing density and ambient temperature interact to influence the physiology and behavior of mice, we systematically varied housing density (1 to 5 mice per cage) and ambient temperature (22, 26, or 30 °C) and measured effects on body weight, food intake, diurnal patterns of locomotor activity and core temperature, fecal corticosterone, and serum cytokine and adipokine panels. Temperatures inside cages housing 5 mice were 1 to 2 °C higher than the ambient temperature. As the ...

  1. Molecular signature of adipose tissue in patients with both Non-Alcoholic Fatty Liver Disease (NAFLD) and Polycystic Ovarian Syndrome (PCOS)

    Baranova, Ancha; Tran, Thuy Phuong; Afendy, Arian; Wang, Lei; Shamsaddini, Amirhossein; Mehta, Rohini; Chandhoke, Vikas; Birerdinc, Aybike; Younossi, Zobair M.

    2013-01-01

    Background Polycystic ovarian syndrome (PCOS) is one of the most common reproductive disorders with strong association with both insulin resistance and non-alcoholic fatty liver disease (NAFLD). To untangle the complex relationship between PCOS and NAFLD, we analyzed serum biomarkers of apoptosis, some adipokines and mRNA profiles in the visceral adipose tissue of obese patients with NAFLD who were also diagnosed with PCOS and compared to a group with NAFLD only. Methods We included patients ...

  2. Cadmium modulates adipocyte functions in metallothionein-null mice

    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.

  3. Adiponectin promotes pancreatic cancer progression by inhibiting apoptosis via the activation of AMPK/Sirt1/PGC-1α signaling

    Huang, Bingqing; Cheng, Xixi; Wang, Dan; Peng, Meiyu; Xue, Zhenyi; Da, Yurong; Ning ZHANG; Yao, Zhi; Li, Min; Xu, Aimin; Zhang, Rongxin

    2014-01-01

    Adiponectin is an adipocyte-secreted adipokine with pleiotropic actions. Clinical evidence has shown that serum adiponectin levels are increased and that adiponectin can protect pancreatic beta cells against apoptosis, which suggests that adiponectin may play an anti-apoptotic role in pancreatic cancer (PC). Here, we investigated the effects of adiponectin on PC development and elucidated the underlying molecular mechanisms. Adiponectin deficiency markedly attenuated pancreatic tumorigenesis ...

  4. Clinical review: Adiponectin biology and its role in inflammation and critical illness

    Robinson, Katherine; Prins, John; Venkatesh, Bala

    2011-01-01

    Adiponectin is an adipokine first described just over a decade ago. Produced almost exclusively by adipocytes, adiponectin circulates in high concentrations in human plasma. Research into this hormone has revealed it to have insulin-sensitizing, anti-inflammatory and cardioprotective roles. This review discusses the history, biology and physiological role of adiponectin and explores its role in disease, with specific focus on adiponectin in inflammation and sepsis. It appears that an inverse ...

  5. Serum Adiponectin in Women with Gestational Diabetes

    2014-01-01

    Background &Objective: Adiponectin is an adipose tissue adipokin that may contribute to obesity and insulin resistantance. The aim of this study was to evaluate the associations between serum concentrations of adiponectin and insulin resistance in gestational diabetes (GDM).Materials & Methods: Serum adiponectin levels, fasting blood sugar (FBS), glycated hemoglobin (HbA1C), insulin levels and blood lipids were measured in 66 women with GDM and 70 pregnant women without GDM. The associations ...

  6. Association between Risk Factors for Vascular Dementia and Adiponectin

    Juhyun Song; Won Taek Lee; Kyung Ah Park; Jong Eun Lee

    2014-01-01

    Vascular dementia is caused by various factors, including increased age, diabetes, hypertension, atherosclerosis, and stroke. Adiponectin is an adipokine secreted by adipose tissue. Adiponectin is widely known as a regulating factor related to cardiovascular disease and diabetes. Adiponectin plasma levels decrease with age. Decreased adiponectin increases the risk of cardiovascular disease and diabetes. Adiponectin improves hypertension and atherosclerosis by acting as a vasodilator and antia...

  7. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome

    Kadowaki, Takashi; Yamauchi, Toshimasa; KUBOTA, Naoto; Hara, Kazuo; Ueki, Kohjiro; Tobe, Kazuyuki

    2006-01-01

    Adiponectin is an adipokine that is specifically and abundantly expressed in adipose tissue and directly sensitizes the body to insulin. Hypoadiponectinemia, caused by interactions of genetic factors such as SNPs in the Adiponectin gene and environmental factors causing obesity, appears to play an important causal role in insulin resistance, type 2 diabetes, and the metabolic syndrome, which are linked to obesity. The adiponectin receptors, AdipoR1 and AdipoR2, which mediate the antidiabetic ...

  8. Adiponectin‐Mediated Modulation of Lymphatic Vessel Formation and Lymphedema

    Shimizu, Yuuki; Shibata, Rei; Ishii, Masakazu; Ohashi, Koji; Kambara, Takahiro; Uemura, Yusuke; Yuasa, Daisuke; Kataoka, Yoshiyuki; Kihara, Shinji; Murohara, Toyoaki; Ouchi, Noriyuki

    2013-01-01

    Background Obesity is linked with an increased risk of lymphedema, which is a serious clinical problem. Adiponectin is a circulating adipokine that is down‐regulated in obese states. We investigated the effects of adiponectin on lymphatic vessel formation in a model of lymphedema and dissected its mechanisms. Methods and Results A mouse model of lymphedema was created via ablation of tail surface lymphatic network. Adiponectin‐knockout mice showed the greater diameter of the injured tail comp...

  9. Adiponectin as a tissue regenerating hormone: more than a metabolic function

    Fiaschi T; Magherini F; Gamberi T; PA.Modesti; Modesti A

    2014-01-01

    The great interest that scientists have for adiponectin is primarily due to its central metabolic role. Indeed, the major function of this adipokine is the control of glucose homeostasis that it exerts regulating liver and muscle metabolism. Adiponectin has insulin-sensitizing action and leads to down-regulation of hepatic gluconeogenesis and an increase of fatty acid oxidation. In addition, adiponectin is reported to play an important role in the inhibition of inflammation. The hormone is se...

  10. Short communication: Circulating and milk adiponectin change differently during energy deficiency at different stages of lactation in dairy cows

    Singh, S.P.; Häussler, S.; Gross, Josef Johann; Schwarz, F.J.; Bruckmaier, Rupert; Sauerwein, H.

    2014-01-01

    Adiponectin, one of the most abundant adipokines in circulation, is known for its role in regulation of body metabolism. The aim of this study was to evaluate the effects of a negative energy balance (NEB) at 2 stages of lactation (lactational NEB at the onset of lactation and an induced NEB by feed restriction near 100 d of lactation) on circulating adiponectin concentrations. We also investigated the effect of feed restriction on adiponectin concentrations in milk and the relationships of b...

  11. Adiponectin and Leptin are Secreted Through Distinct Trafficking Pathways in Adipocytes

    Xie, Linglin; O'Reilly, Cormac P.; Chapes, Stephen K.; Mora, Silvia

    2008-01-01

    Adiponectin and leptin are two adipokines secreted by white adipose tissue that regulate insulin sensitivity. Previously we reported that adiponectin but not leptin release depends on GGA-coated vesicle formation, suggesting that leptin and adiponectin may follow different secretory routes. Here we have examined the intracellular trafficking pathways that lead to the secretion of these two hormones. While adiponectin and leptin displayed distinct localization in the steady-state, treatment of...

  12. Cardiometabolic effects of adiponectin

    Parker-Duffen, Jennifer L.; Walsh, Kenneth

    2013-01-01

    Over the past two decades, adiponectin has been studied in more than eleven thousand publications. A classical adipokine, adiponectin was among the first factors secreted from adipose tissue that were found to promote metabolic function. Circulating levels of adiponectin consistently decline with increasing body mass index. Clinical and basic science studies have identified adiponectin’s cardiovascular-protective actions, providing a mechanistic link to the increased incidence of cardiovascul...

  13. Vascular smooth muscle cell-derived adiponectin: a paracrine regulator of contractile phenotype

    Ding, Min; Carrao, Ana Catarina; Wagner, Robert J.; Xie, Yi; Jin, Yu; Rzucidlo, Eva M.; Yu, Jun; Li, Wei; Tellides, George; Hwa, John; Aprahamian, Tamar R.; Martin, Kathleen A.

    2011-01-01

    Adiponectin is a cardioprotective adipokine derived predominantly from visceral fat. We recently demonstrated that exogenous adiponectin induces vascular smooth muscle cell (VSMC) differentiation via repression of mTORC1 and FoxO4. Here we report for the first time that VSMC express and secrete adiponectin, which acts in an autocrine and paracrine manner to regulate VSMC contractile phenotype. Adiponectin was found to be expressed in human coronary artery and mouse aortic VSMC. Importantly, s...

  14. Obesity, adipose tissue function and the role of vitamin D

    Koszowska, Aneta U.; Nowak, Justyna; Dittfeld, Anna; Brończyk-Puzoń, Anna; Kulpok, Agata; Zubelewicz-Szkodzińska, Barbara

    2014-01-01

    Introduction Obesity is not just a cosmetic problem. Pathological accumulation of body fat can cause many health problems: insulin resistance, impaired glucose tolerance, and diabetes mellitus type 2. It may also increase morbidity and mortality. Adipose tissue plays an important role in body homeostasis by producing and secreting several bioactive proteins known as adipokines: adiponectin, leptin, resistin, visfatin, and apelin, which are involved in the regulation of food intake, glucose an...

  15. Obesity-Associated Biomarkers and Executive Function in Children

    Miller, Alison L.; Jong, Hannah; Lumeng, Julie C.

    2014-01-01

    There is a growing focus on links between obesity and cognitive decline in adulthood, including Alzheimer’s disease. It is also increasingly recognized that obesity in youth is associated with poorer cognitive function, specifically executive functioning skills such as inhibitory control and working memory, which are critical for academic achievement. Emerging literature provides evidence for possible biological mechanisms driven by obesity; obesity-associated biomarkers such as adipokines, o...

  16. Therapies for Prevention and Treatment of Alzheimer's Disease

    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.

  17. Adiponectin and its receptors in the ovary: further evidence for a link between obesity and hyperandrogenism in polycystic ovary syndrome.

    Fabio V Comim

    Full Text Available 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.

  18. Pulmonary hypertension and metabolic syndrome: Possible connection, PPARγ and Caveolin-1

    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.

  19. Hyperresistinemia and metabolic dysregulation: a risky crosstalk in obese breast cancer.

    Crisóstomo, Joana; Matafome, Paulo; Santos-Silva, Daniela; Gomes, Ana L; Gomes, Manuel; Patrício, Miguel; Letra, Liliana; Sarmento-Ribeiro, Ana B; Santos, Lelita; Seiça, Raquel

    2016-08-01

    Breast cancer is the most common malignancy among women worldwide. There is extensive literature on the relationship between body weight and breast cancer risk but some doubts still remain about the role of adipokines per se, the role of insulin and glucose regardless of obesity, as well as the crosstalk between these players. Thus, in this study, we intend to determine the relation between body mass index (BMI), glycaemia, insulinemia, insulin-resistance, blood adipokine levels and tumour characteristics in a Portuguese group of pre- and postmenopausal overweight/obese women with breast cancer. We evaluated clinical and biochemical data in 154 participants, divided in 4 groups: (1) control with BMI 25 kg/m(2), n = 48 (CTOb); (3) breast cancer with BMI 25 kg/m(2), n = 47 (BCOb). In women with breast cancer, we also performed tumour characterization. We found that BCOb present increased fasting blood glucose, insulin, resistin and monocyte chemoattractant protein 1, insulin resistance and more aggressive tumours. Notably, this profile is not correlated with BMI, proposing the involvement of other processes than adiposity. Altogether, our results suggest that glucose dysmetabolism, insulin resistance and changes in adipokine secretion, in particular resistin, may be involved in the development and progression of breast cancer in overweight/obese pre- and postmenopausal women. PMID:26892376

  20. In Utero Nutritional Manipulation Provokes Dysregulated Adipocytokines Production in F1 Offspring in Rats

    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.

  1. Dynamics of protein secretion during adipocyte differentiation.

    Ojima, Koichi; Oe, Mika; Nakajima, Ikuyo; Muroya, Susumu; Nishimura, Takanori

    2016-08-01

    The major functions of adipocytes include both lipid storage and the production of secretory factors. However, the type of proteins released from mouse 3T3-L1 cells during adipocyte differentiation remains poorly understood. We examined the dynamics of secreted proteins during adipocyte differentiation using mass spectrometry (MS) combined with an iTRAQ (®) labeling method that enables the simultaneous analysis of relative protein expression levels. A total of 215 proteins were identified and quantified from approximately 10 000 MS/MS spectra. Of these, approximately 38% were categorized as secreted proteins based on gene ontology classification. Adipokine secretion levels were increased with the progression of differentiation. By contrast, levels of fibril collagen components, such as subunits of type I and III collagens, were decreased during differentiation. Basement membrane components attained their peak levels at day 4 when small lipid droplets accumulated in differentiated 3T3-L1 cells. Simultaneously, peak levels of collagen microfibril components that comprise type V and VI collagen subunits were also observed. Our data demonstrated that extracellular matrix components were predominantly released during the early and middle stages of adipocyte differentiation, with a subsequent increase in the secretion of adipokines. This suggests that 3T3-L1 cells secrete adipokines after their ECM is constructed during adipocyte differentiation. PMID:27516960

  2. Role of omentin and chemerin in metabolic syndrome and tumor diseases.

    Szydło, Błażej; Kiczmer, Paweł; Świętochowska, Elżbieta; Ostrowska, Zofia

    2016-01-01

    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. PMID:27516571

  3. 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.

    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.

  4. WJD 5th Anniversary Special Issues(1): Insulin Benefits of healthy adipose tissue in the treatment of diabetes

    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

  5. Epicardial adipose tissue and its role in cardiac physiology and disease 

    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.

  6. Lower Circulating C1q/TNF-Related Protein-3 (CTRP3 Levels Are Associated with Obesity: A Cross-Sectional Study.

    Risa M Wolf

    Full Text Available C1q/TNF-related protein-3 (CTRP3 is a novel adipokine that lowers blood glucose levels, reduces liver triglyceride synthesis, and is protective against hepatic steatosis in diet-induced obese mouse models. We hypothesized that higher circulating serum levels of CTRP3 would be associated with a lean body mass index (BMI and a more favorable metabolic profile in humans. The aim of this study was to investigate CTRP3 levels in lean individuals compared to obese individuals.This was a cross-sectional study of obese (n=44 and lean control patients (n=60. Fasting metabolic parameters were measured in all patients and serum CTRP3 levels were measured by ELISA.BMI of the lean group was 21.9 ± 0.2 kg/m2 and obese group was 45.2 ± 1.1 kg/m2. We found significantly lower circulating levels of CTRP3 in obese individuals (405 ± 8.3 vs. 436 ± 6.7 ng/mL, p=0.004 compared to the lean group. Serum CTRP3 levels were inversely correlated with BMI (p=0.001, and triglycerides (p<0.001, and significantly associated with gender (p<0.01, ethnicity (p=0.05, HDL-cholesterol (p<0.01, and adiponectin (p<0.01. We found BMI (p<0.01, gender (p<0.01, and ethnicity (p<0.05 to be significant predictors of CTRP3 levels when controlling for age in multiple regression analysis.CTRP3 is a beneficial adipokine whose circulating levels are significantly lower in obese individuals. Obesity causes dysregulation in adipokine production, including the down-regulation of CTRP3. Lower CTRP3 levels may contribute to the pathophysiology of metabolic disorders associated with obesity. Optimizing CTRP3 levels through novel therapies may improve obesity and its comorbidities.

  7. Perinephric and epididymal fat affect hepatic metabolism in rats.

    Ben-Shlomo, Shani; Einstein, Francine H; Zvibel, Isabel; Atias, Dikla; Shlomai, Amir; Halpern, Zamir; Barzilai, Nir; Fishman, Sigal

    2012-01-01

    The present study examined whether the perinephric and epididymal visceral fat (PEVF) depot under short-term excess nutrient protected the liver by trapping nutrient-derived nonesterified free fatty acids (NEFAs) or had deleterious effects on hepatic triglycerides (TGs) accumulation and insulin resistance due to adipokine secretion. Young rats pre-emptively underwent surgical PEVF removal or sham operations and were fed with either high-fat diet (HFD) (PEVF-HFD) or regular chow (RC) (PEVF-RC) for 3 days. Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. Liver TG, serum NEFA, and fat-derived adipokines were assessed. Insulin and lipogenesis signaling were assessed by western blots. Pre-emptive PEVF removal significantly decreases insulin-induced suppression of hepatic glucose production (HGP) both in RC and in HFD-fed rats. In accordance with the clamp results, hepatic TG accumulation is also significantly reduced by PEVF excision both in RC and HFD-fed rats. These results are further validated by insulin signaling results, which show that pre-emptive PEVF removal increases phosphorylation of hepatic Akt, irrespective of diet. Notably, high levels of serum leptin induced by HFD are significantly reduced by pre-emptive PEVF excision. Additionally, expression of lipogenic enzyme p-acetyl-CoA-carboxylase, denoting reduced lipogenesis, is increased in the PEVF-HFD rats. In conclusion, PEVF has a deleterious effect on the liver as a source of insulin resistance-inducing adipokines irrespective of diet, and does not serve as a buffer for excess nutrients. PMID:21818154

  8. Clinical and biochemical effects of a 3-week program of diet combined with spa therapy in obese and diabetic patients: a pilot open study

    Fioravanti, Antonella; Adamczyk, Przemysław; Pascarelli, Nicola Antonio; Giannitti, Chiara; Urso, Renato; Tołodziecki, Michał; Ponikowska, Irena

    2015-07-01

    Obesity is a major risk factor for arterial hypertension, coronary artery disease, dyslipidemias, and type 2 diabetes. Spa therapy has long been used for treating obesity and its comorbidities. Enlargement of adipose tissue has been linked to a dysregulation of adipokine secretion and adipose tissue inflammation. Adipokines are currently investigated as potential drug targets in these conditions. Our primary aim was to assess the clinical efficacy of a 3-week program of diet combined with spa therapy in obese patients with and without type 2 diabetes. The secondary aim was to examine whether this combined program influences the response of serum levels of leptin, adiponectin, visfatin, and high-sensitivity C-reactive protein. Fifty obese males were enrolled and 21 of these featured a type 2 diabetes. During the 3-week period of the study, the patients were on a 1,000-kcal diet and were involved in mineral bath and total body's mud-pack applications (15 procedures). Patients were assessed at baseline and at the end of the therapy for clinical and biochemical parameters (total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, glycemia, and adipokines). We showed that a 3-week program of spa therapy in obese patients induced significant decrease of body weight, body mass index, triglycerides, total cholesterol, low-density lipoprotein (LDL) cholesterol, glycemia, and serum levels of leptin and high-sensitivity C-reactive protein. So, a cycle of mud-bath therapy associated with a controlled diet may be a promising treatment for obesity and type 2 diabetes decreasing body weight and many risk factors for atherosclerosis and metabolic syndrome.

  9. Combined use of serum adiponectin and tumor necrosis factor-alpha receptor 2 levels was comparable to 2-hour post-load glucose in diabetes prediction.

    Yu-Cho Woo

    Full Text Available BACKGROUND: Adipose tissue inflammation and dysregulated adipokine secretion are implicated in obesity-related insulin resistance and type 2 diabetes. We evaluated the use of serum adiponectin, an anti-inflammatory adipokine, and several proinflammatory adipokines, as biomarkers of diabetes risk and whether they add to traditional risk factors in diabetes prediction. METHODS: We studied 1300 non-diabetic subjects from the prospective Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS. Serum adiponectin, tumor necrosis factor-alpha receptor 2 (TNF-α R2, interleukin-6 (IL-6, adipocyte-fatty acid binding protein (A-FABP and high-sensitivity C-reactive protein (hsCRP were measured in baseline samples. RESULTS: Seventy-six participants developed diabetes over 5.3 years (median. All five biomarkers significantly improved the log-likelihood of diabetes in a clinical diabetes prediction (CDP model including age, sex, family history of diabetes, smoking, physical activity, hypertension, waist circumference, fasting glucose and dyslipidaemia. In ROC curve analysis, "adiponectin + TNF-α R2" improved the area under ROC curve (AUC of the CDP model from 0.802 to 0.830 (P = 0.03, rendering its performance comparable to the "CDP + 2-hour post-OGTT glucose" model (AUC = 0.852, P = 0.30. A biomarker risk score, derived from the number of biomarkers predictive of diabetes (low adiponectin, high TNF-α R2, had similar performance when added to the CDP model (AUC = 0.829 [95% CI: 0.808-0.849]. CONCLUSIONS: The combined use of serum adiponectin and TNF-α R2 as biomarkers provided added value over traditional risk factors for diabetes prediction in Chinese and could be considered as an alternative to the OGTT.

  10. Quantitative analysis of secretome from adipocytes regulated by insulin

    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 in our study, such as adiponectin, cathepsin D, cystatin C, resistin, and transferrin. Western blot analysis of these adipo-kines confirmed the quantitative results from mass spectrometry, and revealed individualized secreting pat-terns of these proteins by increasing insulin dose. In addition, 240 proteins were newly identified and quanti-fied as secreted proteins from 3T3-L1 adipocytes in our study, most of which were up-regulated upon insulin treatment. Further comprehensive bioinformatics analysis revealed that the secretory proteins in extra-cellular matrix-receptor interaction pathway and glycan structure degradation pathway were significantly up-regulated by insulin stimulation.

  11. Benefits of Regular Exercise on Inflammatory and Cardiovascular Risk Markers in Normal Weight, Overweight and Obese Adults.

    Olivia Santos Gondim

    Full Text Available Obesity is a worldwide epidemic that increases the risk of several well-known co-morbidities. There is a complicated relationship between adipokines and low-grade inflammation in obesity and cardiovascular disease (CVD. Physical activity practices have beneficial health effects on obesity and related disorders such as hypertension and dyslipidemia. We investigated the effects of 6 and 12 months of moderate physical training on the levels of adipokines and CVD markers in normal weight, overweight and obese volunteers. The 143 participants were followed up at baseline and after six and twelfth months of moderate regular exercise, 2 times a week, for 12 months. The volunteers were distributed into 3 groups: Normal Weight Group (NWG,, Overweight Group (OVG and Obese Group (OBG. We evaluated blood pressure, resting heart rate, anthropometric parameters, body composition, fitness capacity (VO2max and isometric back strength, cardiovascular markers (CRP, total cholesterol, LDL-c, HDL-c, homocysteine and adipokine levels (leptin, adiponectin, resistin, IL-6 and TNF-alpha. There were no significant changes in anthropometric parameters and body composition in any of the groups following 6 and 12 months of exercise training. Leptin, IL-6 levels and systolic blood pressure were significantly elevated in OBG before the training. Regular exercise decreased HDL-c, leptin, adiponectin and resistin levels and diastolic blood pressure in OVG. In OBG, exercise diminished HDL-c, homocysteine, leptin, resistin, IL-6, adiponectin. Moderate exercise had no effect on the body composition; however, exercise did promote beneficial effects on the low-grade inflammatory state and CVD clinical markers in overweight and obese individuals.

  12. Dietary factors and cancer chemoprevention: An overview of obesity-related malignancies

    Murthy N

    2009-01-01

    Full Text Available Obesity is a growing health problem in developed nations and in countries that are in the process of westernization like India. Obesity is linked with several health disorders such as hypertension and cardiovascular diseases, Type 2 diabetes, dyslipidemia and certain cancers. Currently, obesity-related malignancies, e.g., cancers of the breast, prostate and colon are the leading cancers in the industrialized societies. An increased amount of fat or adipose tissue in an overweight or obese person probably influences the development of cancer by releasing several hormone-like factors or adipokines. The majority of adipokines are pro-inflammatory, which promote pathological conditions like insulin resistance and cancer. On the other hand, many recent studies have shown that adiponectin, an anti-inflammatory adipokine, has anti-cancer and insulin-sensitizing effects. Adiponectin exerts its physiological functions chiefly by activation of AMP kinase via adiponectin receptors. Interestingly, several fruits and vegetables may contain adiponectin-like molecules or may increase the biosynthesis of adiponectin in our body. Studies on adiponectin analogues or adiponectin receptor agonists are a promising area of cancer chemoprevention research. In general, fruits and vegetables contain various dietary substances such as vitamins, minerals (like calcium and selenium, fiber and phytochemicals or phenolic compounds (like flavonoids and vanilloids, which may act as anti-cancer agents. Similarly, several dietary constituents including phytochemicals may have anti-obesity effects. Consumption of such dietary compounds along with caloric restriction and physical activity may be helpful in preventing obesity-related cancers. For this review article, we searched PubMed primarily to get the relevant literature.

  13. Angiotensinogen gene silencing reduces markers of inflammation and lipid accumulation in adipocytes

    Wenting eXin

    2013-03-01

    Full Text Available Inflammatory adipokines secreted from adipose tissue are major contributors to obesity-associated inflammation and other metabolic dysfunctions. We and others have recently documented the contribution of adipose tissue renin-angiotensin system (RAS to the pathogenesis of obesity, inflammation and insulin resistance. We hypothesized that adipocyte-derived angiotensinogen (Agt plays a critical role in adipogenesis and/or lipogenesis as well as inflammation. This was tested using 3T3-L1 adipocytes, stably transfected with Agt-shRNA or scrambled Sc-shRNAcas a control. Transfected preadipocytes were differentiated and used to investigate the role of adipose Agt through microarray and PCR analyses and adipokine profiling. As expected, Agt gene silencing significantly reduced the expression of Agt and its hormone product angiotensin II (Ang II, as well as lipid accumulation in 3T3-L1 adipocytes. Microarray studies identified several genes involved in lipid metabolism and inflammatory pathways which were down-regulated by Agt gene inactivation, such as glycerol-3-phosphate dehydrogenase 1 (Gpd1, serum amyloid A 3 (Saa3, nucleotide-binding oligomerization domain containing 1 (Nod1 and signal transducer and activator of transcription 1 (Stat1. Mouse adipogenesis PCR arrays revealed lower expression levels of adipogenic/lipogenic genes such as peroxisome proliferator activated receptor gamma (Pparg, sterol regulatory element binding transcription factor 1 (Srebf1, adipogenin (Adig, and fatty acid binding protein 4 (Fabp4. Further, silencing of Agt gene significantly lowered expression of pro-inflammatory adipokines including interleukin-6 (IL-6, tumor necrosis factor-alpha (TNF-α, and monocyte chemotactic protein-1 (MCP-1. In conclusion, this study directly demonstrates critical effects of Agt in adipocyte metabolism and inflammation and further support a potential role for adipose Agt in the pathogenesis of obesity-associated metabolic alterations.

  14. Long-term angiotensin II AT1 receptor inhibition produces adipose tissue hypotrophy accompanied by increased expression of adiponectin and PPARgamma.

    Zorad, Stefan; Dou, Jing-tao; Benicky, Julius; Hutanu, Daniel; Tybitanclova, Katarina; Zhou, Jin; Saavedra, Juan M

    2006-12-15

    To clarify the mechanism of the effects of angiotensin II AT(1) receptor antagonists on adipose tissue, we treated 8 week-old male Wistar Kyoto rats with the angiotensin II AT(1) receptor antagonist Candesartan cilexetil (10 mg/kg/day) for 18 weeks. Candesartan cilexetil reduced body weight gain, decreased fat tissue mass due to hypotrophy of epididymal and retroperitoneal adipose tissue and decreased adipocyte size without changing the number of adipocytes. Candesartan cilexetil decreased serum leptin levels and epididymal leptin mRNA, increased serum adiponectin levels and epididymal adiponectin mRNA, decreased epididymal tumor necrosis factor alpha (TNFalpha) mRNA, and increased fatty acid synthase mRNA. Considered free of peroxisome proliferator-activated receptor gamma (PPARgamma) agonist activity, Candesartan cilexetil increased epididymal expression of PPARgamma mRNA. The effects of Candesartan cilexetil on adipokine production and release may be attributable to PPARgamma activation and/or decrease in adipocyte cell size. In addition, Candesartan cilexetil treatment increased the expression of epididymal angiotensin II AT(2) receptor mRNA and protein and decreased the expression of renin receptor mRNA. These results suggest that Candesartan cilexetil influences lipid metabolism in adipose tissue by promoting adipose tissue rearrangement and modulating adipokine expression and release. These effects are probably consequences of local angiotensin II AT(1) receptor inhibition, angiotensin II AT(2) receptor stimulation, and perhaps additional angiotensin II-independent mechanisms. Our results indicate that the activity of local renin-angiotensin system plays an important role in adipose tissue metabolism. The decrease in the pro-inflammatory cytokine TNFalpha and the increase in the anti-inflammatory adipokine adiponectin indicate that Candesartan cilexetil may exert significant anti-inflammatory properties. PMID:17064684

  15. Association of circulating omentin-1 level with arterial stiffness and carotid plaque in type 2 diabetes

    Yoo Hye

    2011-11-01

    Full Text Available Abstract Background Adipokines contribute directly to the atherosclerotic process, connecting metabolic disorders such as obesity and diabetes to cardiovascular disease. Omentin-1 is a recently discovered novel adipokine, so data about the relationship of this adipokine to vascular health in type 2 diabetes is limited. Methods We enrolled 60 people with type 2 diabetes, with or without carotid plaque, and 30 participants with normal glucose tolerance. We measured serum omentin-1, high-sensitivity C-reactive protein (hsCRP levels, and the homeostasis model assessment of insulin resistance (HOMA-IR, as well as other cardiovascular risk factors. Vascular health was assessed by brachial ankle pulse wave velocity (baPWV and carotid intima-media thickness (IMT. Results Serum omentin-1 levels were significantly decreased in type 2 diabetes patients compared to normal glucose controls and was further reduced in type 2 diabetes patients with carotid plaque compared to those without carotid plaque. Multiple stepwise regression analysis showed that age, systolic blood pressure, history of use of statins, angiotensin receptor blockers or angiotensin-converting enzyme inhibitors, and serum omentin-1 level were independent factors determining baPWV in people with type 2 diabetes (r2 = 0.637. Furthermore, in multivariate logistic regression analysis, circulating omentin-1 level was an independent decisive factor for the presence of carotid plaque in type 2 diabetes patients, even after adjusting for age, gender, body mass index, systolic blood pressure, fasting blood glucose, low density lipoprotein cholesterol, and history of smoking and medication (odds ratio, 0.621; 95% confidence interval, 0.420-0.919; P = 0.017. Conclusions Circulating omentin-1 level was independently correlated with arterial stiffness and carotid plaque in type 2 diabetes, even after adjusting for other cardiovascular risk factors and detailed medication history.

  16. The inhibition of inflammatory molecule expression on 3T3-L1 adipocytes by berberine is not mediated by leptin signaling

    Choi, Bong-Hyuk; Kim, Yu-Hee; Ahn, In-Sook; Ha, Jung-Heun; Byun, Jae-Min; Do, Myoung-Sool

    2009-01-01

    In our previous study, we have shown that berberine has both anti-adipogenic and anti-inflammatory effects on 3T3-L1 adipocytes, and the anti-adipogenic effect is due to the down-regulation of adipogenic enzymes and transcription factors. Here we focused more on anti-inflammatory effect of berberine using real time RT-PCR and found it changes expressions of adipokines. We hypothesized that anti-adipogenicity of berberine mediates anti-inflammtory effect and explored leptin as a candidate medi...

  17. Plasma levels of resistin predict cardiovascular events

    Vida-Simiti Luminița; Todor Irina; Stoia Mirela; Gherman Claudia; Goidescu Cerasela

    2014-01-01

    Introducere: Un număr de citokine şi adipokine secretate de ţesutul adipos pot influenţa direct peretele vascular. Adiponectina exercită efecte anti-inflamatorii şi ateroprotective. Resistina este exprimată în cantităţi crescute în celulele inflamatorii. Resistina activează direct endoteliul prin suprareglarea moleculelor de adeziune, induce producţia de TNF-α în macrofage, efecte antagonizate de adiponectină. Leptina are multe efecte asupra celulelor din peretele arterial, unele similare cu ...

  18. Peripheral Pathways in the Food-Intake Control towards the Adipose-Intestinal Missing Link

    Hugo Mendieta Zerón; Ma Victoria Domínguez García; María del Socorro Camarillo Romero; Flores-Merino, Miriam V.

    2013-01-01

    In the physiological state a multitude of gut hormones are released into the circulation at the same time depending on the quality and quantity of the diet. These hormones interact with receptors at various points in the “gut-brain axis” to affect short-term and intermediate-term feelings of hunger and satiety. The combined effects of macronutrients on the predominant gut hormone secretion are still poorly understood. Besides, adipokines form an important part of an “adipoinsular axis” dysreg...

  19. Association of Leptin with Body Pain in Women.

    Younger, Jarred; Kapphahn, Kristopher; Brennan, Kathleen; Sullivan, Shannon D; Stefanick, Marcia L

    2016-07-01

    Leptin, an appetite-regulatory hormone, is also known to act as a proinflammatory adipokine. One of the effects of increased systemic leptin concentrations may be greater sensitivity to pain. We report the results of two studies examining the association between leptin and pain: a small pilot longitudinal study, followed by a large cross-sectional study. In Study 1, three women with physician-diagnosed fibromyalgia provided blood draws daily for 25 consecutive days, as well as daily self-reported musculoskeletal pain. Daily fluctuations in serum leptin were positively associated with pain across all three participants (F (1,63) = 12.8, p fibromyalgia. PMID:27028709

  20. A Possible Inflammatory Role of Twist1 in Human White Adipocytes

    Pettersson, A. T.; Laurencikiene, J; Mejhert, N; Naslund, E.; Bouloumie, A.; Dahlman, I; Arner, P; Ryden, M

    2010-01-01

    OBJECTIVE Twist1 is a transcription factor that is highly expressed in murine brown and white adipose tissue (WAT) and negatively regulates fatty acid oxidation in mice. The role of twist1 in WAT is not known and was therefore examined. RESEARCH DESIGN AND METHODS The expression of twist1 was determined by quantitative real-time PCR in different tissues and in different cell types within adipose tissue. The effect of twist1 small interfering RNA on fatty acid oxidation, lipolysis, adipokine s...

  1. Targeting adipose tissue in the treatment of obesity-associated diabetes.

    Kusminski, Christine M; Bickel, Perry E; Scherer, Philipp E

    2016-09-01

    Adipose tissue regulates numerous physiological processes, and its dysfunction in obese humans is associated with disrupted metabolic homeostasis, insulin resistance and type 2 diabetes mellitus (T2DM). Although several US-approved treatments for obesity and T2DM exist, these are limited by adverse effects and a lack of effective long-term glucose control. In this Review, we provide an overview of the role of adipose tissue in metabolic homeostasis and assess emerging novel therapeutic strategies targeting adipose tissue, including adipokine-based strategies, promotion of white adipose tissue beiging as well as reduction of inflammation and fibrosis. PMID:27256476

  2. [Prostate cancer and metabolic syndrome].

    Nagamatsu, Hirotaka; Teishima, Jun; Inoue, Shogo; Hayashi, Tetsutaro; Matsubara, Akio

    2016-01-01

    The prevalence of metabolic syndrome (MS) is increasing in Japan because of westernization of diet and lifestyle. Previous epidemiological studies have demonstrated MS to relate with the malignant potential of prostate cancer (PCa) while its relationship to the risk of PCa has been still controversial. Several pathologies involved in MS, such as insulin resistance, abnormality of secreted adipokines, chronic inflammation, alteration of sex hormones, have been reported to affect the progression of PCa. Based on these evidences, clinical studies for PCa patients have been tried for suppressing the progression of PCa through the management of MS. PMID:26793896

  3. Suppressive actions of eicosapentaenoic acid on lipid droplet formation in 3T3-L1 adipocytes

    Sinclair Andrew J; Manickam Elizabeth; Cameron-Smith David

    2010-01-01

    Abstract Background Lipid droplet (LD) formation and size regulation reflects both lipid influx and efflux, and is central in the regulation of adipocyte metabolism, including adipokine secretion. The length and degree of dietary fatty acid (FA) unsaturation is implicated in LD formation and regulation in adipocytes. The aims of this study were to establish the impact of eicosapentaenoic acid (EPA; C20:5n-3) in comparison to SFA (STA; stearic acid, C18:0) and MUFA (OLA; oleic acid, C18:1n-9) ...

  4. Leptin and Hormones: Energy Homeostasis.

    Triantafyllou, Georgios A; Paschou, Stavroula A; Mantzoros, Christos S

    2016-09-01

    Leptin, a 167 amino acid adipokine, plays a major role in human energy homeostasis. Its actions are mediated through binding to leptin receptor and activating JAK-STAT3 signal transduction pathway. It is expressed mainly in adipocytes, and its circulating levels reflect the body's energy stores in adipose tissue. Recombinant methionyl human leptin has been FDA approved for patients with generalized non-HIV lipodystrophy and for compassionate use in subjects with congenital leptin deficiency. The purpose of this review is to outline the role of leptin in energy homeostasis, as well as its interaction with other hormones. PMID:27519135

  5. Metabolic Effects of Obesity and Its Interaction with Endocrine Diseases.

    Clark, Melissa; Hoenig, Margarethe

    2016-09-01

    Obesity in pet dogs and cats is a significant problem in developed countries, and seems to be increasing in prevalence. Excess body fat has adverse metabolic consequences, including insulin resistance, altered adipokine secretion, changes in metabolic rate, abnormal lipid metabolism, and fat accumulation in visceral organs. Obese cats are predisposed to endocrine and metabolic disorders such as diabetes and hepatic lipidosis. A connection likely also exists between obesity and diabetes mellitus in dogs. No system has been developed to identify obese pets at greatest risk for development of obesity-associated metabolic diseases, and further study in this area is needed. PMID:27297495

  6. Anaplerotic Triheptanoin Diet Enhances Mitochondrial Substrate Use to Remodel the Metabolome and Improve Lifespan, Motor Function, and Sociability in MeCP2-Null Mice

    Min Jung Park; Susan Aja; Qun Li; Alicia L Degano; Judith Penati; Justin Zhuo; Roe, Charles R.; Ronnett, Gabriele V.

    2014-01-01

    Rett syndrome (RTT) is an autism spectrum disorder (ASD) caused by mutations in the X-linked MECP2 gene that encodes methyl-CpG binding protein 2 (MeCP2). Symptoms range in severity and include psychomotor disabilities, seizures, ataxia, and intellectual disability. Symptom onset is between 6-18 months of age, a critical period of brain development that is highly energy-dependent. Notably, patients with RTT have evidence of mitochondrial dysfunction, as well as abnormal levels of the adipokin...

  7. Adiponectin and its association with insulin resistance and type 2 diabetes

    Tianxin Sheng; Kangjuan Yang

    2008-01-01

    Adiponectin is an adipokine, which is expressed in adipose tissue and is thought to play an important role in glucose metabolism. Hypoadiponectinemia can cause reduction of fatty acid oxidation, decreased glucose uptake in skeletal muscle cells, and increased gluconeogenesis in hepatic cells. The level of plasma glucose can be increased. On the other hand, the decrease of fatty acid oxidation increases the level of free fatty acid (FFA), which increases the insulin resistance, and then decreases the glucose uptake, which ultimately causes increased plasma glucose and type 2 diabetes (T2D). This review describes the process from hypoadiponectinemia to T2D and the genesis of hypoadiponeetinemia at a molecular level.

  8. Anti-inflammatory role of GLP-1 and the effect of gastric bypass on diabetes- and obesity-associated inflammation

    Bovbjerg, Kirsten Katrine Lindegaard; Peter M. H. Heegaard; Steensberg, Adam; Mosolff Mathiesen, Jesper

    2014-01-01

    Fedme-associeret type 2 diabetes (T2D) er karakteriseret ved en tilstand af lav kronisk inflammation med overdreven sekretion af pro-inflammatoriske mediatorer, så som IL-6, TNF-α og leptin fra fedtvævet og en reduktion i anti-inflammatorisk adipokine adiponectin. Med T2D følger et sæt metaboliske abnormaliteter, bestående af det metaboliske syndrom, så som forhøjet blodtryk, dyslipidimi og insulin resistens. Selvom de eksakte årsager til påbegyndelsen af klinisk sygdom er stort set uvisse, t...

  9. Testosterone therapy decreases subcutaneous fat and adiponectin in aging men

    Frederiksen, L.; Højlund, K.; Hougaard, D. M.;

    2012-01-01

    -month testosterone therapy did not improve insulin sensitivity. We investigated the effect of testosterone therapy on regional body fat distribution and on the levels of the insulin-sensitizing adipokine, adiponectin, in aging men with low normal bioavailable testosterone levels. DESIGN: A randomized......), visceral adipose tissue (VAT), and thigh subcutaneous fat area (TFA) were measured by magnetic resonance imaging. Adiponectin levels were measured using an in-house immunofluorometric assay. Coefficients (b) represent the placebo-controlled mean effect of intervention. RESULTS: LEFM was decreased (b=–0...

  10. The association of circulating levels of complement-C1q TNF-related protein 5 (CTRP5) with nonalcoholic fatty liver disease and type 2 diabetes: a case–control study

    Emamgholipour, Solaleh; Moradi, Nariman; Beigy, Maani; Shabani, Parisa; Fadaei, Reza; Poustchi, Hossein; Doosti, Mahmood

    2015-01-01

    Background It is well-established that nonalcoholic fatty liver disease (NAFLD) is associated with type 2 diabetes mellitus (T2DM). Complement-C1q TNF-related protein 5 (CTRP5) is a novel adipokine involved in the regulation of lipid and glucose metabolism. We aimed to assess plasma levels of CTRP5 in patients with NAFLD (n = 22), T2DM (n = 22) and NAFLD with T2DM (NAFLD + T2DM) (n = 22) in comparison with healthy subjects (n = 21) and also to study the association between CTRP5 levels and NA...

  11. Chemical chaperones reduce ER stress and adipose tissue inflammation in high fat diet-induced mouse model of obesity.

    Chen, Yaqin; Wu, Zhihong; Zhao, Shuiping; Xiang, Rong

    2016-01-01

    Obesity, which is characteristic by chronic inflammation, is defined as abnormal or excessive fat accumulation in adipose tissues. Endoplasmic reticulum (ER) stress is increased in adipose tissue of obese state and is known to be strongly associated with chronic inflammation. The aim of this study was to investigate the effect of ER stress on adipokine secretion in obese mice and explore the potential mechanisms. In this study, we found high-fat diet induced-obesity contributed to strengthened ER stress and triggered chronic inflammation in adipose tissue. Chemical chaperones, 4-PBA and TUDCA, modified metabolic disorders and decreased the levels of inflammatory cytokines in obese mice fed a high-fat diet. The alleviation of ER stress is in accordance with the decrease of free cholesterol in adipose tissue. Furthermore chemical chaperones suppress NF-κB activity in adipose tissue of obese mice in vivo. In vitro studies showed IKK/NF-κB may be involved in the signal transduction of adipokine secretion dysfunction induced by ER stress. The present study revealed the possibility that inhibition of ER stress may be a novel drug target for metabolic abnormalities associated with obesity. Further studies are now needed to characterize the initial incentive of sustained ER stress in obese. PMID:27271106

  12. Adipose tissue remodeling: its role in energy metabolism and metabolic disorders

    Sung Sik eChoe

    2016-04-01

    Full Text Available The adipose tissue is a central metabolic organ in the regulation of whole-body energy homeostasis. The white adipose tissue (WAT functions as a key energy reservoir for other organs, whereas the brown adipose tissue (BAT accumulates lipids for cold-induced adaptive thermogenesis. Adipose tissues secret various hormones, cytokines, and metabolites (termed as adipokines that control systemic energy balance by regulating appetitive signals from the central nerve system as well as metabolic activity in peripheral tissues. In response to changes in the nutritional status, the adipose tissue undergoes dynamic remodeling, including quantitative and qualitative alterations in adipose tissue resident cells. A growing body of evidence indicates that adipose tissue remodeling in obesity is closely associated with adipose tissue function. Changes in the number and size of the adipocytes affect the microenvironment of expanded fat tissues, accompanied by alterations in adipokine secretion, adipocyte death, local hypoxia, and fatty acid fluxes. Concurrently, stromal vascular cells in the adipose tissue, including immune cells, are involved in numerous adaptive processes, such as dead adipocyte clearance, adipogenesis, and angiogenesis, all of which are dysregulated in obese adipose tissue remodeling. Chronic over-nutrition triggers uncontrolled inflammatory responses, leading to systemic low-grade inflammation and metabolic disorders, such as insulin resistance. This review will discuss current mechanistic understandings of adipose tissue remodeling processes in adaptive energy homeostasis and pathological remodeling of adipose tissue in connection with immune response.

  13. Obesity and asthma: co-morbidity or causal relationship?

    van Huisstede, A; Braunstahl, G J

    2010-09-01

    There is substantial evidence that obesity and asthma are related. "Obese asthma" may be a unique phenotype of asthma, characterized by decreased lung volumes, greater symptoms for a given degree of lung function impairment, destabilization or lack of asthma control, lack of eosinophilic inflammation and a different response to controller medication. Whether this relationship between obesity and asthma is causal or represents co-morbidity due to other factors is unclear. In previous reviews concerning the relationship between obesity and asthma, five hypotheses were put forth. One of these hypotheses is that a low grade systemic inflammation caused by adipokines from the fat tissue causes or enhances bronchial inflammation. In animal models, there is an increasing amount of evidence for the role of adipokines derived from fat tissue in the relationship between obesity and asthma. The data are conflicting in humans. Since obesity is a component of the metabolic syndrome and the metabolic syndrome is also a form of systemic inflammation, it is to be expected that there is a relationship between metabolic syndrome and asthma. The few data that are available show that there is no relationship between metabolic syndrome and asthma, but there is one between the metabolic syndrome and asthma-like symptoms. Further research is needed to confirm the relationship between obesity and asthma in humans, where a rigorous approach in the diagnosis of asthma is essential. PMID:21214041

  14. Integrated data mining of transcriptomic and proteomic datasets to predict the secretome of adipose tissue and muscle in ruminants.

    Bonnet, M; Tournayre, J; Cassar-Malek, I

    2016-08-16

    Adipose tissue and muscle are endocrine organs releasing signalling and mediator proteins termed adipokines and myokines, enabling functioning of the organism and its adaption to a wide range of different challenges such as starvation, overfeeding, stress and diseases. They also contribute to the "adipose-muscular" cross-talk for an integrated control of body mass composition. This article integrates transcriptomic and proteomic data available in ruminant species (mainly in bovine, and when available in ovine and caprine) to computationally predict the large-scale secretome of adipose tissues and muscles. For this purpose predictive bioinformatics algorithms were employed to identify proteins putatively secreted by tissues thanks to a signal peptide. We predicted 1749 secreted proteins that were found from adipose tissues and muscles, more than a half of them being already declared as secreted proteins in public repositories. We also identified 188 and 357 proteins in the predictive secretome of adipose tissues and muscles respectively, only a minor part (3-11%) of them being reported in the overlap of public repositories used for comparison. Functional analysis of these proteins highlights their involvement in biological pathways known to sustain tissue growth and functioning. This strategy allowed us to identify some known and putative novel adipomyokines, adipokines and myokines. However their role and their expression signature depending on rearing practices remain largely to be explored. PMID:27374837

  15. Angiotensin II activates different calcium signaling pathways in adipocytes.

    Dolgacheva, Lyudmila P; Turovskaya, Maria V; Dynnik, Vladimir V; Zinchenko, Valery P; Goncharov, Nikolay V; Davletov, Bazbek; Turovsky, Egor A

    2016-03-01

    Angiotensin II (Ang II) is an important mammalian neurohormone involved in reninangiotensin system. Ang II is produced both constitutively and locally by RAS systems, including white fat adipocytes. The influence of Ang II on adipocytes is complex, affecting different systems of signal transduction from early Са(2+) responses to cell proliferation and differentiation, triglyceride accumulation, expression of adipokine-encoding genes and adipokine secretion. It is known that white fat adipocytes express all RAS components and Ang II receptors (АТ1 and АТ2). The current work was carried out with the primary white adipocytes culture, and Са(2+) signaling pathways activated by Ang II were investigated using fluorescent microscopy. Са(2+)-oscillations and transient responses of differentiated adipocytes to Ang II were registered in cells with both small and multiple lipid inclusions. Using inhibitory analysis and selective antagonists, we now show that Ang II initiates periodic Са(2+)-oscillations and transient responses by activating АТ1 and АТ2 receptors and involving branched signaling cascades:In these cascades, AT1 receptors play the leading role. The results of the present work open a perspective of using Ang II for correction of signal resistance of adipocytes often observed during obesity and type 2diabetes. PMID:26850364

  16. The contribution of visceral fat to improved insulin signaling in Ames dwarf mice.

    Menon, Vinal; Zhi, Xu; Hossain, Tanvir; Bartke, Andrzej; Spong, Adam; Gesing, Adam; Masternak, Michal M

    2014-06-01

    Ames dwarf (Prop1(df), df/df) mice are characterized by growth hormone (GH), prolactin, and thyrotropin deficiency, remarkable extension of longevity and increased insulin sensitivity with low levels of fasting insulin and glucose. Plasma levels of anti-inflammatory adiponectin are increased in df/df mice, while pro-inflammatory IL-6 is decreased in plasma and epididymal fat. This represents an important shift in the balance between pro- and anti-inflammatory adipokines in adipose tissue, which was not exposed to GH signals during development or adult life. To determine the role of adipose tissue in the control of insulin signaling in these long-living mutants, we examined the effects of surgical removal of visceral (epididymal and perinephric) adipose tissue. Comparison of the results obtained in df/df mice and their normal (N) siblings indicated different effects of visceral fat removal (VFR) on insulin sensitivity and glucose tolerance. The analysis of the expression of genes related to insulin signaling indicated that VFR improved insulin action in skeletal muscle in N mice. Interestingly, this surgical intervention did not improve insulin signaling in df/df mice skeletal muscle but caused suppression of the signal in subcutaneous fat. We conclude that altered profile of adipokines secreted by visceral fat of Ames dwarf mice may act as a key contributor to increased insulin sensitivity and extended longevity of these animals. PMID:24690289

  17. Specific dietary patterns and concentrations of adiponectin

    Vajihe Izadi

    2015-01-01

    Full Text Available Background: One of the adipokines mostly secreted from adipose tissue is adiponectin. Adiponectin is well known as the anti-diabetic, anti-obesity and cardio-protective factor. Present study focused on the review the previous studies about relationship between adherence to healthy dietary pattern, independent of one or two special dietary components, and concentration of adiponectin. Materials and Methods: We searched in PubMed search engine from 2003 to July 2014 using the following key words: Healthy dietary pattern, mediterranean dietary pattern, dietary pattern, diet intervention and adiponectin and adipokines. Then, we recruited 10 articles to review in the present study. Results: Cohort studies that are examined this relationship among women showed the strong positive association in this regard. According to cross-sectional studies adherence to healthy dietary pattern like Mediterranian intervention with moderate weight loss had a positive association with concentration of adiponectin. Conclusion: It seems that adherents to the healthy dietary patterns have great levels of circulating adiponectin. However, it is not clear that whether the separate components of healthy dietary patterns like good sources of fats or protein or fibers mostly have important roles in these beneficial effects of such dietary patterns or not.

  18. OXIDATIVE STRESS: ITS ROLE IN INSULIN SECRETION, HORMONE RECEPTION BY ADIPOCYTES AND LIPOLYSIS IN ADIPOSE TISSUE

    V. V. Ivanov

    2014-01-01

    Full Text Available Oxidative stress is one of the pathogenetic components of many diseases during which generation of reactive oxigen species increases and the capacity of the antioxidant protection system diminishes. In the research of the last decades special attention has been given to adipose tissue, production of adipokines by it and their role in development of immunoresistance associated with formation of the metabolic syndrome and diabetes.Search for methods of therapeutic correction of adipokine secretion disorders, their influence on metabolism of separate cells and the organism on the whole as well as development of new approaches to correction of disorders in cell sensitivity to insulin are extremely topical nowadays. Systematization and consolidation of accumulated data allow to determine the strategies of further research more accurately; as a result, we have attempted to summarize and analyze the accumulated data on the role of adipose tissue in oxidative stress development.On the basis of literature data and the results of the personal investigations, the role of adipose tissue in forming oxidative stress in diabetes has been analyzed in the article. Brief description of adipose tissue was given as a secretory organ regulating metabolic processes in adipocytes and influencing functions of various organs and systems of the body. Mechanisms of disorder in insulin secretion as well as development of insulin sesistance in type I diabetes were described along with the contribution of lipolysis in adipose tissue to these processes.

  19. Interaction between Esophageal Squamous Cell Carcinoma and Adipose Tissue in Vitro.

    Nakayama, Atsushi; Aoki, Shigehisa; Uchihashi, Kazuyoshi; Nishijima-Matsunobu, Aki; Yamamoto, Mihoko; Kakihara, Nahoko; Iwakiri, Ryuichi; Fujimoto, Kazuma; Toda, Shuji

    2016-05-01

    Esophageal squamous cell carcinoma (ESCC) develops within the squamous epithelial layer and invades the submucosa to the subadventitia that has adipose tissue (AT). AT seems critical to ESCC progression, but the underlying mechanism is unknown. We aimed to address the association between ESCC and AT in vitro. ESCC cells were cultured on rat or human subcutaneous AT-embedded or -non-embedded collagen gel. AT promoted the growth of ESCC cells and inhibited their apoptosis. AT promoted the expression of the squamous differentiation marker involucrin in ESCC cells. AT accelerated the expression of invasion-related factors in poorly differentiated ESCC cells only. AT promoted the expression of phosphorylated-insulin-like growth factor-1 receptor in ESCC cells, whereas it inhibited that of the human epidermal growth factor receptor 2. Insulin-like growth factor-1, but not leptin, adiponectin, or resistin, promoted and inhibited the growth and apoptosis of ESCC cells, respectively. In turn, ESCC cells decreased the production of these adipokines in AT and the number of preadipocytes and mesenchymal stem cell-like cells, which developed from AT. These results suggest that i) AT may influence the progression of ESCC with increased growth or invasion and decreased apoptosis through insulin-like growth factor-1/insulin-like growth factor-1 receptor signaling, ii) AT may affect human epidermal growth factor receptor 2-targeted therapy; and iii) the cancer cells may affect adipokine production in AT. PMID:26952643

  20. 脂联素及其受体与胰岛素抵抗和运动关系的研究进展%Research Progress on the Relationship among Adiponectin and Its Receptors and Insulin Resistance and Exercise

    李蕾; 胡振东; 薛鹏

    2012-01-01

    对脂联紊及其受体与胰岛素抵抗,脂联素及其受体与运动关系的研究进展进行详细梳理,同时阐述脂联素与瘦素的交互关系.旨在为逐渐明晰运动改善胰岛素敏感性的脂肪因子机制提供理论依据,并提出未来的研究还应更加关注脂肪因子间的交互作用在运动改善胰岛素敏感性中的作用.%The article summarized the research progress on the relationship among adiponectin and its receptors and insulin resistance and exercise, and exposited the interactive relationship between adiponectin and leptin in order to supply theoretical basis for clearing the adipokines mechanism of improving insulin sensitivity by exercise. At last, we proposed the future research would be pay more attention to the fuction of adipokines interactive relationship in improving insulin sensitivity by exercise.

  1. Retinol-binding protein 4 in twins: regulatory mechanisms and impact of circulating and tissue expression levels on insulin secretion and action

    Ribel-Madsen, Rasmus; Friedrichsen, Martin; Vaag, Allan;

    2009-01-01

    OBJECTIVE: Retinol-binding protein (RBP) 4 is an adipokine of which plasma levels are elevated in obesity and type 2 diabetes. The aims of the study were to identify determinants of plasma RBP4 and RBP4 mRNA expression in subcutaneous adipose tissue (SAT) and skeletal muscle and to investigate th...... expression was not associated with circulatory RBP4. CONCLUSIONS: In conclusion, our data indicate that RBP4 levels in plasma, skeletal muscle, and fat may be linked to insulin resistance and type 2 diabetes in a secondary and noncausal manner.......OBJECTIVE: Retinol-binding protein (RBP) 4 is an adipokine of which plasma levels are elevated in obesity and type 2 diabetes. The aims of the study were to identify determinants of plasma RBP4 and RBP4 mRNA expression in subcutaneous adipose tissue (SAT) and skeletal muscle and to investigate the...... twins. Peripheral and hepatic insulin sensitivity was assessed by a euglycemic-hyperinsulinemic clamp, and beta-cell function was estimated from an intravenous glucose tolerance test. RESULTS: The influence of environmental versus genetic factors in the regulation of plasma RBP4 increased with age...

  2. Lack of evidence for intermolecular epistatic interactions between adiponectin and resistin gene polymorphisms in Malaysian male subjects

    Cia-Hin Lau

    2012-01-01

    Full Text Available Epistasis (gene-gene interaction is a ubiquitous component of the genetic architecture of complex traits such as susceptibility to common human diseases. Given the strong negative correlation between circulating adiponectin and resistin levels, the potential intermolecular epistatic interactions between ADIPOQ (SNP+45T > G, SNP+276G > T, SNP+639T > C and SNP+1212A > G and RETN (SNP-420C > G and SNP+299G > A gene polymorphisms in the genetic risk underlying type 2 diabetes (T2DM and metabolic syndrome (MS were assessed. The potential mutual influence of the ADIPOQ and RETN genes on their adipokine levels was also examined. The rare homozygous genotype (risk alleles of SNP-420C > G at the RETN locus tended to be co-inherited together with the common homozygous genotypes (protective alleles of SNP+639T > C and SNP+1212A > G at the ADIPOQ locus. Despite the close structural relationship between the ADIPOQ and RETN genes, there was no evidence of an intermolecular epistatic interaction between these genes. There was also no reciprocal effect of the ADIPOQ and RETN genes on their adipokine levels, i.e., ADIPOQ did not affect resistin levels nor did RETN affect adiponectin levels. The possible influence of the ADIPOQ gene on RETN expression warrants further investigation.

  3. Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders.

    Choe, Sung Sik; Huh, Jin Young; Hwang, In Jae; Kim, Jong In; Kim, Jae Bum

    2016-01-01

    The adipose tissue is a central metabolic organ in the regulation of whole-body energy homeostasis. The white adipose tissue functions as a key energy reservoir for other organs, whereas the brown adipose tissue accumulates lipids for cold-induced adaptive thermogenesis. Adipose tissues secrete various hormones, cytokines, and metabolites (termed as adipokines) that control systemic energy balance by regulating appetitive signals from the central nerve system as well as metabolic activity in peripheral tissues. In response to changes in the nutritional status, the adipose tissue undergoes dynamic remodeling, including quantitative and qualitative alterations in adipose tissue-resident cells. A growing body of evidence indicates that adipose tissue remodeling in obesity is closely associated with adipose tissue function. Changes in the number and size of the adipocytes affect the microenvironment of expanded fat tissues, accompanied by alterations in adipokine secretion, adipocyte death, local hypoxia, and fatty acid fluxes. Concurrently, stromal vascular cells in the adipose tissue, including immune cells, are involved in numerous adaptive processes, such as dead adipocyte clearance, adipogenesis, and angiogenesis, all of which are dysregulated in obese adipose tissue remodeling. Chronic overnutrition triggers uncontrolled inflammatory responses, leading to systemic low-grade inflammation and metabolic disorders, such as insulin resistance. This review will discuss current mechanistic understandings of adipose tissue remodeling processes in adaptive energy homeostasis and pathological remodeling of adipose tissue in connection with immune response. PMID:27148161

  4. Multidisciplinary Approach to the Treatment of Obese Adolescents: Effects on Cardiovascular Risk Factors, Inflammatory Profile, and Neuroendocrine Regulation of Energy Balance

    Ana Raimunda Dâmaso

    2013-01-01

    Full Text Available The prevention of obesity and health concerns related to body fat is a major challenge worldwide. The aim of this study was to investigate the role of a medically supervised, multidisciplinary approach, on reduction in the prevalence of obesity related comorbidities, inflammatory profile, and neuroendocrine regulation of energy balance in a sample of obese adolescents. A total of 97 postpuberty obese adolescents were enrolled in this study. Body composition, neuropeptides, and adipokines were analysed. The metabolic syndrome was defined by the International Diabetes Federation (IDF. The abdominal ultrasonography was performed to measure visceral, subcutaneous fat and hepatic steatosis. All measures were performed at baseline and after one year of therapy. The multidisciplinary management promoted the control of obesity reducing body fat mass. The prevalence of metabolic syndrome, asthma, nonalcoholic fatty liver disease (NAFLD, binge eating, and hyperleptinemia was reduced. An improvement in the inflammatory profile was demonstrated by an increase in anti-inflammatory adiponectin and reduction in proinflammatory adipokines, plasminogen activator inhibitor-1, interleukin-6 concentrations, and in the Lep/Adipo ratio. Moreover, a reduction in the AgRP and an increase in the alfa-MSH were noted. The multidisciplinary approach not only reduced obesity but also is efficacious in cardiovascular risk factors, inflammatory profile, and neuroendocrine regulation of energy balance.

  5. Quercetin Impacts Expression of Metabolism- and Obesity-Associated Genes in SGBS Adipocytes

    Andreas Leiherer

    2016-05-01

    Full Text Available Obesity is characterized by the rapid expansion of visceral adipose tissue, resulting in a hypoxic environment in adipose tissue which leads to a profound change of gene expression in adipocytes. As a consequence, there is a dysregulation of metabolism and adipokine secretion in adipose tissue leading to the development of systemic inflammation and finally resulting in the onset of metabolic diseases. The flavonoid quercetin as well as other secondary plant metabolites also referred to as phytochemicals have anti-oxidant, anti-inflammatory, and anti-diabetic effects known to be protective in view of obesity-related-diseases. Nevertheless, its underlying molecular mechanism is still obscure and thus the focus of this study was to explore the influence of quercetin on human SGBS (Simpson Golabi Behmel Syndrome adipocytes’ gene expression. We revealed for the first time that quercetin significantly changed expression of adipokine (Angptl4, adipsin, irisin and PAI-1 and glycolysis-involved (ENO2, PFKP and PFKFB4 genes, and that this effect not only antagonized but in part even overcompensated the effect mediated by hypoxia in adipocytes. Thus, these results are explained by the recently proposed hypothesis that the protective effect of quercetin is not solely due to its free radical-scavenging activity but also to a direct effect on mitochondrial processes, and they demonstrate that quercetin might have the potential to counteract the development of obesity-associated complications.

  6. IGF-1 and ADMA Levels Are Inversely Correlated in Nondiabetic Ankylosing Spondylitis Patients Undergoing Anti-TNF-Alpha Therapy

    Fernanda Genre

    2014-01-01

    Full Text Available Like rheumatoid arthritis, ankylosing spondylitis (AS is also an inflammatory disease associated with accelerated atherosclerosis and the presence of metabolic syndrome (MeS features. AS patients often display osteoporosis as well as new bone formation. Insulin-like growth factor 1 (IGF-1 is a protein involved in both inflammation and bone metabolism. In the present study we assessed whether disease activity, systemic inflammation, MeS features, adipokines, and biomarkers of endothelial activation were associated with IGF-1 and insulin-like growth factor binding protein-3 (IGFBP-3 levels in a series of 30 nondiabetic AS patients without CV disease undergoing TNF-α antagonist-infliximab therapy. All determinations were made in the fasting state, immediately before an infliximab infusion. Although no association of IGF-1 and IGFBP-3 levels with angiopoietin-2 or osteopontin was found, an inverse correlation between IGF-1 levels and asymmetric dimethylarginine (ADMA, an endogenous endothelial nitric oxide synthase inhibitor that impairs nitric oxide production and secretion promoting endothelial dysfunction, was found (r=-0.397; P=0.04. However, no significant association was found between IGF-1 and IGFBP-3 levels and disease activity, systemic inflammation, metabolic syndrome features, or adipokines. In conclusion, in nondiabetic patients with AS undergoing periodic anti-TNF-α therapy, IGF-1 and ADMA are inversely correlated.

  7. Gender Differences in Fat Distribution and Inflammatory Markers among Arabs

    Abdulaziz Farooq

    2013-01-01

    Full Text Available Recent studies from the Gulf region suggest that compared to men, women have a greater risk of developing metabolic syndrome (MeS. Objective. To investigate gender differences in body composition, adipokines, inflammatory markers, and aerobic fitness in a cohort of healthy Qatari adults. Participants. Healthy Qatari (n=58 were matched for age, gender, and body mass index. Methods. Body composition and regional fat distribution were determined by dual-energy X-ray absorptiometry and computerized tomography. Laboratory assessments included serum levels of fasting glucose, insulin, lipid profile analysis, adipokines, and inflammatory markers. Subjects were also evaluated for aerobic fitness. Results. Women had more adipose tissue in the total abdominal (P=0.04 and abdominal subcutaneous (P=0.07 regions compared to men. Waist circumference and indices of insulin sensitivity were similar; however, women had a more favourable lipid profile than men. Serum adiponectin and leptin levels were significantly higher in women, whereas inflammatory profiles were not different between men and women. Aerobic fitness was lower in women and was associated with abdominal fat accumulation. Conclusion. In premenopausal women, higher levels of adiponectin may support maintenance of insulin sensitivity and normolipidemia despite greater adiposity. However, poor aerobic fitness combined with abdominal fat accumulation may explain their greater future risk of MeS compared with men.

  8. Telmisartan attenuates the inflamed mesenteric adipose tissue in spontaneous colitis by mechanisms involving regulation of neurotensin/microRNA-155 pathway.

    Li, Yi; Zuo, Lugen; Zhu, Weiming; Gong, Jianfeng; Zhang, Wei; Guo, Zhen; Gu, Lili; Li, Ning; Li, Jieshou

    2015-02-15

    Mesenteric adipose tissue hypertrophy is unique to Crohn's disease while the molecular basis of the crosstalk between MAT and the intestinal inflammation is largely unknown. Telmisartan is an angiotensin II type 1 receptor blocker and a peroxisome proliferator-activated receptor-receptor-γ agonist which has beneficial effects on fat distribution and pro-inflammatory adipokine expression. We evaluated the effect of telmisartan upon mesenteric adipose tissue alterations and inflammatory features in IL-10(-)/(-) mice. We found that treatment with telmisartan significantly ameliorated the severity of colitis in IL-10(-)/(-) mice. Additionally, administration of telmisartan was associated with restoration of mesenteric adipose tissue adipocyte morphology and the expression of adipokines. Furthermore, telmisartan treatment suppressed the neurotensin/microRNA-155 pathway in mesenteric adipose tissue from spontaneous colitis which was confirmed by an in vitro study using cultured mesenteric adipose tissue from Crohn's disease patients. Administration of telmisartan showed promising results in spontaneous colitis which was associated with the attenuated mesenteric adipose tissue alteration which at least in part, was associated with its activity in the regulation of the neurotensin/microRNA-155 pathway. These results support the hypothesis that regulating the abnormal immune response in adipose tissue is an important target for the treatment of Crohn's disease. PMID:25576685

  9. Altered adipocyte structure and function in nutritionally programmed microswine offspring.

    DuPriest, E A; Kupfer, P; Lin, B; Sekiguchi, K; Morgan, T K; Saunders, K E; Chatkupt, T T; Denisenko, O N; Purnell, J Q; Bagby, S P

    2012-06-01

    Adipose tissue (AT) dysfunction links obesity of any cause with cardiometabolic disease, but whether early-life nutritional deficiency can program adipocyte dysfunction independently of obesity is untested. In 3-5-month-old juvenile microswine offspring exposed to isocaloric perinatal maternal protein restriction (MPR) and exhibiting accelerated prepubertal fat accrual without obesity, we assessed markers of acquired obesity: adiponectin and tumor necrosis factor (TNF)-α messenger ribonucleic acid (mRNA) levels and adipocyte size in intra-abdominal (ABD-AT) and subcutaneous (SC-AT) adipose tissues. Plasma cortisol, leptin and insulin levels were measured in fetal, neonatal and juvenile offspring. In juvenile low-protein offspring (LPO), adipocyte size in ABD-AT was reduced 22% (P = 0.011 v. controls), whereas adipocyte size in SC-AT was increased in female LPO (P = 0.05) and normal in male LPO; yet, adiponectin mRNA in LPO was low in both sexes and in both depots (P programming of adipocyte size and gene expression and subtly altered glucose homeostasis. Reduced adiponectin mRNA and adipokine dysregulation in juvenile LPO following accelerated growth occurred independently of obesity, adipocyte hypertrophy or inflammatory markers; thus, perinatal MPR and/or growth acceleration can alter adipocyte structure and disturb adipokine homeostasis in metabolically adverse patterns predictive of enhanced disease risk. PMID:25102010

  10. Obesity: single house for many evils.

    Kumar, Ashwini; Nayak, Bibhukalyan P; Kumar, Awanish

    2016-12-01

    World Health Organization (WHO) considers obesity as one of the fastest growing metabolic disorders other than diabetes. It is a complex interplay of lifestyle and associated genes. Obesity has been considered as a disease with multiple targets and very often compared in this sense with its sibling disease type 2 diabetes. The disease is pathology of the adipocytes and develops as a result of hypertrophy and hyperplasia of these cells, former being the major concern but its effects could be seen on various organs in the form of cardio-vascular disease, stroke, cancer, diabetes, sexual dysfunction, respiratory problems and many more. An increase in the lipid content of the adipocytes changes the physiology of these cells towards more inflammatory phenotype. The array of molecules or adipokines secreted by these cells varies in concentration and type among healthy and obese subjects. On one hand where adiponectin concentration decreases, the resistin concentration increases resulting in insulin resistance among many other adipokine related effects. Specifically, an obese person develops hyperlipidemia, insulin resistance, vascular blockage, sleep apnoea, cancer etc. This review is an attempt to focus, in detail, about obesity related complications. PMID:27600644

  11. The multifaceted mechanism of Leptin signaling within tumor microenvironment in driving breast cancer growth and progression.

    Sebastiano eAndò

    2014-11-01

    Full Text Available Adipokines represent likely candidates to mediate the increased breast cancer risk and the enhanced progression associated with obesity. Other contributors to obesity-related cancer progression are insulin/IGF-1 pathways and hormones. Among these, the adipokine leptin is the most intensively studied in both metabolism in general and in cancer due to the fact that leptin levels increase in proportion of fat mass. Leptin is primarily synthesized from adipocytes, but it is also produced by other cells including fibroblasts. In this latter case, it has been well demonstrated how cancer-associated fibroblasts express leptin receptor and secrete leptin which sustains a short autocrine loop and is able to target tumor epithelial cells enhancing breast cancer cell motility and invasiveness. In addition, it has been reported that leptin may induce breast cancer to undergo a transition from epithelial to spindle-like mesenchymal morphology, activating the signaling pathways devoted to the EMT. Thus, it emerges how leptin may play a crucial role in mediating malignant cell and tumor microenvironment interactions. Here, we present an overview of the role of leptin in breast cancer, covering the following topics: 1 leptin as an amplifier of estrogen signaling in tumor epithelial cells contributing to the promotion of carcinogenesis; 2 leptin as a crucial player in mediating tumor-stroma interaction and influencing EMT-linked mechanisms, that may sustain breast cancer growth and progression; 3 leptin and leptin receptor targeting as novel therapeutic strategies for breast cancer treatment.

  12. Fat poetry: a kingdom for PPARγ

    Silvia I Anghel; Walter Wahli

    2007-01-01

    Adipose tissue is not an inert cell mass contributing only to the storage of fat, but a sophisticated ensemble of cellular components with highly specialized and complex functions. In addition to managing the most important energy reserve of the body, it secretes a multitude of soluble proteins called adipokines, which have beneficial or, alternatively,deleterious effects on the homeostasis of the whole body. The expression of these adipokines is an integrated response to various signals received from many organs, which depends heavily on the integrity and physiological status of the adipose tissue. One of the main regulators of gene expression in fat is the transcription factor peroxisome proliferatoractivated receptor γ (PPARγ), which is a fatty acid-and eicosanoid-dependent nuclear receptor that plays key roles in the development and maintenance of the adipose tissue. Furthermore, synthetic PPARγ agonists are therapeutic agents used in the treatment of type 2 diabetes.This review discusses recent knowledge on the link between fat physiology and metabolic diseases, and the roles of PPARγ in this interplay via the regulation of lipid and glucose metabolism. Finally, we assess the putative benefits of targeting this nuclear receptor with still-to-be-identified highly selective PPARγ modulators.

  13. Leptin counteracts the hypoxia-induced inhibition of spontaneously firing hippocampal neurons: a microelectrode array study.

    Gavello, Daniela; Rojo-Ruiz, Jonathan; Marcantoni, Andrea; Franchino, Claudio; Carbone, Emilio; Carabelli, Valentina

    2012-01-01

    Besides regulating energy balance and reducing body-weight, the adipokine leptin has been recently shown to be neuroprotective and antiapoptotic by promoting neuronal survival after excitotoxic and oxidative insults. Here, we investigated the firing properties of mouse hippocampal neurons and the effects of leptin pretreatment on hypoxic damage (2 hours, 3% O(2)). Experiments were carried out by means of the microelectrode array (MEA) technology, monitoring hippocampal neurons activity from 11 to 18 days in vitro (DIV). Under normoxic conditions, hippocampal neurons were spontaneously firing, either with prevailing isolated and randomly distributed spikes (11 DIV), or with patterns characterized by synchronized bursts (18 DIV). Exposure to hypoxia severely impaired the spontaneous activity of hippocampal neurons, reducing their firing frequency by 54% and 69%, at 11 and 18 DIV respectively, and synchronized their firing activity. Pretreatment with 50 nM leptin reduced the firing frequency of normoxic neurons and contrasted the hypoxia-induced depressive action, either by limiting the firing frequency reduction (at both ages) or by increasing it to 126% (in younger neurons). In order to find out whether leptin exerts its effect by activating large conductance Ca(2+)-activated K(+) channels (BK), as shown on rat hippocampal neurons, we applied the BK channel blocker paxilline (1 µM). Our data show that paxilline reversed the effects of leptin, both on normoxic and hypoxic neurons, suggesting that the adipokine counteracts hypoxia through BK channels activation in mouse hippocampal neurons. PMID:22848520

  14. The Role of the Mesentery in Crohn's Disease: The Contributions of Nerves, Vessels, Lymphatics, and Fat to the Pathogenesis and Disease Course.

    Li, Yi; Zhu, Weiming; Zuo, Lugen; Shen, Bo

    2016-06-01

    Crohn's disease (CD) is a complex gastrointestinal disorder involving multiple levels of cross talk between the immunological, neural, vascular, and endocrine systems. The current dominant theory in CD is based on the unidirectional axis of dysbiosis-innate immunity-adaptive immunity-mesentery-body system. Emerging clinical evidence strongly suggests that the axis be bidirectional. The morphologic and/or functional abnormalities in the mesenteric structures likely contribute to the disease progression of CD, to a less extent the disease initiation. In addition to adipocytes, mesentery contains nerves, blood vessels, lymphatics, stromal cells, and fibroblasts. By the secretion of adipokines that have endocrine functions, the mesenteric fat tissue exerts its activity in immunomodulation mainly through response to afferent signals, neuropeptides, and functional cytokines. Mesenteric nerves are involved in the pathogenesis and prognosis of CD mainly through neuropeptides. In addition to angiogenesis observed in CD, lymphatic obstruction, remodeling, and impaired contraction maybe a cause and consequence of CD. Lymphangiogenesis and angiogenesis play a concomitant role in the progress of chronic intestinal inflammation. Finally, the interaction between neuropeptides, adipokines, and vascular and lymphatic endothelia leads to adipose tissue remodeling, which makes the mesentery an active participator, not a bystander, in the disease initiation and precipitation CD. The identification of the role of mesentery, including the structure and function of mesenteric nerves, vessels, lymphatics, and fat, in the intestinal inflammation in CD has important implications in understanding its pathogenesis and clinical management. PMID:27167572

  15. Peroxisome proliferator activated receptors at the crossroad of obesity, diabetes, and pancreatic cancer.

    Polvani, Simone; Tarocchi, Mirko; Tempesti, Sara; Bencini, Lapo; Galli, Andrea

    2016-02-28

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth cause of cancer death with an overall survival of 5% at five years. The development of PDAC is characteristically associated to the accumulation of distinctive genetic mutations and is preceded by the exposure to several risk factors. Epidemiology has demonstrated that PDAC risk factors may be non-modifiable risks (sex, age, presence of genetic mutations, ethnicity) and modifiable and co-morbidity factors related to the specific habits and lifestyle. Recently it has become evident that obesity and diabetes are two important modifiable risk factors for PDAC. Obesity and diabetes are complex systemic and intertwined diseases and, over the years, experimental evidence indicate that insulin-resistance, alteration of adipokines, especially leptin and adiponectin, oxidative stress and inflammation may play a role in PDAC. Peroxisome proliferator activated receptor-γ (PPARγ) is a nuclear receptor transcription factor that is implicated in the regulation of metabolism, differentiation and inflammation. PPARγ is a key regulator of adipocytes differentiation, regulates insulin and adipokines production and secretion, may modulate inflammation, and it is implicated in PDAC. PPARγ agonists are used in the treatment of diabetes and oxidative stress-associated diseases and have been evaluated for the treatment of PDAC. PPARγ is at the cross-road of diabetes, obesity, and PDAC and it is an interesting target to pharmacologically prevent PDAC in obese and diabetic patients. PMID:26937133

  16. Cereal based diets modulate some markers of oxidative stress and inflammation in lean and obese Zucker rats

    Mano Mark

    2011-05-01

    Full Text Available Abstract Background The potential of cereals with high antioxidant capacity for reducing oxidative stress and inflammation in obesity is unknown. This study investigated the impact of wheat bran, barley or a control diet (α-cellulose on the development of oxidative stress and inflammation in lean and obese Zucker rats. Methods Seven wk old, lean and obese male Zucker rats (n = 8/group were fed diets that contained wheat bran, barley or α-cellulose (control. After 3 months on these diets, systolic blood pressure was measured and plasma was analysed for glucose, insulin, lipids, oxygen radical absorbance capacity (ORAC, malondialdehyde, glutathione peroxidase and adipokine concentration (leptin, adiponectin, interleukin (IL-1β, IL-6, TNFα, plasminogen activator inhibitor (PAI-1, monocyte chemotactic protein (MCP-1. Adipokine secretion rates from visceral and subcutaneous adipose tissue explants were also determined. Results Obese rats had higher body weight, systolic blood pressure and fasting blood lipids, glucose, insulin, leptin and IL-1β in comparison to lean rats, and these measures were not reduced by consumption of wheat bran or barley based diets. Serum ORAC tended to be higher in obese rats fed wheat bran and barley in comparison to control (p = 0.06. Obese rats had higher plasma malondialdehyde (p Conclusions A 3-month dietary intervention was sufficient for Zucker obese rats to develop oxidative stress and systemic inflammation. Cereal-based diets with moderate and high antioxidant capacity elicited modest improvements in indices of oxidative stress and inflammation.

  17. New Insight into Adiponectin Role in Obesity and Obesity-Related Diseases

    Ersilia Nigro

    2014-01-01

    Full Text Available Obesity is a major health problem strongly increasing the risk for various severe related complications such as metabolic syndrome, cardiovascular diseases, respiratory disorders, diabetic retinopathy, and cancer. Adipose tissue is an endocrine organ that produces biologically active molecules defined “adipocytokines,” protein hormones with pleiotropic functions involved in the regulation of energy metabolism as well as in appetite, insulin sensitivity, inflammation, atherosclerosis, cell proliferation, and so forth. In obesity, fat accumulation causes dysregulation of adipokine production that strongly contributes to the onset of obesity-related diseases. Several advances have been made in the treatment and prevention of obesity but current medical therapies are often unsuccessful even in compliant patients. Among the adipokines, adiponectin shows protective activity in various processes such as energy metabolism, inflammation, and cell proliferation. In this review, we will focus on the current knowledge regarding the protective properties of adiponectin and its receptors, AdipoRs (“adiponectin system”, on metabolic complications in obesity and obesity-related diseases. Adiponectin, exhibiting antihyperglycemic, antiatherogenic, and anti-inflammatory properties, could have important clinical benefits in terms of development of therapies for the prevention and/or for the treatment of obesity and obesity-related diseases.

  18. The Role of Tumor Necrosis Factor- alpha and Resistin in Nonalcoholic Fatty Liver Disease

    Nonalcoholic fatty liver disease (NAFLD) represents one of the most common liver diseases. It is strongly associated with obesity and insulin resistance and is thought to be a part of the metabolic syndrome. It can progress from simple fatty liver to steatohepatitis, cirrhosis and liver failure. Adipocytokines, synthesized in adipose tissue, are involved in the pathophysiology of many acute and chronic liver diseases. The aim of this study was to investigate the role of Tumor Necrosis Factor-alpha (TNF-alpha) and resistin in the pathogenesis of NAFLD and their correlation to the severity of the disease. Serum concentration of TNF-alpha and resistin were measured in 20 patients with NAFLD and 20 healthy controls with ELISA method. The results of this study revealed that serum levels of both adipokines were significantly elevated in NAFLD patients than controls (P<0.01). Moreover, they were significantly higher in patients with nonalcoholic steatohepatitis than in patients with simple fatty liver. There was a significant positive correlation between TNF-alpha, resistin and each of AST, ALT and HOMA. Similarly, the results showed a significant positive correlation between the two studied adipokines, TNF-alpha and resistin (P<0.001). We conclude that TNF-alpha and resistin have a role in the pathogenesis of NAFLD and they may be promising markers for the progressin to steatohepatitis and inhibition of their activities by drugs may be a new approach for the treatment of NAFLD

  19. Metabolic Risk Susceptibility in Men Is Partially Related to Adiponectin/Leptin Ratio

    Gloria Lena Vega

    2013-01-01

    Full Text Available Background. High adiponectin/leptin ratio may be protective from metabolic risks imparted by high triglyceride, low HDL, and insulin resistance. Methods. This cross-sectional study examines plasma adipokine levels in 428 adult men who were subgrouped according to low (<6.5 μg/mLand high (≥6.5 μg/mLadiponectin levels or a low or high ratio of adiponectin/leptin. Results. Men with high adiponectin/leptin ratio had lower plasma triglyceride and higher HDL cholesterol than those with low ratio. Similarly, those with high adiponectin/leptin ratio had lower TG/HDL cholesterol ratio and HOMA2-IR than those with low ratio. In contrast, levels of adiponectin or the ratio of adiponectin/leptin did not associate with systolic blood pressure. But the ratio of adiponectin/leptin decreased progressively with the increase in the number of risk factors for metabolic syndrome. Conclusion. Adipokine levels may reflect adipose tissue triglyceride storage capacity and insulin sensitivity. Leptin is an index of fat mass, and adiponectin is a biomarker of triglyceride metabolism and insulin sensitivity. Men with high adiponectin/leptin ratios have better triglyceride profile and insulin sensitivity than men with a low ratio regardless of waist girth.

  20. Neural Control of Non-vasomotor Organs in Hypertension.

    Hurr, Chansol; Young, Colin N

    2016-04-01

    Hypertension affects over 25 % of the population with the incidence continuing to rise, due in part to the growing obesity epidemic. Chronic elevations in sympathetic nerve activity (SNA) are a hallmark of the disease and contribute to elevations in blood pressure through influences on the vasculature, kidney, and heart (i.e., neurogenic hypertension). In this regard, a number of central nervous system mechanisms and neural pathways have emerged as crucial in chronically elevating SNA. However, it is important to consider that "sympathetic signatures" are present, with differential increases in SNA to regional organs that are dependent upon the disease progression. Here, we discuss recent findings on the central nervous system mechanisms and autonomic regulatory networks involved in neurogenic hypertension, in both non-obesity- and obesity-associated hypertension, with an emphasis on angiotensin-II, salt, oxidative and endoplasmic reticulum stress, inflammation, and the adipokine leptin. PMID:26957306

  1. The human kidney as a regulator of body cytokine homeostasis

    A. Bonanni

    2011-01-01

    Full Text Available Evidence is accumulating that the human kidney is a major site for the removal of several cytokines and growth factors, which can accumulate in body pools in patients with acute and chronic kidney disease (CKD. In addition, progressive renal failure and the increase in circulating proinflammatory cytokines are associated with mortality, suggesting that altered cytokines handling by the kidney is associated with worse outcome. Also, the kidney itself may be damaged by signals arising by endothelia and peripheral tissues during the course of the metabolic syndrome, type 2 diabetes and obesity. In this paper we provide a review of kidney handling of several adipokines and myokines, with special emphasis to interleukin-6 (IL-6, leptin, resistin and transforming growth factor-beta (TGF-beta.

  2. Dietary Conjugated Linoleic Acid and Hepatic Steatosis: Species-Specific Effects on Liver and Adipose Lipid Metabolism and Gene Expression

    Diwakar Vyas

    2012-01-01

    Full Text Available Objective. To summarize the recent studies on effect of conjugated linoleic acid (CLA on hepatic steatosis and hepatic and adipose lipid metabolism highlighting the potential regulatory mechanisms. Methods. Sixty-four published experiments were summarized in which trans-10, cis-12 CLA was fed either alone or in combination with other CLA isomers to mice, rats, hamsters, and humans were compared. Summary and Conclusions. Dietary trans-10, cis-12 CLA induces a severe hepatic steatosis in mice with a more muted response in other species. Regardless of species, when hepatic steatosis was present, a concurrent decrease in body adiposity was observed, suggesting that hepatic lipid accumulation is a result of uptake of mobilized fatty acids (FA from adipose tissue and the liver's inability to sufficiently increase FA oxidation and export of synthesized triglycerides. The potential role of liver FA composition, insulin secretion and sensitivity, adipokine, and inflammatory responses are discussed as potential mechanisms behind CLA-induced hepatic steatosis.

  3. Human skeletal muscle releases leptin in vivo

    Wolsk, Emil; Grøndahl, Thomas Sahl; Pedersen, Bente Klarlund;

    2012-01-01

    Leptin is considered an adipokine, however, cultured myocytes have also been found to release leptin. Therefore, as proof-of-concept we investigated if human skeletal muscle synthesized leptin by measuring leptin in skeletal muscle biopsies. Following this, we quantified human skeletal muscle and...... adipose tissue leptin release in vivo. We recruited 16 healthy male human participants. Catheters were inserted into the femoral artery and vein draining skeletal muscle, as well as an epigastric vein draining the abdominal subcutaneous adipose tissue. By combining the veno-arterial differences in plasma...... leptin with measurements of blood flow, leptin release from both tissues was quantified. To induce changes in leptin, the participants were infused with either saline or adrenaline in normo-physiological concentrations. The presence of leptin in skeletal muscle was confirmed by western blotting. Leptin...

  4. The impact of obesity towards prostate diseases.

    Parikesit, Dyandra; Mochtar, Chaidir Arief; Umbas, Rainy; Hamid, Agus Rizal Ardy Hariandy

    2016-03-01

    Evidence has supported obesity as a risk factor for both benign prostate hyperplasia (BPH) and prostate cancer (PCa). Obesity causes several mechanisms including increased intra-abdominal pressure, altered endocrine status, increased sympathetic nervous activity, increased inflammation process, and oxidative stress, all of which are favorable in the development of BPH. In PCa, there are several different mechanisms, such as decreased serum testosterone, peripheral aromatization of androgens, insulin resistance, and altered adipokine secretion caused by inflammation, which may precipitate the development of and even cause high-grade PCa. The role of obesity in prostatitis still remains unclear. A greater understanding of the pathogenesis of prostate disease and adiposity could allow the development of new therapeutic markers, prognostic indicators, and drug targets. This review was made to help better understanding of the association between central obesity and prostate diseases, such as prostatitis, BPH, and PCa. PMID:27014656

  5. Anti-inflammatory role of GLP-1 and the effect of gastric bypass on diabetes- and obesity-associated inflammation

    Bovbjerg, Kirsten Katrine Lindegaard

    Obesity-associated type 2 diabetes (T2D) is characterized by a state of chronic, low-grade inflammation with an excessive secretion of pro-inflammatory mediators, such as IL-6, TNF-α, and leptin from the adipose tissue and decrease in the anti-inflammatory adipokine adiponectin. T2D is accompanied...... with a set of metabolic abnormalities comprising the metabolic syndrome, such as hypertension, dyslipidemia, and insulin resistance. Although the exact causes for the onset of clinical disease remain largely unknown, emerging evidence seems to suggest that obesity-induced inflammation, especially in...... molecular mediators have been found following RYGB, suggesting one potential mechanism by which bariatric surgery re-establishes insulin sensitivity.RYGB also enhances circulating levels of certain gastrointestinal-derived hormones, particularly the postprandial secretion of glucagon-like peptide 1 (GLP-1...

  6. Childhood obesity: immune response and nutritional approaches

    Thea eMagrone

    2015-02-01

    Full Text Available Childhood obesity is characterized by a low grade inflammation status depending on the multicellular release of cytokines, adipokines and reactive oxygen species. In particular, the imbalance between anti-inflammatory T regulatory cells and inflammatory T helper 17 cells seems to sustain such a phlogistic condition. Alterations of gut microbiota since childhood also contribute to the maintenance of inflammation. Therefore, besides preventive measures and caloric restrictions, dietary intake of natural products endowed with anti-oxidant and anti-inflammatory activities may represent a valid interventional approach for preventing and/or attenuating the pathological consequences of obesity. In this regard, the use of prebiotics, probiotics, polyphenols, polyunsaturated fatty acids, vitamins and melatonin in human clinical trials will be described.

  7. LC-MS/MS analysis of visceral and subcutaneous adipose tissue proteomes in young goats with focus on innate immunity and inflammation related proteins

    Restelli, Laura; Codrea, Marius Cosmin; Savoini, Giovanni;

    2014-01-01

    protein and gene expression patterns. In ruminants, fat tissues play important biological roles not only for animal health, but also for quality and gain in meat and milk production. Yet very few studies have explored the ruminant adipose tissue proteomes. The aim of our study was to compare subcutaneous...... and visceral adipose tissues of goat, focusing on proteins involved in immune and inflammatory response. A 2-D LC-MS/MS approach followed by cluster analysis shows a clear distinction between subcutaneous and visceral fat tissue proteomes, and qualitative RT-PCR based analysis of 30 potential...... adipokines further confirmed the individual expression patterns of 26 of these, including 7 whose mRNA expression was observed for the first time in adipose tissues. This study provides a first description of adipose tissue proteomes in goat, and presents observations on novel proteins related to metabolic...

  8. Renal involvement in psychological eating disorders.

    Li Cavoli, Gioacchino; Mulè, Giuseppe; Rotolo, Ugo

    2011-01-01

    Psychological eating disorders--anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder--are an increasing public health problem with severe clinical manifestations: hypothermia, hypotension, electrolyte imbalance, endocrine disorders and kidney failure; they are of interest to nephrologists, but pathophysiological mechanisms in determining the renal involvement are still unclear. We describe pathophysiology, histological features and clinical manifestations of the most frequent psychological eating disorders: AN and BN. Regarding AN, we analyze the recent literature, and identify 3 principal pathways towards renal involvement: chronic dehydration-hypokalemia, nephrocalcinosis and chronic rhabdomyolysis. Regarding BN, we describe the correlation between obesity and many proinflammatory cytokines, chemokines, growth factors and adipokines, having potential metabolic and hemodynamic effects on the kidney and an important role in the pathogenesis of obesity-related renal injury, independently of hypertension and diabetes. PMID:22135793

  9. Label-free profiling of white adipose tissue of rats exhibiting high or low levels of intrinsic exercise capacity.

    Bowden-Davies, Kelly; Connolly, Joanne; Burghardt, Paul; Koch, Lauren G; Britton, Steven L; Burniston, Jatin G

    2015-07-01

    Divergent selection has created rat phenotypes of high- and low-capacity runners (HCR and LCR, respectively) that have differences in aerobic capacity and correlated traits such as adiposity. We analyzed visceral adipose tissue of HCR and LCR using label-free high-definition MS (elevated energy) profiling. The running capacity of HCR was ninefold greater than LCR. Proteome profiling encompassed 448 proteins and detected 30 significant (p stress (e.g. 78 kDa glucose response protein), and inflammation (e.g. Ig gamma-2B chain C region). Whereas the abundance antioxidant enzymes such as superoxide dismutase [Cu-Zn] was greater in HCR tissue. Putative adipokines were also detected, in particular protein S100-B, was 431% more abundant in LCR adipose tissue. These findings reveal low running capacity is associated with a pathological profile in visceral adipose tissue proteome despite no detectable differences in mitochondrial protein abundance. PMID:25758023

  10. Ghrelin in Female and Male Reproduction

    Joëlle Dupont

    2010-01-01

    Full Text Available Ghrelin and one of its functional receptors, GHS-R1a (Growth Hormone Secretagogue Receptor 1a, were firstly studied about 15 years. Ghrelin is a multifunctional peptide hormone that affects several biological functions including food intake, glucose release, cell proliferation… Ghrelin and GHS-R1a are expressed in key cells of both male and female reproductive organs in several species including fishes, birds, and mammals suggesting a well-conserved signal through the evolution and a role in the control of fertility. Ghrelin could be a component of the complex series of nutrient sensors such as adipokines, and nuclear receptors, which regulate reproduction in function of the energy stores. The objective of this paper was to report the available information about the ghrelin system and its role at the level of the hypothalamic-pituitary-gonadal axis in both sexes.

  11. On the Significance of New Biochemical Markers for the Diagnosis of Premature Labour

    Rafał Rzepka

    2014-01-01

    Full Text Available Preterm labour is defined as a birth taking place between 22nd and 37th weeks of gestation. Despite numerous studies on the aetiology and pathogenesis of preterm labour, its very cause still remains unclear. The importance of the cytokines and acute inflammation in preterm labour aetiology is nowadays well-proven. However, chronic inflammation as an element of the pathogenesis of premature labour is still unclear. This paper presents a literature review on the damage-associated molecular patterns (DAMPs, receptors for advanced glycation end products (RAGE, negative soluble isoforms of RAGE, chemokine-stromal cell-derived factor-1 (SDF-1 and one of the adipokines, resistin, in the pathogenesis of preterm labour. We conclude that the chronic inflammatory response can play a much more important role in the pathogenesis of preterm delivery than the acute one.

  12. Human serum levels of fetal antigen 1 (FA1/Dlk1) increase with obesity, are negatively associated with insulin sensitivity and modulate inflammation in vitro

    Chacón, M R; Miranda, M; Jensen, C H;

    2008-01-01

    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......OBJECTIVE:To investigate fetal antigen 1 (FA1) protein within the context of human obesity and its relation with insulin sensitivity. SUBJECTS: Cross-sectional study that analyses circulating levels of FA1 in two selected human cohorts: n=127 men for the study of FA1 circulating levels in the...... context of obesity and insulin sensitivity (S(i)); and n=61 severely obese women before and after bariatric surgery. The response in vitro to FA1 protein on human cell lines of monocytes, preadipocytes and mature adipocytes was studied. MEASUREMENTS: Anthropometrical parameters: body mass index, waist...

  13. World endocrinology news

    M A Berkovskaya

    2008-03-01

    Full Text Available • Actuality of the problem of metabolic syndrome: expert opinion. • Chemerin is a novel adipokine associated with obesity and metabolic syndrome. • Brothers of women with polycystic ovary syndrome are characterised by impaired glucose tolerance, reduced insulin sensitivity and related metabolic defects. • Microvascular dysfunction: a potential pathophysiological role in the metabolic syndrome. • Cardiotrophin-1 is expressed in adipose tissue and it is UP-regulated in the metabolic syndrome. • Magnesium Intake, Metabolic Abnormalities, and Inflammation. • Red meat in the diet. • Relationships of maternal and paternal birth weights to features of the metabolic syndrome in adult offspring: an inter-generation study in South India. • The truth about milk! • Therapeutic uses of aromatase inhibitors in men. • Reduction of body weight and co-morbidities by orlistat: The XXL - Primary Health Care Trial

  14. The nitroxide radical TEMPOL prevents obesity, hyperlipidaemia, elevation of inflammatory cytokines, and modulates atherosclerotic plaque composition in apoE(-/-) mice

    Kim, Christine H. J.; Mitchell, James B.; Bursill, Christina A.;

    2015-01-01

    cholesterol, inflammatory cytokines and markers (interleukin-6, IL-6; monocyte-chemotactic protein, MCP-1; myeloperoxidase, MPO; serum amyloid A, SAA; adiponectin; leptin). Plaques in the aortic sinus were analysed for area, and content of collagen, lipid, macrophages and smooth muscle cells. RESULTS: High...... fat feeding resulted in marked increases in body mass and plasma lipid levels. Dietary TEMPOL decreased both parameters. In the high-fat-fed mice significant elevations in plasma lipid levels and the inflammatory markers IL-6, MCP-1, MPO, SAA were detected, along with an increase in leptin and a......OBJECTIVE: The nitroxide compound TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl radical) has been shown to prevent obesity-induced changes in adipokines in cell and animal systems. In this study we investigated whether supplementation with TEMPOL inhibits inflammation and atherosclerosis...

  15. Hypertension and obesity: epidemiology, mechanisms and clinical approach.

    Becton, Lauren J; Shatat, Ibrahim F; Flynn, Joseph T

    2012-08-01

    Obesity-related hypertension in pediatric patients is becoming more prevalent around the world as a consequence of the childhood obesity epidemic. Hypertension and the metabolic abnormalities associated with obesity will significantly increase the health risks for these children as they grow into adulthood. The pathophysiology of obesity-related hypertension is complex, and multiple potential mechanisms likely contribute to the development of higher blood pressure in obese children. These include hyperinsulinemia, activation of the renin-angiotensin-aldosterone system, stimulation of the sympathetic nervous system, abnormalities in adipokines such as leptin, direct effects of perinephric fat on the renal parenchyma, and cytokines acting at the vascular endothelial level. As in any child with elevated blood pressure, diagnostic evaluation should focus on confirmation of hypertension, determine if an underlying cause can be identified and whether hypertensive target organ damage is present. Therapy should begin with lifestyle modifications, but will often need to include one or more antihypertensive medications. PMID:22664863

  16. Circadian Clocks and the Interaction between Stress Axis and Adipose Function

    Isa Kolbe

    2015-01-01

    Full Text Available Many physiological processes and most endocrine functions show fluctuations over the course of the day. These so-called circadian rhythms are governed by an endogenous network of cellular clocks and serve as an adaptation to daily and, thus, predictable changes in the organism’s environment. Circadian clocks have been described in several tissues of the stress axis and in adipose cells where they regulate the rhythmic and stimulated release of stress hormones, such as glucocorticoids, and various adipokine factors. Recent work suggests that both adipose and stress axis clock systems reciprocally influence each other and adrenal-adipose rhythms may be key players in the development and therapy of metabolic disorders. In this review, we summarize our current understanding of adrenal and adipose tissue rhythms and clocks and how they might interact to regulate energy homoeostasis and stress responses under physiological conditions. Potential chronotherapeutic strategies for the treatment of metabolic and stress disorders are discussed.

  17. Interleukin-1-receptor antagonist in type 2 diabetes mellitus

    Larsen, Claus M; Faulenbach, Mirjam; Vaag, Allan;

    2007-01-01

    proliferation, and apoptosis. METHODS: In this double-blind, parallel-group trial involving 70 patients with type 2 diabetes, we randomly assigned 34 patients to receive 100 mg of anakinra (a recombinant human interleukin-1-receptor antagonist) subcutaneously once daily for 13 weeks and 36 patients to receive......BACKGROUND: The expression of interleukin-1-receptor antagonist is reduced in pancreatic islets of patients with type 2 diabetes mellitus, and high glucose concentrations induce the production of interleukin-1beta in human pancreatic beta cells, leading to impaired insulin secretion, decreased cell...... (P=0.03); C-peptide secretion was enhanced (P=0.05), and there were reductions in the ratio of proinsulin to insulin (P=0.005) and in levels of interleukin-6 (P<0.001) and C-reactive protein (P=0.002). Insulin resistance, insulin-regulated gene expression in skeletal muscle, serum adipokine levels...

  18. Pathophysiology of Resistant Hypertension: The Role of Sympathetic Nervous System

    Costas Tsioufis

    2011-01-01

    Full Text Available Resistant hypertension (RH is a powerful risk factor for cardiovascular morbidity and mortality. Among the characteristics of patients with RH, obesity, obstructive sleep apnea, and aldosterone excess are covering a great area of the mosaic of RH phenotype. Increased sympathetic nervous system (SNS activity is present in all these underlying conditions, supporting its crucial role in the pathophysiology of antihypertensive treatment resistance. Current clinical and experimental knowledge points towards an impact of several factors on SNS activation, namely, insulin resistance, adipokines, endothelial dysfunction, cyclic intermittent hypoxaemia, aldosterone effects on central nervous system, chemoreceptors, and baroreceptors dysregulation. The further investigation and understanding of the mechanisms leading to SNS activation could reveal novel therapeutic targets and expand our treatment options in the challenging management of RH.

  19. Greater Omental Pancake Tumour due to Metastasis of Ovarian Cancer – A Cadaveric Study

    Bhusari, Prashant A.; Khairnar, Karan B.

    2014-01-01

    Cancer of ovary is the one of the common of all gynecological tumors and is the leading cause of death among women. A unique attempt is made to trace masses & its causes found in an abdomen of female cadaver during routine anatomy dissection. The mass was thick, hard and somewhat nodular in the region of greater omentum, After dissecting the pelvic cavity, it was found that both the ovaries were bulky, nodular & hard. Whole abdominal cavity was dissected & found that liver also involved by metastasis. Case suggests that there is the development of metastatic omental mass from grade IV ovarian cancer. Primary human omental adipocytes promote homing, migration and invasion of ovarian cancer cells. Adipokines like interleukin-8 (IL-8) mediate these activities. PMID:24596747

  20. Greater Omental Pancake Tumour due to Metastasis of Ovarian Cancer - A Cadaveric Study.

    Bhusari, Prashant A; Khairnar, Karan B

    2014-01-01

    Cancer of ovary is the one of the common of all gynecological tumors and is the leading cause of death among women. A unique attempt is made to trace masses & its causes found in an abdomen of female cadaver during routine anatomy dissection. The mass was thick, hard and somewhat nodular in the region of greater omentum, After dissecting the pelvic cavity, it was found that both the ovaries were bulky, nodular & hard. Whole abdominal cavity was dissected & found that liver also involved by metastasis. Case suggests that there is the development of metastatic omental mass from grade IV ovarian cancer. Primary human omental adipocytes promote homing, migration and invasion of ovarian cancer cells. Adipokines like interleukin-8 (IL-8) mediate these activities. PMID:24596747

  1. Resistin Induces Hypertension and Insulin Resistance in Mice via a TLR4-Dependent Pathway.

    Jiang, Yun; Lu, Linfang; Hu, Youtao; Li, Qiang; An, Chaoqiang; Yu, Xiaolan; Shu, Le; Chen, Ao; Niu, Congcong; Zhou, Lei; Yang, Zaiqing

    2016-01-01

    Resistin, an adipokine involved in insulin resistance (IR) and diabetes, has recently been reported to play a role in cardiovascular events. However, its effect on blood pressure (BP) and the underlying mechanisms remain unclear. In the present study, we showed that resistin induces hypertension and IR in wild type (WT) mice, but not in tlr4(-/-) mice. Resistin upregulated angiotensinogen (Agt) expression in WT mice, whereas it had no effect on tlr4(-/-) mice, or in mice treated with the angiotensin-converting enzyme inhibitor perindopril. Real-time PCR and chromatin immunoprecipitation further confirmed that resistin activates the renin-angiotensin system (RAS) via the TLR4/P65/Agt pathway. This finding suggested an essential role of resistin in linking IR and hypertension, which may offer a novel target in clinic on the study of the association between diabetes and hypertension. PMID:26917360

  2. Clinical implications of adipocytokines and newly emerging metabolic factors with relation to insulin resistance and cardiovascular health

    Sung HeeChoi

    2013-08-01

    Full Text Available Adipose tissue is known to secrete hormones actively and produces many biologically active proteins called adipocytokines. Typically, obesity is followed by low-grade inflammation, which is characterized by increased circulating levels of pro-inflammatory cytokines. Macrophages play a role in the inflammatory process by secreting many cytokines such as tumour necrosis factor-alpha, interleukin-6, resistin and retinol binding protein-4. These cytokines and chemokines participate in low grade pro-inflammatory processes leading to insulin resistance, metabolic impairment and cardiovascular diseases. More metabolic regulators, such as fibroblast growth factor (FGF21, FGF19, FGF1, vaspin and visfatin have now been discovered but their exact roles in human diseases are still unclear. This review focuses on recent research regarding the role of adipokines and new metabolic factors in metabolic derangement or cardiovascular disease.

  3. Effect of Prolactin on the Adipose Tissue – Possible Clinical Implications

    Carmen Iulia Toma

    2014-02-01

    Full Text Available Obesity, only recently recognized as a health problem for the general population, demands a preventive, as well as a therapeutic approach. It is also an active risk factor for disease and disability, its complications cost enormously, and in some countries, its prevalence reached epidemic proportions. During pregnancy and breast-feeding, high levels of prolactin are recognized to influence sugar and lipid metabolism. New information about its involvement in the metabolic status outside pregnancy sustains its reevaluation as a metabolic hormone. In the white adipose tissue, prolactin inhibits lipogenesis and adipokines release, while at the pancreatic level it promotes insulin secretion. It seems that it might be implicated in promoting insulin-resistance, and thus being directly involved in the appearance of the metabolic syndrome.

  4. Obesity and Diabetes: The Increased Risk of Cancer and Cancer-Related Mortality.

    Gallagher, Emily Jane; LeRoith, Derek

    2015-07-01

    Obesity and type 2 diabetes are becoming increasingly prevalent worldwide, and both are associated with an increased incidence and mortality from many cancers. The metabolic abnormalities associated with type 2 diabetes develop many years before the onset of diabetes and, therefore, may be contributing to cancer risk before individuals are aware that they are at risk. Multiple factors potentially contribute to the progression of cancer in obesity and type 2 diabetes, including hyperinsulinemia and insulin-like growth factor I, hyperglycemia, dyslipidemia, adipokines and cytokines, and the gut microbiome. These metabolic changes may contribute directly or indirectly to cancer progression. Intentional weight loss may protect against cancer development, and therapies for diabetes may prove to be effective adjuvant agents in reducing cancer progression. In this review we discuss the current epidemiology, basic science, and clinical data that link obesity, diabetes, and cancer and how treating obesity and type 2 diabetes could also reduce cancer risk and improve outcomes. PMID:26084689

  5. Metformin Impacts the Prognosis of Cancer Patients with Type 2 Diabetes

    Aldea Mihaela

    2014-06-01

    Full Text Available A long term complication of diabetes is the increased susceptibility to develop various malignancies and also to negatively impact the progression of cancer. However, metformin, widely used in the treatment of type II diabetes, seems to impact the outcome of several types of cancer, in terms of overall survival, disease-free survival or rates of recurrences. Metformin might impact cancer through various mechanisms, including reduced insulin and insulin-like growth factor-mediated signaling as well as modulation of inflammation and adipokine activity. This review presents the clinical studies that deal with the prognostic impact of metformin on cancer and discuss the possible reasons for why certain types of cancer are affected by anti-diabetic therapy. In addition, it tries to integrate the preclinical and clinical evidence into guidelines for future prospective clinical studies

  6. Plasma apolipoprotein M is reduced in metabolic syndrome but does not predict intima media thickness

    Dullaart, Robin P F; Plomgaard, Peter; de Vries, Rindert;

    2009-01-01

    S) subjects, and determined whether intima media thickness (IMT) is associated with apoM. METHODS: In 19 non-diabetic subjects with and 60 non-diabetic subjects without MetS (NCEP, ATP III criteria), the relationships of plasma apoM with obesity, glucose, insulin, lipids and adipokines, as well as with IMT...... were determined. RESULTS: Plasma apoM was on average 15% lower in subjects with MetS compared to subjects without MetS (p=0.036). ApoM correlated inversely with body mass index and waist circumference (p<0.001), and positively with total cholesterol, LDL cholesterol and apoA-I (p<0.05). ApoM was not...

  7. Levels of adiponectin and leptin at onset of type 1 diabetes have changed over time in children and adolescents

    Safai, Narges; Eising, Stefanie; Hougaard, David Michael;

    2015-01-01

    Adiponectin and leptin are proteins secreted by the adipose tissue and have an influence on insulin sensitivity and on inflammatory markers. Altered levels could play a part in the pathogenesis of type 1 diabetes mellitus. We determined adiponectin and leptin levels over a nine-year period in...... diagnosed T1D (n = 482) were included, and healthy siblings (n = 479) were chosen as a control group. Leptin levels were significantly higher in recent years (in both patients and siblings), whereas for adiponectin, the levels were lower in recent years in the patient group. Leptin levels were lower in...... children with T1D (RR 0.74, p = 0.003) and in males (RR 0.52, p < 0.001) and increasing with age in both groups. For adiponectin, there was a negative association between level and age in patients. Both adipokines showed a significant correlation with BMI and lower levels in children with blood samples...

  8. Review: adiponectin in retinopathy.

    Fu, Zhongjie; Gong, Yan; Löfqvist, Chatarina; Hellström, Ann; Smith, Lois E H

    2016-08-01

    Neovascular eye diseases are a major cause of blindness including retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration in which new vessel formation is driven by hypoxia or metabolic abnormalities affecting the fuel supply. White-adipose-tissue derived adipokines such as adiponectin modulate metabolic responses. Increasing evidence shows that lack of adiponectin may result in retinal neovascularization. Activation of the adiponectin pathway may in turn restore energy metabolism, to suppress the drive for compensatory but ultimately pathological neovessels of retinopathy. In this review, we will summarize our current knowledge of the role of adiponectin in eye diseases of premature infants, diabetic patients as well as the elderly. Further investigations in this field are likely to lead to new preventative approaches for these diseases. PMID:27155572

  9. Chronic liquid nutrition intake induces obesity and considerable but reversible metabolic alterations in Wistar rats.

    Mikuska, Livia; Vrabcova, Michaela; Tillinger, Andrej; Balaz, Miroslav; Ukropec, Jozef; Mravec, Boris

    2016-06-01

    We have previously described the development of substantial, but reversible obesity in Wistar rats fed with palatable liquid nutrition (Fresubin). In this study, we investigated changes in serum hormone levels, glycemia, fat mass, adipocyte size, and gene expression of adipokines and inflammatory markers in adipose tissue of Wistar rats fed by Fresubin (i) for 5 months, (ii) up to 90 days of age, or (iii) after 90 days of age to characterize metabolic alterations and their reversibility in rats fed with Fresubin. An intra-peritoneal glucose tolerance test was also performed to determine levels of serum leptin, adiponectin, insulin, and C-peptide in 2- and 4-month-old animals. In addition, mesenteric and epididymal adipose tissue weight, adipocyte diameter, and gene expression of pro- and anti-inflammatory adipokines and other markers were determined at the end of the study. Chronic Fresubin intake significantly increased adipocyte diameter, reduced glucose tolerance, and increased serum leptin, adiponectin, insulin, and C-peptide levels. Moreover, gene expression of leptin, adiponectin, CD68, and nuclear factor kappa B was significantly increased in mesenteric adipose tissue of Fresubin fed rats. Monocyte chemotactic protein 1 messenger RNA (mRNA) levels increased in mesenteric adipose tissue only in the group fed Fresubin during the entire experiment. In epididymal adipose tissue, fatty acid binding protein 4 mRNA levels were significantly increased in rats fed by Fresubin during adulthood. In conclusion, chronic Fresubin intake induced complex metabolic alterations in Wistar rats characteristic of metabolic syndrome. However, transition of rats from Fresubin to standard diet reversed these alterations. PMID:26939586

  10. Suppressive actions of eicosapentaenoic acid on lipid droplet formation in 3T3-L1 adipocytes

    Sinclair Andrew J

    2010-06-01

    Full Text Available Abstract Background Lipid droplet (LD formation and size regulation reflects both lipid influx and efflux, and is central in the regulation of adipocyte metabolism, including adipokine secretion. The length and degree of dietary fatty acid (FA unsaturation is implicated in LD formation and regulation in adipocytes. The aims of this study were to establish the impact of eicosapentaenoic acid (EPA; C20:5n-3 in comparison to SFA (STA; stearic acid, C18:0 and MUFA (OLA; oleic acid, C18:1n-9 on 3T3-L1 adipocyte LD formation, regulation of genes central to LD function and adipokine responsiveness. Cells were supplemented with 100 μM FA during 7-day differentiation. Results EPA markedly reduced LD size and total lipid accumulation, suppressing PPARγ, Cidea and D9D/SCD1 genes, distinct from other treatments. These changes were independent of alterations of lipolytic genes, as both EPA and STA similarly elevated LPL and HSL gene expressions. In response to acute lipopolysaccharide exposure, EPA-differentiated adipocytes had distinct improvement in inflammatory response shown by reduction in monocyte chemoattractant protein-1 and interleukin-6 and elevation in adiponectin and leptin gene expressions. Conclusions This study demonstrates that EPA differentially modulates adipogenesis and lipid accumulation to suppress LD formation and size. This may be due to suppressed gene expression of key proteins closely associated with LD function. Further analysis is required to determine if EPA exerts a similar influence on LD formation and regulation in-vivo.

  11. Circulating adipocytokines and chronic kidney disease.

    Katherine T Mills

    Full Text Available BACKGROUND: Adipokines have been associated with atherosclerotic heart disease, which shares many common risk factors with chronic kidney disease (CKD, but their relationship with CKD has not been well characterized. METHODS: We investigated the association of plasma leptin, resistin and adiponectin with CKD in 201 patients with CKD and 201 controls without. CKD was defined as estimated glomerular filtration rate (eGFR <60 mL/min/1.73 m(2 or presence of albuminuria. Quantile regression and logistic regression models were used to examine the association between adipokines and CKD adjusting for multiple confounding factors. RESULTS: Compared to controls, adjusted median leptin (38.2 vs. 17.2 ng/mL, p<0.0001 and adjusted mean resistin (16.2 vs 9.0 ng/mL, p<0.0001 were significantly higher in CKD cases. The multiple-adjusted odds ratio (95% confidence interval of CKD comparing the highest tertile to the lower two tertiles was 2.3 (1.1, 4.9 for leptin and 12.7 (6.5, 24.6 for resistin. Median adiponectin was not significantly different in cases and controls, but the odds ratio comparing the highest tertile to the lower two tertiles was significant (1.9; 95% CI, 1.1, 3.6. In addition, higher leptin, resistin, and adiponectin were independently associated with lower eGFR and higher urinary albumin levels. CONCLUSIONS: These findings suggest that adipocytokines are independently and significantly associated with the risk and severity of CKD. Longitudinal studies are warranted to evaluate the prospective relationship of adipocytokines to the development and progression of CKD.

  12. Maternal blood metal levels and fetal markers of metabolic function

    Exposure to metals commonly found in the environment has been hypothesized to be associated with measures of fetal growth but the epidemiological literature is limited. The Maternal–Infant Research on Environmental Chemicals (MIREC) study recruited 2001 women during the first trimester of pregnancy from 10 Canadian sites. Our objective was to assess the association between prenatal exposure to metals (lead, arsenic, cadmium, and mercury) and fetal metabolic function. Average maternal metal concentrations in 1st and 3rd trimester blood samples were used to represent prenatal metals exposure. Leptin and adiponectin were measured in 1363 cord blood samples and served as markers of fetal metabolic function. Polytomous logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between metals and both high (≥90%) and low (≤10%) fetal adiponectin and leptin levels. Leptin levels were significantly higher in female infants compared to males. A significant relationship between maternal blood cadmium and odds of high leptin was observed among males but not females in adjusted models. When adjusting for birth weight z-score, lead was associated with an increased odd of high leptin. No other significant associations were found at the top or bottom 10th percentile in either leptin or adiponectin models. This study supports the proposition that maternal levels of cadmium influence cord blood adipokine levels in a sex-dependent manner. Further investigation is required to confirm these findings and to determine how such findings at birth will translate into childhood anthropometric measures. - Highlights: • We determined relationships between maternal metal levels and cord blood adipokines. • Cord blood leptin levels were higher among female than male infants. • Maternal cadmium was associated with elevated leptin in male, not female infants. • No significant associations were observed between metals and

  13. Hypoxia dysregulates the production of adiponectin and plasminogen activator inhibitor-1 independent of reactive oxygen species in adipocytes

    Low plasma levels of adiponectin (hypoadiponectinemia) and elevated circulating concentrations of plasminogen activator inhibitor (PAI)-1 are causally associated with obesity-related insulin resistance and cardiovascular disease. However, the mechanism that mediates the aberrant production of these two adipokines in obesity remains poorly understood. In this study, we investigated the effects of hypoxia and reactive oxygen species (ROS) on production of adiponectin and PAI-1 in 3T3-L1 adipocytes. Quantitative PCR and immunoassays showed that ambient hypoxia markedly suppressed adiponectin mRNA expression and its protein secretion, and increased PAI-1 production in mature adipocytes. Dimethyloxallyl glycine, a stabilizer of hypoxia-inducible factor 1α (HIF-1α), mimicked the hypoxia-mediated modulations of these two adipokines. Hypoxia caused a modest elevation of ROS in adipocytes. However, ablation of intracellular ROS by antioxidants failed to alleviate hypoxia-induced aberrant production of adiponectin and PAI-1. On the other hand, the antioxidants could reverse hydrogen peroxide (H2O2)-induced dysregulation of adiponectin and PAI-1 production. H2O2 treatment decreased the expression levels of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein (C/EBPα), but had no effect on HIF-1α, whereas hypoxia stabilized HIF-1α and decreased expression of C/EBPα, but not PPARγ. Taken together, these data suggest that hypoxia and ROS decrease adiponectin production and augment PAI-1 expression in adipocytes via distinct signaling pathways. These effects may contribute to hypoadiponectinemia and elevated PAI-1 levels in obesity, type 2 diabetes, and cardiovascular diseases

  14. Impaired response of mature adipocytes of diabetic mice to hypoxia

    Adipose tissue contains various cells such as infiltrated monocytes/macrophages, endothelial cells, preadipocytes, and adipocytes. Adipocytes have an endocrine function by secreting adipokines such as interleukin (IL)-6, tumor necrosis factor (TNF)-α, leptin, and adiponectin. Dysregulation of adipokines in adipose tissues leads to a chronic low-grade inflammation which could result in atherosclerosis, hypertension, and type 2 diabetes. A sustained inflammatory state, which is characterized by prolonged persistence of macrophages and neutrophils, is found in diabetic wounds. In addition, subcutaneous adipocytes are enormously increased in amount clinically in type 2 diabetes. However, the function of subcutaneous adipocytes, which play an important role in injured tissue subjected to hypoxia, has not been well characterized in vitro due to the difficulty of maintaining mature adipocytes in culture using conventional methods because of their buoyancy. In this study, we established a novel in vitro culture method of mature adipocytes by enclosing them in a hyaluronan (HA) based hydrogel to study their role in response to stress such as hypoxia. BrdU labeling and Ki67 immunostaining experiments showed that hydrogel enclosed mature adipocytes proliferate in vitro. Both mRNA and protein expression analyses for hypoxia regulated genes, such as vascular endothelial growth factor (VEGF) and heme oxygenase 1 (HO1), showed that mature adipocytes of wild type mice respond to hypoxia. In contrast, mature adipocytes of diabetic db/db and TallyHo mice did not efficiently respond to hypoxia. Our studies suggest that mature adipocytes are functionally active cells, and their abnormal function to hypoxia can be one of underlining mechanisms in type 2 diabetes.

  15. Initial responses of articular tissues in a murine high-fat diet-induced osteoarthritis model: pivotal role of the IPFP as a cytokine fountain.

    Munetaka Iwata

    Full Text Available Obesity and high body mass index are associated with a higher incidence of osteoarthritis (OA. The aim of this study is to investigate the involvement of the infrapatellar fat pad (IPFP in the sub-acute effect of a high fat diet (HFD on the development of knee-OA. C57BL/6J male mice were fed either a HFD or a normal diet beginning at seven weeks of age. Tissue sections were evaluated with immunohistological analysis. The IPFP was excised, and mRNA expression profiles were compared using real-time RT-PCR analysis. Osteoarthritic changes were initiated in the HFD group after eight weeks of the HFD. Increased synovial cell number and angiogenesis at the anterior edge of the tibial plateau were exhibited prior to osteophyte formation. Quantitative histological analysis indicated that osteophyte volume was significantly increased in the HFD group after eight weeks, along with an increase in the IPFP volume, the size of individual adipocytes and the number of vessels in the IPFP. Histomorphometrical analysis revealed osteophyte area was significantly associated with IPFP area, individual adipocyte area and vascular area. Real-time RT-PCR analysis demonstrated elevated mRNA expression of inflammatory cytokines, growth factor, and adipokines in the IPFP after eight weeks of the HFD. These findings are in parallel with increased expression of the CD68 macrophage marker after eight weeks of the HFD. Expression levels of the adipokines were significantly correlated with expression of TNF-α, VEGF and TGF-β. Immunohistological analysis revealed that the Nampt protein was highly expressed in the IPFP especially around the site of osteophyte formation. Apoptosis and proliferation of chondrocytes were both enhanced at the site of osteophyte formation, indicating higher cell turnover at this region. These observations suggest the IPFP plays a pivotal role in the formation of osteophytes and functions as a secretory organ in response to a HFD.

  16. Sex dimorphic actions of rosiglitazone in generalised peroxisome proliferator activated receptor-γ (PPAR-γ)-deficient mice

    Duan, S. Z.; Usher, M. G.; Foley, E. L.; Milstone, D. S.; Brosius, F. C.; Mortensen, R. M.

    2010-01-01

    Aims/hypothesis The aim of this study was to determine the dependency on peroxisome-proliferator-activated receptor-γ (PPAR-γ) of insulin sensitisation and glucose homeostasis by thiazolidinediones using a global Ppar-γ (also known as Pparg)-knockout mouse model. Methods Global Mox2-Cre-Ppar-γ-knockout (MORE-PGKO) mice were treated with rosiglitazone and analysed for insulin sensitivity and glucose metabolism. Metabolic and hormonal variables were determined. Adipose and other tissues were measured and analysed for gene expression. Results Rosiglitazone induced regrowth of fat in female but not male MORE-PGKO mice, and only in specific depots. Insulin sensitivity increased but, surprisingly, was not associated with the typical changes in adipokines, plasma NEFA or tissue triacylglycerol. However, increases in alternatively activated macrophage markers, which have been previously associated with metabolic improvement, were observed in the regrown fat. Rosiglitazone improved glucose homeostasis but not insulin sensitivity in male MORE-PGKO mice, with further increase of insulin associated with an apparent expansion of pancreatic islets. Conclusions/interpretation Stimulating fat growth by rosiglitazone is sufficient to improve insulin sensitivity in female mice with 95% PPAR-γ deficiency. This increase in insulin sensitivity is not likely to be due to changes typically seen in adipokines or lipids but may involve changes in macrophage polarisation that occur independent of PPAR-γ. In contrast, rosiglitazone improves glucose homeostasis in male mice with similar PPAR-γ deficiency by increasing insulin production independent of changes in adiposity. Further, the insulin-sensitising effect of rosiglitazone is dependent on PPAR-γ in this male lipodystrophic model. PMID:20401461

  17. Long-Lived αMUPA Mice Show Attenuation of Cardiac Aging and Leptin-Dependent Cardioprotection.

    Esther Levy

    Full Text Available αMUPA transgenic mice spontaneously consume less food compared with their wild type (WT ancestors due to endogenously increased levels of the satiety hormone leptin. αMUPA mice share many benefits with mice under caloric restriction (CR including an extended life span. To understand mechanisms linked to cardiac aging, we explored the response of αMUPA hearts to ischemic conditions at the age of 6, 18, or 24 months. Mice were subjected to myocardial infarction (MI in vivo and to ischemia/reperfusion ex vivo. Compared to WT mice, αMUPA showed functional and histological advantages under all experimental conditions. At 24 months, none of the WT mice survived the first ischemic day while αMUPA mice demonstrated 50% survival after 7 ischemic days. Leptin, an adipokine decreasing under CR, was consistently ~60% higher in αMUPA sera at baseline. Leptin levels gradually increased in both genotypes 24h post MI but were doubled in αMUPA. Pretreatment with leptin neutralizing antibodies or with inhibitors of leptin signaling (AG-490 and Wortmannin abrogated the αMUPA benefits. The antibodies also reduced phosphorylation of the leptin signaling components STAT3 and AKT specifically in the αMUPA myocardium. αMUPA mice did not show elevation in adiponectin, an adipokine previously implicated in CR-induced cardioprotection. WT mice treated for short-term CR exhibited cardioprotection similar to that of αMUPA, however, along with increased adiponectin at baseline. Collectively, the results demonstrate a life-long increased ischemic tolerance in αMUPA mice, indicating the attenuation of cardiac aging. αMUPA cardioprotection is mediated through endogenous leptin, suggesting a protective pathway distinct from that elicited under CR.

  18. Relationship between Body Mass Index, C-Peptide, and Delta-5-Desaturase Enzyme Activity Estimates in Adult Males

    Pickens, C. Austin; Matsuo, Karen H.; Fenton, Jenifer I.

    2016-01-01

    Obesity, in particular abdominal obesity, alters the composition of plasma and tissue fatty acids (FAs), which contributes to inflammation and insulin resistance. FA metabolism is modulated by desaturases and may affect adipokine and insulin secretion. Therefore, we examined relationships between adipokines, a marker of insulin production, and plasma FA desaturase enzyme activity estimates (EAEs) in obesity. Plasma phospholipid (PPL) FAs were isolated from 126 males (ages 48 to 65 years), derivatized, and analyzed using gas chromatography. Delta-6 desaturase (D6D) and delta-5 desaturase (D5D) EAEs were calculated as the ratio of PPL 20:3/18:2 and 20:4/20:3, respectively. In body mass index (BMI) and waist circumference (WC) adjusted polytomous logistic regression analyses, PPL FAs and FA desaturase EAEs were associated with C-peptide and adiponectin. Individuals with elevated D6D EAEs were less likely (OR 0.33) to have serum adiponectin concentrations > 5.37 μg/mL, compared with adiponectin concentrations ≤ 3.62 μg/mL. Individuals with increased D5D EAEs were less likely (OR 0.8) to have C-peptide concentrations ≥ 3.32 ng/mL, and > 1.80 and ≤ 3.29 ng/mL, compared with those with C-peptide ≤ 1.76 ng/mL. The proinflammatory cytokine tumor necrosis factor-α (TNF- α) was positively associated with C-peptide, but TNF- α was not associated with the D5D EAE. C-peptide and adiponectin concentrations are associated with specific PPL FAs and FA desaturase EAEs. The relationship between C-peptide concentrations and D5D EAEs remained significant after adjusting for BMI, WC, and TNF-α. Thus, future research should investigate whether D5D inhibition may occur through a C-peptide mediated pathway. PMID:27023786

  19. Independent Link Between Levels of Proprotein Convertase Subtilisin/Kexin Type 9 and FABP4 in a General Population Without Medication.

    Furuhashi, Masato; Omori, Akina; Matsumoto, Megumi; Kataoka, Yu; Tanaka, Marenao; Moniwa, Norihito; Ohnishi, Hirofumi; Yoshida, Hideaki; Saitoh, Shigeyuki; Shimamoto, Kazuaki; Miura, Tetsuji

    2016-07-15

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to and degrades the low-density lipoprotein (LDL) receptor, leading to hypercholesterolemia and cardiovascular risk. Fatty acid binding protein 4 (FABP4/adipocyte FABP/aP2) is secreted from adipocytes in association with lipolysis, and circulating FABP4 has been reported to act as an adipokine for the development of insulin resistance and atherosclerosis. Elevated serum FABP4 level is associated with obesity, insulin resistance, dyslipidemia, and atherosclerosis. In this study, we examined the association between circulating levels of FABP4 and PCSK9 in a general population. A total of 265 subjects (male/female: 98/167) who were not on medication were recruited from subjects of the Tanno-Sobetsu Study, and concentrations of FABP4 and PCSK9 were measured. The level of FABP4, but not that of PCSK9, showed a gender difference, being higher in women than in men. FABP4 level was independently associated with gender, adiposity, renal dysfunction, and levels of cholesterol and PCSK9. There was a significant and gender-different correlation between PCSK9 level and age: negatively in men (r = -0.250, p = 0.013) and positively in women (r = 0.183, p = 0.018). After adjustment of age, gender, and LDL cholesterol level, PCSK9 level was positively and independently correlated with FABP4 concentration. In conclusion, PCSK9 level is differentially regulated by gender during aging. Circulating FABP4 is independently associated with the PCSK9 level, suggesting that elevation of FABP4 level as an adipokine leads to dyslipidemia through increased PCSK9 level and subsequent degradation of the LDL receptor. PMID:27241838

  20. Circadian clock genes Per1 and Per2 regulate the response of metabolism-associated transcripts to sleep disruption.

    Jana Husse

    Full Text Available Human and animal studies demonstrate that short sleep or poor sleep quality, e.g. in night shift workers, promote the development of obesity and diabetes. Effects of sleep disruption on glucose homeostasis and liver physiology are well documented. However, changes in adipokine levels after sleep disruption suggest that adipocytes might be another important peripheral target of sleep. Circadian clocks regulate metabolic homeostasis and clock disruption can result in obesity and the metabolic syndrome. The finding that sleep and clock disruption have very similar metabolic effects prompted us to ask whether the circadian clock machinery may mediate the metabolic consequences of sleep disruption. To test this we analyzed energy homeostasis and adipocyte transcriptome regulation in a mouse model of shift work, in which we prevented mice from sleeping during the first six hours of their normal inactive phase for five consecutive days (timed sleep restriction--TSR. We compared the effects of TSR between wild-type and Per1/2 double mutant mice with the prediction that the absence of a circadian clock in Per1/2 mutants would result in a blunted metabolic response to TSR. In wild-types, TSR induces significant transcriptional reprogramming of white adipose tissue, suggestive of increased lipogenesis, together with increased secretion of the adipokine leptin and increased food intake, hallmarks of obesity and associated leptin resistance. Some of these changes persist for at least one week after the end of TSR, indicating that even short episodes of sleep disruption can induce prolonged physiological impairments. In contrast, Per1/2 deficient mice show blunted effects of TSR on food intake, leptin levels and adipose transcription. We conclude that the absence of a functional clock in Per1/2 double mutants protects these mice from TSR-induced metabolic reprogramming, suggesting a role of the circadian timing system in regulating the physiological effects

  1. [Markers of metabolic syndrome and peptides regulating metabolism in survivors of childhood acute lymphoblastic leukemia].

    Skoczeń, Szymon; Tomasik, Przemysław; Balwierz, Walentyna; Surmiak, Marcin; Sztefko, Krystyna; Galicka-Latała, Danuta

    2011-01-01

    Along with the growing epidemic of overweight the risk of atherosclerosis, cardiovascular disease morbidity and mortality are increasing markedly. Metabolic syndrome (MS) is a condition clustering together several risk factors of those complications such as visceral obesity, glucose intolerance, arterial hypertension and dislipidemia. The risk of obesity in acute lymphoblastic leukemia (ALL) survivors is higher than in general population. We aimed to assess (1) the relationships between chosen adipokines and neuropeptides, chemotherapy, CRT, and body fatness and (2) evaluate adipokines and neuropeptides concentrations as a new markers of MS in children. We conducted cross-sectional evaluation of 82 ALL survivors (median age: 13.2 years; range: 4,8-26,2; median time from treatment: 3.2 years), including fasting laboratory testing: peptides (leptin, GLP-1, orexin, PYY, apelin), total cholesterol and its fractions, triglycerides; anthropometric measurements (weight, height), systolic and diastolic blood pressure. We estimated percentiles of body mass index and percentiles of blood pressure. Between 82 survivors overweight and diastolic hypertension was diagnosed in 31% of patients (35% in CRT group) and 15% respectively. At least one abnormality in lipids concentrations was found in 43%. Girls were more affected than boys. Statistically significant increased in leptin and apelin concentrations and decreased in soluble leptin receptor concentrations in the overweight group were observed compared to the non overweight subjects. Significant increase in orexin levels in females who had received CRT compared to those who had not received CRT was found. CRT is the main risk factor of elevated of body mass among survivors of childhood leukemia. Dyslipidemia and hypertension, along with increased adiposity indicate higher risk of MS development. Girls are more affected than boys. Leptin, orexin and apelin seem to be good markers of increased adiposity especially after CRT

  2. Aspirin Breaks the Crosstalk between 3T3-L1 Adipocytes and 4T1 Breast Cancer Cells by Regulating Cytokine Production.

    Chia-Chien Hsieh

    Full Text Available Breast cancer is one of the most common cancers in women worldwide. The obesity process is normally accompanied by chronic, low-grade inflammation. Infiltration by inflammatory cytokines and immune cells provides a favorable microenvironment for tumor growth, migration, and metastasis. Epidemiological evidence has shown that aspirin is an effective agent against several types of cancer. The aim of this study is to investigate the anti-inflammatory and anti-cancer effects of aspirin on 3T3-L1 adipocytes, 4T1 murine breast cancer cells, and their crosstalk. The results showed that aspirin treatment inhibited differentiation and lipid accumulation by 3T3-L1 preadipocytes, and decreased the secretion of the inflammatory adipokine MCP-1 after stimulation with tumor necrosis factor (TNF-α or conditioned medium from RAW264.7 cells. In 4T1 cells, treatment with aspirin decreased cell viability and migration, possibly by suppressing MCP-1 and VEGF secretion. Subsequently, culture of 4T1 cells in 3T3-L1 adipocyte-conditioned medium (Ad-CM and co-culture of 3T3-L1 and 4T1 cells using a transwell plate were performed to clarify the relationship between these two cell lines. Aspirin exerted its inhibitory effects in the transwell co-culture system, as well as the conditioned-medium model. Aspirin treatment significantly inhibited the proliferation of 4T1 cells, and decreased the production of MCP-1 and PAI-1 in both the Ad-CM model and co-culture system. Aspirin inhibited inflammatory MCP-1 adipokine production by 3T3-L1 adipocytes and the cell growth and migration of 4T1 cells. It also broke the crosstalk between these two cell lines, possibly contributing to its chemopreventive properties in breast cancer. This is the first report that aspirin's chemopreventive activity supports the potential application in auxiliary therapy against obesity-related breast cancer development.

  3. Maternal blood metal levels and fetal markers of metabolic function

    Ashley-Martin, Jillian [Perinatal Epidemiology Research Unit, Dalhousie University, Halifax, Nova Scotia (Canada); Dodds, Linda, E-mail: l.dodds@dal.ca [Perinatal Epidemiology Research Unit, Dalhousie University, Halifax, Nova Scotia (Canada); Arbuckle, Tye E. [Health Canada, Ottawa (Canada); Ettinger, Adrienne S. [Yale University, New Haven, CT (United States); Shapiro, Gabriel D. [University of Montreal, Montreal, Quebec (Canada); CHU Sainte-Justine Research Centre, Montreal, Quebec (Canada); Fisher, Mandy [Health Canada, Ottawa (Canada); Taback, Shayne [University of Manitoba, Winnipeg, Manitoba (Canada); Bouchard, Maryse F. [University of Montreal, Montreal, Quebec (Canada); Monnier, Patricia [McGill University, Montreal, Quebec (Canada); Dallaire, Renee [Laval University, Quebec City, Quebec (Canada); Fraser, William D. [University of Montreal, Montreal, Quebec (Canada); CHU Sainte-Justine Research Centre, Montreal, Quebec (Canada)

    2015-01-15

    Exposure to metals commonly found in the environment has been hypothesized to be associated with measures of fetal growth but the epidemiological literature is limited. The Maternal–Infant Research on Environmental Chemicals (MIREC) study recruited 2001 women during the first trimester of pregnancy from 10 Canadian sites. Our objective was to assess the association between prenatal exposure to metals (lead, arsenic, cadmium, and mercury) and fetal metabolic function. Average maternal metal concentrations in 1st and 3rd trimester blood samples were used to represent prenatal metals exposure. Leptin and adiponectin were measured in 1363 cord blood samples and served as markers of fetal metabolic function. Polytomous logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between metals and both high (≥90%) and low (≤10%) fetal adiponectin and leptin levels. Leptin levels were significantly higher in female infants compared to males. A significant relationship between maternal blood cadmium and odds of high leptin was observed among males but not females in adjusted models. When adjusting for birth weight z-score, lead was associated with an increased odd of high leptin. No other significant associations were found at the top or bottom 10th percentile in either leptin or adiponectin models. This study supports the proposition that maternal levels of cadmium influence cord blood adipokine levels in a sex-dependent manner. Further investigation is required to confirm these findings and to determine how such findings at birth will translate into childhood anthropometric measures. - Highlights: • We determined relationships between maternal metal levels and cord blood adipokines. • Cord blood leptin levels were higher among female than male infants. • Maternal cadmium was associated with elevated leptin in male, not female infants. • No significant associations were observed between metals and

  4. Metabolic Syndrome, Type 2 Diabetes, and Cancer: Epidemiology and Potential Mechanisms.

    Ben-Shmuel, Sarit; Rostoker, Ran; Scheinman, Eyal J; LeRoith, Derek

    2016-01-01

    Obesity is associated with multiple metabolic disorders that drive cardiovascular disease, T2D and cancer. The doubling in the number of obese adults over the past 3 decades led to the recognition of obesity as a "disease". With over 42 million children obese or overweight, this epidemic is rapidly growing worldwide. Obesity and T2D are both associated together and independently with an increased risk for cancer and a worse prognosis. Accumulating evidence from epidemiological studies revealed potential factors that may explain the association between obesity-linked metabolic disorders and cancer risk. Studies based on the insulin resistance MKR mice, highlighted the roe of the insulin receptor and its downstream signaling proteins in mediating hyperinsulinemia's mitogenic effects. Hypercholesterolemia was also shown to promote the formation of larger tumors and enhancement in metastasis. Furthermore, the conversion of cholesterol into 27-Hydroxycholesterol was found to link high fat diet-induced hypercholesterolemia with cancer pathophysiology. Alteration in circulating adipokines and cytokines are commonly found in obesity and T2D. Adipokines are involved in tumor growth through multiple mechanisms including mTOR, VEGF and cyclins. In addition, adipose tissues are known to recruit and alter macrophage phenotype; these macrophages can promote cancer progression by secreting inflammatory cytokines such as TNF-α and IL-6. Better characterization on the above factors and their downstream effects is required in order to translate the current knowledge into the clinic, but more importantly is to understand which are the key factors that drive cancer in each patient. Until we reach this point, policies and activities toward healthy diets and physical activities remain the best medicine. PMID:25903410

  5. Effects of alpha-lipoic acid on chemerin secretion in 3T3-L1 and human adipocytes.

    Prieto-Hontoria, Pedro L; Pérez-Matute, Patricia; Fernández-Galilea, Marta; López-Yoldi, Miguel; Sinal, Christopher J; Martínez, J Alfredo; Moreno-Aliaga, María J

    2016-03-01

    Chemerin is a novel adipokine associated with obesity and insulin resistance. α-Lipoic acid (α-LA) has shown beneficial properties on diabetes and obesity. The aim of this study was to examine the effects of α-LA on chemerin production in adipocytes in absence or presence of TNF-α, insulin and AICAR. The potential signaling pathways involved in α-LA effects on chemerin were also analyzed. α-LA actions on chemerin were tested in differentiated 3T3-L1 adipocytes and in some cases in human subcutaneous and omental adipocytes. Chemerin mRNA levels were measured by RT-PCR and the amount of chemerin secreted to culture media was determined by ELISA. α-LA induced a concentration-dependent inhibition on both chemerin secretion and mRNA levels in 3T3-L1 adipocytes. The AMPK activator AICAR and the PI3K inhibitor LY294002 dramatically abrogated both chemerin secretion and gene expression, and further potentiated the inhibitory effect of α-LA on chemerin secretion. Insulin was able to partially reverse the inhibitory action of α-LA on chemerin secretion. α-LA also reduced basal chemerin secretion in both subcutaneous and omental adipocytes from overweight/obese subjects. Moreover, α-LA was able to abolish the stimulatory effects of the pro-inflammatory cytokine TNF-α on chemerin secretion. Our data demonstrated the ability of α-LA to inhibit chemerin production, an adipokine associated to obesity and metabolic syndrome, suggesting that the reduction of chemerin could contribute to the antiobesity/antidiabetic properties described for α-LA. PMID:26721419

  6. Gene expression profile of high-fat diet-fed C57BL/6J mice: in search of potential role of azelaic acid.

    Muthulakshmi, Shanmugam; Chakrabarti, Alok K; Mukherjee, Sanjay

    2015-03-01

    High-fat diet (HFD) elevates circulatory fatty acids and influences glucose and fat metabolism. Azelaic acid (AzA), a naturally occurring α,ω-dicarboxylic acid in wheat, rye, barley, oat seeds and sorghum, has been reported to exert antidiabetic effects in HFD-induced type 2 diabetes mellitus (T2DM) C57BL/6J mice. The present study was undertaken to identify the genes that are differentially modulated by treatment with AzA in HFD-fed mice. Mice were fed HFD for 10 weeks and subjected to intragastric administration of 80 mg/kg body weight (BW) of AzA daily along with HFD from 11 to 15 weeks. Lipid profile, adipokines and cytokines were examined in the plasma/liver of mice. Whole genome profiling was performed in the liver of mice using microarray and validated by qRT-PCR, Western blot and immunohistochemical analyses. HFD intake resulted in significantly elevated lipids (except high-density lipoproteins), resistin, tumour necrosis factor alpha and interleukin-6 with marked reduction in adiponectin. Administration of AzA to HFD-fed mice significantly restored the lipids, adipokines and cytokines to near normal. Transcript profiling revealed that HFD intake activated the genes involved in stress response, cell cycle regulation and apoptosis. Treatment with AzA caused increased expression of genes involved in reactive oxygen species (ROS) scavenging, receptor-mediated signalling, transcription, protein modification and insulin signal transduction. AzA activates insulin signal molecules leading to insulin sensitivity. The ability of AzA to modulate the expression of these genes supports the notion that AzA is a promising drug candidate for the treatment of insulin resistance associated with T2DM. PMID:25575741

  7. C1q/Tumor Necrosis Factor-Related Protein 9 Protects against Acute Myocardial Injury through an Adiponectin Receptor I-AMPK-Dependent Mechanism.

    Kambara, Takahiro; Shibata, Rei; Ohashi, Koji; Matsuo, Kazuhiro; Hiramatsu-Ito, Mizuho; Enomoto, Takashi; Yuasa, Daisuke; Ito, Masanori; Hayakawa, Satoko; Ogawa, Hayato; Aprahamian, Tamar; Walsh, Kenneth; Murohara, Toyoaki; Ouchi, Noriyuki

    2015-06-01

    Obesity is a risk factor for cardiovascular disease. C1q/tumor necrosis factor-related protein 9 (CTRP9) is an adipokine that is downregulated by obesity. We investigated the role of CTRP9 in cardiac injury with loss-of-function genetic manipulations and defined the receptor-mediated signaling pathway downstream of this adipokine. CTRP9-knockout (CTRP9-KO) mice at the age of 12 weeks were indistinguishable from wild-type (WT) mice under basal conditions. CTRP9-KO mice had exacerbated contractile left ventricle dysfunction following intraperitoneal injection of lipopolysaccharide (LPS) compared to WT mice. Administration of LPS to CTRP9-KO mice also resulted in increased expression of proinflammatory cytokines and oxidative stress markers in the heart compared to WT mice. Likewise, CTRP9-KO mice showed increased myocardial infarct size and elevated expression of inflammatory mediators in ischemic heart following ischemia and reperfusion compared to WT mice. Treatment of cardiac myocytes with CTRP9 protein led to suppression of LPS-induced expression of proinflammatory genes, which was reversed by blockade of AMPK or ablation of adiponectin receptor I (AdipoR1). Systemic delivery of CTRP9 attenuated LPS-induced cardiac dysfunction in WT mice but not in muscle-specific transgenic mice expressing dominant-negative mutant form of AMPK or in AdipoR1-knockout mice. CTRP9 protects against acute cardiac damage in response to pathological stimuli by suppressing inflammatory reactions through AdipoR1/AMPK-dependent mechanisms. PMID:25870106

  8. Relation of Absolute or Relative Adiposity to Insulin Resistance, Retinol Binding Protein-4, Leptin, and Adiponectin in Type 2 Diabetes

    You Lim Kim

    2012-12-01

    Full Text Available BackgroundCentral fat mass (CFM correlates with insulin resistance and increases the risk of type 2 diabetes and cardiovascular complications; however, peripheral fat mass (PFM is associated with insulin sensitivity. The aim of this study was to investigate the relation of absolute and relative regional adiposity to insulin resistance index and adipokines in type 2 diabetes.MethodsTotal of 83 overweighted-Korean women with type 2 diabetes were enrolled, and rate constants for plasma glucose disappearance (KITT and serum adipokines, such as retinol binding protein-4 (RBP4, leptin, and adiponectin, were measured. Using dual X-ray absorptiometry, trunk fat mass (in kilograms was defined as CFM, sum of fat mass on the lower extremities (in kilograms as PFM, and sum of CFM and PFM as total fat mass (TFM. PFM/TFM ratio, CFM/TFM ratio, and PFM/CFM ratio were defined as relative adiposity.ResultsMedian age was 55.9 years, mean body mass index 27.2 kg/m2, and mean HbA1c level 7.12±0.84%. KITT was positively associated with PMF/TFM ratio, PMF/CFM ratio, and negatively with CFM/TFM ratio, but was not associated with TFM, PFM, or CFM. RBP4 levels also had a significant relationship with PMF/TFM ratio and PMF/CFM ratio. Adiponectin, leptin, and apolipoprotein A levels were related to absolute adiposity, while only adiponectin to relative adiposity. In correlation analysis, KITT in type 2 diabetes was positively related with HbA1c, fasting glucose, RBP4, and free fatty acid.ConclusionThese results suggest that increased relative amount of peripheral fat mass may aggravate insulin resistance in type 2 diabetes.

  9. Bone and energy metabolism parameters in professional cyclists during the Giro d'Italia 3-weeks stage race.

    Giovanni Lombardi

    Full Text Available Cycling is a not weight-bearing activity and is known to induce bone resorption. Stage races are really strenuous endurance performances affecting the energy homeostasis. The recently highlighted link, in the co-regulation of bone and energy metabolism, demonstrates a central role for the equilibrium between carboxylated and undercarboxylated forms of osteocalcin. Aim of this study was to understand the acute physiological responses to a cycling stage race in terms of bone turnover and energy metabolism and the possible co-regulative mechanisms underlying their relationship. We studied nine professional cyclists engaged in 2011 Giro d'Italia stage race. Pre-analytical and analytical phases tightly followed academic and anti-doping authority's recommendations. Bone and energy metabolism markers (bone alkaline phosphatase, tartrate-resistant acid phosphatase 5b, total and undercarboxylated osteocalcin, leptin and adiponectin and related hormones (cortisol and testosterone were measured, by Sandwich Enzyme Immunoassays, at days -1 (pre-race, 12 and 22 during the race. The power output and the energy expenditure (mean and accumulated were derived and correlated with the biochemical indexes. During the race, bone metabolism showed that an unbalance in behalf of resorption, which is enhanced, occurred along with a relative increase in the concentration of the undercarboxylated form of osteocalcin that was indirectly related to the enhanced energy expenditure, through adipokines modifications, with leptin decrease (high energy consumption and adiponectin increase (optimization of energy expenditure. The exertion due to heavy effort induced a decrease of cortisol, while testosterone levels resulted unchanged. In conclusion, during a 3-weeks stage race, bone metabolism is pushed towards resorption. A possible relationship between the bone and the energy metabolisms is suggested by the relative correlations among absolute and relative concentrations

  10. Obesity, Diabetes and Survival in Maintenance Hemodialysis Patients

    Deger, Serpil M.; Ellis, Charles D.; Bian, Ahuia; Shintani, Ayumi; Ikizler, T. Alp; Hung, Adriana M.

    2016-01-01

    Increased body mass index (BMI) confers a survival advantage in maintenance hemodialysis (MHD) patients. Diabetic (DM) patients undergoing MHD have worse survival. There are limited studies examining the effect of obesity on the risk of death among MHD patients with diabetes. Ninety-eight MHD patients were studied for median follow-up time of 78 months. Patients were classified according to the presence of obesity (BMI ≥ 30 kg/m2) or DM. Primary outcome was all-cause mortality. Cox regression was used to evaluate the effect of obesity on time to death. Effect modification and mediation analysis were also performed. Mean age was 49 ± 13 years, 66% were male, 48% were obese and 34% were diabetic. Mortality rates (per 100 person years) were: 3.4 for non-diabetic obese, 8.6 for non-diabetic non-obese, 14.3 for diabetic non-obese and 18.1 for diabetic obese patients. Log-rank comparing diabetic obese versus non diabetic obese was significant (p=0.007). Diabetes was associated with an increased risk of mortality after adjustment for potential mediators. Effect modification of obesity in the mortality risk was different between patients with and without diabetes. With adjustment for adipokines, a greater effect modification by diabetes was observed whereas adjustment for inflammatory marker did not influence the effect modification. Diabetic obese MHD patients have increased mortality risk compared to non-diabetic obese. Obesity does not offer survival benefits in Diabetic obese MHD patients and potentially may have detrimental effects. Larger studies evaluating the effect of adipokines and obesity in outcomes in the diabetic MHD population need to be undertaken. PMID:24467439

  11. Globular adiponectin induces a pro-inflammatory response in human astrocytic cells

    Wan, Zhongxiao; Mah, Dorrian; Simtchouk, Svetlana [School of Health and Exercise Sciences, University of British Columbia Okanagan, Kelowna, BC (Canada); Klegeris, Andis [Department of Biology, University of British Columbia Okanagan, Kelowna, BC (Canada); Little, Jonathan P., E-mail: jonathan.little@ubc.ca [School of Health and Exercise Sciences, University of British Columbia Okanagan, Kelowna, BC (Canada)

    2014-03-28

    Highlights: • Adiponectin receptors are expressed in human astrocytes. • Globular adiponectin induces secretion of IL-6 and MCP-1 from cultured astrocytes. • Adiponectin may play a pro-inflammatory role in astrocytes. - Abstract: Neuroinflammation, mediated in part by activated brain astrocytes, plays a critical role in the development of neurodegenerative disorders, including Alzheimer’s disease (AD). Adiponectin is the most abundant adipokine secreted from adipose tissue and has been reported to exert both anti- and pro-inflammatory effects in peripheral tissues; however, the effects of adiponectin on astrocytes remain unknown. Shifts in peripheral concentrations of adipokines, including adiponectin, could contribute to the observed link between midlife adiposity and increased AD risk. The aim of the present study was to characterize the effects of globular adiponectin (gAd) on pro-inflammatory cytokine mRNA expression and secretion in human U373 MG astrocytic cells and to explore the potential involvement of nuclear factor (NF)-κB, p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK) and phosphatidylinositide 3-kinases (PI3 K) signaling pathways in these processes. We demonstrated expression of adiponectin receptor 1 (adipoR1) and adipoR2 in U373 MG cells and primary human astrocytes. gAd induced secretion of interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1, and gene expression of IL-6, MCP-1, IL-1β and IL-8 in U373 MG cells. Using specific inhibitors, we found that NF-κB, p38MAPK and ERK1/2 pathways are involved in gAd-induced induction of cytokines with ERK1/2 contributing the most. These findings provide evidence that gAd may induce a pro-inflammatory phenotype in human astrocytes.

  12. Impaired response of mature adipocytes of diabetic mice to hypoxia

    Hong, Seok Jong, E-mail: seok-hong@northwestern.edu; Jin, Da P.; Buck, Donald W.; Galiano, Robert D.; Mustoe, Thomas A., E-mail: tmustoe@nmh.org

    2011-10-01

    Adipose tissue contains various cells such as infiltrated monocytes/macrophages, endothelial cells, preadipocytes, and adipocytes. Adipocytes have an endocrine function by secreting adipokines such as interleukin (IL)-6, tumor necrosis factor (TNF)-{alpha}, leptin, and adiponectin. Dysregulation of adipokines in adipose tissues leads to a chronic low-grade inflammation which could result in atherosclerosis, hypertension, and type 2 diabetes. A sustained inflammatory state, which is characterized by prolonged persistence of macrophages and neutrophils, is found in diabetic wounds. In addition, subcutaneous adipocytes are enormously increased in amount clinically in type 2 diabetes. However, the function of subcutaneous adipocytes, which play an important role in injured tissue subjected to hypoxia, has not been well characterized in vitro due to the difficulty of maintaining mature adipocytes in culture using conventional methods because of their buoyancy. In this study, we established a novel in vitro culture method of mature adipocytes by enclosing them in a hyaluronan (HA) based hydrogel to study their role in response to stress such as hypoxia. BrdU labeling and Ki67 immunostaining experiments showed that hydrogel enclosed mature adipocytes proliferate in vitro. Both mRNA and protein expression analyses for hypoxia regulated genes, such as vascular endothelial growth factor (VEGF) and heme oxygenase 1 (HO1), showed that mature adipocytes of wild type mice respond to hypoxia. In contrast, mature adipocytes of diabetic db/db and TallyHo mice did not efficiently respond to hypoxia. Our studies suggest that mature adipocytes are functionally active cells, and their abnormal function to hypoxia can be one of underlining mechanisms in type 2 diabetes.

  13. Metabolic syndrome in rheumatoid arthritis: role of adiponectin (preliminary results

    Yulia Nikolaevna Gorbunova

    2013-01-01

    Full Text Available The clinical value of the disorders and diseases integrated within the metabolic syndrome (MS is in the combination of traditional risk factors for cardiovascular diseases (CVD, which significantly accelerates the development of cardiovascular events (CVEs. The detection rate for MS in patients with rheumatoid arthritis (RA is shown to be higher than in the controls regardless of the diagnostic criteria for MS. At present, there are confusing data on the role of adipokins in RA. Objective: to determine the rate of MS and its components in RA patients and the association of the level of adipokin (adiponectin with the components of MS in relation to the duration of RA. Subjects and methods: The investigation enrolled 69 RA patients divided into two groups: 1 34 patients with early-stage (<2-year RA and 2 35 patients with end-stage (>2-year RA. Results. MS occurred in 12 (17.4% of the 69 patients with RA. There was central (abdominal obesity in 37 (53.6% patients with RA, hypertension in 29 (42%, low high-density cholesterol levels in 20 (29%, hyperglycemia in 11 (15.9%, and hypertriglyceridemia in 10 (14.5%. According to the presence or absence of MS, the patients were divided into 2 groups: 1 12 patients with MS; 2 57 without MS. In the patients with RA and MS, the duration of the disease was shorter; DAS28 and CDAI were higher than in those without MS: 15.4 [7; 24] months versus 51.8 [6; 72] months; DAS28 was 5.8 [4.9; 6.7] scores versus 5.1 [4.5; 5.8] scores; CDAI: 34.8 [21.8; 41.4] scores versus 24.2 [18; 31] scores, respectively (p < 0.05 in all cases. The serum level of adiponectin was lower: 13.1 [5.7; 10.7] ng/ml versus 20.6 [6.9; 30.9] ng/ml in the patients with RA and MS as compared to those without MS; but there were no significant differences. In the patients with early-end RA, the rate of MS was twice higher than that in those with end-stage RA; however, the differences were statistically insignificant (p = 0.1. The components of MS

  14. Adipose tissue dysregulation and reduced insulin sensitivity in non-obese individuals with enlarged abdominal adipose cells

    Hammarstedt Ann

    2012-09-01

    Full Text Available 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 cause systemic insulin resistance in the absence of adipose tissue metabolic dysfunction. To determine if this holds true for humans, we studied the relationship between insulin resistance and markers of adipose tissue dysfunction in non-obese individuals. Method 32 non-obese first-degree relatives of Type 2 diabetic patients were recruited. Glucose tolerance was determined by an oral glucose tolerance test and insulin sensitivity was measured with the hyperinsulinaemic-euglycaemic clamp. Blood samples were collected and subcutaneous abdominal adipose tissue biopsies obtained for gene/protein expression and adipocyte cell size measurements. Results Our findings show that also in non-obese individuals low insulin sensitivity is associated with signs of adipose tissue metabolic dysfunction characterized by low expression of GLUT4, altered adipokine profile and enlarged adipocyte cell size. In this group, insulin sensitivity is positively correlated to GLUT4 mRNA (R = 0.49, p = 0.011 and protein (R = 0.51, p = 0.004 expression, as well as with circulating adiponectin levels (R = 0.46, 0 = 0.009. In addition, insulin sensitivity is inversely correlated to circulating RBP4 (R = −0.61, 0 = 0.003 and adipocyte cell size (R = −0.40, p = 0.022. Furthermore, these features are inter-correlated and also associated with other clinical features of the metabolic syndrome in the absence of obesity. No association could be found

  15. Proteinuria and its relation to diverse biomarkers and body mass index in chronic hemodialysis

    Trimarchi H

    2013-06-01

    Full Text Available Hernán Trimarchi,1 Alexis Muryan,2 María-Soledad Raña,1 Pedro Paggi,2 Fernando Lombi,1 Mariano Forrester,1 Vanesa Pomeranz,1 Alejandra Karl,1 Mirta Alonso,2 Pablo Young,3 Mariana Dicugno2 1Department of Nephrology, 2Department of Biochemistry, 3Department of Internal Medicine Services, Hospital Británico de Buenos Aires, Buenos Aires, Argentina Background: Certain adipokines exert direct effects on proteinuria, a cardiovascular risk factor ignored in hemodialysis. We measured different adipokines according to body mass index (BMI in relation to proteinuria. Methods: Patients numbered 57: group A (GA, BMI 30, n = 20. There were no statistical differences in age, sex, time on dialysis, cause of renal failure, diabetes, hypertension, C-reactive protein, or nutritional status. Measures were taken of 24-hour diuresis and proteinuria, ultrafiltration, albumin, pro-brain natriuretic peptide (Pro-BNP, insulin, adiponectin, leptin, and ghrelin. Results: Proteinuria was significantly higher in GC versus (vs GA (1.5 g/day, range 0.30–14 vs 0.72 g/day, range 0.1–2.7; P 0.05. In GA, elevated levels of Pro-BNP, adiponectin, and ghrelin were associated with lower degrees of proteinuria. Significant correlations were found between adiponectin and leptin (ρ = -0.54, P = 0.03, and adiponectin and Pro-BNP (ρ= 0.59, P = 0.02. Though not significant, there were more diabetics in GC (GA four, GB three, GC ten. As BMI increased in GB and GC, Pro-BNP, adiponectin, and ghrelin levels decreased significantly, while proteinuria, insulin, and homeostasis model assessment of insulin resistance increased. Leptin levels were significantly elevated in GC vs GA and GB. In GC, ghrelin correlated significantly with Pro-BNP (ρ= 0.51, P = 0.03, while leptin correlation with Pro-BNP was inverse and significant in GA (ρ = -0.74, P > 0.001 and inverse and nonsignificant in GB and GC. Conclusion: In patients with BMI < 25, higher adiponectin, ghrelin, and Pro-BNP levels

  16. Association Between Thyrotropin Levels and Insulin Sensitivity in Euthyroid Obese Adolescents

    Javed, Asma; Balagopal, P. Babu; Vella, Adrian; Fischer, Philip R.; Piccinini, Francesca; Dalla Man, Chiara; Cobelli, Claudio; Giesler, Paula D.; Laugen, Jeanette M.

    2015-01-01

    Background: Thyrotropin (TSH) levels display a positive association with body mass index (BMI), and the prevalence of isolated hyperthyrotropinemia is higher in obese adolescents compared to their normal weight controls. However, the metabolic significance of the higher TSH in obese adolescents is less clear. The objective of this study was to determine the relationship between TSH concentrations and insulin sensitivity, lipids, and adipokines in euthyroid, non-diabetic, obese adolescents. Methods: Thirty-six euthyroid, non-diabetic, obese adolescents between the ages of 12 and 18 years underwent a 75 g oral glucose tolerance test. Insulin sensitivity (Si) and pancreatic β-cell function as assessed by disposition index (DI) were measured using the oral glucose minimal model approach. Cholesterol (total, low-density lipoprotein [LDL-C], and high-density lipoprotein [HDL-C]), triglycerides (TG), interleukin-6 (IL-6), total and high molecular weight (HMW) adiponectin, and retinol binding protein-4 (RBP4) were also determined. Associations between measures of thyroid function and Si, DI, lipids, and adipokines were computed using Pearson's correlation coefficient and multiple regression analysis. Results: The mean age of the subjects was 14.3±1.88 years, and the mean BMI was 32.5±4.65 kg/m2; 97% were non-Hispanic white and 47% were male. The mean TSH was 2.7±1.2 mIU/L. Increasing serum TSH was correlated with decreasing Si (log Si) in the entire cohort (p=0.03), but this relationship persisted only in males (p=0.02). The correlation between TSH and Si in males remained significant after adjusting for BMI (p=0.02). There was no correlation between TSH and pancreatic β-cell function as assessed by DI (p=0.48). TSH correlated positively with LDL-C (p=0.04) and IL-6 (p=0.03), but these associations vanished or weakened after adjusting for BMI (LDL-C p-value=0.44; IL-6 p-value=0.07). Conclusions: This study suggests a sex-specific association between TSH and insulin

  17. The associations between serum adiponectin, leptin, C-reactive protein, insulin, and serum long-chain omega-3 fatty acids in Labrador Retrievers

    Streeter RM

    2015-04-01

    Full Text Available Renee M Streeter,1 Angela M Struble,1 Sabine Mann,2 Daryl V Nydam,2 John E Bauer,3 Marta G Castelhano,1 Rory J Todhunter,1 Bethany P Cummings,4 Joseph J Wakshlag11Department of Clinical Sciences, 2Department of Population Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA; 3Department of Clinical Sciences, Texas A&M University, College Station, TX, USA; 4Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USAAbstract: Obesity has been associated with an increased inflammatory response and insulin resistance due to adipose tissue–derived adipokines and increases in C-reactive protein (CRP. Dogs appear to be similar to other species with the exception of adiponectin, which might not be affected by obesity status. Serum long-chain polyunsaturated fatty acid concentrations have been positively and negatively associated with serum adipokines. The aim of the study was to examine the relationship between leptin, CRP, adiponectin, and insulin to body condition score (BCS and to the long-chain omega-3 fatty acids in serum lipoproteins, including alpha-linolenic acid, eicosapentaenoic acid (EPA, docosapentanenoic acid (DPA, and docosahexaenoic acid (DHA as a reflection of dietary omega-3 status in the Labrador Retriever. Seventy-seven Labrador Retrievers were evaluated for BCS, percent fasting serum lipoprotein fatty acid concentrations, as well as serum leptin, adiponectin, insulin, and CRP. A multivariable general linear regression model was constructed to examine the association between the dependent variables leptin, CRP, adiponectin, and insulin and the predictor variables of BCS, age, and sex, as well as concentrations of alpha-linolenic acid, EPA, DHA, and DPA. Adiponectin concentration was positively associated with age (P<0.0008, EPA (P=0.027 and negatively associated with DHA (P=0.008. Leptin concentration was positively associated with an increased DHA (P=0.009, BCS (P

  18. Frequency and significance of the novel single nucleotide missense polymorphism Val109Asp in the human gene encoding omentin in Caucasian patients with type 2 diabetes mellitus or chronic inflammatory bowel diseases

    Buechler Christa

    2007-02-01

    Full Text Available Background The omental adipose tissue is pathogenetically involved in both type 2 diabetes mellitus (T2D and chronic inflammatory bowel diseases (IBD such as Ulcerative colitis (UC and Crohn's Disease (CD. Thus, adipokines secreted from omental adipose tissue might play an important role in these diseases. Omentin represents a new adipokine expressed in and secreted by omental adipose tissue. Therefore, it was the aim to investigate the putative role of a newly described sequence missense variation in the human omentin gene. Methods The Val109Asp single nucleotide miss-sense polymorphism and the His86His polymorphism in exon-4 of the omentin gene were newly identified by random sequencing. Only the miss-sense polymorphism was investigated further. Genotyping was performed by restriction fragment length polymorphism (RFLP analysis of amplified DNA fragments. Three different cohorts of well-characterized individuals were included in the study. 114 patients suffering from T2D, 190 patients suffering from IBD (128 with CD and 62 with UC and 276 non-diabetic healthy controls without any history for IBD were analyzed. Results The following allelic frequencies were determined: controls: Val-allele: 0.26, Asp-allele: 0.74; T2D: Val-allele: 0.3, Asp-allele: 0.7; IBD: Val-allel: 0.31, Asp-allele: 0.69. UC and CD patients did not differ in regard to the allelic frequency. Similarly, controls, T2D patients and IBD patients did not show significant differences in genotype distribution among each other. Disease manifestation and pattern of infestation were not related to genotype subgroups, neither in CD nor in UC. Furthermore, there was no significant association between genotype subgroups and anthropometric or laboratory parameters in T2D patients. Conclusion Based on sequence comparisons and homology searches, the amino acid position 109 is conserved in the omentin gene of humans, mice and chimpanzee but is not completely conserved between other omentin

  19. Association between variants in the genes for leptin, leptin receptor, and proopiomelanocortin with chronic heart failure in the Czech population.

    Bienertová-Vasků, Julie Anna; Spinarová, Lenka; Bienert, Petr; Vasků, Anna

    2009-03-01

    Patients with chronic heart failure (CHF) express enhanced catabolic metabolism finally resulting in overall weight loss, whereas adipokines might play a crucial role in signaling among tissues. The aim of this study was to investigate the possible associations of defined variability in leptin (dbSNP ID rs7799039), proopiomelanocortin (dbSNP ID rs3754860 and dbSNP ID rs1009388), and leptin receptor gene (dbSNP rs1137101) with CHF and evaluate their potential as the CHF susceptibility genes. The case-control study comprised a total of 372 patients of Caucasian origin with chronic heart failure (New York Heart Association [NYHA] functional classes II-IV, ejection fraction (EF) <40%) and 407 healthy controls. They were genotyped for the leptin (LEP) -2548 G/A, leptin receptor (LEPR) Gln223Arg, and proopiomelanocortin (POMC) RsaI (5'-untranslated region) and C1032G variants (intron 1) using PCR-based methodology. No case-control differences in genotype as well as allele frequencies were observed between CHF patients and controls. We constructed POMC RsaI/C1032G haplotypes, having found no significant association with body mass index (BMI), left ventricle ejection fraction (LVEF), left ventricle hypertrophy (LVH) and diabetes mellitus (DM). Multivariate regression analyses revealed an approximately 2-fold risk for NYHA class IV associated with the LEPR Gln223Arg (P = 0.0000001, odds ratio [OR] = 2.10, 95% confidence interval [CI] = 1.56-2.84); it also displayed an independent prediction role for LVEF in heart failure cases of all etiologies (P = 0.002, OR = 4.05, 95% CI = 1.36-10.06). In subanalyses according to CHF etiology the LEPR Gln223Arg showed an independent prediction role for NYHA IV in IHD patients (P = 0.0001, OR = 2.50, 95% CI = 1.69-3.82) and both for NYHA IV(P = 0.007, OR = 2.04, 95% CI = 1.20-3.84) and LVEF (P = 0.004, OR = 11.87, 95% CI = 2.08-55.6) in DCMP patients. The role of the polymorphic variants in the genes encoding for adipokines as potential

  20. Endogenous and exogenous factors influencing the concentrations of adiponectin in body fluids and tissues in the bovine.

    Sauerwein, Helga; Häußler, Susanne

    2016-07-01

    Adiponectin, one of the messenger molecules secreted from adipose tissue that are collectively termed adipokines, has been demonstrated to play a central role in lipid and glucose metabolism in humans and laboratory rodents; it improves insulin sensitivity and exerts antidiabetic and antiinflammatory actions. Adiponectin is synthesized as a 28 kDa monomer but is not secreted as such; instead, it is glycosylated and undergoes multimerization to form different molecular weight multimers before secretion. Adiponectin is one of the most abundant adipokines (μg/mL range) in the circulation. The concentrations are negatively correlated with adipose depot size, in particular with visceral fat mass in humans. Adiponectin exerts its effects by activating a range of different signaling molecules via binding to 2 transmembrane receptors, adiponectin receptor 1 and adiponectin receptor 2. The adiponectin receptor 1 is expressed primarily in the skeletal muscle, whereas adiponectin receptor 2 is predominantly expressed in the liver. Many of the functions of adiponectin are relevant to growth, lactation, and health and are thus of interest in both beef and dairy production systems. Studies on the role of the adiponectin protein in cattle have been impeded by the lack of reliable assays for bovine adiponectin. Although there are species-specific bovine adiponectin assays commercially available, they suffer from a lack of scientific peer-review of validity. Quantitative data about the adiponectin protein in cattle available in the literature emerged only during the last 3 yr and were largely based on Western blotting using either antibodies against human adiponectin or partial peptides from the bovine sequence. Using native bovine high-molecular-weight adiponectin purified from serum, we were able to generate a polyclonal antiserum that can be used for Western blot but also in an ELISA system, which was recently validated. The objective of this review is to provide an overview

  1. Liuwei Dihuang, a traditional Chinese herbal formula, suppresses chronic inflammation and oxidative stress in obese rats

    Benjamin Perry; Junzeng Zhang; Tarek Saleh; Yanwen Wang

    2014-01-01

    OBJECTIVE:To investigate the anti-inlfammatory, anti-oxidative stress, and adipokine-ameliorating effects of Liuwei Dihuang (LWDH), a traditional Chinese herbal formula, in obese rats. METHODS:After 2 weeks of acclimation with free access to regular rodent chow and water, obese-prone-caesarean-derived (OP-CD) rats were fed a modified AIN-93G diet containing 60% energy from fat. Treatment was performed twice daily by gavage feeding with 500, 1 500, or 3 500 mg/kg body weight LWDH suspended in water (n=12 rats per group). Twelve obese-resistant-CD (OR-CD) rats were fed the atherogenic diet and gavaged with water, and served as the normal control. Blood biomarkers of inflammation, oxidative stress and adiponectin were measured post-sacriifce and used to determine the treatment effect of LWDH and assess the suitability of OR/OP-CD rats for studying these parameters. RESULTS:After 9 weeks of treatment, LWDH lowered serum C-reactive protein (CRP) and tumour necrosis factor-α (TNF-α) levels. Serum interleukin-6 (IL-6) levels showed a tendency towards reduction, but were not signiifcantly different from the OP-CD control. Liver superoxide dismutase (SOD) activity was increased in response to all three doses of LWDH, while the levels of reduced (GSH) and oxidized glutathione (GSSG) and thiobarbituric acid reactive substances (TBARS) were unchanged. Serum adiponectin levels were increased in response to oral administration of LWDH at the dose of either 500 or 1 500 mg/kg body weight. In addition, comparisons between OR-CD and OP-CD rats revealed differential, and for some biomarkers, conflicting characteristics of high-fat diet-fed OP-CD rats in reference to obese human subjects in terms of inlfammatory and oxidative stress biomarkers and circulating adiponectin levels. CONCLUSION: The results show, for the ifrst time, the anti-inlfammatory, anti-oxidative stress and adiponectin-ameliorating effects of LWDH in obese rats. The suitability of the OR/OP-CD rat model as a

  2. Fetuin-A induces cytokine expression and suppresses adiponectin production.

    Anita M Hennige

    Full Text Available BACKGROUND: The secreted liver protein fetuin-A (AHSG is up-regulated in hepatic steatosis and the metabolic syndrome. These states are strongly associated with low-grade inflammation and hypoadiponectinemia. We, therefore, hypothesized that fetuin-A may play a role in the regulation of cytokine expression, the modulation of adipose tissue expression and plasma concentration of the insulin-sensitizing and atheroprotective adipokine adiponectin. METHODOLOGY AND PRINCIPAL FINDINGS: Human monocytic THP1 cells and human in vitro differenttiated adipocytes as well as C57BL/6 mice were treated with fetuin-A. mRNA expression of the genes encoding inflammatory cytokines and the adipokine adiponectin (ADIPOQ was assessed by real-time RT-PCR. In 122 subjects, plasma levels of fetuin-A, adiponectin and, in a subgroup, the multimeric forms of adiponectin were determined. Fetuin-A treatment induced TNF and IL1B mRNA expression in THP1 cells (p<0.05. Treatment of mice with fetuin-A, analogously, resulted in a marked increase in adipose tissue Tnf mRNA as well as Il6 expression (27- and 174-fold, respectively. These effects were accompanied by a decrease in adipose tissue Adipoq mRNA expression and lower circulating adiponectin levels (p<0.05, both. Furthermore, fetuin-A repressed ADIPOQ mRNA expression of human in vitro differentiated adipocytes (p<0.02 and induced inflammatory cytokine expression. In humans in plasma, fetuin-A correlated positively with high-sensitivity C-reactive protein, a marker of subclinical inflammation (r = 0.26, p = 0.01, and negatively with total- (r = -0.28, p = 0.02 and, particularly, high molecular weight adiponectin (r = -0.36, p = 0.01. CONCLUSIONS AND SIGNIFICANCE: We provide novel evidence that the secreted liver protein fetuin-A induces low-grade inflammation and represses adiponectin production in animals and in humans. These data suggest an important role of fatty liver in the pathophysiology of insulin resistance and

  3. Combined Ethanol Extract of Grape Pomace and Omija Fruit Ameliorates Adipogenesis, Hepatic Steatosis, and Inflammation in Diet-Induced Obese Mice

    Su-Jung Cho

    2013-01-01

    Full Text Available The aim of this study was to evaluate the long-term effects of grape pomace ethanol extract (GPE with or without omija fruit ethanol extract (OFE on adiposity, hepatic steatosis, and inflammation in diet-induced obese mice. Male C57BL/6J mice were fed a high-fat diet (HFD as the control diet and HFD plus GPE (0.5%, w/w with or without OFE (0.05%, w/w as the experimental diet for 12 weeks. GPE alone did not significantly affect adipogenesis and hepatic steatosis. However, the supplementation of GPE + OFE significantly lowered body weight gain, white adipose tissue weight, adipocyte size, and plasma free fatty acid and adipokines (leptin, PAI-1, IL-6, and MCP-1 levels in HFD-fed mice compared to those of the control group. These beneficial effects of GPE + OFE were partly related to the decreased expression of lipogenic and inflammatory genes in white adipose tissue. GPE + OFE supplementation also significantly lowered liver weight and ameliorated fatty liver by inhibiting expression of hepatic genes involved in fatty acid and cholesterol syntheses as well as inflammation and by activating hepatic fatty acid oxidation. These findings suggest that the combined ethanol extract of grape pomace and omija fruit has the potential to improve adiposity and fatty liver in diet-induced obese mice.

  4. Calorie Restriction with a High-Fat Diet Effectively Attenuated Inflammatory Response and Oxidative Stress-Related Markers in Obese Tissues of the High Diet Fed Rats

    Seungae Park

    2012-01-01

    Full Text Available Obesity characterized by increased mass of adipose tissue leads to systemic inflammation. Calorie restriction (CR improves parameters associated with immune response and antioxidant defense. We hypothesized that CR with a high fat diet (HFCR regulates local and systemic inflammation and oxidative stress damage in a high fat diet induced obesity (HF group. We investigated effect of HFCR on inflammation and oxidative stress-related markers in liver and adipose tissues as well as adipokines in plasma. HFCR lowered liver triglyceride levels, total cholesterol levels, and the plasma leptin/adiponectin ratio to normal levels and improved glucose tolerance. HFCR also improved fatty liver and normalized adipocyte size and morphology. HFCR reduced lipid peroxidation and decreased the expression levels of inducible nitric oxide synthetase, cyclooxygenase-2, NF-E2-related factor, and heme oxygenase-1 in the liver. Moreover, HFCR suppressed the expression levels of C- reactive protein and manganese superoxide dismutase in the adipose tissue in the HF group. These results suggest that HFCR may have beneficial effects on inflammation and oxidative stress as well as lipid profiles in the HF diet induced obesity. Moreover, HFCR may be a good way to increase compliance in obese patients and to prevent obesity induced complications without changes in dietary pattern.

  5. Phlorizin Supplementation Attenuates Obesity, Inflammation, and Hyperglycemia in Diet-Induced Obese Mice Fed a High-Fat Diet

    Su-Kyung Shin

    2016-02-01

    Full Text Available Obesity, along with its related complications, is a serious health problem worldwide. Many studies reported the anti-diabetic effect of phlorizin, while little is known about its anti-obesity effect. We investigated the beneficial effects of phlorizin on obesity and its complications, including diabetes and inflammation in obese animal. Male C57BL/6J mice were divided into three groups and fed their respective experimental diets for 16 weeks: a normal diet (ND, 5% fat, w/w, high-fat diet (HFD, 20% fat, w/w, or HFD supplemented with phlorizin (PH, 0.02%, w/w. The findings revealed that the PH group had significantly decreased visceral and total white adipose tissue (WAT weights, and adipocyte size compared to the HFD. Plasma and hepatic lipids profiles also improved in the PH group. The decreased levels of hepatic lipids in PH were associated with decreased activities of enzymes involved in hepatic lipogenesis, cholesterol synthesis and esterification. The PH also suppressed plasma pro-inflammatory adipokines levels such as leptin, adipsin, tumor necrosis factor-α, monocyte chemoattractant protein-1, interferon-γ, and interleukin-6, and prevented HFD-induced collagen accumulation in the liver and WAT. Furthermore, the PH supplementation also decreased plasma glucose, insulin, glucagon, and homeostasis model assessment of insulin resistance levels. In conclusion, phlorizin is beneficial for preventing diet-induced obesity, hepatic steatosis, inflammation, and fibrosis, as well as insulin resistance.

  6. Impact of Doxorubicin Treatment on the Physiological Functions of White Adipose Tissue.

    Luana Amorim Biondo

    Full Text Available White adipose tissue (WAT plays a fundamental role in maintaining energy balance and important endocrine functions. The loss of WAT modifies adipokine secretion and disrupts homeostasis, potentially leading to severe metabolic effects and a reduced quality of life. Doxorubicin is a chemotherapeutic agent used clinically because of its good effectiveness against various types of cancer. However, doxorubicin has deleterious effects in many healthy tissues, including WAT, liver, and skeletal and cardiac muscles. Our objective was to investigate the effects of doxorubicin on white adipocytes through in vivo and in vitro experiments. Doxorubicin reduced the uptake of glucose by retroperitoneal adipocytes and 3T3-L1 cells via the inhibition of AMP-activated protein kinase Thr172 phosphorylation and glucose transporter 4 content. Doxorubicin also reduced the serum level of adiponectin and, to a greater extent, the expression of genes encoding lipogenic (Fas and Acc and adipogenic factors (Pparg, C/ebpa, and Srebp1c in retroperitoneal adipose tissue. In addition, doxorubicin inhibited both lipogenesis and lipolysis and reduced the hormone-sensitive lipase and adipose tissue triacylglycerol lipase protein levels. Therefore, our results demonstrate the impact of doxorubicin on WAT. These results are important to understand some side effects observed in patients receiving chemotherapy and should encourage new adjuvant treatments that aim to inhibit these side effects.

  7. Inflammation of the infrapatellar fat pad.

    Eymard, Florent; Chevalier, Xavier

    2016-07-01

    The infrapatellar fat pad (IFP) of Hoffa's fat pad is the main adipose structure within the knee joint. It is located between the joint capsule and the synovial membrane, which lines its posterior aspect. The IFP is composed chiefly of adipocytes and receives an abundant supply of blood vessels and nerves. Immune cells can infiltrate the IFP, which can become a major source of numerous proinflammatory mediators (cytokines and adipokines). The physiological role for the IFP remains unclear but may involve shock absorption and the protection of adjacent tissues. Hoffa's disease is characterized by inflammation, hypertrophy, and fibrosis of the pad in response to repetitive trauma. Anterior knee pain is the most common symptom. In advanced forms, metaplasia of the IFP may result in the development of a sometimes sizable osteochondroma. The IFP may also contribute to the pathophysiology of knee osteoarthritis, in particular via procatabolic and proinflammatory effects on its synovial lining. Finally, in patients with knee osteoarthritis, inflammation of the IFP may be a source of pain. PMID:27068617

  8. Association of Trabecular Bone Score with Inflammation and Adiposity in Patients with Psoriasis: Effect of Adalimumab Therapy

    Hernández, José L.; López-Mejías, Raquel; Blanco, Ricardo; Pina, Trinitario; Ruiz, Sheila; Sierra, Isabel; Ubilla, Begoña; Mijares, Verónica; González-López, Marcos A.; Armesto, Susana; Corrales, Alfonso; Pons, Enar; Fuentevilla, Patricia; González-Vela, Carmen; González-Gay, Miguel Á.

    2016-01-01

    Studies on trabecular bone score (TBS) in psoriasis are lacking. We aim to assess the association between TBS and inflammation, metabolic syndrome features, and serum adipokines in 29 nondiabetic patients with psoriasis without arthritis, before and after 6-month adalimumab therapy. For that purpose, adjusted partial correlations and stepwise multivariable linear regression analysis were performed. No correlation was found between TBS and disease severity. TBS was negatively associated with weight, BMI, waist perimeter, fat percentage, and systolic and diastolic blood pressure before and after adalimumab. After 6 months of therapy, a negative correlation between TBS and insulin resistance (p = 0.02) and leptin (p = 0.01) and a positive correlation with adiponectin were found (p = 0.01). The best set of predictors for TBS values at baseline were female sex (p = 0.015), age (p = 0.05), and BMI (p = 0.001). The best set of predictors for TBS following 6 months of biologic therapy were age (p = 0.001), BMI (p therapy. Moreover, serum adiponectin levels seem to be an independent variable related to TBS values, after adalimumab therapy. PMID:27293954

  9. CDK4 is an essential insulin effector in adipocytes

    Lagarrigue, Sylviane; Lopez-Mejia, Isabel C.; Denechaud, Pierre-Damien; Escoté, Xavier; Castillo-Armengol, Judit; Jimenez, Veronica; Chavey, Carine; Giralt, Albert; Lai, Qiuwen; Zhang, Lianjun; Martinez-Carreres, Laia; Delacuisine, Brigitte; Annicotte, Jean-Sébastien; Blanchet, Emilie; Huré, Sébastien; Abella, Anna; Tinahones, Francisco J.; Vendrell, Joan; Dubus, Pierre; Bosch, Fatima; Kahn, C. Ronald; Fajas, Lluis

    2015-01-01

    Insulin resistance is a fundamental pathogenic factor that characterizes various metabolic disorders, including obesity and type 2 diabetes. Adipose tissue contributes to the development of obesity-related insulin resistance through increased release of fatty acids, altered adipokine secretion, and/or macrophage infiltration and cytokine release. Here, we aimed to analyze the participation of the cyclin-dependent kinase 4 (CDK4) in adipose tissue biology. We determined that white adipose tissue (WAT) from CDK4-deficient mice exhibits impaired lipogenesis and increased lipolysis. Conversely, lipolysis was decreased and lipogenesis was increased in mice expressing a mutant hyperactive form of CDK4 (CDK4R24C). A global kinome analysis of CDK4-deficient mice following insulin stimulation revealed that insulin signaling is impaired in these animals. We determined that insulin activates the CCND3-CDK4 complex, which in turn phosphorylates insulin receptor substrate 2 (IRS2) at serine 388, thereby creating a positive feedback loop that maintains adipocyte insulin signaling. Furthermore, we found that CCND3 expression and IRS2 serine 388 phosphorylation are increased in human obese subjects. Together, our results demonstrate that CDK4 is a major regulator of insulin signaling in WAT. PMID:26657864

  10. Adiponectin Enhances Cold-Induced Browning of Subcutaneous Adipose Tissue via Promoting M2 Macrophage Proliferation.

    Hui, Xiaoyan; Gu, Ping; Zhang, Jialiang; Nie, Tao; Pan, Yong; Wu, Donghai; Feng, Tianshi; Zhong, Cheng; Wang, Yu; Lam, Karen S L; Xu, Aimin

    2015-08-01

    Adiponectin is an abundant adipokine with pleiotropic protective effects against a cluster of obesity-related cardiometabolic disorders. However, its role in adaptive thermogenesis has scarcely been explored. Here we showed that chronic cold exposure led to a markedly elevated production of adiponectin in adipocytes of subcutaneous white adipose tissue (scWAT), which in turn bound to M2 macrophages in the stromal vascular fraction. Chronic cold exposure-induced accumulation of M2 macrophages, activation of beige cells, and thermogenic program were markedly impaired in scWAT of adiponectin knockout (ADN KO) mice, whereas these impairments were reversed by replenishment with adiponectin. Mechanistically, adiponectin was recruited to the cell surface of M2 macrophages via its binding partner T-cadherin and promoted the cell proliferation by activation of Akt, consequently leading to beige cell activation. These findings uncover adiponectin as a key efferent signal for cold-induced adaptive thermogenesis by mediating the crosstalk between adipocytes and M2 macrophages in scWAT. PMID:26166748

  11. Relationship between chronic kidney disease and metabolic syndrome: current perspectives

    Nashar K

    2014-09-01

    Full Text Available Khaled Nashar,1 Brent M Egan2 1Division of Nephrology and Hypertension, Allegheny General Hospital, Pittsburgh, PA, USA; 2Care Coordination Institute and Greenville Health System, Greenville, SC, USA Abstract: Both metabolic syndrome (MetS and chronic kidney disease (CKD are increasing in incidence and lead to significant cardiovascular morbidity and mortality. The relationship between these two entities is complex. Individual components of the MetS are known risk factors for incident kidney disease, but it is not clear how the clustering of these components is linked to the development and progression of kidney disease. Cross-sectional studies show an association of the MetS and prevalent CKD; however, one cannot draw conclusions as to which came first – the MetS or the kidney disease. Observational studies suggest a relationship between MetS and incident CKD, but they also demonstrate the development of MetS in patients with established CKD. These observations suggest a bidirectional relationship. A better understanding of the relationship between components of the MetS and whether and how these components contribute to progression of CKD and incident cardiovascular disease could inform more effective prevention strategies. Keywords: obesity, insulin resistance, hypertension, oxdative stress, inflammation, adipokines 

  12. ERp46 binds to AdipoR1, but not AdipoR2, and modulates adiponectin signalling

    The pleiotropic effects of the insulin-sensitizing adipokine adiponectin are mediated, at least in part, by two seven-transmembrane domain receptors AdipoR1 and AdipoR2. Recent reports indicate a role for AdipoR-binding proteins, namely APPL1, RACK1 and CK2β, in proximal signal transduction events. Here we demonstrate that endoplasmic reticulum protein 46 (ERp46) interacts specifically with AdipoR1 and provide evidence that ERp46 modulates adiponectin signalling. Co-immunoprecipitation followed by mass spectrometry identified ERp46 as an AdipoR1-, but not AdipoR2-, interacting protein. Analysis of truncated constructs and GST-fusion proteins revealed the interaction was mediated by the cytoplasmic, N-terminal residues (1-70) of AdipoR1. Indirect immunofluorescence microscopy and subcellular fractionation studies demonstrated that ERp46 was present in the ER and the plasma membrane (PM). Transient knockdown of ERp46 increased the levels of AdipoR1, and AdipoR2, at the PM and this correlated with increased adiponectin-stimulated phosphorylation of AMPK. In contrast, adiponectin-stimulated phosphorylation of p38MAPK was reduced following ERp46 knockdown. Collectively these results establish ERp46 as the first AdipoR1-specific interacting protein and suggest a role for ERp46 in adiponectin receptor biology and adiponectin signalling.

  13. Hypolipemic effect of Garcinia cambogia in obese women.

    Vasques, Carlos A R; Schneider, Ricardo; Klein-Júnior, Luiz C; Falavigna, Andressa; Piazza, Ivone; Rossetto, Simone

    2014-06-01

    Garcinia cambogia seems to promote weight reduction and improvement on lipid profile by its major compound, hydroxycitric acid (HCA), blocking ATP-citratelyase, potentially inhibiting lipogenesis. Furthermore, it is suggested that its extract is able to change the adipokine levels. Thus, the aim of this study was to analyse the effect of G. cambogia on the lipid profile, endocrine, calorimetric and anthropometric parameters of obese women. The women (BMI > 25 kg/m(2) ; age 25-60 years), divided in treated (n = 30) and control (n = 13) groups, received 2.4 g (800 mg 3×/day) of garcinia extract (50% of HCA) or placebo during 60 days, respectively, as well as dietary control. Weight, BMI, waist-hip ratio and percentage of fat mass, resting metabolic rate, respiratory coefficient, triglycerides (TG), total cholesterol, HDL and LDL, leptin and insulin serum levels were evaluated. TG was significantly reduced in the treated group (p = 0.0002) and the post-treatment variation was different compared to the placebo group (p = 0.04). No significant response was observed on other variables of the lipid profile, or on the anthropometric and calorimetric parameters. Leptin and insulin levels did not change significantly after the treatment. The short-term treatment with G. cambogia demonstrated a hypotriglyceridemic effect, which does not appear to be related to changes in leptinemia. PMID:24133059

  14. Increased hypothalamic 5-HT2A receptor gene expression and effects of pharmacologic 5-HT2A receptor inactivation in obese Ay mice

    Serotonin (5-hydroxytryptamine; 5-HT) 2A receptors contribute to the effects of 5-HT on platelet aggregation and vascular smooth muscle cell proliferation, and are reportedly involved in decreases in plasma levels of adiponectin, an adipokine, in diabetic subjects. Here, we report that systemic administration of sarpogrelate, a 5-HT2A receptor antagonist, suppressed appetite and increased hypothalamic pro-opiomelanocortin and cocaine- and amphetamine-regulated transcript, corticotropin releasing hormone, 5-HT2C, and 5-HT1B receptor gene expression. Ay mice, which have ectopic expression of the agouti protein, significantly increased hypothalamic 5-HT2A receptor gene expression in association with obesity compared with wild-type mice matched for age. Systemic administration of sarpogrelate suppressed overfeeding, body weight gain, and hyperglycemia in obese Ay mice, whereas it did not increase plasma adiponectin levels. These results suggest that obesity increases hypothalamic 5-HT2A receptor gene expression, and pharmacologic inactivation of 5-HT2A receptors inhibits overfeeding and obesity in Ay mice, but did not increase plasma adiponectin levels

  15. Advances in Integrating Traditional and Omic Biomarkers When Analyzing the Effects of the Mediterranean Diet Intervention in Cardiovascular Prevention.

    Fitó, Montserrat; Melander, Olle; Martínez, José Alfredo; Toledo, Estefanía; Carpéné, Christian; Corella, Dolores

    2016-01-01

    Intervention with Mediterranean diet (MedDiet) has provided a high level of evidence in primary prevention of cardiovascular events. Besides enhancing protection from classical risk factors, an improvement has also been described in a number of non-classical ones. Benefits have been reported on biomarkers of oxidation, inflammation, cellular adhesion, adipokine production, and pro-thrombotic state. Although the benefits of the MedDiet have been attributed to its richness in antioxidants, the mechanisms by which it exercises its beneficial effects are not well known. It is thought that the integration of omics including genomics, transcriptomics, epigenomics, and metabolomics, into studies analyzing nutrition and cardiovascular diseases will provide new clues regarding these mechanisms. However, omics integration is still in its infancy. Currently, some single-omics analyses have provided valuable data, mostly in the field of genomics. Thus, several gene-diet interactions in determining both intermediate (plasma lipids, etc.) and final cardiovascular phenotypes (stroke, myocardial infarction, etc.) have been reported. However, few studies have analyzed changes in gene expression and, moreover very few have focused on epigenomic or metabolomic biomarkers related to the MedDiet. Nevertheless, these preliminary results can help to better understand the inter-individual differences in cardiovascular risk and dietary response for further applications in personalized nutrition. PMID:27598147

  16. Circumventricular organs: targets for integration of circulating fluid and energy balance signals?

    Mimee, Andrea; Smith, Pauline M; Ferguson, Alastair V

    2013-09-10

    The subfornical organ (SFO), as one of the sensory circumventricular organs (CVOs), is among the only central nervous system structures which interfaces directly with circulating substances that do not cross the blood brain barrier. Here we describe a growing literature showing that circulating indicators of cardiovascular (angiotensin II, osmolarity, calcium, sodium) and metabolic (adiponectin, amylin, glucose, ghrelin, leptin) statuses influence the excitability of single SFO neurons. Single cell electrophysiological studies from our laboratory have demonstrated excitatory effects of angiotensin II on individual SFO neurons, and changes in angiotensin II receptor expression in this CVO in hypertensive states emphasize the dynamic contribution of SFO neurons to the regulation of fluid balance. Furthermore, we have shown both depolarizing and hyperpolarizing effects of the adipokines adiponectin and leptin in SFO cells, and highlight that conditions of fasting in the case of adiponectin, and obesity in the case of leptin, alter the sensitivity of SFO neurons to these circulating factors. The results examined in this review provide evidence for a role of the SFO as a mediator and integrative structure in the maintenance of cardiovascular and metabolic functions. PMID:23458630

  17. ADIPONECTIN AND C-REACTIVE PROTEIN RELATIONSHIP IN PLASMA AND ADIPOSE TISSUE (STUDY AMONG HEALTHY OBESE EGYPTIAN FEMALES)

    The adipokine, adiponectin inhibits vascular inflammation and acts as an endogenous modulator of obesity - linked diseases. High - sensitive C-reactive protein (hs-CRP) is recently debated as a risk factor and mediator for atherosclerosis. The present study investigated the association between adiponectin and hs-CRP in plasma and adipose tissue, and their relation to body composition and insulin sensitivity in a cohort of normal (30 subjects), obese (30 subjects) and morbidly - obese females (10 subjects). Messenger RNA (mRNA) expression of CRP and adiponectin in human adipose tissue were measured using real-time polymerase chain reaction. Plasma adiponectin and insulin were measured using radioimmunoassay methods, while, plasma hs-CRP was measured using ultrasensitive latex method.Results showed that adiponectin was negatively correlated with weight, BMI and insulin sensitivity index, and positively correlated with HDLc. The plasma hs-CRP levels were negatively correlated with plasma adiponectin. The plasma adiponectin levels being significantly lower and plasma hs-CRP being significantly higher in obese than normal females. Real- Time PCR analysis revealed the expression of CRP m-RNA in human adipose tissue and this was inversely correlated to adiponectin m RNA. These results suggest that elevation of CRP and reduction of adiponectin could emerge as mediators of atherogenesis and insulin resistance

  18. Beneficial role of vitamin K supplementation on insulin sensitivity, glucose metabolism, and the reduced risk of type 2 diabetes: A review.

    Manna, Prasenjit; Kalita, Jatin

    2016-01-01

    Micronutrients are gaining acceptance as an important nutritional therapy for the prevention and/or management of diabetes and its associated health risks. Although a very small quantity of micronutrients are required for specific functions in our bodies, moderate deficiencies can lead to serious health issues. Impaired insulin sensitivity and glucose intolerance play a major role in the development of diabetic pathophysiology. Vitamin K is well known for its function in blood coagulation. Moreover, several human studies reported the beneficial role of vitamin K supplementation in improving insulin sensitivity and glucose tolerance, preventing insulin resistance, and reducing the risk of type 2 diabetes (T2 D). Both animal and human studies have suggested that vitamin K-dependent protein (osteocalcin [OC]), regulation of adipokine levels, antiinflammatory properties, and lipid-lowering effects may mediate the beneficial function of vitamin K in insulin sensitivity and glucose tolerance. This review for the first time provides an overview of the currently available preclinical and clinical evidences on the effect of vitamin K supplementation in the management of insulin sensitivity and glucose tolerance. The outcome of this review will increase understanding for the development of a novel adjuvant therapy to achieve better control of glycemia and improve the lives of diabetic patients. PMID:27133809

  19. Relationship between adiponectin, obesity and insulin resistance

    Guilherme Ardenghi Balsan

    2015-02-01

    Full Text Available Objectives: the conditions of obesity and overweight pose a major risk for a number of comorbidities, including clinical syndromes resulting from atherosclerotic disease. Recent studies strongly indicate that adipose tissue is an active endocrine organ that secretes bioactive factors such as adipokines. Adiponectin appears to have a regulatory role in the mechanism of insulin resistance and in the development of atherosclerosis. This systematic review aims to evaluate the anti-atherogenic effects of adiponectin and its properties to improve and mimic metabolic and vascular actions of insulin and its influence on endothelial function. Methods: a qualitative, exploratory and literature review was performed in the PubMed, Portal Capes and Scielo databases using as key-words "adiponectin", "obesity", "insulin resistance", "anti-inflammatory", "therapeutic strategies" and "future prospects". Results: evidence suggests that adiponectin has anti-atherogenic properties with anti-inflammatory effects on the vascular wall. Moreover, it modifies the vascular intracellular signaling and has indirect antioxidant effects on the human myocardium. On the other hand, there are studies suggesting that increased levels of adiponectin are paradoxically associated with a worse prognosis in heart failure syndrome, although the mechanisms are not clear. Conclusion: it is not clear whether adiponectin levels have any clinical significance for risk stratification in cardiovascular disease or if they simply reflect the activation of complex underlying mechanisms. Changes in lifestyle and some drug treatments for hypertension and coronary heart disease have shown significant effect to increase adiponectin levels, and simultaneously decrease in insulin resistance and endothelial dysfunction.

  20. Chronic Kidney Disease, Obesity, and Hypertension: The Role of Leptin and Adiponectin

    M. Tesauro

    2012-01-01

    Full Text Available Chronic kidney disease is a major public health problem and characterized by a progressive loss in renal function over a period of months or years as defined by structural or functional abnormalities of the kidney. Several elements contribute to determine a progression of the kidney injury, inducing a worsening of renal damage and accelerating the decline of renal function: obesity and hypertension are two known factors of kidney progression. Remarkable improvements have been recently achieved in the study of the endocrine features of the adipose tissue and have been able to produce hormone-like peptides named adipokines or adipocytokines. Among these adipocytokines, which represent a link between obesity, hypertension, and chronic nephropathy, leptins and adiponectin appear to play an important role. Leptin not only is a prohypertension element (renal progression factor through the activation sympathetic nervous, but also is able to induce prosclerotic effects directly on the kidney. In contrast, a decline of adiponectin levels has been shown to be related to a picture of hypertension: an endothelial dysfunction has been described as the main pathogenic mechanism responsible for this phenomenon.

  1. Association of Increased Serum Leptin with Ameliorated Anemia and Malnutrition in Stage 5 Chronic Kidney Disease Patients after Parathyroidectomy.

    Jiang, Yao; Zhang, Jingjing; Yuan, Yanggang; Zha, Xiaoming; Xing, Changying; Shen, Chong; Shen, Zhixiang; Qin, Chao; Zeng, Ming; Yang, Guang; Mao, Huijuan; Zhang, Bo; Yu, Xiangbao; Sun, Bin; Ouyang, Chun; Xu, Xueqiang; Ge, Yifei; Wang, Jing; Zhang, Lina; Cheng, Chen; Yin, Caixia; Zhang, Jing; Chen, Huimin; Ma, Haoyang; Wang, Ningning

    2016-01-01

    Leptin is an adipokine that regulates various metabolism, but its association with secondary hyperparathyroidism (SHPT), a clinical manifestation of chronic kidney disease-mineral and bone disorder (CKD-MBD), remains obscure. Parathyroidectomy (PTX) is recommended for severe SHPT patients. Here, the associations between circulating leptin and clinical characteristics in CKD patients were investigated. Effects of PTX on leptin production were analyzed in vivo and in vitro. Controls and CKD patients had approximate serum leptin levels in that a larger proportion of CKD patients with body mass index (BMI) leptin was related to anemia, albumin, and bone metabolism disorders in CKD patients. Lower intact parathyroid hormone (PTH) was related with higher leptin in PTX patients group. Severe SHPT inhibited uremia-enhanced leptin production in 3T3-L1 adipocytes, which was attenuated after PTX. High levels of PTH were found to reduce Akt phosphorylation and leptin production in vitro but high levels of calcium and phosphorus were not. Successful PTX was found to improve anemia and malnutrition in severe SHPT patients, and this was correlated with increased circulating leptin levels via up-regulated Akt signaling in adipocytes. These findings indicated the therapeutic potential of leptin and related target pathway for improving survival and quality of life in CKD. PMID:27307101

  2. Rs9939609 Variant of the Fat Mass and Obesity-Associated Gene and Trunk Obesity in Adolescents

    Harald Mangge

    2011-01-01

    Full Text Available A common T/A polymorphism (rs9939609 in the fat mass and obesity associated (FTO gene was found associated with early-onset and severe obesity in both adults and children. However, recent observations failed to find associations of FTO with obesity. To investigate the genetic background of early obesity, we analysed the single nucleotide polymorphism (SNP rs9939609 of FTO in 371 styrian adolescents towards degree of obesity, subcutaneous adipose tissue (SAT-distribution determined by lipometry, early metabolic and preatherosclerotic symptoms. The percentage of AA homozygotes for the rs9939609 SNP of FTO was significantly increased in the obese adolescents. Compared to the TT wildtype, AA homozygotes showed significantly elevated values of SAT thickness at the trunk-located lipometer measure points neck and frontal chest, body weight, body mass index, waist, and hip circumference. No associations were found with carotis communis intima media thickness, systolic, diastolic blood pressure, ultrasensitive C-reactive protein (US-CRP, homocystein, total cholesterol, triglycerides, HDL cholesterol, oxidized LDL, fasted glucose, insulin, HOMA-index, liver transaminases, uric acid, and adipokines like resistin, leptin, and adiponectin. Taken together, to the best of our knowledge we are the first to report that the rs9939609 FTO SNP is associated with trunk weighted obesity as early as in adolescence.

  3. Rs9939609 variant of the fat mass and obesity-associated gene and trunk obesity in adolescents.

    Mangge, Harald; Renner, Wilfried; Almer, Gunter; Weghuber, Daniel; Möller, Reinhard; Horejsi, Renate

    2011-01-01

    A common T/A polymorphism (rs9939609) in the fat mass and obesity associated (FTO) gene was found associated with early-onset and severe obesity in both adults and children. However, recent observations failed to find associations of FTO with obesity. To investigate the genetic background of early obesity, we analysed the single nucleotide polymorphism (SNP) rs9939609 of FTO in 371 styrian adolescents towards degree of obesity, subcutaneous adipose tissue (SAT)-distribution determined by lipometry, early metabolic and preatherosclerotic symptoms. The percentage of AA homozygotes for the rs9939609 SNP of FTO was significantly increased in the obese adolescents. Compared to the TT wildtype, AA homozygotes showed significantly elevated values of SAT thickness at the trunk-located lipometer measure points neck and frontal chest, body weight, body mass index, waist, and hip circumference. No associations were found with carotis communis intima media thickness, systolic, diastolic blood pressure, ultrasensitive C-reactive protein (US-CRP), homocystein, total cholesterol, triglycerides, HDL cholesterol, oxidized LDL, fasted glucose, insulin, HOMA-index, liver transaminases, uric acid, and adipokines like resistin, leptin, and adiponectin. Taken together, to the best of our knowledge we are the first to report that the rs9939609 FTO SNP is associated with trunk weighted obesity as early as in adolescence. PMID:21318054

  4. Perivascular adipose tissue: An unique fat compartment relevant for the cardiometabolic syndrome.

    Siegel-Axel, D I; Häring, H U

    2016-03-01

    Type 2 diabetes and its major risk factor, obesity, are an increasing worldwide health problem. The exact mechanisms that link obesity with insulin resistance, type 2 diabetes, hypertension, cardiovascular complications and renal diseases, are still not clarified sufficiently. Adipose tissue in general is an active endocrine and paracrine organ that may influence the development of these disorders. Excessive body fat in general obesity may also cause quantitative and functional alterations of specific adipose tissue compartments. Beside visceral and subcutaneous fat depots which exert systemic effects by the release of adipokines, cytokines and hormones, there are also locally acting fat depots such as peri- and epicardial fat, perivascular fat, and renal sinus fat. Perivascular adipose tissue is in close contact with the adventitia of large, medium and small diameter arteries, possesses unique features differing from other fat depots and may act also independently of general obesity. An increasing number of studies are dealing with the "good" or "bad" characteristics and functions of normally sized and dramatically increased perivascular fat mass in lean or heavily obese individuals. This review describes the origin of perivascular adipose tissue, its different locations, the dual role of a physiological and unphysiological fat mass and its impact on diabetes, cardiovascular and renal diseases. Clinical studies, new imaging methods, as well as basic research in cell culture experiments in the last decade helped to elucidate the various aspects of the unique fat compartment. PMID:26995737

  5. Metabolic alterations following visceral fat removal and expansion: Beyond anatomic location.

    Foster, Michelle T; Pagliassotti, Michael J

    2012-10-01

    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. Pathological significance of visceral fat accumulation is also attributed to adipose depot/adipocyte-specific characteristics, specifically differences in structural, physiologic and metabolic characteristics compared with subcutaneous fat. Fat manipulations, such as removal or transplantation, have been utilized to identify location dependent or independent factors that play a role in metabolic dysregulation. Obesity-induced alterations in adipose tissue function/intrinsic characteristics, but not mass, appear to be responsible for obesity-induced metabolic dysregulation, thus "quality" is more important than "quantity." This review summarizes the implications of obesity-induced metabolic dysfunction as it relates to anatomic site and inherent adipocyte characteristics. PMID:23700533

  6. Placental restriction of fetal growth decreases IGF1 and leptin mRNA expression in the perirenal adipose tissue of late gestation fetal sheep.

    Duffield, Jaime A; Vuocolo, Tony; Tellam, Ross; Yuen, Bernard S; Muhlhausler, Beverly S; McMillen, I Caroline

    2008-05-01

    Placental restriction (PR) of fetal growth results in a low birth weight and an increased visceral fat mass in postnatal life. We investigated whether PR alters expression of genes that regulate adipogenesis [IGF1, IGF1 receptor (IGF1R), IGF2, IGF2R, proliferator-activated receptor-gamma, retinoid-X-receptor-alpha], adipocyte metabolism (lipoprotein lipase, G3PDH, GAPDH) and adipokine signaling (leptin, adiponectin) in visceral adipose tissue before birth. PR was induced by removal of the majority of endometrial caruncles in nonpregnant ewes before mating. Fetal blood samples were collected from 116 days gestation, and perirenal visceral adipose tissue (PAT) was collected from PR and control fetuses at 145 days. PAT gene expression was measured by quantitative RT-PCR. PR fetuses had a lower weight (PR 2.90 +/- 0.32 kg; control, 5.12 +/- 0.24 kg; P visceral adipose tissue, which may alter the functional development of the perirenal fat depot and contribute to altered leptin signaling in the growth-restricted newborn and the subsequent emergence of an increased visceral adiposity. PMID:18272661

  7. Metabolic effects of intra-abdominal fat in GHRKO mice.

    Masternak, Michal M; Bartke, Andrzej; Wang, Feiya; Spong, Adam; Gesing, Adam; Fang, Yimin; Salmon, Adam B; Hughes, Larry F; Liberati, Teresa; Boparai, Ravneet; Kopchick, John J; Westbrook, Reyhan

    2012-02-01

    Mice with targeted deletion of the growth hormone receptor (GHRKO mice) are growth hormone (GH) resistant, small, obese, hypoinsulinemic, highly insulin sensitive and remarkably long-lived. To elucidate the unexpected coexistence of adiposity with improved insulin sensitivity and extended longevity, we examined effects of surgical removal of visceral (epididymal and perinephric) fat on metabolic traits related to insulin signaling and longevity. Comparison of results obtained in GHRKO mice and in normal animals from the same strain revealed disparate effects of visceral fat removal (VFR) on insulin and glucose tolerance, adiponectin levels, accumulation of ectopic fat, phosphorylation of insulin signaling intermediates, body temperature, and respiratory quotient (RQ). Overall, VFR produced the expected improvements in insulin sensitivity and reduced body temperature and RQ in normal mice and had opposite effects in GHRKO mice. Some of the examined parameters were altered by VFR in opposite directions in GHRKO and normal mice, and others were affected in only one genotype or exhibited significant genotype × treatment interactions. Functional differences between visceral fat of GHRKO and normal mice were confirmed by measurements of adipokine secretion, lipolysis, and expression of genes related to fat metabolism. We conclude that in the absence of GH signaling, the secretory activity of visceral fat is profoundly altered and unexpectedly promotes enhanced insulin sensitivity. The apparent beneficial effects of visceral fat in GHRKO mice may also explain why reducing adiposity by calorie restriction fails to improve insulin signaling or further extend longevity in these animals. PMID:22040032

  8. Anti-Inflammatory Action of Keratinocyte-Derived Vaspin: Relevance for the Pathogenesis of Psoriasis.

    Saalbach, Anja; Tremel, Jenny; Herbert, Diana; Schwede, Katharina; Wandel, Elke; Schirmer, Christine; Anderegg, Ulf; Beck-Sickinger, Annette G; Heiker, John T; Schultz, Stephan; Magin, Thomas; Simon, Jan C

    2016-03-01

    Impaired cross talk between keratinocytes (KCs) and immune cells is believed to contribute to the pathogenesis of chronic inflammatory skin diseases, such as psoriasis. We have previously identified KCs as a rich source of the serpin protease inhibitor vaspin (serpinA12), originally described as an adipokine in adipose tissue. Herein, we studied whether dysregulated vaspin expression in KCs contributes to the pathogenesis of psoriasis. We found vaspin expression to be closely associated to epidermal differentiation, with low levels in proliferating KCs and high levels in differentiated cells. Consistently, in human psoriasis and in a mouse model of a psoriasis-like skin inflammation, epidermal vaspin expression was significantly down-regulated. Down-regulation of vaspin in KCs resulted in decreased expression of differentiation-associated genes and up-regulation of interferon-inducible and inflammation-associated psoriasis signature genes. Vaspin was also shown to modulate the communication between KCs and inflammatory cells under co-culture conditions. A decrease in vaspin expression in KCs stimulated the secretion of tumor necrosis factor-α, IL-1β, IL-6, IL-8, and monocyte chemoattractant protein-1 by co-cultured dendritic cells, macrophages, monocytes, and neutrophils. Consequently, the application of vaspin inhibited myeloid cell infiltration in a mouse model of a psoriasis-like skin inflammation. In conclusion, vaspin expression by maturing KCs modulates cutaneous immune responses and may be involved in the pathogenesis of psoriasis. PMID:26783881

  9. Resistin enhances the expansion of regulatory T cells through modulation of dendritic cells

    Han Seung

    2010-06-01

    Full Text Available Abstract Background Resistin, a member of adipokine family, is known to be involved in the modulation of immune responses including inflammatory activity. Interestingly, resistin is secreted by adipocytes in mice and rats whereas it is secreted by leukocytes in humans. However, the mechanism behind the effect of resistin on the expansion of regulatory T cells (Tregs remains poorly understood. Therefore, we examined regulatory effect of resistin on the induction and cellular modification of Tregs. Results Both protein and mRNA expression of FoxP3, a representative marker of Tregs, increased in a dose-dependent manner when peripheral blood mononuclear cells were treated with resistin. At the same time, resistin had no direct effect on the induction of FoxP3 in CD4+ T cells, suggesting an indirect role through other cells type(s. Since DCs are an important player in the differentiation of T cells, we focused on the role of DCs in the modulation of Tregs by resistin. Resistin suppressed the expression of interferon regulatory factor (IRF-1 and its target cytokines, IL-6, IL-23p19 and IL-12p40, in DCs. Furthermore, FoxP3 expression is increased in CD4+ T cells when co-cultured with DCs and concomitantly treated with resistin. Conclusion Our results suggest that resistin induces expansion of functional Tregs only when co-cultured with DCs.

  10. Sex differences in human adipose tissues – the biology of pear shape

    Karastergiou Kalypso

    2012-05-01

    Full Text Available Abstract Women have more body fat than men, but in contrast to the deleterious metabolic consequences of the central obesity typical of men, the pear-shaped body fat distribution of many women is associated with lower cardiometabolic risk. To understand the mechanisms regulating adiposity and adipose tissue distribution in men and women, significant research attention has focused on comparing adipocyte morphological and metabolic properties, as well as the capacity of preadipocytes derived from different depots for proliferation and differentiation. Available evidence points to possible intrinsic, cell autonomous differences in preadipocytes and adipocytes, as well as modulatory roles for sex steroids, the microenvironment within each adipose tissue, and developmental factors. Gluteal-femoral adipose tissues of women may simply provide a safe lipid reservoir for excess energy, or they may directly regulate systemic metabolism via release of metabolic products or adipokines. We provide a brief overview of the relationship of fat distribution to metabolic health in men and women, and then focus on mechanisms underlying sex differences in adipose tissue biology.

  11. Stressed Liver and Muscle Call on Adipocytes with FGF21

    YongdeLuo

    2013-12-01

    Full Text Available Fibroblast growth factor 21 (FGF21 is an emerging regulator of local and systemic metabolic homeostasis. Treatment with pharmacological levels of FGF21 alleviates obesity and associated metabolic diseases including diabetes. However, beyond antiobesogenic effects, the normal roles and underlying mechanisms of FGF21 as an endocrine hormone remain unclear. A recent wave of studies has revealed that FGF21 is a stress-induced endocrine factor in liver, muscle and other tissues that targets adipose tissue and adipocytes through FGFR1-betaKlotho (KLB complex. Adipose tissues and adipocytes within diverse tissues respond with metabolites and adipokine signals that affect functions of body tissues systemically and cells within local microenvironment adjacent to adipocytes. Normally this is to prevent impaired tissue-specific function and damage to diverse tissues secreting FGF21 in response to chronic stress. Therefore, diverse stressed tissues and the adipose tissue and adipocytes constitute a beneficial endocrine and paracrine communication network through FGF21. Here we attempt to unify these developments with beneficial pharmacological effects of FGF21 on obesity in respect to inter-organ stress communication and mechanisms.

  12. Association of adipocyte genes with ASP expression: a microarray analysis of subcutaneous and omental adipose tissue in morbidly obese subjects

    Lu HuiLing

    2010-01-01

    Full Text Available Abstract Background Prevalence of obesity is increasing to pandemic proportions. However, obese subjects differ in insulin resistance, adipokine production and co-morbidities. Based on fasting plasma analysis, obese subjects were grouped as Low Acylation Stimulating protein (ASP and Triglyceride (TG (LAT vs High ASP and TG (HAT. Subcutaneous (SC and omental (OM adipose tissues (n = 21 were analysed by microarray, and biologic pathways in lipid metabolism and inflammation were specifically examined. Methods LAT and HAT groups were matched in age, obesity, insulin, and glucose, and had similar expression of insulin-related genes (InsR, IRS-1. ASP related genes tended to be increased in the HAT group and were correlated (factor B, adipsin, complement C3, p Results HAT adipose tissue demonstrated increased lipid related genes for storage (CD36, DGAT1, DGAT2, SCD1, FASN, and LPL, lipolysis (HSL, CES1, perilipin, fatty acid binding proteins (FABP1, FABP3 and adipocyte differentiation markers (CEBPα, CEBPβ, PPARγ. By contrast, oxidation related genes were decreased (AMPK, UCP1, CPT1, FABP7. HAT subjects had increased anti-inflammatory genes TGFB1, TIMP1, TIMP3, and TIMP4 while proinflammatory PIG7 and MMP2 were also significantly increased; all genes, p Conclusion Taken together, the profile of C5L2 receptor, ASP gene expression and metabolic factors in adipose tissue from morbidly obese HAT subjects suggests a compensatory response associated with the increased plasma ASP and TG.

  13. Anorexia Nervosa and Its Associated Endocrinopathy in Young People.

    Misra, Madhusmita; Klibanski, Anne

    2016-01-01

    Anorexia nervosa (AN) is a condition of severe undernutrition associated with adaptive changes in many endocrine axes. These changes include hypogonadotropic hypogonadism, acquired growth hormone resistance with low insulin-like growth factor 1 (IGF-1) levels, hypercortisolemia, altered secretion of adipokines and appetite-regulating hormones, and low bone mineral density (BMD). Bone health is impaired subsequent to a low body mass index, decreased lean mass, and the endocrine changes described above. In addition to low areal BMD, AN is characterized by a decrease in volumetric BMD, changes in bone geometry, and reductions in strength estimates, leading to an increased risk for fracture. Weight restoration is essential for restoration of normal endocrine function; however, hypercortisolemia, high peptide YY levels, and ghrelin dynamics may not completely normalize. In some patients, hypogonadotropic hypogonadism persists despite weight restoration. Weight gain and menstrual recovery are critical for improving bone health in AN; however, residual deficits may persist. Physiologic estrogen replacement using transdermal, but not oral, estrogen increases bone accrual in adolescents with AN, while bisphosphonates improve BMD in adults. Recombinant human IGF-1 and teriparatide have been used in a few studies as bone anabolic therapies. More data are necessary to determine the optimal therapeutic strategies for low BMD in AN. PMID:26863308

  14. Chronic obstructive pulmonary disease and glucose metabolism: a bitter sweet symphony

    Mirrakhimov Aibek E

    2012-10-01

    Full Text Available Abstract Chronic obstructive pulmonary disease, metabolic syndrome and diabetes mellitus are common and underdiagnosed medical conditions. It was predicted that chronic obstructive pulmonary disease will be the third leading cause of death worldwide by 2020. The healthcare burden of this disease is even greater if we consider the significant impact of chronic obstructive pulmonary disease on the cardiovascular morbidity and mortality. Chronic obstructive pulmonary disease may be considered as a novel risk factor for new onset type 2 diabetes mellitus via multiple pathophysiological alterations such as: inflammation and oxidative stress, insulin resistance, weight gain and alterations in metabolism of adipokines. On the other hand, diabetes may act as an independent factor, negatively affecting pulmonary structure and function. Diabetes is associated with an increased risk of pulmonary infections, disease exacerbations and worsened COPD outcomes. On the top of that, coexistent OSA may increase the risk for type 2 DM in some individuals. The current scientific data necessitate a greater outlook on chronic obstructive pulmonary disease and chronic obstructive pulmonary disease may be viewed as a risk factor for the new onset type 2 diabetes mellitus. Conversely, both types of diabetes mellitus should be viewed as strong contributing factors for the development of obstructive lung disease. Such approach can potentially improve the outcomes and medical control for both conditions, and, thus, decrease the healthcare burden of these major medical problems.

  15. The Effect of Pericellular Oxygen Levels on Proteomic Profile and Lipogenesis in 3T3-L1 Differentiated Preadipocytes Cultured on Gas-Permeable Cultureware.

    Martin Weiszenstein

    Full Text Available Pericellular oxygen concentration represents an important factor in the regulation of cell functions, including cell differentiation, growth and mitochondrial energy metabolism. Hypoxia in adipose tissue has been associated with altered adipokine secretion profile and suggested as a possible factor in the development of type 2 diabetes. In vitro experiments provide an indispensable tool in metabolic research, however, physical laws of gas diffusion make prolonged exposure of adherent cells to desired pericellular O2 concentrations questionable. The aim of this study was to investigate the direct effect of various O2 levels (1%, 4% and 20% O2 on the proteomic profile and triglyceride accumulation in 3T3-L1 differentiated preadipocytes using gas-permeable cultureware. Following differentiation of cells under desired pericellular O2 concentrations, cell lysates were subjected to two-dimensional gel electrophoresis and protein visualization using Coomassie blue staining. Spots showing differential expression under hypoxia were analyzed using matrix-assisted laser desorption/ionization mass spectrometry. All identified proteins were subjected to pathway analysis. We observed that protein expression of 26 spots was reproducibly affected by 4% and 1% O2 (17 upregulated and 9 downregulated. Pathway analysis showed that mitochondrial energy metabolism and triglyceride synthesis were significantly upregulated by hypoxia. In conclusion, this study demonstrated the direct effects of pericellular O2 levels on adipocyte energy metabolism and triglyceride synthesis, probably mediated through the reversed tricarboxylic acid cycle flux.

  16. Visceral adiposity, insulin resistance and cancer risk

    Donohoe, Claire L

    2011-06-22

    Abstract Background There is a well established link between obesity and cancer. Emerging research is characterising this relationship further and delineating the specific role of excess visceral adiposity, as opposed to simple obesity, in promoting tumorigenesis. This review summarises the evidence from an epidemiological and pathophysiological perspective. Methods Relevant medical literature was identified from searches of PubMed and references cited in appropriate articles identified. Selection of articles was based on peer review, journal and relevance. Results Numerous epidemiological studies consistently identify increased risk of developing carcinoma in the obese. Adipose tissue, particularly viscerally located fat, is metabolically active and exerts systemic endocrine effects. Putative pathophysiological mechanisms linking obesity and carcinogenesis include the paracrine effects of adipose tissue and systemic alterations associated with obesity. Systemic changes in the obese state include chronic inflammation and alterations in adipokines and sex steroids. Insulin and the insulin-like growth factor axis influence tumorigenesis and also have a complex relationship with adiposity. There is evidence to suggest that insulin and the IGF axis play an important role in mediating obesity associated malignancy. Conclusions There is much evidence to support a role for obesity in cancer progression, however further research is warranted to determine the specific effect of excess visceral adipose tissue on tumorigenesis. Investigation of the potential mechanisms underpinning the association, including the role of insulin and the IGF axis, will improve understanding of the obesity and cancer link and may uncover targets for intervention.

  17. Ultrasound and Biochemical Diagnostic Tools for the Characterization of Vulnerable Carotid Atherosclerotic Plaque.

    Lechareas, Simeon; Yanni, Amalia E; Golemati, Spyretta; Chatziioannou, Achilles; Perrea, Despoina

    2016-01-01

    Stroke is a leading cause of morbidity and mortality worldwide, and characterization of vulnerable carotid plaque remains the spearhead of scientific research. Plaque destabilization, the key factor that induces the series of events leading to the clinical symptoms of carotid artery disease, is a consequence of complex mechanical, structural and biochemical processes. Novel imaging and molecular markers have been studied as predictors of disease outcome with promising results. The aim of this review is to present the current state of research on the association between ultrasound-derived echogenicity indices and blood parameters indicative of carotid plaque stability and activity. Bibliographic research revealed that there are limited available data. Among the biomarkers studied, those related to oxidative stress, lipoproteins and diabetes/insulin resistance are associated with echolucent plaques, whereas adipokines are associated with echogenic plaques. Biomarkers of inflammation and coagulation have not exhibited any conclusive relationship with plaque echogenicity, and it is not possible to come to any conclusion regarding calcification-, apoptosis- and neo-angiogenesis-related parameters because of the extremely limited bibliographic data. PMID:26493239

  18. Inflammation et immunité : implications dans l’obésité et le diabète de type 2

    Akhtar Khan Naim

    2006-09-01

    Full Text Available The evidences have been increasingly accumulated on the implication of inflammatory mediators like tumor necrosis factor-α (TNF-α and interleukin-6 (IL-6 in the pathological states related to insulin resistance like obesity, type 2 diabetes and atherosclerosis. There seems a link between insulin resistance and these pro-inflammatory agents, secreted by macrophages and adipocytes. Th (helper cells are differentiated into either Th1 or Th2 phenotypes. It is generally considered that Th1 phenotype is pro-inflammatory whereas Th2 phenotype exerts anti-inflammatory (protective effects. The upregulation of Th1 phenotype may aggravate these pathologies. One of the adipokines, i.e., adiponectin, and insulin act as anti-inflammatory agents. Insulin also favours the differentiation of Th cells into Th2 phenotype. TNF-α and IL-6 might counter balance the action of insulin by interfering with insulin receptor signalling in these pathological situations. The agonists of PPARα and PPARγ, and n-3 polyunsaturated fatty acids may exert an anti-inflammatory effect by shifting Th1/Th2 balance to Th2 phenotype. The factors, implicated in the secretion of inflammatory mediators are not well known, though the role of glucose-induced oxidative stress has been underlined. In this article, we shed light on the cross-talk between pro- and anti-inflammatory agents in these patho-physiological states related to insulin resistance.

  19. Adiponectin induces A20 expression in adipose tissue to confer metabolic benefit.

    Hand, Laura E; Usan, Paola; Cooper, Garth J S; Xu, Lance Y; Ammori, Basil; Cunningham, Peter S; Aghamohammadzadeh, Reza; Soran, Handrean; Greenstein, Adam; Loudon, Andrew S I; Bechtold, David A; Ray, David W

    2015-01-01

    Obesity is a major risk factor for metabolic disease, with white adipose tissue (WAT) inflammation emerging as a key underlying pathology. We detail that mice lacking Reverbα exhibit enhanced fat storage without the predicted increased WAT inflammation or loss of insulin sensitivity. In contrast to most animal models of obesity and obese human patients, Reverbα(-/-) mice exhibit elevated serum adiponectin levels and increased adiponectin secretion from WAT explants in vitro, highlighting a potential anti-inflammatory role of this adipokine in hypertrophic WAT. Indeed, adiponectin was found to suppress primary macrophage responses to lipopolysaccharide and proinflammatory fatty acids, and this suppression depended on glycogen synthase kinase 3β activation and induction of A20. Attenuated inflammatory responses in Reverbα(-/-) WAT depots were associated with tonic elevation of A20 protein and ex vivo shown to depend on A20. We also demonstrate that adipose A20 expression in obese human subjects exhibits a negative correlation with measures of insulin sensitivity. Furthermore, bariatric surgery-induced weight loss was accompanied by enhanced WAT A20 expression, which is positively correlated with increased serum adiponectin and improved metabolic and inflammatory markers, including C-reactive protein. The findings identify A20 as a mediator of adiponectin anti-inflammatory action in WAT and a potential target for mitigating obesity-related pathology. PMID:25190567

  20. Effects of adipocyte-secreted factors on decidualized endometrial cells: modulation of endometrial receptivity in vitro.

    Gamundi-Segura, Silvia; Serna, Jose; Oehninger, Sergio; Horcajadas, Jose A; Arbones-Mainar, Jose M

    2015-09-01

    Obesity is defined as an excessive accumulation of adipose tissue that may lead to health complications. Mounting evidence indicates that obesity has a negative impact on fertility. Yet, the link between adipose tissue biology and infertility remains unclear. We aimed to investigate the communication between the adipose tissue and the reproductive system and the importance of this cross talk for the development of a receptive endometrium. To that end, we generated an in vitro model with endometrial and adipocyte cell lines. Sexual hormones, progesterone and estradiol, were used to decidualize endometrial cells and sensitize adipocytes. Decidualization produced a simultaneous increase of adipokine receptors in endometrial cells paralleling changes in their receptivity status. Furthermore, sensitization of 3T3-L1 adipocytes increased mRNA levels of leptin and resistin and decreased the expression of adiponectin and chemerin levels. This was accompanied by increased isoproterenol-induced lipolysis and reduced insulin-stimulated glucose uptake. Lastly, conditioned culture medium of those sensitized adipocytes was used to feed endometrial cells. This treatment resulted in (i) upregulation of genes previously identified as positive regulators of endometrial receptivity, such as leukemia inhibitory factor and glutathione peroxidase 3, and (ii) downregulation of interleukin-15 and mucin1, both genes negatively related with endometrial receptivity. Our results indicate that the endocrine communication between adipose tissue and the reproductive system is bidirectional and stress the importance of the adipose tissue to modulate the reproductive fitness. PMID:25686566

  1. The Effect of Eight Weeks of Intense Aerobic Exercise on Chemerin and

    S Moradi

    2015-09-01

    Full Text Available Background & aim: Adipokines, including omentin and chemerin, are cytokines that are mainly secreted by adipose tissue. The aim of the present study was to investigate the effect of eight weeks of intense aerobic exercise on chemerin and omentin plasma levels in female Sprague Dawely rats. Methods: In the present experimental study, 35 two-month old Sprague Dawely rats were randomly divided into two groups: control (15 rats and training (20 rats. The training program included aerobic exercises which were conducted increasingly five times a week for 8 weeks. Blood samples were taken 24 h after the last training session. After eight weeks, an independent t-test and Pearson's correlation coefficient were used for data analysis. Results: The results showed that there was significant difference between omentin serum levels (p=0.012 and chemerin serum levels (p=0.003 in rats that had undergone exercises with high intensity program as compared to the control group. In addition, no significant correlation was observed between omentin and chemerin levels (p=0.08. Conclusion: According to the results of the present study as well as the importance of omentin and chemerin level changes, it seems that the training time must be more than 8 weeks and the exercise intensity should be tailored to the individual's fitness level. Otherwise, subjects are not able to perform the exercise program properly.

  2. Anthocyanin-Rich Juice Lowers Serum Cholesterol, Leptin, and Resistin and Improves Plasma Fatty Acid Composition in Fischer Rats.

    Daniela Graf

    Full Text Available Obesity and obesity-associated diseases e.g. cardiovascular diseases and type 2 diabetes are spread worldwide. Anthocyanins are supposed to have health-promoting properties, although convincing evidence is lacking. The aim of the present study was to investigate the effect of anthocyanins on several risk factors for obesity-associated diseases. Therefore, Fischer rats were fed anthocyanin-rich grape-bilberry juice or an anthocyanin-depleted control juice for 10 weeks. Intervention with anthocyanin-rich grape-bilberry juice reduced serum cholesterol and tended to decrease serum triglycerides. No effects were seen for serum non-esterified fatty acids, glucose, and insulin. Anthocyanin-rich grape-bilberry juice intervention reduced serum leptin and resistin, but showed no influence on serum adiponectin and secretion of adipokines from mesenteric adipose tissue. Furthermore, anthocyanin-rich grape-bilberry juice increased the proportion of polyunsaturated fatty acids and decreased the amount of saturated fatty acids in plasma. These results indicate that anthocyanins possess a preventive potential for obesity-associated diseases.

  3. The association of carotid intima media thickness with retinol binding protein-4 and total and high molecular weight adiponectin in type 2 diabetic patients

    Mansouri Masoumeh

    2012-08-01

    Full Text Available Abstract Background The aim of this study was to investigate whether carotid intima media thickness (CIMT is associated with serum level of retinol- binding protein-4 (RBP4 and total and high molecular weight (HMW adiponectin in type 2 diabetes (T2DM without clinical symptom of atherosclerotic disease. Method 101 type 2 diabetic patients (mean age, 53.63 ± 8.42 years and 42 body mass index (BMI matched control (mean age 50.1 ± 8.4 were recruited. The CIMT was assessed by using B-mode ultrasonography, while serum levels of RBP4 and total and HMW adiponectin were measured by using enzyme linked immunosorbant assay (ELISA. Linear regression analysis was performed with CIMT as dependent variable and adipokines and cardio metabolic risk factors as independent variables. Result The CIMT was higher in diabetic group compared to control group (p Age (B = 0.44 P Conclusion In conclusion, the present study showed that serum levels of RBP4 or total and HMW adiponectin were not potential predictors of CIMT in type 2 diabetic patients who exposed to this risk factor at least for nine years.

  4. Could gestational diabetes mellitus be managed through dietary bioactive compounds? Current knowledge and future perspectives.

    Santangelo, Carmela; Zicari, Alessandra; Mandosi, Elisabetta; Scazzocchio, Beatrice; Mari, Emanuela; Morano, Susanna; Masella, Roberta

    2016-04-14

    Gestational diabetes mellitus (GDM) is a serious problem growing worldwide that needs to be addressed with urgency in consideration of the resulting severe complications for both mother and fetus. Growing evidence indicates that a healthy diet rich in fruit, vegetables, nuts, extra-virgin olive oil and fish has beneficial effects in both the prevention and management of several human diseases and metabolic disorders. In this review, we discuss the latest data concerning the effects of dietary bioactive compounds such as polyphenols and PUFA on the molecular mechanisms regulating glucose homoeostasis. Several studies, mostly based on in vitro and animal models, indicate that dietary polyphenols, mainly flavonoids, positively modulate the insulin signalling pathway by attenuating hyperglycaemia and insulin resistance, reducing inflammatory adipokines, and modifying microRNA (miRNA) profiles. Very few data about the influence of dietary exposure on GDM outcomes are available, although this approach deserves careful consideration. Further investigation, which includes exploring the 'omics' world, is needed to better understand the complex interaction between dietary compounds and GDM. PMID:26879600

  5. Crosstalk between adiponectin and IGF-IR in breast cancer

    Loredana eMauro

    2015-07-01

    Full Text Available Obesity is a chronic and multifactorial disorder that is reaching epidemic proportions. It is characterized by an enlarged mass of adipose tissue caused by a combination of size increase of preexisting adipocytes (hypertrophy and de novo adipocyte differentiation (hyperplasia. Obesity is related to many metabolic disorders like hypertension, type 2 diabetes, metabolic syndrome, cardiovascular disease, and it is associated with an increased risk of cancer development in different tissues including breast. Adipose tissue is now regarded as not just a storage reservoir for excess energy, but rather as an endocrine organ, secreting a large number of bioactive molecules called adipokines. Among these, adiponectin represents the most abundant adipose tissue-excreted protein, which exhibits insulin-sensitizing, anti-inflammatory and antiatherogenic properties. The serum concentrations of adiponectin are inversely correlated with body mass index. Recently, low levels of plasma adiponectin have been associated with an increased risk for obesity-related cancers and development of more aggressive phenotype, concomitantly with alterations in the bioavailability of Insulin-like Growth Factor-I (IGF-I and IGF-I Receptor (IGF-IR signaling pathways. In this review we discuss the cross-talk between adiponectin/AdipoR1 and IGF-I/IGF-IR in breast cancer.

  6. ADIPOQ single nucleotide polymorphism: Association with adiponectin and lipoproteins levels restricted to men

    Luciane Viater Tureck

    2015-09-01

    Full Text Available Adiponectin is an adipokine inversely correlated with obesity, which has beneficial effect on insulin resistance and lipid metabolism. Considering its potential as a therapeutic target in the metabolic disorder contexts, and in order to add knowledge in the area, our study evaluated the ADIPOQ 276G > T polymorphism effect on adiponectin levels, and on lipoproteins of clinical interest in a population sample composed of 211 healthy individuals. Significant effects were observed only among men: the carriers of heterozygous genotype (GT showed high levels of adiponectin (p = 0.018, while the rare homozygous genotype (TT gave its carriers a negative phenotype, represented by higher levels of low density lipoprotein cholesterol (LDL-C (p = 0.004 and p = 0.005 and total cholesterol (TC (p = 0.010 and p = 0.005 compared to carriers of other genotypes (GG and GT respectively, the independent effect of SNP on LDL-C and TC levels was confirmed by multiple regression analysis (p = 0.008 and p = 0.044. We found no evidence of correlation between circulating adiponectin levels and biochemical markers, which suggests, therefore, an SNP 276G > T independent effect on adiponectin levels and on lipoprotein metabolism in men enrolled in this study.

  7. Multiple Hits, Including Oxidative Stress, as Pathogenesis and Treatment Target in Non-Alcoholic Steatohepatitis (NASH

    Daisuke Kawai

    2013-10-01

    Full Text Available Multiple parallel hits, including genetic differences, insulin resistance and intestinal microbiota, account for the progression of non-alcoholic steatohepatitis (NASH. Multiple hits induce adipokine secretion, endoplasmic reticulum (ER and oxidative stress at the cellular level that subsequently induce hepatic steatosis, inflammation and fibrosis, among which oxidative stress is considered a key contributor to progression from simple fatty liver to NASH. Although several clinical trials have shown that anti-oxidative therapy can effectively control hepatitis activities in the short term, the long-term effect remains obscure. Several trials of long-term anti-oxidant protocols aimed at treating cerebrovascular diseases or cancer development have failed to produce a benefit. This might be explained by the non-selective anti-oxidative properties of these drugs. Molecular hydrogen is an effective antioxidant that reduces only cytotoxic reactive oxygen species (ROS and several diseases associated with oxidative stress are sensitive to hydrogen. The progress of NASH to hepatocellular carcinoma can be controlled using hydrogen-rich water. Thus, targeting mitochondrial oxidative stress might be a good candidate for NASH treatment. Long term clinical intervention is needed to control this complex lifestyle-related disease.

  8. Molecular Mechanisms and New Treatment Strategies for Non-Alcoholic Steatohepatitis (NASH

    Akinobu Takaki

    2014-04-01

    Full Text Available Non-alcoholic steatohepatitis (NASH is a severe form of non-alcoholic fatty liver disease (NAFLD, in which most patients exhibit non-progressive, non-alcoholic fatty liver (NAFL attributable to simple steatosis. Multiple hits, including genetic differences, fat accumulation, insulin resistance and intestinal microbiota changes, account for the progression of NASH. NAFLD is strongly associated with obesity, which induces adipokine secretion, endoplasmic reticulum (ER and oxidative stress at the cellular level, which in turn induces hepatic steatosis, inflammation and fibrosis. Among these factors, gut microbiota are acknowledged as having an important role in initiating this multifactorial disease. Oxidative stress is considered to be a key contributor in the progression from NAFL to NASH. Macrophage infiltration is apparent in NAFL and NASH, while T-cell infiltration is apparent in NASH. Although several clinical trials have shown that antioxidative therapy with vitamin E can effectively control hepatitis pathology in the short term, the long-term effects remain obscure and have often proved to be ineffective in many other diseases. Several long-term antioxidant protocols have failed to reduce mortality. New treatment modalities that incorporate current understanding of NAFLD molecular pathogenesis must be considered.

  9. Role of Hepatic Progenitor Cells in Nonalcoholic Fatty Liver Disease Development: Cellular Cross-Talks and Molecular Networks

    Eugenio Gaudio

    2013-10-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD includes a spectrum of diseases ranging from simple fatty liver to nonalcoholic steatohepatitis, (NASH which may progress to cirrhosis and hepatocellular carcinoma. NASH has been independently correlated with atherosclerosis progression and cardiovascular risk. NASH development is characterized by intricate interactions between resident and recruited cells that enable liver damage progression. The increasing general agreement is that the cross-talk between hepatocytes, hepatic stellate cells (HSCs and macrophages in NAFLD has a main role in the derangement of lipid homeostasis, insulin resistance, danger recognition, immune tolerance response and fibrogenesis. Moreover, several evidences have suggested that hepatic stem/progenitor cell (HPCs activation is a component of the adaptive response of the liver to oxidative stress in NAFLD. HPC activation determines the appearance of a ductular reaction. In NASH, ductular reaction is independently correlated with progressive portal fibrosis raising the possibility of a periportal fibrogenetic pathway for fibrogenesis that is parallel to the deposition of subsinusoidal collagen in zone 3 by HSCs. Recent evidences indicated that adipokines, a class of circulating factors, have a key role in the cross-talk among HSCs, HPCs and liver macrophages. This review will be focused on cellular cross-talk and the relative molecular networks which are at the base of NASH progression and fibrosis.

  10. Association between Metabolic Syndrome and Cancer.

    Uzunlulu, Mehmet; Telci Caklili, Ozge; Oguz, Aytekin

    2016-01-01

    Growing data show the association of metabolic syndrome (MetS) or its components with cancer development and cancer-related mortality. It is suggested that in MetS and cancer association, insulin resistance and insulin-like growth factor 1 system play a key role, especially adipokines secreted from visceral adipocytes, free fatty acids and aromatase activity contribute to this process. It is also reported that MetS has a link with colorectal, breast, endometrial, pancreas, primary liver and, although controversial, prostate cancer. Although every component of MetS is known to have an association with cancer development, it is still debated whether the effects of these components are additive or synergistic. On the other hand, in the association between MetS and cancer, the role of antidiabetic and antihypertensive treatments including thiazolidinedione, insulin, angiotensin receptor blockers is also suggested. The primary approach in MetS-cancer relation is to prevent risk factors. Life style changes including weight loss and a healthy diet are known to decrease cancer risk in normal population. It is postulated that an insulin-sensitizing agent, metformin, has cancer-preventing effects on diabetic patients. This review discusses the relationship between MetS and cancer from different aspects and examines this relationship in some of the cancers suggested to be linked with MetS. PMID:26895247

  11. Metabolic signals in human puberty: effects of over and undernutrition.

    Martos-Moreno, G A; Chowen, J A; Argente, J

    2010-08-01

    Puberty in mammals is associated with important physical and psychological changes due to the increase in sex steroids and growth hormone (GH). Indeed, an increase in growth velocity and the attainment of sexual maturity for future reproductive function are the hallmark changes during this stage of life. Both growth and reproduction consume high levels of energy, requiring suitable energy stores to face these physiological functions. During the last two decades our knowledge concerning how peptides produced in the digestive tract (in charge of energy intake) and in adipose tissue (in charge of energy storage) provide information regarding metabolic status to the central nervous system (CNS) has increased dramatically. Moreover, these peptides have been shown to play an important role in modulating the gonadotropic axis with their absence or an imbalance in their secretion being able to disturb pubertal onset or progression. In this article we will review the current knowledge concerning the role played by leptin, the key adipokine in energy homeostasis, and ghrelin, the only orexigenic and growth-promoting peptide produced by the digestive tract, on sexual development. The normal evolutionary pattern of these peripherally produced metabolic signals throughout human puberty will be summarized. The effect of two opposite situations of chronic malnutrition, obesity and anorexia, on these signals and how they influence the course of puberty will also be discussed. Finally, we will briefly mention other peptides derived from the digestive tract (such as PYY) that may be involved in the regulatory link between energy homeostasis and sexual development. PMID:20026379

  12. Cardiovascular Disease in South Asian Migrants.

    Fernando, Eshan; Razak, Fahad; Lear, Scott A; Anand, Sonia S

    2015-09-01

    Cardiovascular disease (CVD) represents a significant cause of global mortality and morbidity. South Asians (SAs) have a particularly high burden of coronary artery disease (CAD). This review describes current literature regarding the prevalence, incidence, etiology, and prognosis of CVD in SA migrants to high-income nations. We conducted a narrative review of CVD in the SA diaspora through a search of MEDLINE and PubMed. We included observational studies, randomized clinical trials, nonsystematic reviews, systematic reviews, and meta-analyses written in English. Of 15,231 articles identified, 827 articles were screened and 124 formed the basis for review. SA migrants have a 1.5-2 times greater prevalence of CAD than age- and sex-adjusted Europids. Increased abdominal obesity and body fat and increased burden of type 2 diabetes mellitus and dyslipidemia appear to be primary drivers of the excess CAD burden in SAs. Sedentary lifestyle and changes in diet after immigration are important contributors to weight gain and adiposity. Early life factors, physical activity patterns and, in some cases, reduced adherence to medical therapy may contribute to increased CVD risks in SAs. Novel biomarkers like leptin and adipokines may show distinct patterns in SAs and provide insights into cardiometabolic risk determinants. In conclusion, SAs have distinct CVD risk predispositions, with a complex relationship to cultural, innate, and acquired factors. Although CVD risk factor management and treatment among SAs is improving, opportunities exist for further advances. PMID:26321436

  13. Effects of a vildagliptin/metformin combination on markers of atherosclerosis, thrombosis, and inflammation in diabetic patients with coronary artery disease

    Klempfner Robert

    2012-06-01

    Full Text Available Abstract Background Diabetic patients present with an accelerated atherosclerotic process and an increased risk for future cardiovascular events. In addition to the risk imposed by the disease itself, pharmacological treatment adds also a sizable risk, especially if certain classes of antidiabetic drugs are employed. Animal evidence indicates that dipeptidyl peptidase-4 inhibitors have anti-atherosclerotic effects, yet clinical data are scarcely available. Design We plan to prospectively investigate the effects of dipeptidyl peptidase-4 inhibition with vildagliptin on a number of atherothrombotic markers and adipokines in patients with proven atherosclerosis and type 2 diabetes. The selected markers are: interleukin-6, high sensitivity C reactive protein, interleukin 1-beta, total adiponectin levels, matrix metallo-proteinase 9 and platelet reactivity testing. Sixty eligible patients will be randomized in a 2:1 ratio to vildagliptin/metformin or metformin only treatment, for a 3-month duration treatment. Blood sampling for the proposed investigations will be taken at enrollment and immediately after completion of the study period. Discussion Demonstrating antiatherothrombotic properties of dipeptidyl peptidase-4 inhibitors on proven markers is of substantial clinical significance. Coupled with their proven good safety profile these findings could translate into a significant clinical benefit.

  14. Hypoxia, Oxidative Stress and Fat

    Nikolaus Netzer

    2015-06-01

    Full Text Available Metabolic disturbances in white adipose tissue in obese individuals contribute to the pathogenesis of insulin resistance and the development of type 2 diabetes mellitus. Impaired insulin action in adipocytes is associated with elevated lipolysis and increased free fatty acids leading to ectopic fat deposition in liver and skeletal muscle. Chronic adipose tissue hypoxia has been suggested to be part of pathomechanisms causing dysfunction of adipocytes. Hypoxia can provoke oxidative stress in human and animal adipocytes and reduce the production of beneficial adipokines, such as adiponectin. However, time-dose responses to hypoxia relativize the effects of hypoxic stress. Long-term exposure of fat cells to hypoxia can lead to the production of beneficial substances such as leptin. Knowledge of time-dose responses of hypoxia on white adipose tissue and the time course of generation of oxidative stress in adipocytes is still scarce. This paper reviews the potential links between adipose tissue hypoxia, oxidative stress, mitochondrial dysfunction, and low-grade inflammation caused by adipocyte hypertrophy, macrophage infiltration and production of inflammatory mediators.

  15. Obesity as a Major Risk Factor for Cancer

    Giovanni De Pergola

    2013-01-01

    Full Text Available The number of cancer cases caused by being obese is estimated to be 20% with the increased risk of malignancies being influenced by diet, weight change, and body fat distribution together with physical activity. Reports from the International Agency for Research into Cancer and the World Cancer Research Fund (WCRF have shown that the strongest evidence exists for an association of obesity with the following cancer types: endometrial, esophageal adenocarcinoma, colorectal, postmenopausal breast, prostate, and renal, whereas the less common malignancies are leukemia, non-Hodgkin’s lymphoma, multiple myeloma, malignant melanoma, and thyroid tumours. To be able to develop novel methods in prevention and treatment, we first must understand the underlying processes which link cancer to obesity. Four main systems have been identified as potential producers of cancer in obesity: insulin, insulin-like growth factor-I, sex steroids, and adipokines. Various novel candidate mechanisms have been proposed: chronic inflammation, oxidative stress, crosstalk between tumour cells and surrounding adipocytes, migrating adipose stromal cells, obesity-induced hypoxia, shared genetic susceptibility, and the functional defeat of immune function. Herein, we review the major pathogenic links between obesity and susceptibility to cancer.

  16. Cellular and molecular mechanisms in liver fibrogenesis.

    Novo, Erica; Cannito, Stefania; Paternostro, Claudia; Bocca, Claudia; Miglietta, Antonella; Parola, Maurizio

    2014-04-15

    Liver fibrogenesis is a dynamic and highly integrated molecular, tissue and cellular process, potentially reversible, that drives the progression of chronic liver diseases (CLD) towards liver cirrhosis and hepatic failure. Hepatic myofibroblasts (MFs), the pro-fibrogenic effector cells, originate mainly from activation of hepatic stellate cells and portal fibroblasts being characterized by a proliferative and survival attitude. MFs also contract in response to vasoactive agents, sustain angiogenesis and recruit and modulate activity of cells of innate or adaptive immunity. Chronic activation of wound healing and oxidative stress as well as derangement of epithelial-mesenchymal interactions are "major" pro-fibrogenic mechanisms, whatever the etiology. However, literature has outlined a complex network of pro-fibrogenic factors and mediators proposed to modulate CLD progression, with some of them being at present highly debated in the field, including the role of epithelial to mesenchymal transition and Hedgehog signaling pathways. Hypoxia and angiogenesis as well as inflammasomes are recently emerged as ubiquitous pro-inflammatory and pro-fibrogenic determinants whereas adipokines are mostly involved in CLD related to metabolic disturbances (metabolic syndrome and/or obesity and type 2 diabetes). Finally, autophagy as well as natural killer and natural killer-T cells have been recently proposed to significantly affect fibrogenic CLD progression. PMID:24631571

  17. The Deep Correlation between Energy Metabolism and Reproduction: A View on the Effects of Nutrition for Women Fertility.

    Fontana, Roberta; Della Torre, Sara

    2016-02-01

    In female mammals, mechanisms have been developed, throughout evolution, to integrate environmental, nutritional and hormonal cues in order to guarantee reproduction in favorable energetic conditions and to inhibit it in case of food scarcity. This metabolic strategy could be an advantage in nutritionally poor environments, but nowadays is affecting women's health. The unlimited availability of nutrients, in association with reduced energy expenditure, leads to alterations in many metabolic pathways and to impairments in the finely tuned inter-relation between energy metabolism and reproduction, thereby affecting female fertility. Many energetic states could influence female reproductive health being under- and over-weight, obesity and strenuous physical activity are all conditions that alter the profiles of specific hormones, such as insulin and adipokines, thus impairing women fertility. Furthermore, specific classes of nutrients might affect female fertility by acting on particular signaling pathways. Dietary fatty acids, carbohydrates, proteins and food-associated components (such as endocrine disruptors) have per se physiological activities and their unbalanced intake, both in quantitative and qualitative terms, might impair metabolic homeostasis and fertility in premenopausal women. Even though we are far from identifying a "fertility diet", lifestyle and dietary interventions might represent a promising and invaluable strategy to manage infertility in premenopausal women. PMID:26875986

  18. Emergence of sfrp5 as a pleiotropic adipocytokine and its association with wnt signaling.

    Jaikanth, C; Gurumurthy, P; Indhumathi, T; Cherian, K M

    2014-07-01

    The status of being a non communicable disease held by obesity is slowly fading . It is gaining a more contagious , literally communicable and deadly status . The downstream co--morbidities associated with it are endless. Hence the world is promoting the slogan "FAT TO FIT" . The view on the white adipose tissue as a fat storage organ is now being changed to an endocrine organ. The secreted hormones are called adipocytokines which act in an autocrine/paracine/endocrine fashion to exhibit its effects. Like any hormone it has positive as well as negative influence over the body. SFRP5 is a recently identified novel adipocytokine and it falls under the category of being a good adipokine proving a positive influence . Plasma SFRP5 levels are significantly decreased in patients with obesity, insulin resistance and diabetes that contribute to the major components of the metabolic syndrome and other disease conditions like atherosclerosis, autoimmune disorders etc. This review article focuses on the comprehensive effects of SFRP5 on all the major systems of the body and its association with the Wnt signalling pathways. PMID:25003224

  19. Peripheral Pathways in the Food-Intake Control towards the Adipose-Intestinal Missing Link

    Hugo Mendieta Zerón

    2013-01-01

    Full Text Available In the physiological state a multitude of gut hormones are released into the circulation at the same time depending on the quality and quantity of the diet. These hormones interact with receptors at various points in the “gut-brain axis” to affect short-term and intermediate-term feelings of hunger and satiety. The combined effects of macronutrients on the predominant gut hormone secretion are still poorly understood. Besides, adipokines form an important part of an “adipoinsular axis” dysregulation which may contribute to β-cell failure and hence to type 2 diabetes mellitus (T2DM. Even more, gestational diabetes mellitus (GDM and T2DM seem to share a genetic basis. In susceptible individuals, chronic exaggerated stimulation of the proximal gut with fat and carbohydrates may induce overproduction of an unknown factor that causes impairment of incretin production and/or action, leading to insufficient or untimely production of insulin, so that glucose intolerance develops. The bypass of the duodenum and jejunum might avoid a putative hormone overproduction in the proximal foregut in diabetic patients that might counteract the action of insulin, while the early presentation of undigested or incompletely digested food to the ileum may anticipate the production of hormones such as GLP1, further improving insulin action.

  20. An Evolutionary Perspective of Nutrition and Inflammation as Mechanisms of Cardiovascular Disease

    María Esther Rubio-Ruiz

    2015-01-01

    Full Text Available When cardiovascular diseases are viewed from an evolutionary biology perspective, a heightened thrifty and an inflammatory design could be their mechanisms. Human ancestors confronted a greater infectious load and were subjected to the selection for proinflammatory genes and a strong inflammatory function. Ancestors also faced starvation periods that pressed for a thrifty genotype which caused fat accumulation. The pressure of sustaining gluconeogenesis during periods of poor nourishment selected individuals with insulin resistance. Obesity induces a proinflammatory state due to the secretion of adipokines which underlie cardiometabolic diseases. Our actual lifestyle needs no more of such proinflammatory and thrifty genotypes and these ancestral genes might increase predisposition to diseases. Risk factors for atherosclerosis and diabetes are based on inflammatory and genetic foundations that can be accounted for by excess fat. Longevity has also increased in recent times and is related to a proinflammatory response with cardiovascular consequences. If human ancestral lifestyle could be recovered by increasing exercise and adapting a calorie restriction diet, obesity would decrease and the effects on chronic low-grade inflammation would be limited. Thereby, the rates of both atherosclerosis and diabetes could be reduced.