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Sample records for leptin resistance obesity

  1. Elevated hypothalamic TCPTP in obesity contributes to cellular leptin resistance

    Science.gov (United States)

    Loh, Kim; Fukushima, Atsushi; Zhang, Xinmei; Galic, Sandra; Briggs, Dana; Enriori, Pablo J.; Simonds, Stephanie; Wiede, Florian; Reichenbach, Alexander; Hauser, Christine; Sims, Natalie A.; Bence, Kendra K.; Zhang, Sheng; Zhang, Zhong-Yin; Kahn, Barbara B.; Neel, Benjamin G.; Andrews, Zane B.; Cowley, Michael A.; Tiganis, Tony

    2011-01-01

    SUMMARY In obesity, anorectic responses to leptin are diminished, giving rise to the concept of ‘leptin resistance’. Increased expression of protein tyrosine phosphatase 1B (PTP1B) has been associated with the attenuation of leptin signaling and development of cellular leptin resistance. Here we report that hypothalamic levels of the tyrosine phosphatase TCPTP are also elevated in obesity to attenuate the leptin response. We show that mice that lack TCPTP in neuronal cells have enhanced leptin sensitivity and are resistant to high fat diet-induced weight gain and the development of leptin resistance. Also, intracerebroventricular administration of a TCPTP inhibitor enhances leptin signaling and responses in mice. Moreover, the combined deletion of TCPTP and PTP1B in neuronal cells has additive effects in the prevention of diet-induced obesity. Our results identify TCPTP as a critical negative regulator of hypothalamic leptin signaling and causally link elevated TCPTP to the development of cellular leptin resistance in obesity. PMID:22000926

  2. [Contribution of leptin in the development of insulin resistance in pregnant women with obesity].

    Science.gov (United States)

    Tarasenko, K

    2014-03-01

    The aim of the present study was to investigate contribution of leptin in the development of insulin resistance in obese pregnant women depending on the obesity class as well as its effect on the progression of pregnancy. 36 pregnant women of I and II obesity classes and 21 pregnant women with normal body mass participated in the study. Concentrations of insulin, leptin and C-reactive protein in blood serum were measured with immunoenzymatic assays. Insulin resistance (IR) was determined with the Caro index. Contribution of leptin to development of IR was assessed with the ratio "leptin/Caro index". An increase of leptin concentration in blood serum was found in pregnant women with obesity compared to healthy controls. Moreover, the ratio "leptin/Caro index" increased with IR progression and reached maximum in the group with obesity class II, where it was 5.8 times higher than in the control group. An increased frequency of gestoses and placentary dysfunction were manifestations of weakening of adaptive mechanisms of the organism associated with the IR progression and increased role of leptin in its development. Therefore, activation of adipocyte function through the increased leptin secretion and increased ratio "leptin/Caro index" reflects the important role of leptin in pathogenesis of IR in pregnant women with obesity.

  3. Leptin receptor 170 kDa (OB-R170) protein expression is reduced in obese human skeletal muscle: a potential mechanism of leptin resistance

    DEFF Research Database (Denmark)

    Fuentes, T; Ara, I; Guadalupe-Grau, A

    2010-01-01

    To examine whether obesity-associated leptin resistance could be due to down-regulation of leptin receptors (OB-Rs) and/or up-regulation of suppressor of cytokine signalling 3 (SOCS3) and protein tyrosine phosphatase 1B (PTP1B) in skeletal muscle, which blunt janus kinase 2-dependent leptin...

  4. Relationships between changes in leptin and insulin resistance levels in obese individuals following weight loss

    Directory of Open Access Journals (Sweden)

    Tsu-Nai Wang

    2013-08-01

    Full Text Available Obesity can augment insulin resistance (IR, leading to increased risk of diabetes and heart disease. Leptin, ghrelin, and various fatty acids present in the cell membrane may modulate IR. In this study, we aimed to investigate the impact of weight loss on IR, serum leptin/ghrelin levels, and erythrocyte fatty acids, and studied the associations between changes in these variables. A total of 35 obese (body mass index ≥ 27 adults participated in a weight loss program for 3 months. IR was assessed using homeostasis model assessment for insulin resistance (HOMA-IR. The obese participants had a mean weight loss of 5.6 ± 3.8 kg followed by a 16.7% and 23.3% reduction in HOMA-IR and leptin (p  0.05 levels. After adjusting for age, gender, changes in ghrelin, and body fat, we found a significant correlation between decreases in leptin and less risk of no improvement in HOMA-IR levels [odds ratio (OR = 0.69, p = 0.039]. In conclusion, a moderate weight reduction in obese participants over a short period significantly improved IR. This weight reduction concomitantly decreased serum leptin, increased ghrelin, and elevated some erythrocyte unsaturates. Only leptin correlated independently with IR improvement upon multivariable logistic regression analysis, which indicates that leptin may play a role in the modulation of IR following weight loss.

  5. Epac2a-null mice exhibit obesity-prone nature more susceptible to leptin resistance.

    Science.gov (United States)

    Hwang, M; Go, Y; Park, J-H; Shin, S-K; Song, S E; Oh, B-C; Im, S-S; Hwang, I; Jeon, Y H; Lee, I-K; Seino, S; Song, D-K

    2017-02-01

    The exchange protein directly activated by cAMP (Epac), which is primarily involved in cAMP signaling, has been known to be essential for controlling body energy metabolism. Epac has two isoforms: Epac1 and Epac2. The function of Epac1 on obesity was unveiled using Epac1 knockout (KO) mice. However, the role of Epac2 in obesity remains unclear. To evaluate the role of Epac2 in obesity, we used Epac2a KO mice, which is dominantly expressed in neurons and endocrine tissues. Physiological factors related to obesity were analyzed: body weight, fat mass, food intake, plasma leptin and adiponectin levels, energy expenditure, glucose tolerance, and insulin and leptin resistance. To determine the mechanism of Epac2a, mice received exogenous leptin and then hypothalamic leptin signaling was analyzed. Epac2a KO mice appeared to have normal glucose tolerance and insulin sensitivity until 12 weeks of age, but an early onset increase of plasma leptin levels and decrease of plasma adiponectin levels compared with wild-type mice. Acute leptin injection revealed impaired hypothalamic leptin signaling in KO mice. Consistently, KO mice fed a high-fat diet (HFD) were significantly obese, presenting greater food intake and lower energy expenditure. HFD-fed KO mice were also characterized by greater impairment of hypothalamic leptin signaling and by weaker leptin-induced decrease in food consumption compared with HFD-fed wild-type mice. In wild-type mice, acute exogenous leptin injection or chronic HFD feeding tended to induce hypothalamic Epac2a expression. Considering that HFD is an inducer of hypothalamic leptin resistance and that Epac2a functions in pancreatic beta cells during demands of greater work load, hypothalamic Epac2a may have a role in facilitating leptin signaling, at least in response to higher metabolic demands. Thus, our data indicate that Epac2a is critical for preventing obesity and thus Epac2a activators may be used to manage obesity and obesity-mediated metabolic

  6. Role of leptin resistance in the development of obesity in older patients

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    Carter S

    2013-07-01

    Full Text Available Sophie Carter,1,* Alexandre Caron,2,* Denis Richard,2 Frédéric Picard1 1Faculty of Pharmacy, 2Faculty of Medicine, Dept Anatomy and Physiology, Université Laval, Québec, QC, Canada *These authors contributed equally to the work Abstract: Obesity is a global epidemic associated with aging-like cellular processes; in both aging and obesity, resistance to hormones such as insulin and leptin can be observed. Leptin is a circulating hormone/cytokine with central and peripheral effects that is released mainly by subcutaneous white adipose tissue. Centrally, leptin controls food intake, energy expenditure, and fat distribution, whereas it controls (among several others insulin sensitivity, free fatty acids (FFAs oxidation, and lipolysis in the periphery. Aging is associated with important changes in both the distribution and the composition of adipose tissue. Fat is redistributed from the subcutaneous to the visceral depot and increased inflammation participates in adipocyte dysfunction. This redistribution of adipose tissue in favor of visceral fat influences negatively both longevity and healthy aging as shown in numerous animal models. These modifications observed during aging are also associated with leptin resistance. This resistance blunts normal central and peripheral functions of leptin, which leads to a decrease in neuroendocrine function and insulin sensitivity, an imbalance in energy regulation, and disturbances in lipid metabolism. Here, we review how age-related leptin resistance triggers metabolic disturbances and affects the longevity of obese patients. Furthermore, we discuss the potential impacts of leptin resistance on the decline of brown adipose tissue thermogenesis observed in elderly individuals. Keywords: leptin, obesity, aging, insulin sensitivity, brown adipose tissue

  7. Flurbiprofen ameliorated obesity by attenuating leptin resistance induced by endoplasmic reticulum stress.

    Science.gov (United States)

    Hosoi, Toru; Yamaguchi, Rie; Noji, Kikuko; Matsuo, Suguru; Baba, Sachiko; Toyoda, Keisuke; Suezawa, Takahiro; Kayano, Takaaki; Tanaka, Shinpei; Ozawa, Koichiro

    2014-03-01

    Endoplasmic reticulum (ER) stress, caused by the accumulation of unfolded proteins, is involved in the development of obesity. We demonstrated that flurbiprofen, a nonsteroidal anti-inflammatory drug (NSAID), exhibited chaperone activity, which reduced protein aggregation and alleviated ER stress-induced leptin resistance, characterized by insensitivity to the actions of the anti-obesity hormone leptin. This result was further supported by flurbiprofen attenuating high-fat diet-induced obesity in mice. The other NSAIDs tested did not exhibit such effects, which suggested that this anti-obesity action is mediated independent of NSAIDs. Using ferriteglycidyl methacrylate beads, we identified aldehyde dehydrogenase as the target of flurbiprofen, but not of the other NSAIDs. These results suggest that flurbiprofen may have unique pharmacological properties that reduce the accumulation of unfolded proteins and may represent a new class of drug for the fundamental treatment of obesity.

  8. The cellular and molecular bases of leptin and ghrelin resistance in obesity.

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    Cui, Huxing; López, Miguel; Rahmouni, Kamal

    2017-06-01

    Obesity, a major risk factor for the development of diabetes mellitus, cardiovascular diseases and certain types of cancer, arises from a chronic positive energy balance that is often due to unlimited access to food and an increasingly sedentary lifestyle on the background of a genetic and epigenetic vulnerability. Our understanding of the humoral and neuronal systems that mediate the control of energy homeostasis has improved dramatically in the past few decades. However, our ability to develop effective strategies to slow the current epidemic of obesity has been hampered, largely owing to the limited knowledge of the mechanisms underlying resistance to the action of metabolic hormones such as leptin and ghrelin. The development of resistance to leptin and ghrelin, hormones that are crucial for the neuroendocrine control of energy homeostasis, is a hallmark of obesity. Intensive research over the past several years has yielded tremendous progress in our understanding of the cellular pathways that disrupt the action of leptin and ghrelin. In this Review, we discuss the molecular mechanisms underpinning resistance to leptin and ghrelin and how they can be exploited as targets for pharmacological management of obesity.

  9. Relationship between peripheral leptin receptor and leptin in obese subjects

    International Nuclear Information System (INIS)

    Sun Junjiang; Du Tongxin; Wang Zizheng; Wang Shukui; Huang Min

    2002-01-01

    Objective: To investigate the relationship between leptin resistance and leptin receptor in obese subjects. Methods: Forty-four individuals undergoing surgery, exclusive of diabetic mellitus, chronic inflammatory and malignant diseases, were divided into 3 groups according to the body mass index (BMI), normal controls (n=15), weight excess (n=14), and obesity group (n=15). Fasting serum leptin were detected via ELISA kits, leptin receptor (Bmax) in peripheral adipose tissues was detected by radioligand assay. Results: Serum leptin levels were higher significantly in weight excess and obesity cases groups (10.3±4.45 and 13.2±3.26 vs 5.51±3.23 μg/L, both P<0.05, respectively) compared with normal control group, suggesting the existence of leptin resistance, while the leptin receptor of the weight excess and obese groups decreased significantly than that of normal control group (36.9 ± 5.89 and 24.3 ± 3.95 vs 76.5 ± 35.3 fmol/mg protein, both P<0.01, respectively), there was no statistical differences for Kd value among three groups. Also, there was a negative correlation between BMI and leptin receptor (r=-0.613, P<0.05), and no significant correlation was found between serum leptin and peripheral leptin receptor. Conclusion: The result suggested that there was expression of leptin receptor in peripheral adipose tissues and low level of leptin receptor expression may contribute to the development of leptin resistance and obesity

  10. Changes of serum leptin and their relationships with insulin resistance in patients with simple obesity and patients with type 2 diabetes mellitus complicated with obesity

    International Nuclear Information System (INIS)

    Zhang Lei; Changzhou Wujin People's Hospital of Jiangsu Province, Changzhou; Shi Linlin; Lu Dan; Zhang Lei; Wang Qing; Yao Wenhua

    2005-01-01

    Objective: To study the changes of serum leptin in patients with simple obesity and patients with type 2 diabetes mellitus complicated with obesity in order to explore the relationship of leptin and insulin resistance and the role of leptin in the occurrence of type 2 diabetes mellitus. Methods: 60 cases of simple obesity, 60 cases of type 2 diabetes mellitus and 30 cases of normal control were included according to the diagnostic criteria of obesity and type 2 diabetes mellitus. the levels of fasting serum leptin, fasting serum insulin, fasting glucose, fasting blood lipid were measured in all cases. The body mass index (BMI) and insulin action index were calculated. Results: The level of BMI, serum leptin, serum insulin, blood lipid were significantly higher in patients with simple obesity and with type 2 diabetes mellitus complicated with obesity than in normal control cases, while (IAI) was significantly lower. The levels of free serum leptin, serum insulin, free glucose, and blood lipid were significantly higher in patients with type 2 diabetes mellitus complicated with obesity than in patients with simple obesity, while IAI was significantly lower. The level of serum leptin was positively correlated with BMI (r=0.48, P<0.55) and fasting serum leptin (r=0.55, P<0.05) and negatively correlated with IAI (r=-0.47, P<0.05) in patients with type 2 diabetes complicated with obesity. Conclusion: The overexpression of serum leptin may play an important role in the occurrence of the insulin resistance and type 2 diabetes mellitus in obesity patients. (authors)

  11. Ciliary neurotrophic factor activates leptin-like pathways and reduces body fat, without cachexia or rebound weight gain, even in leptin-resistant obesity.

    Science.gov (United States)

    Lambert, P D; Anderson, K D; Sleeman, M W; Wong, V; Tan, J; Hijarunguru, A; Corcoran, T L; Murray, J D; Thabet, K E; Yancopoulos, G D; Wiegand, S J

    2001-04-10

    Ciliary Neurotrophic Factor (CNTF) was first characterized as a trophic factor for motor neurons in the ciliary ganglion and spinal cord, leading to its evaluation in humans suffering from motor neuron disease. In these trials, CNTF caused unexpected and substantial weight loss, raising concerns that it might produce cachectic-like effects. Countering this possibility was the suggestion that CNTF was working via a leptin-like mechanism to cause weight loss, based on the findings that CNTF acts via receptors that are not only related to leptin receptors, but also similarly distributed within hypothalamic nuclei involved in feeding. However, although CNTF mimics the ability of leptin to cause fat loss in mice that are obese because of genetic deficiency of leptin (ob/ob mice), CNTF is also effective in diet-induced obesity models that are more representative of human obesity, and which are resistant to leptin. This discordance again raised the possibility that CNTF might be acting via nonleptin pathways, perhaps more analogous to those activated by cachectic cytokines. Arguing strongly against this possibility, we now show that CNTF can activate hypothalamic leptin-like pathways in diet-induced obesity models unresponsive to leptin, that CNTF improves prediabetic parameters in these models, and that CNTF acts very differently than the prototypical cachectic cytokine, IL-1. Further analyses of hypothalamic signaling reveals that CNTF can suppress food intake without triggering hunger signals or associated stress responses that are otherwise associated with food deprivation; thus, unlike forced dieting, cessation of CNTF treatment does not result in binge overeating and immediate rebound weight gain.

  12. Studies on leptin utilizing to obesity

    International Nuclear Information System (INIS)

    Zhao Minghui

    2001-01-01

    Leptin is a hormone synthesized and secreted by lipid cells. It is a product encoded and expressed by the obese gene. Administration of recombinant leptin decreases food intake, increases energy expenditure and promotes weight loss. Most studies indicate that leptin is a main regulating factor of catabolism and anabolism of adipose tissue. The circulating leptin level is a sensitive index which indicates the confusion of the rate of lipid metabolism such as hyperlipemia, lipo-liver and so on. The human leptin radioimmunoassay has been developed to quantitate human leptin in plasma or serum, and to further investigate the relationship between serum leptin concentration and body fat, gender, age, sexual hormones, endocrine of insulin, etc. Especially, serum leptin concentrations are correlated with body-mass-index (BMI), suggesting that most obese persons are resistant to leptin; Those who are relatively deficient of leptin may become the good candidates of leptin treatment in the future. The discovery and application of leptin make the study of obesity, non-insulin dependent diabetes and other correlation diseases enter a new stage

  13. LEPTIN RESISTANCE AND TYPE 2 DIABETES

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    O. M. Oleshchuk

    2017-07-01

    Full Text Available Leptin is one of adipocyte-secreted hormones. It signals to the brain and other tissues about the status of body energy reserves. Circulating leptin levels are directly proportional to the amount of the body fat. Leptin concentration increases when surfeit and decreases during fasting. Obese patients are hyperleptinemic compared with thin persons and they are tolerant to the central hypothalamic effects of leptin. The reduced sensitivity toward exogenous and endogenous leptin is commonly referred to as leptin resistance. Alterations in the signaling of the long isoform of the leptin receptor play the crucial role in leptin resistance. Surfeit may induce leptin resistance and other metabolic sequelae of obesity. Leptin insensitivity and insulin resistance play a major role in the development of type 2 diabetes. Metformin remains the preferred first-line pharmacologic agent for the treatment of type 2 diabetes. It reduces hepatic glucose production, increases glucose uptake in peripheral tissue and can lead to weight loss. Metformin decreases both insulin and leptin concentration, restores the sensitivity to these hormones. But some studies have shown poor relationship between metformin action and leptin level. And the mechanism of metformin action on leptin resistance remains unclear. Thus, these issues should be studied as well as polymorphisms in genes encoding metformin action.

  14. Polymorphism in leptin receptor gene was associated with obesity in ...

    African Journals Online (AJOL)

    The mutation in leptin receptor (LEPR) gene causes splicing abnormality that resulted in truncated receptor, aberrant signal transduction, leptin resistance, and obesity. This study aims to determine the association of LEPR gene polymorphisms, rs1137100 and rs1137101, on phenotype and leptin level between obese and ...

  15. LEPTIN AND OBESITY – NEUROENDOCRINE , METABOLIC AND ATHEROGENIC EFFECTS OF LEPTIN

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    Mišo Šabovič

    2003-01-01

    Full Text Available Background. Leptin is an adipocyte-derived hormone that was recently discovered. Leptin and leptin resistance play an important role in the pathogenesis of obesity. Leptin acts by binding to specific receptors in the hypothalamus to alter the expression of several neuropeptides that regulate food intake and energy expenditure. As commonly found, obese persons have leptin resistance and consequently attenuated effects of leptin. Mechanism underlying leptin resistance has not been explained yet: it might be the result of a receptor or post receptor defect, impaired transport of leptin through cerebrovascular barrier or inactivation of leptin by binding proteins. Phase I and II clinical trials proved that recombinant leptin administration to humans is safe. First results of the current phase III clinical trials demonstrated that leptin is moderately effective in the treatment of obesity.Conclusions. Beside anti-obesity effect, leptin can have important metabolic and neuroendocrine effects. It is involved in glucose metabolism and insulin secretion, pathogenesis of polymetabolic syndrome, diabetes and arterial hypertension. In addition it affects some processes of atherothrombosis. It interacts with and significantly influences hypothalamic-pituitaryadrenal, thyroid, sexual glands and growth hormone axes. Explaining the mechanism of leptin resistance could be important for understanding the pathogenesis of obesity and associated pathologic states as polymetabolic syndrom, diabetes, arterial hipertension and atherothrombosis.

  16. Modulation of leptin resistance by food compounds.

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    Aragonès, Gerard; Ardid-Ruiz, Andrea; Ibars, Maria; Suárez, Manuel; Bladé, Cinta

    2016-08-01

    Leptin is mainly secreted by white adipose tissue and regulates energy homeostasis by inhibiting food intake and stimulating energy expenditure through its action in neuronal circuits in the brain, particularly in the hypothalamus. However, hyperleptinemia coexists with the loss of responsiveness to leptin in common obese conditions. This phenomenon has been defined as leptin resistance and the restoration of leptin sensitivity is considered to be a useful strategy to treat obesity. This review summarizes the existing literature on potentially valuable nutrients and food components to reverse leptin resistance. Notably, several food compounds, such as teasaponins, resveratrol, celastrol, caffeine, and taurine among others, are able to restore the leptin signaling in neurons by overexpressing anorexigenic peptides (proopiomelanocortin) and/or repressing orexigenic peptides (neuropeptide Y/agouti-related peptide), thus decreasing food intake. Additionally, some nutrients, such as vitamins A and D, can improve leptin transport through the blood-brain barrier. Therefore, food components can improve leptin resistance by acting at different levels of the leptin pathway; moreover, some compounds are able to target more than one feature of leptin resistance. However, systematic studies are necessary to define the actual effectiveness of each compound. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Body Fat Distribution, Serum Leptin, And Insulin Resistance In Obese Subjects With Obstructive Sleep Apnoea

    OpenAIRE

    Hassan ZA*,Attia MF**, Ahmed AH**;Hassan HA***,

    2006-01-01

    Obstructive sleep apnoea (OS A) is strongly associated with obesity and is characterized by endocrine and metabolic changes. The aim of the present study is to clarify whether there is interrelationship between body fat, serum leptin, glucose-insulin metabolism and OSA. Subjects and measurements: we studied 23 obese subjects with OSA (13 males,& 10 females; age mean 36 ± 4.4 years; BMI: 31.7 ± 3.6 kg/m2; WHR: 1.2 ± .25 in males and 0.81+.5 in females ;Apnoea Index "AI"( 9.2 ±6.1) event/hour o...

  18. Serum leptin and insulin tests in obesity

    International Nuclear Information System (INIS)

    Yang Yin; Jiang Xiaojin; Leng Xiumei

    2001-01-01

    Objective: To study the clinical significance and the relations of leptin and insulin on obesity group. Methods: Leptin and insulin were tested with radioimmunoassay (RIA) in pre-obesity group and obesity group respectively. Results: Serum leptin and insulin levels were significantly elevated in obesity group compare with the controls (P<0.01). Conclusion: Changing with insulin, the elevation of leptin in obesity group has been identified as an important agent of diabetes mellitus (DM)

  19. Maternal malnutrition and offspring sex determine juvenile obesity and metabolic disorders in a swine model of leptin resistance.

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    Alicia Barbero

    Full Text Available The present study aimed to determine, in a swine model of leptin resistance, the effects of type and timing of maternal malnutrition on growth patterns, adiposity and metabolic features of the progeny when exposed to an obesogenic diet during their juvenile development and possible concomitant effects of the offspring sex. Thus, four groups were considered. A CONTROL group involved pigs born from sows fed with a diet fulfilling their daily maintenance requirements for pregnancy. The treated groups involved the progeny of females fed with the same diet but fulfilling either 160% or 50% of pregnancy requirements during the entire gestation (OVERFED and UNDERFED, respectively or 100% of requirements until Day 35 of pregnancy and 50% of such amount from Day 36 onwards (LATE-UNDERFED. OVERFED and UNDERFED offspring were more prone to higher corpulence and fat deposition from early postnatal stages, during breast-feeding; adiposity increased significantly when exposed to obesogenic diets, especially in females. The effects of sex were even more remarkable in LATE-UNDERFED offspring, which had similar corpulence to CONTROL piglets; however, females showed a clear predisposition to obesity. Furthermore, the three groups of pigs with maternal malnutrition showed evidences of metabolic syndrome and, in the case of individuals born from OVERFED sows, even of insulin resistance and the prodrome of type-2 diabetes. These findings support the main role of early nutritional programming in the current rise of obesity and associated diseases in ethnics with leptin resistance.

  20. Roux-en-Y gastric bypass surgery suppresses hypothalamic PTP1B protein level and alleviates leptin resistance in obese rats.

    Science.gov (United States)

    Liu, Jia-Yu; Mu, Song; Zhang, Shu-Ping; Guo, Wei; Li, Qi-Fu; Xiao, Xiao-Qiu; Zhang, Jun; Wang, Zhi-Hong

    2017-09-01

    The present study aimed to explore the effect of Roux-en-Y gastric bypass (RYGB) surgery on protein tyrosine phosphatase 1B (PTP1B) expression levels and leptin activity in hypothalami of obese rats. Obese rats induced by a high-fat diet (HFD) that underwent RYGB (n=11) or sham operation (SO, n=9), as well as an obese control cohort (Obese, n=10) and an additional normal-diet group (ND, n=10) were used. Food efficiency was measured at 8 weeks post-operation. Plasma leptin levels were evaluated and hypothalamic protein tyrosine phosphatase 1B (PTP1B) levels and leptin signaling activity were examined at the genetic and protein levels. The results indicated that food efficiency was typically lower in RYGB rats compared with that in the Obese and SO rats. In the RYGB group, leptin receptor expression and proopiomelanocortin was significantly higher, while Neuropeptide Y levels were lower than those in the Obese and SO groups. Furthermore, the gene and protein expression levels of PTP1B in the RYGB group were lower, while levels of phosphorylated signal transducer and activator of transcription 3 protein were much higher compared with those in the Obese and SO groups. In conclusion, RYGB surgery significantly suppressed hypothalamic PTP1B protein expression. PTP1B regulation may partially alleviate leptin resistance.

  1. The effects of losartan on memory performance and leptin resistance induced by obesity and high-fat diet in adult male rats.

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    Sharieh Hosseini, Seyydeh Gohar; Khatamsaz, Saeed; Shariati, Mehrdad

    2014-01-01

    Leptin is a hormone secreted by adipose tissue and is involved not only in the regulation of feeding and energy expenditure, but also its role in memory enhancement has been demonstrated as well. The partial transfer of leptin across the blood-brain barrier in obese individuals causes leptin resistance and prevents leptin reaching brain. On the other hand, studies have shown that angiotensin antagonists such as losartan can improve memory and learning abilities. The aim of this study was to evaluate the effects of losartan on improving memory and leptin resistance induced by high fat diet in obese rats. 40 Wistar male rats were divided in 4 groups: control (C), losartan (LOS), high-fat diet (HFD) and high-fat diet and losartan (HFD and LOS). The spatial memory performances of the rats were assessed in the Morris water maze after 2 months of treatment. Then they were weighed and serum levels of leptin and triglyceride were measured. In spite of receiving high-fat diet, no significant differences in body weight were observed in the (HFD & LOS) group. In the Morris water maze trial, the (LOS) and (HFD & LOS) groups also showed a significant reduction (P <0.05) in latency and path length. In addition, a significant decrease (P <0.05) in serum levels of leptin and no significant difference in serum levels of triglyceride was observed in the (HFD & LOS) group. Losartan can improve leptin resistance induced by obesity and high fat diet. At the same time, it modulates body weight and enhances learning and memory.

  2. Hyperleptinemia is required for the development of leptin resistance.

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    Zachary A Knight

    2010-06-01

    Full Text Available Leptin regulates body weight by signaling to the brain the availability of energy stored as fat. This negative feedback loop becomes disrupted in most obese individuals, resulting in a state known as leptin resistance. The physiological causes of leptin resistance remain poorly understood. Here we test the hypothesis that hyperleptinemia is required for the development of leptin resistance in diet-induced obese mice. We show that mice whose plasma leptin has been clamped to lean levels develop obesity in response to a high-fat diet, and the magnitude of this obesity is indistinguishable from wild-type controls. Yet these obese animals with constant low levels of plasma leptin remain highly sensitive to exogenous leptin even after long-term exposure to a high fat diet. This shows that dietary fats alone are insufficient to block the response to leptin. The data also suggest that hyperleptinemia itself can contribute to leptin resistance by downregulating cellular response to leptin as has been shown for other hormones.

  3. Early-postnatal changes in adiposity and lipids profile by transgenerational developmental programming in swine with obesity/leptin resistance.

    Science.gov (United States)

    Gonzalez-Bulnes, Antonio; Astiz, Susana; Ovilo, Cristina; Lopez-Bote, Clemente J; Sanchez-Sanchez, Raul; Perez-Solana, Maria L; Torres-Rovira, Laura; Ayuso, Miriam; Gonzalez, Jorge

    2014-10-01

    Maternal malnutrition during pregnancy, both deficiency and excess, induces changes in the intrauterine environment and the metabolic status of the offspring, playing a key role in the growth, status of fitness/obesity and appearance of metabolic disorders during postnatal life. There is increasing evidence that these effects may not be only limited to the first generation of descendants, the offspring directly exposed to metabolic challenges, but to subsequent generations. This study evaluated, in a swine model of obesity/leptin resistance, the existence and extent of transgenerational developmental programming effects. Pre- and postnatal development, adiposity and metabolic features were assessed in the second generation of piglets, descendant of sows exposed to either undernutrition or overnutrition during pregnancy. The results indicated that these piglets exhibited early-postnatal increases in adiposity and disturbances in lipid profiles compatible with the early prodrome of metabolic syndrome, with liver tissue also displaying evidence of paediatric liver disease. These features indicative of early-life metabolic disorders were more evident in the males that were descended from overfed grandmothers and during the transition from milk to solid feeding. Thus, this study provides evidence supporting transgenerational developmental programming and supports the necessity for the development of strategies for avoiding the current epidemics of childhood overweight and obesity. © 2014 Society for Endocrinology.

  4. Leptin receptor in peripheral adipose tissues of obese subjects

    International Nuclear Information System (INIS)

    Du Tongxin; Sun Junjiang; Wang Zizheng; Wang Shukui; Fu Lei; Han Liu

    2002-01-01

    Objective: To investigate the relationship between leptin receptor and obesity by studying the leptin receptor density B max and dissociation constant K d in peripheral adipose tissue in subjects with different body weight mass (BMI). Methods: Leptin receptor density B max and K d were assayed via radioligand method in 71 cases, including 32 classified as obese, 19 over-weight and 20 normal control. Results: With the escalating of BMI, the leptin receptor density significantly decreased in obese and over-weight group compared with that in normal control (both P d values were of no differences among all three groups suggesting no correlation between the binding ability of leptin to its receptor and BMI. A negative correlation between BMI and B max (r=-0.76, P<0.01) displayed after all. Conclusion: Leptin receptor density correlates with the BMI in obese cases and it suggests that the down-regulation of leptin receptor may contribute to the occurrence of leptin resistance and obesity after-wards

  5. Changes of serum leptin and other related hormones levels in simple obese children

    International Nuclear Information System (INIS)

    Xiao Jinhua; Wang Yaping; Xu Yan; Gao Yufeng

    2001-01-01

    Objective: To measure the serum leptin concentration in simple obese children together with other four kinds of related hormones. Methods: Serum Leptin, Ins, T 3 , T 4 and GH levels were measured by radioimmunoassay in thirty-eight obese children and thirty healthy controls. Results: The levels of serum leptin, Ins and T 3 in obese group were dramatically higher than those in control group (all P 4 concentration between simple obese children and control group (P > 0.05), Serum GH levels was significantly decreased in simple obese children (P < 0.01). There was a positive correlation between serum leptin levels and lns levels (r = 0.46, P < 0.01). Conclusion: In simple obese children there were leptin resistance and endocrine metabolic disturbances, the later might be correlated with the increasing of serum leptin levels; It is suggested that Leptin resistance might play a key role in the development of obesity

  6. Dietary components in the development of leptin resistance.

    Science.gov (United States)

    Vasselli, Joseph R; Scarpace, Philip J; Harris, Ruth B S; Banks, William A

    2013-03-01

    Classically, leptin resistance has been associated with increased body fat and circulating leptin levels, and the condition is believed to contribute to the onset and/or maintenance of obesity. Although a great deal is known about the central nervous system mechanisms mediating leptin resistance, considerably less is known about the role of diet in establishing and maintaining this altered hormonal state. An exciting new finding has recently been published demonstrating the existence of leptin resistance in normal-weight rats with lean leptin levels by feeding them a high-concentration-fructose diet. This finding has opened the possibility that specific macronutrients may be capable of inducing leptin resistance, independently of the amount of body fat or circulating leptin present in the treated animals. This review describes several lines of research that have recently emerged indicating that specific types of dietary sugars and fats are capable of inducing leptin resistance in experimental rodent models. The results further show that diet-induced leptin resistance is capable of increasing energy intake and elevating body weight gain under appropriate dietary challenges. It appears that biological mechanisms on multiple levels may underlie the dietary induction of leptin resistance, including alterations in the leptin blood-to-brain transport system, in peripheral glucose metabolism, and in central leptin receptor signaling pathways. What is clear from the findings reviewed here is that diet-induced leptin resistance can occur in the absence of elevated circulating leptin levels and body weight, rendering it a potential cause and/or predisposing factor to excess body weight gain and obesity.

  7. Dietary Components in the Development of Leptin Resistance123

    Science.gov (United States)

    Vasselli, Joseph R.; Scarpace, Philip J.; Harris, Ruth B. S.; Banks, William A.

    2013-01-01

    Classically, leptin resistance has been associated with increased body fat and circulating leptin levels, and the condition is believed to contribute to the onset and/or maintenance of obesity. Although a great deal is known about the central nervous system mechanisms mediating leptin resistance, considerably less is known about the role of diet in establishing and maintaining this altered hormonal state. An exciting new finding has recently been published demonstrating the existence of leptin resistance in normal-weight rats with lean leptin levels by feeding them a high-concentration-fructose diet. This finding has opened the possibility that specific macronutrients may be capable of inducing leptin resistance, independently of the amount of body fat or circulating leptin present in the treated animals. This review describes several lines of research that have recently emerged indicating that specific types of dietary sugars and fats are capable of inducing leptin resistance in experimental rodent models. The results further show that diet-induced leptin resistance is capable of increasing energy intake and elevating body weight gain under appropriate dietary challenges. It appears that biological mechanisms on multiple levels may underlie the dietary induction of leptin resistance, including alterations in the leptin blood-to-brain transport system, in peripheral glucose metabolism, and in central leptin receptor signaling pathways. What is clear from the findings reviewed here is that diet-induced leptin resistance can occur in the absence of elevated circulating leptin levels and body weight, rendering it a potential cause and/or predisposing factor to excess body weight gain and obesity. PMID:23493533

  8. Leptin and Leptin Resistance in the Pathogenesis of Obstructive Sleep Apnea: A Possible Link to Oxidative Stress and Cardiovascular Complications

    Directory of Open Access Journals (Sweden)

    Slava Berger

    2018-01-01

    Full Text Available Obesity-related sleep breathing disorders such as obstructive sleep apnea (OSA and obesity hypoventilation syndrome (OHS cause intermittent hypoxia (IH during sleep, a powerful trigger of oxidative stress. Obesity also leads to dramatic increases in circulating levels of leptin, a hormone produced in adipose tissue. Leptin acts in the hypothalamus to suppress food intake and increase metabolic rate. However, obese individuals are resistant to metabolic effects of leptin. Leptin also activates the sympathetic nervous system without any evidence of resistance, possibly because these effects occur peripherally without a need to penetrate the blood-brain barrier. IH is a potent stimulator of leptin expression and release from adipose tissue. Hyperleptinemia and leptin resistance may upregulate generation of reactive oxygen species, increasing oxidative stress and promoting inflammation. The current review summarizes recent data on a possible link between leptin and oxidative stress in the pathogenesis of sleep breathing disorders.

  9. Analysis of changes of serum leptin, C-peptide levels and peripheral fat tissue leptin receptor expression in obesity

    International Nuclear Information System (INIS)

    Du Tongxin; Sun Junjiang; Wang Shukui; Fu Lei

    2002-01-01

    Objective: To explore the mechanism of obesity and obesity accompanied type two diabetes mellitus by investigating changes of serum leptin, C-peptide (C-P) levels and leptin receptor expression in peripheral adipose tissues. Methods: Peripheral leptin receptor density was measured via radio-ligand binding method, serum leptin and C - P levels were measured via radioimmunoassay in 91 cases (38 in obesity group, 23 in over weight, and 30 in normal controls). Results: With the increase of body mass index (BMI), the peripheral leptin receptor density of the over weight and obese cases decreased and was mash less than that of normal cases (both p<0.01, respectively). There was no statistical differences for Kd value among the three groups, suggesting no associated change between the binding ability of leptin receptor to its ligand. There was a negative correlation between BMI and leptin receptor density (r = -0.70, p < 0.01). The serum leptin and C-P levels in weight excess and obese subjects with type two DM were both increased, but significantly higher in obese group than those in weight excess group (p < 0.01). The increase of C-P was much marked than that of leptin. Serum C-P level was positively correlated with BMI. Conclusion: Changes of serum leptin, C-P levels and peripheral leptin receptor expression in cases with simple obesity and obesity accompanied with type two DM were related closely with BMI. Type 2 DM in obese subjects was related with leptin resistance and insulin resistance

  10. Adiponectin, Leptin, and Leptin Receptor in Obese Patients with Type 2 Diabetes Treated with Insulin Detemir

    Directory of Open Access Journals (Sweden)

    Paweł Olczyk

    2017-07-01

    Full Text Available The aim of the present study is to quantitatively assess the expression of selected regulatory molecules, such as leptin, leptin receptor, and adiponectin in the blood of obese patients with type 2 diabetes both before treatment and after six months of pharmacological therapy with the long-lasting insulin analogue, insulin detemir. A significant decrease in the analysed regulatory molecules, i.e., leptin receptor and adiponectin, was found in blood plasma of the patients with untreated type 2 diabetes. These changes were accompanied by an increase in plasma leptin concentrations. Insulin treatment resulted in the normalization of plasma leptin receptor and adiponectin concentrations. The circulating leptin level did not change following anti-diabetic therapy with insulin detemir. Gender was a significant factor modifying the circulating level of all the analysed regulatory active compounds. Bioinformatic analysis was performed using Matlab with the Signal Processing Toolbox. The conducted discriminant analysis revealed that the leptin receptor, Δw(19, and adiponectin, Δw(21, were the parameters undergoing the most significant quantitative changes during the six-month therapy with insulin detemir. The conducted examinations indicated the contribution of adipocytokines—the biologically-active mediators of systemic metabolism, such as leptin and adiponectin in the pathomechanism of disorders being the basis for obesity which leads to development of insulin resistance, which, in turn, results in the occurrence of type 2 diabetes.

  11. Gene expression of leptin, resistin, and adiponectin in the white adipose tissue of obese patients with non-alcoholic fatty liver disease and insulin resistance.

    Science.gov (United States)

    Baranova, Ancha; Gowder, Shobha J; Schlauch, Karen; Elariny, Hazem; Collantes, Rochelle; Afendy, Arian; Ong, Janus P; Goodman, Zachary; Chandhoke, Vikas; Younossi, Zobair M

    2006-09-01

    Adipose tissue is an active endocrine organ that secretes a variety of metabolically important substances including adipokines. These factors affect insulin sensitivity and may represent a link between obesity, insulin resistance, type 2 diabetes (DM), and nonalcoholic fatty liver disease (NAFLD). This study uses real-time polymerase chain reaction (PCR) quantification of mRNAs encoding adiponectin, leptin, and resistin on snap-frozen samples of intra-abdominal adipose tissue of morbidly obese patients undergoing bariatric surgery. Morbidly obese patients undergoing bariatric surgery were studied. Patients were classified into two groups: Group A (with insulin resistance) (N=11; glucose 149.84 +/- 40.56 mg/dL; serum insulin 8.28 +/- 3.52 microU/mL), and Group B (without insulin resistance) (N=10; glucose 102.2 +/- 8.43 mg/dL; serum insulin 3.431 +/- 1.162 microU/mL). Adiponectin mRNA in intra-abdominal adipose tissue and serum adiponectin levels were significantly lower in Group A compared to Group B patients (P<0.016 and P<0.03, respectively). Although serum resistin was higher in Group A than in Group B patients (P<0.005), resistin gene expression was not different between the two groups. Finally, for leptin, neither serum level nor gene expression was different between the two groups. Serum adiponectin level was the only predictor of nonalcoholic steatohepatitis (NASH) in this study (P=0.024). Obese patients with insulin resistance have decreased serum adiponectin and increased serum resistin. Additionally, adiponectin gene expression is also decreased in the adipose tissue of these patients. This low level of adiponectin expression may predispose patients to the progressive form of NAFLD or NASH.

  12. HF diets increase hypothalamic PTP1B and induce leptin resistance through both leptin-dependent and -independent mechanisms

    Science.gov (United States)

    White, Christy L.; Whittington, Amy; Barnes, Maria J.; Wang, Zhong; Bray, George A.; Morrison, Christopher D.

    2009-01-01

    Protein tyrosine phosphatase 1B (PTP1B) contributes to leptin resistance by inhibiting intracellular leptin receptor signaling. Mice with whole body or neuron-specific deletion of PTP1B are hypersensitive to leptin and resistant to diet-induced obesity. Here we report a significant increase in PTP1B protein levels in the mediobasal hypothalamus (P = 0.003) and a concomitant reduction in leptin sensitivity following 28 days of high-fat (HF) feeding in rats. A significant increase in PTP1B mRNA levels was also observed in rats chronically infused with leptin (3 μg/day icv) for 14 days (P = 0.01) and in leptin-deficient ob/ob mice infused with leptin (5 μg/day sc for 14 days; P = 0.003). When saline-infused ob/ob mice were placed on a HF diet for 14 days, an increase in hypothalamic PTP1B mRNA expression was detected (P = 0.001) despite the absence of circulating leptin. In addition, although ob/ob mice were much more sensitive to leptin on a low-fat (LF) diet, a reduction in this sensitivity was still observed following exposure to a HF diet. Taken together, these data indicate that hypothalamic PTP1B is specifically increased during HF diet-induced leptin resistance. This increase in PTP1B is due in part to chronic hyperleptinemia, suggesting that hyperleptinemia is one mechanism contributing to the development of leptin resistance. However, these data also indicate that leptin is not required for the increase in hypothalamic PTP1B or the development of leptin resistance. Therefore, additional, leptin-independent mechanisms must exist that increase hypothalamic PTP1B and contribute to leptin resistance. PMID:19017730

  13. Leptin (Obesity Protein) and Breast Cancer Metastasis

    National Research Council Canada - National Science Library

    Surmacz, Eva

    2002-01-01

    ...). Leptin, a 16 kDa protein product of the OB (obesity) gene is a cytokine reported to be secreted mainly from adipocytes and has been shown to control body fat mass and food intake by providing information to the central nervous system (2...

  14. Baseline leptin and leptin reduction predict improvements in metabolic variables and long-term fat loss in obese children and adolescents: a prospective study of an inpatient weight-loss program

    NARCIS (Netherlands)

    Murer, S.B.; Knopfli, B.H.; Aeberli, I.; Jung, A.; Wildhaber, J.; Wildhaber-Brooks, J.; Zimmermann, M.B.

    2011-01-01

    Background: It is unclear whether high plasma leptin in obese individuals represents leptin resistance or whether individuals with marked reductions in leptin concentrations in response to weight loss may be at greater risk of regaining weight. Moreover, whether changes in leptin predict metabolic

  15. Molecular characterization of leptin (obese) gene in domesticated ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-03-06

    Mar 6, 2009 ... National Bureau of Animal Genetic Resources, Karnal, ... Leptin is obesity gene involved in production and reproduction traits in domestic animals. In the ..... leptin concentration, growth, feed intake, feeding behavior, and.

  16. Flurbiprofen ameliorates glucose deprivation-induced leptin resistance

    Directory of Open Access Journals (Sweden)

    Toru Hosoi

    2016-09-01

    Full Text Available Leptin resistance is one of the mechanisms involved in the pathophysiology of obesity. The present study showed that glucose deprivation inhibited leptin-induced phosphorylation of signal transducer and activator of transcription 3 (STAT3 and signal transducer and activator of transcription 5 (STAT5 in neuronal cells. Flurbiprofen reversed glucose deprivation-mediated attenuation of STAT3, but not STAT5 activation, in leptin-treated cells. Glucose deprivation increased C/EBP-homologous protein (CHOP and glucose regulated protein 78 (GRP78 induction, indicating the activation of unfolded protein responses (UPR. Flurbiprofen did not affect the glucose deprivation-induced activation of UPR, but did attenuate the glucose deprivation-mediated induction of AMP-activated protein kinase (AMPK phosphorylation. Flurbiprofen may ameliorate glucose deprivation-induced leptin resistance in neuronal cells.

  17. Perilipin ablation results in a lean mouse with aberrant adipocyte lipolysis, enhanced leptin production, and resistance to diet-induced obesity.

    Science.gov (United States)

    Tansey, J T; Sztalryd, C; Gruia-Gray, J; Roush, D L; Zee, J V; Gavrilova, O; Reitman, M L; Deng, C X; Li, C; Kimmel, A R; Londos, C

    2001-05-22

    Perilipin coats the lipid droplets of adipocytes and is thought to have a role in regulating triacylglycerol hydrolysis. To study the role of perilipin in vivo, we have created a perilipin knockout mouse. Perilipin null (peri(-/-)) and wild-type (peri(+/+)) mice consume equal amounts of food, but the adipose tissue mass in the null animals is reduced to approximately 30% of that in wild-type animals. Isolated adipocytes of perilipin null mice exhibit elevated basal lipolysis because of the loss of the protective function of perilipin. They also exhibit dramatically attenuated stimulated lipolytic activity, indicating that perilipin is required for maximal lipolytic activity. Plasma leptin concentrations in null animals were greater than expected for the reduced adipose mass. The peri(-/-) animals have a greater lean body mass and increased metabolic rate but they also show an increased tendency to develop glucose intolerance and peripheral insulin resistance. When fed a high-fat diet, the perilipin null animals are resistant to diet-induced obesity but not to glucose intolerance. The data reveal a major role for perilipin in adipose lipid metabolism and suggest perilipin as a potential target for attacking problems associated with obesity.

  18. Leptin rapidly improves glucose homeostasis in obese mice by increasing hypothalamic insulin sensitivity.

    Science.gov (United States)

    Koch, Christiane; Augustine, Rachael A; Steger, Juliane; Ganjam, Goutham K; Benzler, Jonas; Pracht, Corinna; Lowe, Chrishanthi; Schwartz, Michael W; Shepherd, Peter R; Anderson, Greg M; Grattan, David R; Tups, Alexander

    2010-12-01

    Obesity is associated with resistance to the actions of both leptin and insulin via mechanisms that remain incompletely understood. To investigate whether leptin resistance per se contributes to insulin resistance and impaired glucose homeostasis, we investigated the effect of acute leptin administration on glucose homeostasis in normal as well as leptin- or leptin receptor-deficient mice. In hyperglycemic, leptin-deficient Lep(ob/ob) mice, leptin acutely and potently improved glucose metabolism, before any change of body fat mass, via a mechanism involving the p110α and β isoforms of phosphatidylinositol-3-kinase (PI3K). Unlike insulin, however, the anti-diabetic effect of leptin occurred independently of phospho-AKT, a major downstream target of PI3K, and instead involved enhanced sensitivity of the hypothalamus to insulin action upstream of PI3K, through modulation of IRS1 (insulin receptor substrate 1) phosphorylation. These data suggest that leptin resistance, as occurs in obesity, reduces the hypothalamic response to insulin and thereby impairs peripheral glucose homeostasis, contributing to the development of type 2 diabetes.

  19. Better prognosis in overweight/obese coronary heart disease patients with high plasma levels of leptin.

    Science.gov (United States)

    Simiti, Luminita Animarie Vida; Todor, Irina; Stoia, Mirela Anca; Goidescu, Cerasela Mihaela; Anton, Florin Petru; Farcas, Anca Daniela

    2016-01-01

    The involvement of leptin in atherosclerosis is very complex, including inflammation, the oxidative stress and thrombosis. Leptin has atherogenic and also antiatherogenic actions. In obesity elevated leptin levels are not sufficient to prevent disturbances of energy balance, suggesting that obese people are leptin resistant. The aim of the study was to investigate the relationship between baseline plasma levels of leptin and the incidence of new ischemic events in patients with CHD. Plasma levels of leptin in fifty nine consecutive patients (29 men and 30 women) with CHD hospitalized in the County Emergency Clinical Hospital of Cluj-Napoca were measured using commercially available ELISA at admission. Patients with active infectious disease, neoplasia, acute coronary syndrome, stroke, hepatic or renal failure and severe heart failure were excluded The relationship between leptin levels and incident cardiovascular events (angina, nonfatal myocardial infarction or heart failure) over two years follow-up was studied using MEDCALC version 9.6. 73.6% patients with CHD were overweight or suffered of obesity. There were no significant differences between women and men regarding the plasma levels of leptin, the body mass index (BMI), the number of rehospitalizations, rehospitalizations/patient, diabetes mellitus, hypertension or dyslipidemia. Only in women plasma levels of leptin are correlated with BMI. As compared with men with overweight and obesity (BMI≥25kg/m(2)), plasma levels of leptin were significantly higher in women with overweight and obesity (3905.97±463.91 pg/ml vs 1835.17±533.9 pg/ml) (p2000 pg/ml and BMI >28kg/m(2) had a better prognosis, suggesting a protective role of leptin in overweight/mild obesity.

  20. Altered gut microbiota and endocannabinoid system tone in obese and diabetic leptin-resistant mice: impact on apelin regulation in adipose tissue

    Directory of Open Access Journals (Sweden)

    Lucie eGeurts

    2011-07-01

    Full Text Available Growing evidence supports the role of gut microbiota in the development of obesity, type 2 diabetes and low-grade inflammation. The endocrine activity of adipose tissue has been found to contribute to the regulation of glucose homeostasis and low-grade inflammation. Among the key hormones produced by this tissue, apelin has been shown to regulate glucose homeostasis. Recently, it has been proposed that gut microbiota participate in adipose tissue metabolism via the endocannabinoid system and gut microbiota-derived compounds, namely lipopolysaccharide (LPS. We have investigated gut microbiota composition in obese and diabetic leptin-resistant mice (db/db by combining pyrosequencing and phylogenetic microarray analysis of 16S ribosomal RNA gene sequences. We observed a significant higher abundance of Firmicutes, Proteobacteria and Fibrobacteres phyla in db/db mice compared to lean mice. The abundance of 10 genera was significantly affected by the genotype. We identified the roles of the endocannabinoid system and LPS in the regulation of apelinergic system tone (apelin and APJ mRNA expression in genetic obese and diabetic mice. By using in vivo and in vitro models, we have demonstrated that both the endocannabinoid system and low-grade inflammation differentially regulate apelin and APJ mRNA expression in adipose tissue. Finally, deep-gut microbiota profiling revealed that the gut microbial community of type 2 diabetic mice is significantly different from that of their lean counterparts. This indicates specific relationships between the gut microbiota and the regulation of the apelinergic system. However, the exact roles of specific bacteria in shaping the phenotype of db/db mice remain to be determined.

  1. ENU mutagenesis identifies mice with morbid obesity and severe hyperinsulinemia caused by a novel mutation in leptin.

    Directory of Open Access Journals (Sweden)

    Chen-Jee Hong

    Full Text Available BACKGROUND: Obesity is a multifactorial disease that arises from complex interactions between genetic predisposition and environmental factors. Leptin is central to the regulation of energy metabolism and control of body weight in mammals. METHODOLOGY/PRINCIPAL FINDINGS: To better recapitulate the complexity of human obesity syndrome, we applied N-ethyl-N-nitrosourea (ENU mutagenesis in combination with a set of metabolic assays in screening mice for obesity. Mapping revealed linkage to the chromosome 6 within a region containing mouse Leptin gene. Sequencing on the candidate genes identified a novel T-to-A mutation in the third exon of Leptin gene, which translates to a V145E amino acid exchange in the leptin propeptide. Homozygous Leptin(145E/145E mutant mice exhibited morbid obesity, accompanied by adipose hypertrophy, energy imbalance, and liver steatosis. This was further associated with severe insulin resistance, hyperinsulinemia, dyslipidemia, and hyperleptinemia, characteristics of human obesity syndrome. Hypothalamic leptin actions in inhibition of orexigenic peptides NPY and AgRP and induction of SOCS1 and SOCS3 were attenuated in Leptin(145E/145E mice. Administration of exogenous wild-type leptin attenuated hyperphagia and body weight increase in Leptin(145E/145E mice. However, mutant V145E leptin coimmunoprecipitated with leptin receptor, suggesting that the V145E mutation does not affect the binding of leptin to its receptor. Molecular modeling predicted that the mutated residue would form hydrogen bond with the adjacent residues, potentially affecting the structure and formation of an active complex with leptin receptor within that region. CONCLUSIONS/SIGNIFICANCE: Thus, our evolutionary, structural, and in vivo metabolic information suggests the residue 145 as of special function significance. The mouse model harboring leptin V145E mutation will provide new information on the current understanding of leptin biology and novel mouse

  2. Bone mass regulation of leptin and postmenopausal osteoporosis with obesity.

    Science.gov (United States)

    Legiran, Siswo; Brandi, Maria Luisa

    2012-09-01

    Leptin has been known to play a role in weight regulation through food intake and energy expenditure. Leptin also has an important role in bone metabolism. The role of leptin is determined by leptin receptors, either central or peripheral to the bones. We discuss the role of leptin on bone and molecular genetics of osteoporosis in postmenopausal obese women. The role of leptin in bone preserves bone mineral density (BMD) through increased OPG levels leading to bind RANKL, resulting in reducing osteoclast activity. The estrogen role on bone is also mediated by RANKL and OPG. In postmenopausal women who have estrogen deficiency, it increases the rate of RANKL, which increases osteoclastogenesis. Obese individuals who have a high level of leptin will be effected by bone protection. There are similarities in the mechanism between estrogen and leptin in influencing the process of bone remodeling. It may be considered that the role of estrogen can be replaced by leptin. Molecular genetic aspects that play a role in bone remodeling, such as leptin, leptin receptors, cytokines (e.g. RANK, RANKL, and OPG), require further study to be useful, especially regarding osteoporosis therapy based on genetic analysis.

  3. Comparison with ancestral diets suggests dense acellular carbohydrates promote an inflammatory microbiota, and may be the primary dietary cause of leptin resistance and obesity

    Directory of Open Access Journals (Sweden)

    Spreadbury I

    2012-07-01

    Full Text Available Ian SpreadburyGastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, CanadaAbstract: A novel hypothesis of obesity is suggested by consideration of diet-related inflammation and evolutionary medicine. The obese homeostatically guard their elevated weight. In rodent models of high-fat diet-induced obesity, leptin resistance is seen initially at vagal afferents, blunting the actions of satiety mediators, then centrally, with gastrointestinal bacterial-triggered SOCS3 signaling implicated. In humans, dietary fat and fructose elevate systemic lipopolysaccharide, while dietary glucose also strongly activates SOCS3 signaling. Crucially however, in humans, low-carbohydrate diets spontaneously decrease weight in a way that low-fat diets do not. Furthermore, nutrition transition patterns and the health of those still eating diverse ancestral diets with abundant food suggest that neither glycemic index, altered fat, nor carbohydrate intake can be intrinsic causes of obesity, and that human energy homeostasis functions well without Westernized foods containing flours, sugar, and refined fats. Due to being made up of cells, virtually all "ancestral foods" have markedly lower carbohydrate densities than flour- and sugar-containing foods, a property quite independent of glycemic index. Thus the "forgotten organ" of the gastrointestinal microbiota is a prime candidate to be influenced by evolutionarily unprecedented postprandial luminal carbohydrate concentrations. The present hypothesis suggests that in parallel with the bacterial effects of sugars on dental and periodontal health, acellular flours, sugars, and processed foods produce an inflammatory microbiota via the upper gastrointestinal tract, with fat able to effect a "double hit" by increasing systemic absorption of lipopolysaccharide. This model is consistent with a broad spectrum of reported dietary phenomena. A diet of grain-free whole foods with carbohydrate from cellular

  4. Leptin production during early starvation in lean and obese women.

    Science.gov (United States)

    Klein, S; Horowitz, J F; Landt, M; Goodrick, S J; Mohamed-Ali, V; Coppack, S W

    2000-02-01

    We evaluated abdominal adipose tissue leptin production during short-term fasting in nine lean [body mass index (BMI) 21 +/- 1 kg/m(2)] and nine upper body obese (BMI 36 +/- 1 kg/m(2)) women. Leptin kinetics were determined by arteriovenous balance across abdominal subcutaneous adipose tissue at 14 and 22 h of fasting. At 14 h of fasting, net leptin release from abdominal adipose tissue in obese subjects (10.9 +/- 1.9 ng x 100 g tissue x (-1) x min(-1)) was not significantly greater than the values observed in the lean group (7.6 +/- 2.1 ng x 100 g(-1) x min(-1)). Estimated whole body leptin production was approximately fivefold greater in obese (6.97 +/- 1.18 microg/min) than lean subjects (1.25 +/- 0.28 microg/min) (P production rates decreased in both lean and obese groups (to 3.10 +/- 1.31 and 10.5 +/- 2.3 ng x 100 g adipose tissue(-1) x min(-1), respectively). However, the relative declines in both arterial leptin concentration and local leptin production in obese women (arterial concentration 13.8 +/- 4.4%, local production 10.0 +/- 12.3%) were less (P lean women (arterial concentration 39.0 +/- 5.5%, local production 56.9 +/- 13.0%). This study demonstrates that decreased leptin production accounts for the decline in plasma leptin concentration observed after fasting. However, compared with lean women, the fasting-induced decline in leptin production is blunted in women with upper body obesity. Differences in leptin production during fasting may be responsible for differences in the neuroendocrine response to fasting previously observed in lean and obese women.

  5. Leptin, adiponectin, leptin to adiponectin ratio and insulin resistance in depressive women.

    Science.gov (United States)

    Zeman, Miroslav; Jirak, Roman; Jachymova, Marie; Vecka, Marek; Tvrzicka, Eva; Zak, Ales

    2009-01-01

    Depressive disorder (DD) is associated with an increased risk of type 2 diabetes mellitus (DM2) and cardiovascular disease (CVD). It was suggested, that metabolic syndrome (MetS), cluster of metabolic and hormonal changes, such as insulin resistence (IR), abdominal obesity, dyslipidemia, arterial hypertension and elevated fasting glycaemia, could stand behind the connection. Recent findings have shown, that adipocytokines leptin and adiponectin might play a role in both depression and MetS. The aim of this pilot study was to observe the plasma concentrations of leptin, adiponectin, leptin-to-adiponectin ratio and indices of IR in women with depressive disorder. The plasma leptin, adiponectin, parameters of lipid and glucose homeostasis and indices of IR were investigated in a group of 38 women with DD. The results were compared with those of 38 healthy women of the control group, matched for age. Depressive women differed significantly from the controls in higher concentrations of plasma leptin (p insulin (p insulin sensitivity was lower (p <0.01). HAM-D score of DD cases correlated negatively with adiponectin (r = - 0.3505; p < 0.05), independently of HOMA-IR. We have not found in DD group any differences between the drug free patients and those treated either with escitaloprame alone or in the combination with mirtazapine. The results of the pilot study presented support the hypothesis that at least part of DD cases has increased leptin serum levels and certain features of MetS. It could be the factor connecting depression with an increased risk of either DM2 or CVD.

  6. Leptin, An Adipokine With Central Importance in the Global Obesity Problem.

    Science.gov (United States)

    Mechanick, Jeffrey I; Zhao, Shan; Garvey, W Timothy

    2017-12-13

    Leptin has central importance in the global obesity and cardiovascular disease problem. Leptin is principally secreted by adipocytes and acts in the hypothalamus to suppress appetite and food intake, increase energy expenditure, and regulate body weight. Based on clinical translation of specific and networked actions, leptin affects the cardiovascular system and may be a marker and driver of cardiometabolic risk factors with interventions that are actionable by cardiologists. Leptin subnetwork analysis demonstrates a statistically significant role for ethnoculturally and socioeconomically appropriate lifestyle intervention in cardiovascular disease. Emergent mechanistic components and potential diagnostic or therapeutic targets include hexokinase 3, urocortins, clusterin, sialic acid-binding immunoglobulin-like lectin 6, C-reactive protein, platelet glycoprotein VI, albumin, pentraxin 3, ghrelin, obestatin prepropeptide, leptin receptor, neuropeptide Y, and corticotropin-releasing factor receptor 1. Emergent associated symptoms include weight change, eating disorders, vascular necrosis, chronic fatigue, and chest pain. Leptin-targeted therapies are reported for lipodystrophy and leptin deficiency, but they are investigational for leptin resistance, obesity, and other chronic diseases. Copyright © 2017 World Heart Federation (Geneva). Published by Elsevier B.V. All rights reserved.

  7. Obesity and the Ageing Brain: Could Leptin Play a Role in Neurodegeneration?

    Directory of Open Access Journals (Sweden)

    G. H. Doherty

    2011-01-01

    Full Text Available Obesity and ageing are both characteristics of the human population that are on the increase across the globe. It has long been established that ageing is the major risk factor for neurodegenerative conditions such as Alzheimer's disease, and it is becoming increasingly evident that obesity is another such factor. Leptin resistance or insensitivity has been uncovered as a cause of obesity, and in addition the leptin signalling system is less potent in the elderly. Taken together, these findings reveal that this molecule may be a link between neurodegeneration and obesity or ageing. It is now known that leptin has beneficial effects on both the survival and neurophysiology of the neurons that are lost in Alzheimer's disease suggesting that it may be an important research target in the quest for strategies to prevent, halt, or cure this condition.

  8. Adiponectin and leptin in overweight/obese and lean women with polycystic ovary syndrome.

    Science.gov (United States)

    Chen, Chin-I; Hsu, Ming-I; Lin, Shyh-Hsiang; Chang, Yuan-Chin I; Hsu, Chun-Sen; Tzeng, Chii-Ruey

    2015-04-01

    The objective of this study was to evaluate the adiponectin and leptin levels in overweight/obese and lean women with polycystic ovary syndrome (PCOS). This was a retrospective study. Of the 422 studied patients, 224 women with PCOS and 198 women without PCOS were evaluated. Insulin resistance and the metabolic components were assessed. The adiponectin and leptin levels were also evaluated. Adiponectin was negatively correlated with insulin resistance, body mass index (BMI), and total testosterone, triglyceride, and low-density lipoprotein (LDL) levels; conversely, leptin reversed the aforementioned reaction and was negatively correlated with adiponectin levels. The adiponectin to leptin ratios were significantly lower in PCOS women than in those without PCOS. Compared to women with non-PCOS, overweight/obese women with PCOS had lower serum adiponectin levels than women without PCOS, which was not the case for lean women. Conversely, lean women with PCOS had higher serum leptin levels than those without PCOS, which was not the case for overweight/obese women. Adipose tissue might play an important role in the metabolic complications in women with PCOS. To study the impact of obesity biomarkers in women with PCOS, overweight/obese and lean women should be considered separately.

  9. Renaissance of leptin for obesity therapy

    DEFF Research Database (Denmark)

    Quarta, Carmelo; Sánchez-Garrido, Miguel A; Tschöp, Matthias H

    2016-01-01

    evident that leptin as a stand-alone therapy is not an effective approach, the potential for employing sensitising pharmacology to unleash the weight-lowering properties of leptin has injected new hope into the field. Fascinatingly, these leptin-sensitising agents seem to act via distinct metabolic...

  10. [Obesity and leptin association in three Chilean aboriginal populations].

    Science.gov (United States)

    Pérez, F; Santos, J L; Albala, C; Calvillán, M; Carrasco, E

    2000-01-01

    Although there is a clear relationship between body mass index and leptin levels, few authors have addressed the possible influence of ethnic factors on these levels. To measure serum leptin in three different Chilean aboriginal populations. Fasting serum leptin and insulin levels were measured by radioimmunoassay in 345 rural mapuche individuals, 247 rural aymara subjects and 162 urban mapuche subjects. A body mass index of 27.5 kg/m2 was used as cutoff point to classify study subjects. Among the three ethnic groups, women had serum leptin levels three times higher than men. In all three ethnic groups, there was a significant association between leptin levels, body mass index and gender (r2 = 0.32 and 0.5 p mapuche, r2 = 0.32 and 0.5 p mapuche populations). No differences in leptin levels were observed for the interaction between age and insulin. The increments per quartile in leptin levels were lower among mapuche than aymara individuals. Rural mapuche individuals have a high frequency of obesity. However their leptin levels are lower than those of aymara or urban mapuche populations. The higher leptin levels observed in urban mapuche subjects could be due to environmental influences.

  11. Obesity, Fat Mass and Immune System: Role for Leptin

    Directory of Open Access Journals (Sweden)

    Vera Francisco

    2018-06-01

    Full Text Available Obesity is an epidemic disease characterized by chronic low-grade inflammation associated with a dysfunctional fat mass. Adipose tissue is now considered an extremely active endocrine organ that secretes cytokine-like hormones, called adipokines, either pro- or anti-inflammatory factors bridging metabolism to the immune system. Leptin is historically one of most relevant adipokines, with important physiological roles in the central control of energy metabolism and in the regulation of metabolism-immune system interplay, being a cornerstone of the emerging field of immunometabolism. Indeed, leptin receptor is expressed throughout the immune system and leptin has been shown to regulate both innate and adaptive immune responses. This review discusses the latest data regarding the role of leptin as a mediator of immune system and metabolism, with particular emphasis on its effects on obesity-associated metabolic disorders and autoimmune and/or inflammatory rheumatic diseases.

  12. Leptin ameliorates ischemic necrosis of the femoral head in rats with obesity induced by a high-fat diet.

    Science.gov (United States)

    Zhou, Lu; Jang, Kyu Yun; Moon, Young Jae; Wagle, Sajeev; Kim, Kyoung Min; Lee, Kwang Bok; Park, Byung-Hyun; Kim, Jung Ryul

    2015-03-23

    Obesity is a risk factor for ischemic necrosis of the femoral head (INFH). The purpose of this study was to determine if leptin treatment of INFH stimulates new bone formation to preserve femoral head shape in rats with diet-induced obesity. Rats were fed a high-fat diet (HFD) or normal chow diet (NCD) for 16 weeks to induce progressive development of obesity. Avascular necrosis of the femoral head (AVN) was surgically induced. Adenovirus-mediated introduction of the leptin gene was by intravenous injection 2 days before surgery-induced AVN. At 6 weeks post-surgery, radiologic and histomorphometric assessments were performed. Leptin signaling in tissues was examined by Western blot. Osteogenic markers were analyzed by real-time RT-PCR. Radiographs showed better preservation of femoral head architecture in the HFD-AVN-Leptin group than the HFD-AVN and HFD-AVN-LacZ groups. Histology and immunohistochemistry revealed the HFD-AVN-Leptin group had significantly increased osteoblastic proliferation and vascularity in infarcted femoral heads compared with the HFD-AVN and HFD-AVN-LacZ groups. Intravenous injection of leptin enhanced serum VEGF levels and activated HIF-1α pathways. Runx 2 and its target genes were significantly upregulated in the HFD-AVN-Leptin group. These results indicate that leptin resistance is important in INFH pathogenesis. Leptin therapy could be a new strategy for INFH.

  13. The changes of serum leptin and insulin contents in elderly male patients with obesity-related hypertension

    International Nuclear Information System (INIS)

    Zhan Hao; Huang Daijuan; Yuan Bin; He Yong; Zhang Yongxue

    2004-01-01

    To study the contents of serum leptin and insulin in elderly male patients with obesity-related hypertension, the levels of serum leptin and insulin in 21 normotensive cases and 41 hypertensive cases of them were determined by RIA. The results showed that the levels of serum leptin and insulin between hypertensives and normotensives in the non-obese groups were not significantly different (P>0.05). Compared with normotensives, the levels of serum leptin and insulin of hypertensives in the obese groups remarkably increased 1.8μg/L and 2.7 mIU/L respectively (P<0.01). The levels of serum leptin and insulin in the patients with obesity - related hypertension were markedly higher than those in the patients with non-obesity-related hypertension and elevated 2.7μg/L and 4.7mIU/L (P<0.01) respectively. Insulin-sensitivity index (ISI) successively decreased in the groups of HBPOb, NBPOb, HBPNOb and NBPNOb (relative ISI 0.50, 0.68, 0.92, 1 respectively). It is concluded that leptin-resistance and insulin-resistance exist in male elderly patients with obesity-related hypertension

  14. Leptin activates oxytocin neurons of the hypothalamic paraventricular nucleus in both control and diet-induced obese rodents.

    Directory of Open Access Journals (Sweden)

    Mario Perello

    Full Text Available The adipocyte-derived hormone leptin acts in the brain to reduce body weight and fat mass. Recent studies suggest that parvocellular oxytocin (OXT neurons of the hypothalamic paraventricular nucleus (PVN can mediate body weight reduction through inhibition of food intake and increased energy expenditure. However, the role of OXT neurons of the PVN as a primary target of leptin has not been investigated. Here, we studied the potential role of OXT neurons of the PVN in leptin-mediated effects on body weight regulation in fasted rats. We demonstrated that intracerebroventricular (ICV leptin activates STAT3 phosphorylation in OXT neurons of the PVN, showed that this occurs in a subpopulation of OXT neurons that innervate the nucleus of the solitary tract (NTS, and provided further evidence suggesting a role of OXT to mediate leptin's actions on body weight. In addition, our results indicated that OXT neurons are responsive to ICV leptin and mediate leptin effects on body weight in diet induced obese (DIO rats, which are resistant to the anorectic effects of the hormone. Thus, we conclude that leptin targets a specific subpopulation of parvocellular OXT neurons of the PVN, and that this action may be important for leptin's ability to reduce body weight in both control and obese rats.

  15. Leptin Production by Encapsulated Adipocytes Increases Brown Fat, Decreases Resistin, and Improves Glucose Intolerance in Obese Mice.

    Directory of Open Access Journals (Sweden)

    David J DiSilvestro

    Full Text Available The neuroendocrine effects of leptin on metabolism hold promise to be translated into a complementary therapy to traditional insulin therapy for diabetes and obesity. However, injections of leptin can provoke inflammation. We tested the effects of leptin, produced in the physiological adipocyte location, on metabolism in mouse models of genetic and dietary obesity. We generated 3T3-L1 adipocytes constitutively secreting leptin and encapsulated them in a poly-L-lysine membrane, which protects the cells from immune rejection. Ob/ob mice (OB were injected with capsules containing no cells (empty, OB[Emp], adipocytes (OB[3T3], or adipocytes overexpressing leptin (OB[Lep] into both visceral fat depots. Leptin was found in the plasma of OB[Lep], but not OB[Emp] and OB[3T3] mice at the end of treatment (72 days. The OB[Lep] and OB[3T3] mice have transiently suppressed appetite and weight loss compared to OB[Emp]. Only OB[Lep] mice have greater brown fat mass, metabolic rate, and reduced resistin plasma levels compared to OB[Emp]. Glucose tolerance was markedly better in OB[Lep] vs. OB[Emp] and OB[3T3] mice as well as in wild type mice with high-fat diet-induced obesity and insulin resistance treated with encapsulated leptin-producing adipocytes. Our proof-of-principle study provides evidence of long-term improvement of glucose tolerance with encapsulated adipocytes producing leptin.

  16. Kadar leptin saliva dan kejadian karies gigi anak obesitas (Salivary leptin levels and caries incidence in obese children

    Directory of Open Access Journals (Sweden)

    Elfrida Atzmaryanni

    2013-09-01

    Full Text Available Background: Children with obesity have a lower incidence of caries. Salivary leptin levels of obese children is higher than normal children. Leptin is protein hormone, contained in saliva. Salivary proteins maintain the balance of the ecosystem in the mouth. Purpose: The article was aimed to study the correlation of salivary leptin levels with caries incidence in obese children. Review: Mouth is reflection of the health status and so many changes occur as a weight gain. Child with obesity has a low incidence of caries than normal. This condition is associated with changes in oral cavity, especially the increase in salivary leptin. Caries is a disease of hard tissues cause by the activty of microorganisms, especially Streptococcus mutans. Salivary proteins maintain the balance of the ecosystem in the mouth. Leptin is a protein saliva, produced predominantly in adipose tissue and conduct active transport to saliva. Salivary leptin works in two ways: as an antimicrobial which prevents the attachment of bacteria on tooth surface or by inducing cytokine that affect the immune system in oral cavity. Conclusion: Salivary leptin is higher in obese children than in normal children. The low incidence of caries on obesity is associated with salivary leptin. Alteration in salivary composition and flow rate also decreased caries in obesity.Latar belakang: Anak yang mengalami obesitas memiliki insiden karies yang rendah. Kadar leptin saliva anak obesitas lebih tinggi dari anak normal. Leptin merupakan salah satu protein hormon yang terdapat di saliva. Protein saliva berfungsi untuk menjaga keseimbangan ekosistem di mulut. Tujuan: Artikel ini bertujuan mempelajari hubungan antara kadar leptin di dalam saliva dengan kejadian karies anak obesitas. Tinjauan pustaka: Rongga mulut merupakan cerminan dari status kesehatan dan banyak perubahan yang terjadi seiring peningkatan berat badan seseorang. Anak Obesitas memiliki insiden karies yang rendah jika dibandingkan

  17. Agrarian diet and diseases of affluence – Do evolutionary novel dietary lectins cause leptin resistance?

    Directory of Open Access Journals (Sweden)

    Jönsson Tommy

    2005-12-01

    Full Text Available Abstract Background The global pattern of varying prevalence of diseases of affluence, such as obesity, cardiovascular disease and diabetes, suggests that some environmental factor specific to agrarian societies could initiate these diseases. Presentation of the hypothesis We propose that a cereal-based diet could be such an environmental factor. Through previous studies in archaeology and molecular evolution we conclude that humans and the human leptin system are not specifically adapted to a cereal-based diet, and that leptin resistance associated with diseases of affluence could be a sign of insufficient adaptation to such a diet. We further propose lectins as a cereal constituent with sufficient properties to cause leptin resistance, either through effects on metabolism central to the proper functions of the leptin system, and/or directly through binding to human leptin or human leptin receptor, thereby affecting the function. Testing the hypothesis Dietary interventions should compare effects of agrarian and non-agrarian diets on incidence of diseases of affluence, related risk factors and leptin resistance. A non-significant (p = 0.10 increase of cardiovascular mortality was noted in patients advised to eat more whole-grain cereals. Our lab conducted a study on 24 domestic pigs in which a cereal-free hunter-gatherer diet promoted significantly higher insulin sensitivity, lower diastolic blood pressure and lower C-reactive protein as compared to a cereal-based swine feed. Testing should also evaluate the effects of grass lectins on the leptin system in vivo by diet interventions, and in vitro in various leptin and leptin receptor models. Our group currently conducts such studies. Implications of the hypothesis If an agrarian diet initiates diseases of affluence it should be possible to identify the responsible constituents and modify or remove them so as to make an agrarian diet healthier.

  18. Common Genetic Components of Obesity Traits and Serum Leptin

    DEFF Research Database (Denmark)

    Hasselbalch, Ann L; Benyamin, Beben; Visscher, Peter M

    2008-01-01

    To estimate common and distinct genetic influences on a panel of obesity-related traits and serum leptin level in adults. In a cross-sectional study of 625 Danish, adult, healthy, monozygotic, and same-sex dizygotic twin pairs of both genders, we carried out detailed anthropometry (height, weight...... components, which suggests that it is important to distinguish between the different phenotypes in the search for genes involved in the development of obesity.Obesity (2008) doi:10.1038/oby.2008.440........ For leptin vs. the various measures of overall and local fatness the correlations ranged from 0.54 to 0.74 in men and from 0.48 to 0.75 in women. All correlations were significantly different genetic...

  19. Leptin, adiponectin and serotonin levels in lean and obese dogs.

    Science.gov (United States)

    Park, Hyung-Jin; Lee, Sang-Eun; Oh, Jung-Hyun; Seo, Kyoung-Won; Song, Kun-Ho

    2014-05-13

    Serotonin (5-hydroytryptamine or 5HT) is associated with numerous behavioral and psychological factors and is a biochemical marker of mood. 5HT is involved in the hypothalamic regulation of energy consumption. 5HT controls appetite in the central nerve system (CNS) and stimulates intestinal mobility. There are few studies looking at the role of 5HT and the relationship between peripheral circulating serotonin and obesity. The aim of this study was to find any differences in leptin, adiponectin, and 5HT between lean and obese dogs and to identify correlations among these factors. Leptin, triglyceride (TG) and cholesterol levels were higher in the obese group (all p obese group (p obesity in dogs. To the best of our knowledge, this is the first study to evaluate peripheral 5HT levels in obese dogs. From this research, we can assume that 5HT may be correlated with canine obesity. Further studies will be needed to further elucidate the role of low serum 5HT levels in canine obesity.

  20. OBESITY, LEPTIN, AND CORONARY HEART DISEASE

    OpenAIRE

    Hergenf, Gülay

    2016-01-01

    Obesity is an important health problem both in developed and developing countries. Obesity is an abnormal increase in body weight due to fat deposition. The real cause of obesity is unknown but genetic, environmental factors and family eating habits, hormonal, and psychological factors have roles. Regardless of the origin of the disease, obesity develops when caloric intake exceeds the caloric needs of the individual. Adipose tissue is not merely a fat store, it is metabolically active and al...

  1. GLP-1/glucagon coagonism restores leptin responsiveness in obese mice chronically maintained on an obesogenic diet

    DEFF Research Database (Denmark)

    Clemmensen, Christoffer; Chabenne, Joseph; Finan, Brian

    2014-01-01

    We recently reported restoration of leptin responsiveness in diet-induced obese (DIO) mice using a pharmacologically optimized, polyethylene-glycolated (PEG)-leptin analog in combination with exendin-4 or FGF21. However, the return of leptin action required discontinuation of high-fat diet (HFD...... cotreatment. In summary, we report that GLP-1/glucagon coagonism restores leptin responsiveness in mice maintained on a HFD, thus emphasizing the translational value of this polypharmacotherapy for the treatment of obesity and diabetes....

  2. Clinical value of combined determining leptin, T and E2 in male teenager obesity patients

    International Nuclear Information System (INIS)

    Bai Zhenlian; Lv Tongqin; Wu Qiuhua

    2006-01-01

    To study clinical significance of combined detection of leptin, T and E 2 for teenager obesity patients, levels of leptin, T and E 2 in male teenagers obesity patients and male adult obesity patients were determined by RIA. The result showed that in all obesity patients, the levels of leptin and E 2 were much higher than those in normal controls and T was lower than that in normal controls. After treatment, leptin and E 2 were decreased and T was increased significantly in teenager obesity patients, but only leptin was decreased in adult obesity patients. All results indicate that combined detection of leptin, T and E 2 could find endocrine and metabolism disorder of obese teenagers at early stage, instituting prevention and treatment without delay.(authors)

  3. Insulin and leptin relations in obesity: a multimedia approach.

    Science.gov (United States)

    Yokaichiya, Daniela K; Galembeck, Eduardo; Torres, Bayardo B; Da Silva, José Antônio; de Araujo, Daniele R

    2008-09-01

    Obesity has been recognized as a worldwide public health problem. It significantly increases the chances of developing several diseases, including Type II diabetes. The roles of insulin and leptin in obesity involve reactions that can be better understood when they are presented step by step. The aim of this work was to design software with data from some of the most recent publications on obesity, especially those concerning the roles of insulin and leptin in this metabolic disturbance. The most notable characteristic of this software is the use of animations representing the cellular response together with the presentation of recently discovered mechanisms on the participation of insulin and leptin in processes leading to obesity. The software was field tested in the Biochemistry of Nutrition web-based course. After using the software and discussing its contents in chatrooms, students were asked to answer an evaluation survey about the whole activity and the usefulness of the software within the learning process. The teaching assistants (TA) evaluated the software as a tool to help in the teaching process. The students' and TAs' satisfaction was very evident and encouraged us to move forward with the software development and to improve the use of this kind of educational tool in biochemistry classes.

  4. Relationship between expression of leptin receptors mRNA in breast tissue, plasma leptin level in breast cancer patients with obesity and clinical pathologic data

    International Nuclear Information System (INIS)

    Li Chunrui; Liu Wenli; Sun Hanying; Zhou Jianfeng

    2007-01-01

    In order to investigate the expression of leptin receptors mRNA in breast tissue and plasma leptin levels in breast cancer patients with obesity and their relationship with clinical pathologic data, 124 subjects who were either obesity or had suffered from breast benign disease with obesity, or breast cancer with obesity were entered into this study. The levels of plasma leptin in all subjects were determined and leptin receptors mRNA expression levels were measured by RT-PCR in breast tissue of breast cancer patients with obesity and breast benign disease with obesity. The results showed that plasma leptin levels in breast cancer patients with obesity were significantly higher than those in breast benign disease with obesity and obesity patients alone (P<0.05). The expression of the leptin receptor long form [-Lep-R(L)-] mRNA and the leptin receptor short form [-Lep-R(S)-] mRNA in breast tissue of breast cancer patients with obesity were significantly higher than that in breast tissue of breast benign disease patients with obesity (P<0.05). The plasma leptin level had remarkable positive correlation with the expressions of the Lep-R(L) mRNA and the Lep-R(S) mRNA. The plasma leptin level and leptin receptors mRNA expression levels in patients were not correlated with the axillary node metastasis, menopause, the TNM stage or pathological type. Therefore, leptin may have a promoting effect on the carcinogenesis of breast cancer. (authors)

  5. Plasma resistin, adiponectin and leptin levels in relation to insulin resistance

    International Nuclear Information System (INIS)

    Shousha, M.A.; Soliman, S.E.T.

    2010-01-01

    Adipose tissue regulates insulin sensitivity via the circulating adipo cytokines, adiponectin, resistin and leptin. The objective of this study was to compare the levels of resistin, adiponectin and leptin in lean and obese subjects and determine the relationship between circulating adipocytokines and insulin resistance. We examined plasma levels of resistin, adiponectin and leptin in 20 lean subjects with mean body mass index (BMI) of 24, and, 36 nondiabetic obese individuals with mean BMI 34. Insulin resistance was assessed using the homeostasis model assessment ratio (HOMA-R) formula derived from fasting insulin and glucose levels. Resistin levels were not significantly different between the two groups but were significantly higher in women compared with men, 30.4±6.5 vs. 14.4±2.9 mg/l, P<0.01. Resistin did not correlate with BMI but did significantly correlate with HOMA-R, P < 0.01, and this correlation remained significant after adjustment for gender and BMI. Adiponectin levels were significantly reduced in obese compared with lean subjects, P < 0.005 and higher in women, P< 0.001. Adiponectin levels showed significant correlation with HOMA-R and this correlation remained significant after adjustment for gender and BMI. Leptin levels were significantly higher in obese subjects and women and correlated with resistin, but, didn't correlate with HOMA-R. In this small group of patients we demonstrated that insulin resistance correlated most strongly and reciprocally with adiponectin levels. Significant correlation between resistin levels and insulin resistance was also observed. Although a similar trend was apparent for leptin, the correlation with insulin resistance did not achieve statistical significance

  6. Restoration of leptin responsiveness in diet-induced obese mice using an optimized leptin analog in combination with exendin-4 or FGF21

    NARCIS (Netherlands)

    Müller, Timo D.; Sullivan, Lorraine M.; Habegger, Kirk; Yi, Chun-Xia; Kabra, Dhiraj; Grant, Erin; Ottaway, Nickki; Krishna, Radha; Holland, Jenna; Hembree, Jazzminn; Perez-Tilve, Diego; Pfluger, Paul T.; DeGuzman, Michael J.; Siladi, Marc E.; Kraynov, Vadim S.; Axelrod, Douglas W.; DiMarchi, Richard; Pinkstaff, Jason K.; Tschöp, Matthias H.

    2012-01-01

    The identification of leptin as a mediator of body weight regulation provided much initial excitement for the treatment of obesity. Unfortunately, leptin monotherapy is insufficient in reversing obesity in rodents or humans. Recent findings suggest that amylin is able to restore leptin sensitivity

  7. Selective Deletion of Leptin Signaling in Endothelial Cells Enhances Neointima Formation and Phenocopies the Vascular Effects of Diet-Induced Obesity in Mice.

    Science.gov (United States)

    Hubert, Astrid; Bochenek, Magdalena L; Schütz, Eva; Gogiraju, Rajinikanth; Münzel, Thomas; Schäfer, Katrin

    2017-09-01

    Obesity is associated with elevated circulating leptin levels and hypothalamic leptin resistance. Leptin receptors (LepRs) are expressed on endothelial cells, and leptin promotes neointima formation in a receptor-dependent manner. Our aim was to examine the importance of endothelial LepR (End.LepR) signaling during vascular remodeling and to determine whether the cardiovascular consequences of obesity are because of hyperleptinemia or endothelial leptin resistance. Mice with loxP-flanked LepR alleles were mated with mice expressing Cre recombinase controlled by the inducible endothelial receptor tyrosine kinase promoter. Obesity was induced with high-fat diet. Neointima formation was examined after chemical carotid artery injury. Morphometric quantification revealed significantly greater intimal hyperplasia, neointimal cellularity, and proliferation in End.LepR knockout mice, and similar findings were obtained in obese, hyperleptinemic End.LepR wild-type animals. Analysis of primary endothelial cells confirmed abrogated signal transducer and activator of transcription-3 phosphorylation in response to leptin in LepR knockout and obese LepR wild-type mice. Quantitative PCR, ELISA, and immunofluorescence analyses revealed increased expression and release of endothelin-1 in End.LepR-deficient and LepR-resistant cells, and ET receptor A/B antagonists abrogated their paracrine effects on murine aortic smooth muscle cell proliferation. Reduced expression of peroxisome proliferator-activated receptor-γ and increased nuclear activator protein-1 staining was observed in End.LepR-deficient and LepR-resistant cells, and peroxisome proliferator-activated receptor-γ antagonization increased endothelial endothelin-1 expression. Our findings suggest that intact endothelial leptin signaling limits neointima formation and that obesity represents a state of endothelial leptin resistance. These observations and the identification of endothelin-1 as soluble mediator of the

  8. Long-term correction of obesity and diabetes in genetically obese mice by a single intramuscular injection of recombinant adeno-associated virus encoding mouse leptin

    Science.gov (United States)

    Murphy, John E.; Zhou, Shangzhen; Giese, Klaus; Williams, Lewis T.; Escobedo, Jaime A.; Dwarki, Varavani J.

    1997-01-01

    The ob/ob mouse is genetically deficient in leptin and exhibits a phenotype that includes obesity and non-insulin-dependent diabetes melitus. This phenotype closely resembles the morbid obesity seen in humans. In this study, we demonstrate that a single intramuscular injection of a recombinant adeno-associated virus (AAV) vector encoding mouse leptin (rAAV-leptin) in ob/ob mice leads to prevention of obesity and diabetes. The treated animals show normalization of metabolic abnormalities including hyperglycemia, insulin resistance, impaired glucose tolerance, and lethargy. The effects of a single injection have lasted through the 6-month course of the study. At all time points measured the circulating levels of leptin in the serum were similar to age-matched control C57 mice. These results demonstrate that maintenance of normal levels of leptin (2–5 ng/ml) in the circulation can prevent both the onset of obesity and associated non-insulin-dependent diabetes. Thus a single injection of a rAAV vector expressing a therapeutic gene can lead to complete and long-term correction of a genetic disorder. Our study demonstrates the long-term correction of a disease caused by a genetic defect and proves the feasibility of using rAAV-based vectors for the treatment of chronic disorders like obesity. PMID:9391128

  9. Effects of obesity and exercise on testicular leptin signal transduction and testosterone biosynthesis in male mice.

    Science.gov (United States)

    Yi, Xuejie; Gao, Haining; Chen, Dequan; Tang, Donghui; Huang, Wanting; Li, Tao; Ma, Tie; Chang, Bo

    2017-04-01

    To explore the role of the testicular leptin and JAK-STAT[leptin (LEP)-JAK-STAT] pathway in testosterone biosynthesis during juvenile stages and exercise for weight loss, male C57BL/6J mice were randomly divided into normal-diet and high-fat diet groups. After 10 wk, mice in the high-fat diet-fed group were further divided randomly into obese control, obese moderate-volume exercise, and obese high-volume exercise groups. Mice in the obese moderate-volume exercise group were provided with 2 h/day, 6 days/wk swimming exercise for 8 wk, and mice in the obese high-volume exercise group underwent twice the amount of daily exercise intervention as the obese moderate-volume exercise group. The results showed that a high-fat diet causes obesity, leptin resistance, inhibition of the testicular LEP-JAK-STAT pathway, decreased mRNA and protein expression of steroidogenic factor-1, steroidogenic acute regulatory protein, and the P -450 side-chain cleavage enzyme, a decrease in the serum testosterone-to-estradiol ratio, and declines in sperm quality parameters. Both moderate and high-volume exercise were able to reduce body fat and increase the mRNA and protein expression of LEP-JAK-STAT, but only moderate exercise significantly increased the mRNA and protein expression of steroidogenic factor-1, steroidogenic acute regulatory protein, and P -450 side-chain cleavage enzyme and significantly reversed the serum testosterone-to-estradiol ratio and sperm quality parameters. These findings suggest that by impairing the testicular LEP-JAK-STAT pathway, early-stage obesity inhibits the biosynthesis of testosterone and sexual development and reduces male reproductive potential. Long-term moderate and high-volume exercise can effectively reduce body fat and improve obesity-induced abnormalities in testicular leptin signal transduction, whereas only moderate-volume exercise can reverse the negative impacts of obesity on male reproductive function. Copyright © 2017 the American

  10. Obese Neuronal PPARγ Knockout Mice Are Leptin Sensitive but Show Impaired Glucose Tolerance and Fertility.

    Science.gov (United States)

    Fernandez, Marina O; Sharma, Shweta; Kim, Sun; Rickert, Emily; Hsueh, Katherine; Hwang, Vicky; Olefsky, Jerrold M; Webster, Nicholas J G

    2017-01-01

    The peroxisome-proliferator activated receptor γ (PPARγ) is expressed in the hypothalamus in areas involved in energy homeostasis and glucose metabolism. In this study, we created a deletion of PPARγ brain-knockout (BKO) in mature neurons in female mice to investigate its involvement in metabolism and reproduction. We observed that there was no difference in age at puberty onset between female BKOs and littermate controls, but the BKOs gave smaller litters when mated and fewer oocytes when ovulated. The female BKO mice had regular cycles but showed an increase in the number of cycles with prolonged estrus. The mice also had increased luteinizing hormone (LH) levels during the LH surge and histological examination showed hemorrhagic corpora lutea. The mice were challenged with a 60% high-fat diet (HFD). Metabolically, the female BKO mice showed normal body weight, glucose and insulin tolerance, and leptin levels but were protected from obesity-induced leptin resistance. The neuronal knockout also prevented the reduction in estrous cycles due to the HFD. Examination of ovarian histology showed a decrease in the number of primary and secondary follicles in both genotypes due to the HFD, but the BKO ovaries showed an increase in the number of hemorrhagic follicles. In summary, our results show that neuronal PPARγ is required for optimal female fertility but is also involved in the adverse effects of diet-induced obesity by creating leptin resistance potentially through induction of the repressor Socs3. Copyright © 2017 by the Endocrine Society.

  11. The Effects of Reduction Mammaplasty on Serum Leptin Levels and Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Hakan Uzun

    2015-01-01

    Full Text Available Background. The reduction mammaplasty has been a well-executed and known procedure in which considerable amount of fatty tissue is removed from the body. The authors aimed to show the effects of the reduction mammaplasty on serum leptin levels and insulin resistance. Methods. 42 obese female patients who had gigantomastia were operated on. We recorded patients’ demographic and preoperative data, including age, weight, height, and body mass index. Fasting serum leptin, glucose, and insulin levels were noted. Homeostasis model assessment scores were calculated. At the postoperative 8th week, patients were reevaluated in terms of above parameters assessing the presence of any difference. Results. Serum leptin levels were decreased postoperatively and the decrease was statistically significant. We were able to show a decrease in homeostasis model assessment score, which indicated an increase in insulin sensitivity, and this change was statistically significant. A significant correlation between body mass index and leptin change was found postoperatively. Conclusion. Reduction mammaplasty is not solely an aesthetic procedure but it decreases serum leptin levels and increases insulin sensitivity, which may help obese women to reduce their cardiovascular risk.

  12. Importance of leptin signaling and signal transducer and activator of transcription-3 activation in mediating the cardiac hypertrophy associated with obesity.

    Science.gov (United States)

    Leifheit-Nestler, Maren; Wagner, Nana-Maria; Gogiraju, Rajinikanth; Didié, Michael; Konstantinides, Stavros; Hasenfuss, Gerd; Schäfer, Katrin

    2013-07-11

    The adipokine leptin and its receptor are expressed in the heart, and leptin has been shown to promote cardiomyocyte hypertrophy in vitro. Obesity is associated with hyperleptinemia and hypothalamic leptin resistance as well as an increased risk to develop cardiac hypertrophy and heart failure. However, the role of cardiac leptin signaling in mediating the cardiomyopathy associated with increased body weight is unclear, in particular, whether it develops subsequently to cardiac leptin resistance or overactivation of hypertrophic signaling pathways via elevated leptin levels. The cardiac phenotype of high-fat diet (HFD)-induced obese wildtype (WT) mice was examined and compared to age-matched genetically obese leptin receptor (LepR)-deficient (LepRdb/db) or lean WT mice. To study the role of leptin-mediated STAT3 activation during obesity-induced cardiac remodeling, mice in which tyrosine residue 1138 within LepR had been replaced with a serine (LepRS1138) were also analyzed. Obesity was associated with hyperleptinemia and elevated cardiac leptin expression in both diet-induced and genetically obese mice. Enhanced LepR and STAT3 phosphorylation levels were detected in hearts of obese WT mice, but not in those with LepR mutations. Moreover, exogenous leptin continued to induce cardiac STAT3 activation in diet-induced obese mice. Although echocardiography revealed signs of cardiac hypertrophy in all obese mice, the increase in left ventricular (LV) mass and diameter was significantly more pronounced in LepRS1138 animals. LepRS1138 mice also exhibited an increased activation of signaling proteins downstream of LepR, including Jak2 (1.8-fold), Src kinase (1.7-fold), protein kinase B (1.3-fold) or C (1.6-fold). Histological analysis of hearts revealed that the inability of leptin to activate STAT3 in LepRdb/db and LepRS1138 mice was associated with reduced cardiac angiogenesis as well as increased apoptosis and fibrosis. Our findings suggest that hearts from obese mice

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

    International Nuclear Information System (INIS)

    Das, Suvarthi; Kumar, Ashutosh; Seth, Ratanesh Kumar; Tokar, Erik J.; Kadiiska, Maria B.; Waalkes, Michael P.; Mason, Ronald P.; Chatterjee, Saurabh

    2013-01-01

    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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-06-15

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

  15. Modulation of leptin, insulin, and growth hormone in obese pony mares under chronic nutritional restriction and supplementation with ractopamine hydrochloride.

    Science.gov (United States)

    Buff, Preston R; Johnson, Philip J; Wiedmeyer, Charles E; Ganjam, Venkataseshu K; Messer Iv, Nat T; Keisler, Duane H

    2006-01-01

    Horses fed beyond their nutritional requirement and that are physically inactive will develop obesity, which is often accompanied by insulin resistance and heightened risk of laminitis. The use of pharmacologic agents in combination with nutritional restriction may promote weight loss in obese horses unable to exercise because of laminitic pain. This study shows that reducing feed intake of brome grass hay to 75% of ad libitum intake in obese pony mares reduces body weight without induced exercise. Additional supplementation of ractopamine hydrochloride for 6 weeks resulted in a tendency for increased weight loss. Subsequent modulation of obesity-associated hormones, leptin and insulin, as a result of caloric restriction was observed.

  16. The influence of leptin on Th1/Th2 balance in obese children with asthma

    Directory of Open Access Journals (Sweden)

    Doaa Mohammed Youssef

    2013-09-01

    Full Text Available OBJECTIVE: In individuals with asthma, obesity induces the production of leptin and is associated with disease severity. Our objective was to evaluate the levels of serum leptin and their effect on Th1/Th2 balance in obese and non-obese children with asthma, as well as to investigate the association between serum leptin levels and clinical outcomes. METHODS: We evaluated 50 atopic children with physician-diagnosed moderate-to-severe persistent asthma and 20 controls. The children with asthma were divided into two groups, by body mass index percentile: obese (n = 25 and non-obese (n = 25. From all subjects, we collected peripheral blood samples in order to determine the levels of leptin, IFN-γ, and IL-4. Asthma severity was assessed by an asthma symptom score, and the results were correlated with the parameters studied. RESULTS: Serum leptin levels were significantly higher in the obese asthma group than in the non-obese asthma group, as well as being significantly higher in the children with asthma than in the controls, whereas IFN-γ levels were significantly higher and IL-4 levels were significantly lower in the obese asthma group than in the non-obese asthma group. In addition, the obese asthma group showed higher asthma symptom scores and significantly lower FEV1 (% of predicted than did the non-obese asthma group. There was a significant positive correlation between leptin and IFN-γ levels only in the obese asthma group. CONCLUSIONS: Although leptin is involved in the pathogenesis of asthma in obese and non-obese children, its effect is more pronounced in the former. In the presence of high leptin levels, only obese children with asthma exhibited Th1 polarization, with higher IFN-γ levels and greater asthma severity.

  17. Leptin - a link between obesity and osteoarthritis. applications for prevention and treatment.

    Science.gov (United States)

    Vuolteenaho, Katriina; Koskinen, Anna; Moilanen, Eeva

    2014-01-01

    Osteoarthritis (OA) is the most common cause of musculoskeletal disability and pain in the world. The current drug treatment for OA is symptom relieving, and there is an urgent need for treatments that could retard, prevent or repair cartilage destruction in OA. Obesity is a major risk factor for OA. Traditionally, it has been thought to contribute to the development of OA by increasing the load on weight-bearing joints. However, this appears to be an over-simplification, because obesity is also linked to OA in the hand and finger joints. Recent studies have shown that adipocytokine leptin is a possible link between obesity and OA: Leptin levels in synovial fluid are increased in obese patients, leptin receptor (Ob-R) is expressed in cartilage, and leptin induces the production of matrix metalloproteinases (MMPs), pro-inflammatory mediators and nitric oxide (NO) in chondrocytes. Furthermore, according to the very recent findings, not only leptin levels in the joint but also leptin sensitivity in the cartilage are enhanced in obese OA patients. The findings supporting leptin as a causative link between obesity and OA offer leptin as a potential target to the development of disease-modifying drugs for osteoarthritis (DMOAD), especially for obese patients. © 2013 Nordic Pharmacological Society. Published by John Wiley & Sons Ltd.

  18. Transgenic neuronal expression of proopiomelanocortin attenuates hyperphagic response to fasting and reverses metabolic impairments in leptin-deficient obese mice.

    Science.gov (United States)

    Mizuno, Tooru M; Kelley, Kevin A; Pasinetti, Giulio M; Roberts, James L; Mobbs, Charles V

    2003-11-01

    Hypothalamic proopiomelanocortin (POMC) gene expression is reduced in many forms of obesity and diabetes, particularly in those attributable to deficiencies in leptin or its receptor. To assess the functional significance of POMC in mediating metabolic phenotypes associated with leptin deficiency, leptin-deficient mice bearing a transgene expressing the POMC gene under control of the neuron-specific enolase promoter were produced. The POMC transgene attenuated fasting-induced hyperphagia in wild-type mice. Furthermore, the POMC transgene partially reversed obesity, hyperphagia, and hypothermia and effectively normalized hyperglycemia, glucosuria, glucose intolerance, and insulin resistance in leptin-deficient mice. Effects of the POMC transgene on glucose homeostasis were independent of the partial correction of hyperphagia and obesity. Furthermore, the POMC transgene normalized the profile of hepatic and adipose gene expression associated with gluconeogenesis, glucose output, and insulin sensitivity. These results indicate that central POMC is a key modulator of glucose homeostasis and that agonists of POMC products may provide effective therapy in treating impairments in glucose homeostasis when hypothalamic POMC expression is reduced, as occurs with leptin deficiency, hypothalamic damage, and aging.

  19. Protection against high-fat diet-induced obesity in Helz2-deficient male mice due to enhanced expression of hepatic leptin receptor.

    Science.gov (United States)

    Yoshino, Satoshi; Satoh, Tetsurou; Yamada, Masanobu; Hashimoto, Koshi; Tomaru, Takuya; Katano-Toki, Akiko; Kakizaki, Satoru; Okada, Shuichi; Shimizu, Hiroyuki; Ozawa, Atsushi; Tuchiya, Takafumi; Ikota, Hayato; Nakazato, Yoichi; Mori, Munemasa; Matozaki, Takashi; Sasaki, Tsutomu; Kitamura, Tadahiro; Mori, Masatomo

    2014-09-01

    Obesity arises from impaired energy balance, which is centrally coordinated by leptin through activation of the long form of leptin receptor (Leprb). Obesity causes central leptin resistance. However, whether enhanced peripheral leptin sensitivity could overcome central leptin resistance remains obscure. A peripheral metabolic organ targeted by leptin is the liver, with low Leprb expression. We here show that mice fed a high-fat diet (HFD) and obese patients with hepatosteatosis exhibit increased expression of hepatic helicase with zinc finger 2, a transcriptional coactivator (Helz2), which functions as a transcriptional coregulator of several nuclear receptors, including peroxisome proliferator-activated receptor γ in vitro. To explore the physiological importance of Helz2, we generated Helz2-deficient mice and analyzed their metabolic phenotypes. Helz2-deficient mice showing hyperleptinemia associated with central leptin resistance were protected against HFD-induced obesity and had significantly up-regulated hepatic Leprb expression. Helz2 deficiency and adenovirus-mediated liver-specific exogenous Leprb overexpression in wild-type mice significantly stimulated hepatic AMP-activated protein kinase on HFD, whereas Helz2-deficient db/db mice lacking functional Leprb did not. Fatty acid-β oxidation was increased in Helz2-deficeint hepatocytes, and Helz2-deficient mice revealed increased oxygen consumption and decreased respiratory quotient in calorimetry analyses. The enhanced hepatic AMP-activated protein kinase energy-sensing pathway in Helz2-deficient mice ameliorated hyperlipidemia, hepatosteatosis, and insulin resistance by reducing lipogenic gene expression and stimulating lipid-burning gene expression in the liver. These findings together demonstrate that Helz2 deficiency ameliorates HFD-induced metabolic abnormalities by stimulating endogenous hepatic Leprb expression, despite central leptin resistance. Hepatic HELZ2 might be a novel target molecule for

  20. Leptin: A biomarker for sleep disorders?

    OpenAIRE

    Pan, Weihong; Kastin, Abba J.

    2013-01-01

    Leptin, a pleiotropic protein hormone produced mainly by fat cells, regulates metabolic activity and many other physiological functions. The intrinsic circadian rhythm of blood leptin is modulated by gender, development, feeding, fasting, sleep, obesity, and endocrine disorders. Hyperleptinemia is implicated in leptin resistance. To determine the specificity and sensitivity of leptin concentrations in sleep disorders, we summarize here the alterations of leptin in four conditions in animal an...

  1. Leptin Action on GABAergic Neurons Prevents Obesity and Reduces Inhibitory Tone to POMC Neurons

    OpenAIRE

    Vong, Linh; Ye, Chianping; Yang, Zongfang; Choi, Brian; Chua, Streamson; Lowell, Bradford B.

    2011-01-01

    Leptin acts in the brain to prevent obesity. The underlying neurocircuitry responsible for this is poorly understood, in part due to incomplete knowledge regarding first order, leptin-responsive neurons. To address this, we and others have been removing leptin receptors from candidate first order neurons. While functionally relevant neurons have been identified, the observed effects have been small suggesting that most first order neurons remain unidentified. Here we take an alternative appro...

  2. Adiponectin but not leptin is involved in early hepatic disease in morbidly obese patients.

    Science.gov (United States)

    Hindle, Anna Katharine; Edwards, Claire; Mendonsa, Alisha; Rojkind, Marcos; McCaffrey, Tim; Fu, Sidney; Brody, Fred

    2010-07-01

    Pathologic changes in the liver are common in morbidly obese patients, and insulin resistance may potentiate the progression of nonalcoholic steatohepatitis to fibrosis and cirrhosis. This study investigates the impact of leptin and adiponectin in morbidly obese diabetic and nondiabetic patients with regard to histopathologic changes in the liver. Thirty-seven morbidly obese patients who underwent bariatric surgery with liver biopsies were enrolled in the study. Fourteen were diabetic and 23 were nondiabetic. Intraoperative liver tissue was sent for histopathologic analysis and extraneous intraoperative tissue was snap-frozen in liquid nitrogen. Total RNA was extracted and RNA was reverse transcribed to cDNA. Real-time quantitative PCR was performed to determine relative gene expression levels. The data were analyzed using a logarithmic transformation and normalized by 18S ribosome expression. Student's t test was used for statistical analysis with p < or = 0.05 as significant. Adiponectin expression was downregulated 4.4-fold (p < or = 0.05) in liver samples with evidence of inflammation on pathology. When hepatic inflammation was evaluated separately, there were no statistically significant differences in adiponectin levels between the diabetic and nondiabetic patients. However, overall adiponectin levels in hepatic samples of diabetic patients were 3.8-fold higher than those of nondiabetic patients (p < or = 0.05). There were no significant differences in leptin levels regardless of hepatic pathology or diabetic status. This study illustrates that there is a downregulation of adiponectin in morbidly obese patients with inflammatory infiltrates in the liver. Variations in adiponectin levels could be an indicator of disease progression since inflammatory infiltrates are commonly associated with nonalcoholic steatohepatitis (NASH) in morbidly obese patients. Currently, we are using human myofibroblasts derived from livers of morbidly obese people to further

  3. Altered gut microbiota and endocannabinoid system tone in obese and diabetic leptin-resistant mice: impact on apelin regulation in adipose tissue

    NARCIS (Netherlands)

    Geurts, L.; Vos, de W.M.

    2011-01-01

    Growing evidence supports the role of gut microbiota in the development of obesity, type 2 diabetes, and low-grade inflammation. The endocrine activity of adipose tissue has been found to contribute to the regulation of glucose homeostasis and low-grade inflammation. Among the key hormones produced

  4. Benefits of resistance exercise in lean women with fibromyalgia: involvement of IGF-1 and leptin.

    Science.gov (United States)

    Bjersing, Jan L; Larsson, Anette; Palstam, Annie; Ernberg, Malin; Bileviciute-Ljungar, Indre; Löfgren, Monika; Gerdle, Björn; Kosek, Eva; Mannerkorpi, Kaisa

    2017-03-14

    Chronic pain and fatigue improves by exercise in fibromyalgia (FM) but underlying mechanisms are not known. Obesity is increased among FM patients and associates with higher levels of pain. Symptom improvement after aerobic exercise is affected by body mass index (BMI) in FM. Metabolic factors such as insulin-like growth factor 1 (IGF-1) and leptin may be involved. In this study, the aim was to evaluate the role of metabolic factors in lean, overweight and obese women during resistance exercise, in relation to symptom severity and muscle strength in women with FM. Forty-three women participated in supervised progressive resistance exercise, twice weekly for 15-weeks. Serum free and total IGF-1, IGF-binding protein 3 (IGFBP3), adiponectin, leptin and resistin were determined at baseline and after 15-weeks. Level of current pain was rated on a visual analogue scale (0-100 mm). Level of fatigue was rated by multidimensional fatigue inventory (MFI-20) subscale general fatigue (MFIGF). Knee extension force, elbow flexion force and handgrip force were assessed by dynamometers. Free IGF-1 (p = 0.047), IGFBP3 (p = 0.025) and leptin (p = 0.008) were significantly decreased in lean women (n = 18), but not in the overweight (n = 17) and the obese (n = 8). Lean women with FM benefited from resistance exercise with improvements in current pain (p= 0.039, n = 18), general fatigue (MFIGF, p = 0.022, n = 18) and improved elbow-flexion force (p = 0.017, n = 18). In overweight and obese women with FM there was no significant improvement in pain or fatigue but an improvement in elbow flexion (p = 0.049; p = 0.012) after 15 weeks of resistance exercise. The clearest clinical response to resistance exercise was found in lean patients with FM. In these individuals, individualized resistance exercise was followed by changes in IGF-1 and leptin, reduced pain, fatigue and improved muscular strength. In overweight and obese women FM

  5. Reference values for serum leptin in healthy non-obese children and adolescents

    DEFF Research Database (Denmark)

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

    2016-01-01

    . Methods: A total of 1193 healthy, non-obese Danish schoolchildren (730 girls, 463 boys) aged 6–18 years (median 11.9) were examined by trained medical staff. Serum leptin and sOB-R concentrations in venous fasting blood samples were quantitated by immunoassay. Percentile curves of leptin, sOB-R, and free...

  6. Leptin levels are associated with fat oxidation and dietary-induced weight loss in obesity

    DEFF Research Database (Denmark)

    Verdich, C; Toubro, S; Buemann, B

    2001-01-01

    To examine the relationship between fasting plasma leptin and 24-hour energy expenditure (EE), substrate oxidation, and spontaneous physical activity (SPA) in obese subjects before and after a major weight reduction compared with normal weight controls. To test fasting plasma leptin, substrate...

  7. Acute insulin-induced elevations of circulating leptin and feeding inhibition in lean but not obese rats.

    Science.gov (United States)

    Singh, Kimberly A; Boozer, Carol N; Vasselli, Joseph R

    2005-08-01

    Insulin has been shown to stimulate leptin mRNA expression acutely in rat adipose tissue, but its short-term effects on circulating leptin levels, and subsequent feeding behavior, have not been well described. We used 11-mo-old female selectively bred obesity-resistant (OR) and obesity-prone (OP) Sprague-Dawley rats maintained on laboratory chow to investigate this question. At testing, body weights and basal leptin levels of the OP rats were significantly elevated compared with the OR rats. In the 3-h fasted state, injection of 2.0 U insulin/kg ip resulted in significant elevations of plasma leptin at 4 h postinjection in both OP and OR groups (hour 4, +2.50 and +5.98 ng/ml, respectively). In separate feeding tests with the same groups, intake of laboratory chow pellets was significantly inhibited during hours 2-4 after 2.0 U/kg of insulin in the OR (-80.1%, P < 0.05), but not in the OP group, compared with intake after saline injections. In feeding tests with palatable moderately high-fat pellets after 2.0 and 3.0 U insulin/kg ip, significant decreases between hours 2 and 4 in intake were seen in the OR group only (-41.0 and -68.3%, respectively). Thus feeding inhibition coincides with insulin-induced elevations of plasma leptin in lean but not obese Sprague-Dawley rats. Our data suggest that elevations of leptin within the physiological range may contribute to short-term inhibition of food intake in rats and that this process may be stimulated by feeding-related insulin release.

  8. In middle-aged and old obese patients, training intervention reduces leptin level: A meta-analysis.

    Directory of Open Access Journals (Sweden)

    Ildikó Rostás

    Full Text Available Leptin is one of the major adipokines in obesity that indicates the severity of fat accumulation. It is also an important etiological factor of consequent cardiometabolic and autoimmune disorders. Aging has been demonstrated to aggravate obesity and to induce leptin resistance and hyperleptinemia. Hyperleptinemia, on the other hand, may promote the development of age-related abnormalities. While major weight loss has been demonstrated to ameliorate hyperleptinemia, obese people show a poor tendency to achieve lasting success in this field. The question arises whether training intervention per se is able to reduce the level of this adipokine.We aimed to review the literature on the effects of training intervention on peripheral leptin level in obesity during aging, in order to evaluate the independent efficacy of this method. In the studies that were included in our analysis, changes of adiponectin levels (when present were also evaluated.3481 records were identified through searching of PubMed, Embase and Cochrane Library Database. Altogether 19 articles were suitable for analyses.Empirical research papers were eligible provided that they reported data of middle-aged or older (above 45 years of age overweight or obese (body mass index above 25 individuals and included physical training intervention or at least fitness status of groups together with corresponding blood leptin values.We used random effect models in each of the meta-analyses calculating with the DerSimonian and Laird weighting methods. I-squared indicator and Q test were performed to assess heterogeneity. To assess publication bias Egger's test was applied. In case of significant publication bias, the Duval and Tweedie's trim and fill algorithm was used.Training intervention leads to a decrease in leptin level of middle-aged or older, overweight or obese male and female groups, even without major weight loss, indicated by unchanged serum adiponectin levels. Resistance training

  9. Early childhood BMI trajectories in monogenic obesity due to leptin, leptin receptor, and melanocortin 4 receptor deficiency.

    Science.gov (United States)

    Kohlsdorf, Katja; Nunziata, Adriana; Funcke, Jan-Bernd; Brandt, Stephanie; von Schnurbein, Julia; Vollbach, Heike; Lennerz, Belinda; Fritsch, Maria; Greber-Platzer, Susanne; Fröhlich-Reiterer, Elke; Luedeke, Manuel; Borck, Guntram; Debatin, Klaus-Michael; Fischer-Posovszky, Pamela; Wabitsch, Martin

    2018-02-27

    To evaluate whether early childhood body mass index (BMI) is an appropriate indicator for monogenic obesity. A cohort of n = 21 children living in Germany or Austria with monogenic obesity due to congenital leptin deficiency (group LEP, n = 6), leptin receptor deficiency (group LEPR, n = 6) and primarily heterozygous MC4 receptor deficiency (group MC4R, n = 9) was analyzed. A control group (CTRL) was defined that consisted of n = 22 obese adolescents with no mutation in the above mentioned genes. Early childhood (0-5 years) BMI trajectories were compared between the groups at selected time points. The LEP and LEPR group showed a tremendous increase in BMI during the first 2 years of life with all patients displaying a BMI >27 kg/m 2 (27.2-38.4 kg/m 2 ) and %BMI P95 (percentage of the 95th percentile BMI for age and sex) >140% (144.8-198.6%) at the age of 2 years and a BMI > 33 kg/m 2 (33.3-45.9 kg/m 2 ) and %BMI P95  > 184% (184.1-212.6%) at the age of 5 years. The MC4R and CTRL groups had a later onset of obesity with significantly lower BMI values at both time points (p BMI trajectories in this pediatric cohort with monogenic obesity we suggest that BMI values >27.0 kg/m 2 or %BMI P95  > 140% at the age of 2 years and BMI values >33.0 kg/m 2 or %BMI P95  > 184% at the age of 5 years may be useful cut points to identify children who should undergo genetic screening for monogenic obesity due to functionally relevant mutations in the leptin gene or leptin receptor gene.

  10. Influence of dexamethasone and weight loss on the regulation of serum leptin levels in obese individuals

    Directory of Open Access Journals (Sweden)

    D.D.G. Lerario

    2001-04-01

    Full Text Available The adipocyte hormone leptin is thought to serve as a signal to the central nervous system reflecting the status of fat stores. Serum leptin levels and adipocyte leptin messenger RNA levels are clearly increased in obesity. Nevertheless, the factors regulating leptin production are not fully understood. The aim of this study was to determine the effects of in vivo administration of the synthetic glucocorticoid dexamethasone and weight loss on serum leptin levels in two independent protocols. Twenty-five obese subjects were studied (18 women and 7 men, mean age 26.6 ± 6 years, BMI 31.1 ± 2.5 kg/m², %fat 40.3 ± 8.3 and compared at baseline to 22 healthy individuals. Serum levels of leptin, insulin, proinsulin and glucose were assessed at baseline and after ingestion of dexamethasone, 4 mg per day (2 mg, twice daily for two consecutive days. To study the effects of weight loss on serum leptin, 17 of the obese subjects were submitted to a low-calorie dietary intervention trial for 8 weeks and again blood samples were collected. Serum leptin levels were significantly higher in the obese group compared to the control group and a high positive correlation between leptinemia and the magnitude of fat mass was found (r = 0.88, P<0.0001. After dexamethasone, there was a significant increase in serum leptin levels (22.9 ± 12.3 vs 51.4 ± 23.3 ng/ml, P<0.05. Weight loss (86.1 ± 15.1 vs 80.6 ± 14.2 kg, P<0.05 led to a reduction in leptin levels (25.13 ± 12.8 vs 15.9 ± 9.1 ng/ml, P<0.05. We conclude that serum leptin levels are primordially dependent on fat mass magnitude. Glucocorticoids at supraphysiologic levels are potent secretagogues of leptin in obese subjects and a mild fat mass reduction leads to a disproportionate decrease in serum leptin levels. This suggests that, in addition to the changes in fat mass, complex nutritional and hormonal interactions may also play an important role in the regulation of leptin levels.

  11. Serum level of orexin-A, leptin, adiponectin and insulin in north Indian obese women.

    Science.gov (United States)

    Mishra, Sameeksha; Gupta, Vani; Mishra, Supriya; Sachan, Rekha; Asthana, Akash

    2017-12-01

    Obesity is regulated by different metabolic factors like leptin, adiponectin insulin and neuropeptide orexin-A. The aim of this study is to assess the role of these hormones and their interrelationship with obesity in north Indian women. A total of 168 obese women with Body Mass Index (BMI)>30kg/m 2 and 150 lean women (BMIWomen with obesity were further subdivided into two groups according to their BMI, 71 overweight women with the BMI 25-29.9kg/m 2 (mean±S.D: 27.87±0.71) and the 97 obese women with BMI>30kg/m 2 (34.68±1.90). Orexin -A, leptin and adiponectin were estimated using quantitative sandwich enzyme linked immunoassay and insulin was estimated by using an immuno-radiometric assay. Orexin -A and adiponectin level were significantly lower however, leptin and inulin level were significantly higher in obese women as compared with control group. Further, the one- way group analysis showed that the orexin -A and adiponectin level were significantly lower but leptin and insulin level was significantly higher in obese women as compared to overweight and control group respectively. Result showed that the level of adiponectin, leptin, orexin-A and insulin play an important role in the regulation of energy expenditure. In obesity, the activity of these peptides is disturbed. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  12. Study on the plasma leptin level and leptin mRNA expression in cancerous breast tissue in patients with breast carcinoma complicated with obesity

    International Nuclear Information System (INIS)

    Li Chunrui; Liu Wenli; Sun Hanying; Zhou Jianfeng

    2006-01-01

    Objective: To study the plasma leptin level and leptin mRNA expression in cancerous breast tissue in patients with breast cancer complicated with obesity. Methods: Plasma leptin levels were measured with RIA in 48 breast cancer patients with obesity, 36 patients with various benign breast disorders and obesity and 40 controls (with simple obesity only). The leptin mRNA expression in the surgical specimens from the 84 patients with breast disease was also examined with RT-PCR, Results: The plasma leptin levels in the breast cancer patients (12.02 ± 1.23 μg/L) were significantly higher than those in patients with benign breast disorders (9.84 ± 0.98 μg/L) and controls (9.79 ± 1.16 μg/L) (both P<0.05). The expression levels of leptin mRNA in specimens from malignant breast disease (0.71 ± 0.32), were significantly higher than those in specimens from benign breast diseases (0.41 ± 0.26) (P<0.05), The plasma leptin levels and the tissue leptin mRNA expression levels were mutually positively correlated (r=0.4220 ,P 0.0180). These levels were not correlated with the presence of axillary metastasis, TMN stage, menstrual status, pathological classification and other parameters. Conclusion: Leptin might be a promotive factor in the development of breast cancer. (authors)

  13. Leptin deficiency-induced obesity affects the density of mast cells in abdominal fat depots and lymph nodes in mice

    Directory of Open Access Journals (Sweden)

    Altintas Mehmet M

    2012-02-01

    Full Text Available Abstract Background Mast cells are implicated in the pathogenesis of obesity and insulin resistance. Here, we explored the effects of leptin deficiency-induced obesity on the density of mast cells in metabolic (abdominal fat depots, skeletal muscle, and liver and lymphatic (abdominal lymph nodes, spleen, and thymus organs. Fourteen-week-old male leptin-deficient ob/ob mice and their controls fed a standard chow were studied. Tissue sections were stained with toluidine blue to determine the density of mast cells. CD117/c-kit protein expression analysis was also carried out. Furthermore, mast cells containing immunoreactive tumor necrosis factor-α (TNF-α, a proinflammatory cytokine involved in obesity-linked insulin resistance, were identified by immunostaining. Results ob/ob mice demonstrated adiposity and insulin resistance. In abdominal fat depots, mast cells were distributed differentially. While most prevalent in subcutaneous fat in controls, mast cells were most abundant in epididymal fat in ob/ob mice. Leptin deficiency-induced obesity was accompanied by a 20-fold increase in the density of mast cells in epididymal fat, but a 13-fold decrease in subcutaneous fat. This finding was confirmed by CD117/c-kit protein expression analysis. Furthermore, we found that a subset of mast cells in epididymal and subcutaneous fat were immunoreactive for TNF-α. The proportion of mast cells immunoreactive for TNF-α was higher in epididymal than in subcutaneous fat in both ob/ob and control mice. Mast cells were also distributed differentially in retroperitoneal, mesenteric, and inguinal lymph nodes. In both ob/ob mice and lean controls, mast cells were more prevalent in retroperitoneal than in mesenteric and inguinal lymph nodes. Leptin deficiency-induced obesity was accompanied by increased mast cell density in all lymph node stations examined. No significant difference in the density of mast cells in skeletal muscle, liver, spleen, and thymus was

  14. Reference values for serum leptin in healthy non-obese children and adolescents.

    Science.gov (United States)

    Lausten-Thomsen, Ulrik; Christiansen, Michael; Louise Hedley, Paula; Esmann Fonvig, Cilius; Stjernholm, Theresa; Pedersen, Oluf; Hansen, Torben; Holm, Jens-Christian

    2016-11-01

    Adipokines are biologically active, low-molecular weight peptides, which play a major role in metabolic homeostasis in humans. Leptin has gained increasing attention in pediatrics as a biomarker for various metabolic pathologies. Yet, its usefulness is hampered by the relative lack of reference values from pediatric settings. Accordingly, this study aims to evaluate serum concentrations of leptin, soluble leptin receptor (sOB-R), and free leptin index (FLI) in healthy Danish schoolchildren aged 6-18 years and subsequently to establish reference intervals across sex and age groups. A total of 1193 healthy, non-obese Danish schoolchildren (730 girls, 463 boys) aged 6-18 years (median 11.9) were examined by trained medical staff. Serum leptin and sOB-R concentrations in venous fasting blood samples were quantitated by immunoassay. Percentile curves of leptin, sOB-R, and free leptin index were calculated using the General Additive Model for Location Scale and Shape (GAMLSS). Significant age and sex-dependent differences in circulating leptin levels were found. In boys, the median leptin concentration for all ages combined was 3.35 μg/L (95%-interval: 0.71-22.47) and in girls, it was 9.89 ng/L (95%-interval: 2.06-41.49). For SOB-R, no sex-specific difference was found, and the median sOB-R concentration was 8.24 μg/L (IQR: 3.58-23.74; range: < 1.56-744.15). We demonstrated an age-dependent correlation with both serum leptin concentration and free leptin index with a gradual and significant increase in girls throughout childhood and adolescence and a significantly higher leptin concentration and free leptin index bell-shaped peak in early adolescence in boys.

  15. Adiponectin, Leptin, and Chemerin in Elderly Patients with Type 2 Diabetes Mellitus: A Close Linkage with Obesity and Length of the Disease

    Science.gov (United States)

    Brandão Proença, Jorge; Neuparth, Maria João

    2014-01-01

    Obesity, insulin resistance, and aging are closely associated and adipokines seem to have a crucial role in their pathophysiology. We aim to study the relationship between aging and chemerin, adiponectin, and leptin levels in type 2 diabetes mellitus (T2DM). Age correlated positively with chemerin and leptin and inversely with adiponectin. Body mass index (BMI) correlated positively with leptin (in males) and chemerin and inversely with adiponectin. The patients with ≥65 years (n = 34) showed significantly higher leptin and chemerin and lower adiponectin levels than middle-aged (38–64 years) patients (n = 39) and controls (n = 20). After statistical adjustment for length of disease, there was a loss of significance, between T2DM groups, for adiponectin and, in female, for leptin. In the older group, BMI correlated with adiponectin and with leptin, but not with chemerin. Adiponectin and leptin levels in elderly T2DM patients seem to be closely linked to obesity and to length of the disease. In elderly T2DM patients, chemerin concentrations are increased and seem to be independent of length of disease and BMI, suggesting that adipocyte dysfunction is enhanced with aging. The understanding of the glucose homeostasis impairment in the elderly is mandatory in order to achieve ways to improve their quality of life and longevity. PMID:25105135

  16. Role of baseline leptin and ghrelin levels on body weight and fat mass changes after an energy-restricted diet intervention in obese women: effects on energy metabolism.

    Science.gov (United States)

    Labayen, Idoia; Ortega, Francisco B; Ruiz, Jonatan R; Lasa, Arrate; Simón, Edurne; Margareto, Javier

    2011-06-01

    Hormones related to energy balance control may play an important role on weight loss resistance after low-caloric diet (LCD) intervention. To investigate the predictive value of baseline leptin and ghrelin on body fat mass (FM) loss after 12 wk of LCD intervention and to study whether these associations could be related to changes in resting metabolic rate (RMR). The study comprised a total of 78 obese women (age 36.7 ± 7 yr). We measured, before and after the LCD intervention, FM (dual-energy x-ray absorptiometry) and RMR (kilojoules per kilogram body weight per day, indirect calorimetry). We also analyzed fasting serum leptin and ghrelin, and leptin to ghrelin ratio was calculated. FM and RMR changes (data at baseline - data after the intervention) were assessed. Baseline serum leptin (r = -0.301; age- and baseline FM-adjusted P = 0.009) and ghrelin (r = 0.314, adjusted P = 0.014) levels as well as leptin to ghrelin levels (r = -0.331; adjusted P = 0.009) were significantly correlated with FM changes. Leptin to ghrelin ratio was significantly correlated with RMR at baseline and after the LCD (both P Baseline leptin to ghrelin ratio significantly predicted changes in RMR after the LCD (r = 0.298; P = 0.019) regardless of age, baseline RMR, and total body weight (r = 0.307; P = 0.016) or FM loss (r = 0.312; P = 0.015). Obese women with higher leptin and lower ghrelin levels at baseline seem to be more resistant to FM loss. The leptin to ghrelin ratio could be proposed as a biomarker for predicting metabolic adaptations to energy restriction treatment and, if confirmed in future studies, as a predictor of treatment success/failure.

  17. Central obesity, leptin and cognitive decline: the Sacramento Area Latino Study on Aging.

    Science.gov (United States)

    Zeki Al Hazzouri, Adina; Haan, Mary N; Whitmer, Rachel A; Yaffe, Kristine; Neuhaus, John

    2012-01-01

    Central obesity is a risk factor for cognitive decline. Leptin is secreted by adipose tissue and has been associated with better cognitive function. Aging Mexican Americans have higher levels of obesity than non-Hispanic Whites, but no investigations examined the relationship between leptin and cognitive decline among them or the role of central obesity in this association. We analyzed 1,480 dementia-free older Mexican Americans who were followed over 10 years. Cognitive function was assessed every 12-15 months with the Modified Mini Mental State Exam (3MSE) and the Spanish and English Verbal Learning Test (SEVLT). For females with a small waist circumference (≤35 inches), an interquartile range difference in leptin was associated with 35% less 3MSE errors and 22% less decline in the SEVLT score over 10 years. For males with a small waist circumference (≤40 inches), an interquartile range difference in leptin was associated with 44% less 3MSE errors and 30% less decline in the SEVLT score over 10 years. There was no association between leptin and cognitive decline among females or males with a large waist circumference. Leptin interacts with central obesity in shaping cognitive decline. Our findings provide valuable information about the effects of metabolic risk factors on cognitive function. Copyright © 2012 S. Karger AG, Basel.

  18. Liuwei Dihuang Lowers Body Weight and Improves Insulin and Leptin Sensitivity in Obese Rats

    Directory of Open Access Journals (Sweden)

    Benjamin Perry

    2012-01-01

    Full Text Available The present study was aimed at investigating the efficacy and mechanism(s of action of a Chinese herbal formulation, Liuwei Dihuang (LWDH, as a prospective natural weight-lowering product. Following a 2-week acclimation period, 48 obesity-prone (OP-CD rats were divided into 4 groups (n=12 each. One group served as a positive control for obesity (OP, while the other 3 were challenged twice daily by oral gavage with total daily dosages of 500, 1500, or 3500 mg/kg BW LWDH, respectively, for 10 weeks. One group (n=12 of obesity-resistant (OR-CD rats served as the normal control group. All rats were fed the same AIN-93G diet modified to contain 60% energy from fat. The highest LWDH dose significantly reduced body weight during the last 4 weeks of treatment. Food intake was reduced beginning in week 2. The high LWDH dose lowered serum triglyceride (TG and nonesterified fatty acid (NEFA levels and body fat. Both the high and medium doses also lowered serum leptin and insulin levels. Liver function testing revealed no adverse side effects under the current experimental conditions. The results of the present study suggest that LWDH has potential as a preventive or therapeutic natural product against overweight and obesity.

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

    DEFF Research Database (Denmark)

    Newson, R. B.; Jones, M.; Forsberg, B.

    2014-01-01

    BackgroundCross-sectional and longitudinal reports show that obese adults have more asthma than non-obese adults. A proposed mechanism is via effects of adipokines (leptin and adiponectin) on the immune system. ObjectiveWe wished to measure the associations of asthma and other atopic diseases wit...

  20. Three months of high-fructose feeding fails to induce excessive weight gain or leptin resistance in mice.

    Directory of Open Access Journals (Sweden)

    Erik J Tillman

    Full Text Available High-fructose diets have been implicated in obesity via impairment of leptin signaling in humans and rodents. We investigated whether fructose-induced leptin resistance in mice could be used to study the metabolic consequences of fructose consumption in humans, particularly in children and adolescents. Male C57Bl/6 mice were weaned to a randomly assigned diet: high fructose, high sucrose, high fat, or control (sugar-free, low-fat. Mice were maintained on their diets for at least 14 weeks. While fructose-fed mice regularly consumed more kcal and expended more energy, there was no difference in body weight compared to control by the end of the study. Additionally, after 14 weeks, both fructose-fed and control mice displayed similar leptin sensitivity. Fructose-feeding also did not change circulating glucose, triglycerides, or free fatty acids. Though fructose has been linked to obesity in several animal models, our data fail to support a role for fructose intake through food lasting 3 months in altering of body weight and leptin signaling in mice. The lack of impact of fructose in the food of growing mice on either body weight or leptin sensitivity over this time frame was surprising, and important information for researchers interested in fructose and body weight regulation.

  1. Changes of serum leptin, adiponection and insulin levels in females with simple obesity

    International Nuclear Information System (INIS)

    Wei Tao; Duan Wennuo; Ma Yongxiu; Chen Yanping

    2004-01-01

    Objective: To study the changes of serum leptin, insulin and adiponectin levels and their relationship with BMI in females with simple obesity. Methods: Serum leptin, adiponectin and insulin levels were measured with RIA in 48 pre-obese females (BMI=23-24.9 kg/m 2 ), 40 females with simple obesity, (BMI≥25 kg/m 2 ) and 42 female controls (BMI 18-22.9 kg/m 2 ). Correlations among these variables were studied. Results: Serum leptin, insulin levels were significantly higher and serum adiponectin levels were significantly lower in both the pre-obese and obese females than those in controls. Serum leptin, insulin levels were positively correlated to BMI; Serum adiponectin levels were negatively correlated to BMI. Conclusion: Within normal range of BMI, the leptin-insulin feedback mechanism provided satisfactory self-regulation. However, with excessive BMI, this dynamic equilibrium would be disrupted. The defective equilibrium, together with the abnormal low adiponectin level, would predispose to the development of diabetes mellitus. (authors)

  2. Relationship and significance of serum leptin with blood insulin and lipid in 6-13 years old obese children

    International Nuclear Information System (INIS)

    Sheng Chunyong; Wang Chunlan; Zhang Linong

    2005-01-01

    To explore relationship and significance of Serum Leptin with BMI, Insulin, triglyceride (TG) and total cholesterol (TC) in obese children aged 6-13 years. Serum Leptin of school-age children 118 (64 male, 54 female; normal non-obese 56 and obese 62) were deter- mined and compared with BMI, Insulin, TG and TC. The results showed that: (1) Each index of obese children was remarkably higher than that of non-obese children (P 0.05). (3) Leptin was poritinely corelation with BMI, insulin, TG and TC(P=0.001). Leptin level in serum may varied according to sex, BMI or blood lipid level. It is of great significance in prevention and treatment of obesity to use drug which may improve Leptin receptor effect. (authors)

  3. Leptin in sarcopenic visceral obesity: possible link between adipocytes and myocytes.

    Directory of Open Access Journals (Sweden)

    Katsuhiko Kohara

    Full Text Available The combination of sarcopenia, age-related loss of muscle strength and mass, and obesity has been recognized as a new category of obesity among the elderly. Given that leptin has been hypothesized to be involved in the pathogenesis of sarcopenic obesity, we investigated the relationship between plasma leptin levels and thigh muscle sarcopenia and visceral obesity. Thigh muscle cross-sectional area (CSA and visceral fat area were measured using computed tomography as indices for muscle mass and visceral fat, respectively, in 782 middle-aged to elderly subjects (303 men and 479 women, participating in a medical check-up program. Visceral obesity was defined as visceral fat area >100 cm², and sarcopenia was defined as < (one standard deviation--mean of thigh muscle CSA/body weight of young subjects [aged <50 years].Thigh muscle CSA was significantly and negatively associated with plasma levels of leptin in both men (β = -0.28, p<0.0001 and women (β = -0.20, p<0.0001, even after correcting for other confounding parameters, including age, body weight, body height, visceral fat area, blood pressure, homeostatic model assessment index, and high sensitive C reactive protein. Subjects were divided into four groups based on presence or absence of sarcopenia or visceral obesity. Plasma levels of leptin were higher in subjects with sarcopenic visceral obesity than in those with either sarcopenia or visceral obesity alone. These findings indicate that sarcopenic visceral obesity is a more advanced, and suggest that leptin may link visceral obesity and sarcopenia.

  4. Acute regulation of plasma leptin by isoprenaline in lean and obese fasted subjects.

    Science.gov (United States)

    Baynes, K C R; Nicholas, M D; Shojaee-Moradie, F; Umpleby, A M; Giannoulis, M G

    2006-07-01

    In human obesity, there is some evidence for impaired adrenergic sensitivity with respect to catecholamine-induced lipolysis. The beta-adrenoceptor agonist isoprenaline has been shown to suppress plasma leptin levels in lean humans in vivo. We hypothesized that a reduced adrenergic sensitivity in obese humans would result in impaired suppression of leptin secretion. Eight obese [Ob, body mass index (BMI) = 33.3 kg/m2] and seven lean (Ln, BMI = 21.8 kg/m2) men were studied after an overnight fast. Intravenous isoprenaline infusion was initiated at a rate of 8 ng/kg/min, titrated up to 24 ng/kg/min over 30 min and continued at this rate for a further 120 min with continuous electrocardiogram monitoring. Baseline fasting plasma leptin was higher in obese compared with lean subjects (Ob 12.2 +/- 1.8, Ln 2.6 +/- 0.6 ng/ml, p fasting glycerol as a measure of lipolysis was similar in both groups (Ob 62.9 +/- 7.6, Ln 42.4 +/- 8.9 micromol/l) and increased from baseline to 150 min by equivalent amounts (Ob +66.9%, Ln +81.2%, p = NS). Plasma leptin decreased from baseline to 150 min with similar relative changes in both groups (Ob -29.2%, Ln -27.8%). Obese subjects show a similar lipolytic and leptin response to acute isoprenaline infusion compared with lean subjects. Impaired beta-adrenergic-induced inhibition of leptin secretion does not appear to contribute to hyperleptinaemia in obese human subjects.

  5. Diet-Induced Growth Is Regulated via Acquired Leptin Resistance and Engages a Pomc-Somatostatin-Growth Hormone Circuit

    Directory of Open Access Journals (Sweden)

    Heiko Löhr

    2018-05-01

    Full Text Available Summary: Anorexigenic pro-opiomelanocortin (Pomc/alpha-melanocyte stimulating hormone (αMSH neurons of the hypothalamic melanocortin system function as key regulators of energy homeostasis, also controlling somatic growth across different species. However, the mechanisms of melanocortin-dependent growth control still remain ill-defined. Here, we reveal a thus-far-unrecognized structural and functional connection between Pomc neurons and the somatotropic hypothalamo-pituitary axis. Excessive feeding of larval zebrafish causes leptin resistance and reduced levels of the hypothalamic satiety mediator pomca. In turn, this leads to reduced activation of hypophysiotropic somatostatin (Sst-neurons that express the melanocortin receptor Mc4r, elevated growth hormone (GH expression in the pituitary, and enhanced somatic growth. Mc4r expression and αMSH responsiveness are conserved in Sst-expressing hypothalamic neurons of mice. Thus, acquired leptin resistance and attenuation of pomca transcription in response to excessive caloric intake may represent an ancient mechanism to promote somatic growth when food resources are plentiful. : The melanocortin system controls energy homeostasis and somatic growth, but the underlying mechanisms are elusive. Löhr et al. identify a functional neural circuit in which Pomc neurons stimulate hypothalamic somatostatin neurons, thereby inhibiting hypophyseal growth hormone production. Excessive feeding and acquired leptin resistance attenuate this pathway, allowing faster somatic growth when food resources are rich. Keywords: Pomc neuron, somatostatin neuron, somatic growth, growth hormone, melanocortin system, high-fat diet, obesity, leptin resistance, zebrafish, mouse

  6. Impaired clearance of influenza A virus in obese, leptin receptor deficient mice is independent of leptin signaling in the lung epithelium and macrophages.

    Directory of Open Access Journals (Sweden)

    Kathryn A Radigan

    Full Text Available During the recent H1N1 outbreak, obese patients had worsened lung injury and increased mortality. We used a murine model of influenza A pneumonia to test the hypothesis that leptin receptor deficiency might explain the enhanced mortality in obese patients.We infected wild-type, obese mice globally deficient in the leptin receptor (db/db and non-obese mice with tissue specific deletion of the leptin receptor in the lung epithelium (SPC-Cre/LepR fl/fl or macrophages and alveolar type II cells (LysM-Cre/Lepr fl/fl with influenza A virus (A/WSN/33 [H1N1] (500 and 1500 pfu/mouse and measured mortality, viral clearance and several markers of lung injury severity.The clearance of influenza A virus from the lungs of mice was impaired in obese mice globally deficient in the leptin receptor (db/db compared to normal weight wild-type mice. In contrast, non-obese, SP-C-Cre+/+/LepR fl/fl and LysM-Cre+/+/LepR fl/fl had improved viral clearance after influenza A infection. In obese mice, mortality was increased compared with wild-type mice, while the SP-C-Cre+/+/LepR fl/fl and LysM-Cre+/+/LepR fl/fl mice exhibited improved survival.Global loss of the leptin receptor results in reduced viral clearance and worse outcomes following influenza A infection. These findings are not the result of the loss of leptin signaling in lung epithelial cells or macrophages. Our results suggest that factors associated with obesity or with leptin signaling in non-myeloid populations such as natural killer and T cells may be associated with worsened outcomes following influenza A infection.

  7. Deletion of Suppressor of Cytokine Signaling 3 from Forebrain Neurons Delays Infertility and Onset of Hypothalamic Leptin Resistance in Response to a High Caloric Diet.

    Science.gov (United States)

    McEwen, Hayden J L; Inglis, Megan A; Quennell, Janette H; Grattan, David R; Anderson, Greg M

    2016-07-06

    The cellular processes that cause high caloric diet (HCD)-induced infertility are poorly understood but may involve upregulation of suppressor of cytokine signaling (SOCS-3) proteins that are associated with hypothalamic leptin resistance. Deletion of SOCS-3 from brain cells is known to protect mice from diet-induced obesity, but the effects on HCD-induced infertility are unknown. We used neuron-specific SOCS3 knock-out mice to elucidate this and the effects on regional hypothalamic leptin resistance. As expected, male and female neuron-specific SOCS3 knock-out mice were protected from HCD-induced obesity. While female wild-type mice became infertile after 4 months of HCD feeding, infertility onset in knock-out females was delayed by 4 weeks. Similarly, knock-out mice had delayed leptin resistance development in the medial preoptic area and anteroventral periventricular nucleus, regions important for generation of the surge of GnRH and LH that induces ovulation. We therefore tested whether the suppressive effects of HCD on the estradiol-induced GnRH/LH surge were overcome by neuron-specific SOCS3 knock-out. Although only 20% of control HCD-mice experienced a preovulatory-like LH surge, LH surges could be induced in almost all neuron-specific SOCS3 knock-out mice on this diet. In contrast to females, HCD-fed male mice did not exhibit any fertility decline compared with low caloric diet-fed males despite their resistance to the satiety effects of leptin. These data show that deletion of SOCS3 delays the onset of leptin resistance and infertility in HCD-fed female mice, but given continued HCD feeding this state does eventually occur, presumably in response to other mechanisms inhibiting leptin signal transduction. Obesity is commonly associated with infertility in humans and other animals. Treatments for human infertility show a decreased success rate with increasing body mass index. A hallmark of obesity is an increase in circulating leptin levels; despite this, the

  8. Clinical significance of determination of changes of serum leptin and E2 levels in females children with simple obesity

    International Nuclear Information System (INIS)

    Bai Hua; Qian Mingzhu

    2007-01-01

    Objective: To investigate the clinical significance of changes of serum leptin and E 2 levels in females children with simple obesity. Methods: Serum levels of leptin and E 2 were detected with RIA in 32 females children with simple obesity and 35 controls. Results: In the children with simple obesity the serum leptin and E 2 levels were significantly higher than those in controls (P 2 levels is of help for judgement of severity of obesity as well as outcome prediction in female children. (authors)

  9. The effect of obesity on inflammatory cytokine and leptin production following acute mental stress.

    Science.gov (United States)

    Caslin, H L; Franco, R L; Crabb, E B; Huang, C J; Bowen, M K; Acevedo, E O

    2016-02-01

    Obesity may contribute to cardiovascular disease (CVD) risk by eliciting chronic systemic inflammation and impairing the immune response to additional stressors. There has been little assessment of the effect of obesity on psychological stress, an independent risk factor for CVD. Therefore, it was of interest to examine interleukin-6, tumor necrosis factor-α, interleukin-1β (IL-1β), interleukin-1 receptor antagonist (IL-1Ra), and leptin following an acute mental stress task in nonobese and obese males. Twenty college-aged males (21.3 ± 0.56 years) volunteered to participate in a 20-min Stroop color-word and mirror-tracing task. Subjects were recruited for obese (body mass index: BMI > 30) and nonobese (BMI stress task elicited an increase in heart rate, catecholamines, and IL-1β in all subjects. Additionally, acute mental stress increased cortisol concentrations in the nonobese group. There was a significant reduction in leptin in obese subjects 30 min posttask compared with a decrease in nonobese subjects 120 min posttask. Interestingly, the relationship between the percent change in leptin and IL-1Ra at 120 min posttask in response to an acute mental stress task was only observed in nonobese individuals. This is the first study to suggest that adiposity in males may impact leptin and inflammatory signaling mechanisms following acute mental stress. © 2015 Society for Psychophysiological Research.

  10. Relationship of obesity with serum concentrations of leptin, CRP and IL-6 in breast cancer survivors

    International Nuclear Information System (INIS)

    Babaei, Z; Mosapour, A.; Moslemi, D.; Parsian, H.; Pouramir, M.; Khafri, S.

    2015-01-01

    Introduction: Several mechanisms have been proposed to explain the adverse effect of obesity on quality of life among women with breast cancer, including alteration in some inflammatory markers. The aim of this study was to determine the status of serum levels of leptin, IL-6 and CRP in obese, overweight and normal weight breast cancer survivors in order to determine the relationship between inflammatory markers’ levels and obesity. Materials and methods: This cross-sectional study was done on 75 women with breast cancer, 30 obese, 15 overweight and 30 normal weight patients. Serum leptin, IL-6, CRP, total protein, albumin and lipid profile as well as anthropometric parameters were measured in three groups. Results: Serum leptin levels of obese patients were significantly higher than those of overweight and normal weight patients ( P < 0.05). Higher serum CRP and lower albumin levels were observed in obese patients in comparison with normal weight patients ( P < 0.05). HDL-C level was significantly different between overweight and normal weight patients ( P < 0.05). Significant differences in serum IL-6 levels were not observed between the study groups ( P > 0.05). Moreover, multiple regression analysis showed that leptin was significantly associated with BMI ( P < 0.001), while albumin was negatively correlated with BMI ( P < 0.05). CRP levels were significantly correlated with BMI and waist-to-hip ratio (WHR) ( P < 0.05). Conclusions: In conclusion, high leptin levels and alteration in acute phase proteins in obese patients may exaggerate the inflammation status. As inflammation has the potential to increase the susceptibility of the patients to metastasis development, it is necessary to decline its rate.

  11. Obesity, Serum Resistin and Leptin Levels Linked to Coronary Artery Disease

    Directory of Open Access Journals (Sweden)

    Farzaneh Montazerifar

    Full Text Available Abstract Background: Clinical studies have demonstrated that adipocytokines play an important role in developing atherosclerotic cardiovascular diseases. Objective: The aim of study was to evaluate the relationship between serum resistin and leptin levels with obesity and coronary artery disease (CAD. Methods: In a cross-sectional study, we assessed the levels of serum resistin and leptin, C-reactive protein (CRP, lipid profile and cardiac enzyme tests (AST, CPK, LDH, CK-MB in 40 CAD patients compared to 40 healthy controls. Anthropometric measurements including weight and height for calculating of body mass index (BMI, and waist circumference (WC were performed for evaluation of obesity. Results: CAD patients had increased levels of leptin and CRP, (p < 0.001, cholesterol (p < 0.05, triglyceride (p < 0.01, and WC (p < 0.05 compared to healthy controls. There was no statistical difference between CAD and control subjects for resistin (p = 0.058. In a multiple regression analysis, only an association between serum leptin with BMI (β = 0.480, p < 0.05 and WC (β = 1.386, p < 0.05 was found. Conclusions: The findings suggest that leptin is a better marker of fat mass value than resistin and may be considered an independent risk factor for cardiac disorders that is largely dependent on obesity. However, further prospective studies are needed to confirm these results.

  12. Reanalysis of parabiosis of obesity mutants in the age of leptin.

    Science.gov (United States)

    Zeng, Wenwen; Lu, Yi-Hsueh; Lee, Jonah; Friedman, Jeffrey M

    2015-07-21

    In this study we set out to explain the differing effects of parabiosis with genetically diabetic (db) mice versus administration of recombinant leptin. Parabiosis of db mutant, which overexpress leptin, to wildtype (WT) or genetically obese (ob) mice has been reported to cause death by starvation, whereas leptin infusions do not produce lethality at any dose or mode of delivery tested. Leptin is not posttranslationally modified other than a single disulphide bond, raising the possibility that it might require additional factor(s) to exert the maximal appetite-suppressing effect. We reconfirmed the lethal effect of parabiosis of db mutant on WT mice and further showed that this lethality could not be rescued by administration of ghrelin or growth hormone. We then initiated a biochemical fractionation of a high-molecular-weight leptin complex from human plasma and identified clusterin as a major component of this leptin-containing complex. However, in contrast to previous reports, we failed to observe a leptin-potentiating effect of either exogenous or endogenous clusterin, and parabiosis of db clusterin(-/-) double-mutant to WT mice still caused lethality. Intriguingly, in parabiotic pairs of two WT mice, leptin infusion into one of the mice led to an enhanced starvation response during calorie restriction as evidenced by increased plasma ghrelin and growth-hormone levels. Moreover, leptin treatment resulted in death of the parabiotic pairs. These data suggest that the appetite suppression in WT mice after parabiosis to db mutants is the result of induced hyperleptinemia combined with the stress or other aspect(s) of the parabiosis procedure.

  13. Correlations of serum levels of leptin and other related factor (NPY, ADP) in female children with simple obesity

    International Nuclear Information System (INIS)

    Bai Hua; Wei Chunlei; Qian Mingzhu

    2008-01-01

    Objective: To study the changes of serum levels of leptin, NPY and ADP in female children with simple obesity. Methods: Serum levels of leptin, NPY and ADP were measured with radioimmunoassay (RIA) in 32 female children with simple obesity and 35 controls. Results: The serum levels of leptin, NPY were significantly higher in the obese children than those in controls (P<0.01), while the serum levels of ADP were significantly lower (P<0.01). Serum leptin levels were significantly positively correlated (r=0.6014, P<0.01) with NPY levels but were negatively correlated (r=-0.4786, P<0.01) with adiponectin (ADP) levels. Conclusion: Determination of serum leptin, NPY and ADP levels is of help for judgement of degree of obesity as wen as outcome prediction in female children. (authors)

  14. Leptin, Leptin Soluble Receptor, and the Free Leptin Index following a Diet and Physical Activity Lifestyle Intervention in Obese Males and Females

    Directory of Open Access Journals (Sweden)

    Jeffrey E. Herrick

    2016-01-01

    Full Text Available Leptin (LEP is associated with appetite regulation and metabolism. Concentration is linear with adiposity, suggesting LEP resistance. LEP circulates freely and bound with its soluble receptor (sOB-r; the ratio is the free leptin index (FLI, an index of leptin resistance; lower FLI suggests reduced biological action. Purpose. The aim was to determine the effect of changes in adipose tissue distribution on LEP, sOB-r, and FLI following 6 months (6 M of a diet/exercise weight loss program (WLP. In addition, we aim to identify predictors of the FLI. Methods. 6 M WLP consisted of diet/lifestyle interventions following ADA guidelines. Body composition was assessed by DXA. LEP and sOB-r analysis were done via ELISA. Results. 10 adults completed the WLP. Significant reductions were seen in total fat percentage (% fat, nontrunk fat, (NTF, and trunk fat (TF from base to 3 m and 6 M (p≤0.05. The FLI were reduced at 3 M and 6 M for males and 6 M for females. Total body fat and body weight predicted the FLI in both sexes. Conclusions. LEP and FLI reductions following 6 M of WLP were achieved independent of sOB-r changes. We also demonstrate that the FLI can be predicted noninvasively through total fat mass and body weight in kilograms.

  15. Maternal obesity (Class I-III), gestational weight gain and maternal leptin levels during and after pregnancy : a prospective cohort study

    OpenAIRE

    Carlhäll, Sara; Bladh, Marie; Brynhildsen, Jan; Claesson, Ing-Marie; Josefsson, Ann; Sydsjö, Gunilla; Thorsell, Annika; Blomberg, Marie

    2016-01-01

    Background Maternal obesity is accompanied by maternal and fetal complications during and after pregnancy. The risks seem to increase with degree of obesity. Leptin has been suggested to play a role in the development of obesity related complications. Whether maternal leptin levels differ between obese and morbidly obese women, during and after pregnancy, have to our knowledge not been previously described. Neither has the association between maternal leptin levels and gestational weight gain...

  16. Leptin, soluble leptin receptor, and free leptin index in patients with metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Elena N. Smirnova

    2017-06-01

    Full Text Available Aim. To assess the levels of leptin, its soluble receptor, and index of the formation of free leptin in metabolic syndrome (MS. Materials and methods. The study included 110 individuals with obesity and overweight. The group 1 consisted of 70 patients with MS (IDF, 2005, the average body mass index (BMI 38.4 ± 4.4 kg/m2, aged 48.2 ± 2.4 years, with arterial hypertension (AH 1–2 degree, without regular antihypertensive therapy. Group 2 – "healthy" obesity accounted for 40 patients aged 38.4 ± 6.2 years, BMI 36.0 ± 5.5 kg/m2 without hypertension and metabolic disorders. Group 3 consisted of 30 healthy persons, BMI 27.1 ± 1.3 kg/m2. All patients were evaluated for insulin, HOMA index, leptin, leptin receptor, leptin free index (calculated as the ratio of leptin (ng/ml to the leptin receptor (ng/ml, multiplied by 100. Results: In patients with MS as compared to other two groups there were higher levels of HOMA IR index, leptin and free leptin index. Values of leptin receptor in groups 1 and 2 did not differ significantly and were lower than in healthy persons. The free leptin index was significantly higher in MS group relative to the group 2 and 15 times higher than in the healthy individuals. Free leptin index correlated with values of BMI (R = 0.32; p = 0.02, blood pressure (R = 0.3; p = 0.04, uric acid (R = 0.27; p = 0.04, triglycerides (R = 0.42; p = 0.02, index HOMA-IR (R = 0.45; p = 0.02. Conclusions: Reduction of soluble leptin receptor, depending on the degree of abdominal obesity, may cause progression of leptin resistance in patients with MS. The levels of leptin and soluble leptin receptor appears to have dramatical gender differences. Calculation of free leptin index should be used for the objective evaluation of leptin resistance, regardless of gender, degree of obesity, and other metabolic parameters.

  17. Polymorphism in leptin receptor gene was associated with obesity in ...

    African Journals Online (AJOL)

    Pramudji Hastuti

    2016-01-11

    Jan 11, 2016 ... This study aims to determine the association of LEPR gene polymorphisms, rs1137100 and rs1137101, on .... and that leptin levels were correlated with type 2 diabetes mel- .... Research using statistical meta-analysis [36,37] found ... and changes in glucose homeostasis in response to regular exercise.

  18. Intermittent hypoxia increases insulin resistance in genetically obese mice.

    Science.gov (United States)

    Polotsky, Vsevolod Y; Li, Jianguo; Punjabi, Naresh M; Rubin, Arnon E; Smith, Philip L; Schwartz, Alan R; O'Donnell, Christopher P

    2003-10-01

    Obstructive sleep apnoea, a syndrome that leads to recurrent intermittent hypoxia, is associated with insulin resistance in obese individuals, but the mechanisms underlying this association remain unknown. We utilized a mouse model to examine the effects of intermittent hypoxia on insulin resistance in lean C57BL/6J mice and leptin-deficient obese (C57BL/6J-Lepob) mice. In lean mice, exposure to intermittent hypoxia for 5 days (short term) resulted in a decrease in fasting blood glucose levels (from 173 +/- 11 mg dl-1 on day 0 to 138 +/- 10 mg dl-1 on day 5, P obese mice, short-term intermittent hypoxia led to a decrease in blood glucose levels accompanied by a 607 +/- 136 % (P intermittent hypoxia was completely abolished by prior leptin infusion. Obese mice exposed to intermittent hypoxia for 12 weeks (long term) developed a time-dependent increase in fasting serum insulin levels (from 3.6 +/- 1.1 ng ml-1 at baseline to 9.8 +/- 1.8 ng ml-1 at week 12, P intermittent hypoxia is dependent on the disruption of leptin pathways.

  19. Determination of Insulin Resistance and Beta Cell Function in Healthy Obese and Non-obese Individuals

    International Nuclear Information System (INIS)

    Kazmi, A.; Sattar, A.; Tariq, K. M.; Najamussahar; Hashim, R.; Almani, M. I.

    2013-01-01

    Objective: To determine insulin resistance and beta cell function in healthy obese and nonobese individuals of the local population. Study Design: Case control study. Place and Duration of Study: AFIP Rawalpindi in collaboration with department of medicine military hospital(MH) Rawalpindi, from Aug 2008 to Mar 2009. Methods: Eighty obese(n=40) and non-obese(n=40) subjects were selected by non-probability convenience sampling. Plasma insulin, glucose, and serum total cholestrol were estimated in fasting state. Insulin resistance was calculated by HOMA-IR and beta cell function by HOMA- equation. Results: Significant differences were observed between obese and non-obese individuals regarding insulin resistance, beta cell function, and BMI and serum total cholesterol. Mean insulin resistance in obese group was found to be 11.1 +- 5.1(range 7.0-16.2) and in non-obese group it was 0.9+-0.4 (range 0.5-1.3). This difference was highly significant (p=0.001). There was a highly significant difference between the two groups in term of beta cell function with mean rank 60.1 for obese group and 20.9 non obese groups (Asym sig. 2 tailed 0.000). Also the correlation (r = 0.064) between insulin resistance and beta cell function in obese group is highly significant (p = 0.000). Mean serum leptin levels were lower (6.3 ng/ml) in non-obese, and high (57.2 ng/ml) in the obese group. Conclusions: Insulin resistance is found higher in obese individuals. Beta cell function is significantly different between obese and non-obese groups. (author)

  20. Pleotropic effects of leptin to reverse insulin resistance and diabetic ketoacidosis

    DEFF Research Database (Denmark)

    Perry, Rachel J; Petersen, Kitt Falk; Shulman, Gerald I.

    2016-01-01

    In this review we discuss the mechanisms for the pleotropic effects of leptin replacement therapy to reverse liver and muscle insulin resistance in lipodystrophic individuals, as well as insulin-independent effects of leptin replacement therapy to suppress white adipose tissue lipolysis, hepatic...

  1. Is fasting leptin associated with insulin resistance among nondiabetic individuals? The Miami Community Health Study

    DEFF Research Database (Denmark)

    Donahue, R P; Prineas, R J; Donahue, R D

    1999-01-01

    Whether serum leptin levels are associated with insulin resistance independent of the effects of hyperinsulinemia and adiposity is an important unanswered question. We examined the relationship between the rate of insulin-mediated glucose uptake and serum leptin concentrations among nondiabetic men...

  2. Circulating Irisin Levels Are Not Regulated by Nutritional Status, Obesity, or Leptin Levels in Rodents.

    Science.gov (United States)

    Quiñones, Mar; Folgueira, Cintia; Sánchez-Rebordelo, Estrella; Al-Massadi, Omar

    2015-01-01

    Irisin is a cleaved and secreted fragment of fibronectin type III domain containing 5 (FNDC5) that is mainly released by skeletal muscle and was proposed to mediate the beneficial effects of exercise on metabolism. In the present study we aim to investigate the regulation of the circulating levels of irisin in obese animal models (diet-induced obese (DIO) rats and leptin-deficient (ob/ob) mice), as well as the influence of nutritional status and leptin. Irisin levels were measured by Enzyme-Linked Immunosorbent Assay (ELISA) and Radioimmunoassay (RIA). Serum irisin levels remained unaltered in DIO rats and ob/ob mice. Moreover, its circulating levels were also unaffected by fasting, leptin deficiency, and exogenous leptin administration in rodents. In spite of these negative results we find a negative correlation between irisin and insulin in DIO animals and a positive correlation between irisin and glucose under short-term changes in nutritional status. Our findings indicate that serum irisin levels are not modulated by different physiological settings associated to alterations in energy homeostasis. These results suggest that in rodents circulating levels of irisin are not involved in the pathophysiology of obesity and could be unrelated to metabolic status; however, further studies should clarify its precise role in states of glucose homeostasis imbalance.

  3. Circulating Irisin Levels Are Not Regulated by Nutritional Status, Obesity, or Leptin Levels in Rodents

    Directory of Open Access Journals (Sweden)

    Mar Quiñones

    2015-01-01

    Full Text Available Irisin is a cleaved and secreted fragment of fibronectin type III domain containing 5 (FNDC5 that is mainly released by skeletal muscle and was proposed to mediate the beneficial effects of exercise on metabolism. In the present study we aim to investigate the regulation of the circulating levels of irisin in obese animal models (diet-induced obese (DIO rats and leptin-deficient (ob/ob mice, as well as the influence of nutritional status and leptin. Irisin levels were measured by Enzyme-Linked Immunosorbent Assay (ELISA and Radioimmunoassay (RIA. Serum irisin levels remained unaltered in DIO rats and ob/ob mice. Moreover, its circulating levels were also unaffected by fasting, leptin deficiency, and exogenous leptin administration in rodents. In spite of these negative results we find a negative correlation between irisin and insulin in DIO animals and a positive correlation between irisin and glucose under short-term changes in nutritional status. Our findings indicate that serum irisin levels are not modulated by different physiological settings associated to alterations in energy homeostasis. These results suggest that in rodents circulating levels of irisin are not involved in the pathophysiology of obesity and could be unrelated to metabolic status; however, further studies should clarify its precise role in states of glucose homeostasis imbalance.

  4. Daily rhythms of plasma melatonin, but not plasma leptin or leptin mRNA, vary between lean, obese and type 2 diabetic men.

    Directory of Open Access Journals (Sweden)

    Simone Mäntele

    Full Text Available Melatonin and leptin exhibit daily rhythms that may contribute towards changes in metabolic physiology. It remains unclear, however, whether this rhythmicity is altered in obesity or type 2 diabetes (T2DM. We tested the hypothesis that 24-hour profiles of melatonin, leptin and leptin mRNA are altered by metabolic status in laboratory conditions. Men between 45-65 years old were recruited into lean, obese-non-diabetic or obese-T2DM groups. Volunteers followed strict sleep-wake and dietary regimes for 1 week before the laboratory study. They were then maintained in controlled light-dark conditions, semi-recumbent posture and fed hourly iso-energetic drinks during wake periods. Hourly blood samples were collected for hormone analysis. Subcutaneous adipose biopsies were collected 6-hourly for gene expression analysis. Although there was no effect of subject group on the timing of dim light melatonin onset (DLMO, nocturnal plasma melatonin concentration was significantly higher in obese-non-diabetic subjects compared to weight-matched T2DM subjects (p<0.01 and lean controls (p<0.05. Two T2DM subjects failed to produce any detectable melatonin, although did exhibit plasma cortisol rhythms comparable to others in the group. Consistent with the literature, there was a significant (p<0.001 effect of subject group on absolute plasma leptin concentration and, when expressed relative to an individual's 24-hour mean, plasma leptin showed significant (p<0.001 diurnal variation. However, there was no difference in amplitude or timing of leptin rhythms between experimental groups. There was also no significant effect of time on leptin mRNA expression. Despite an overall effect (p<0.05 of experimental group, post-hoc analysis revealed no significant pair-wise effects of group on leptin mRNA expression. Altered plasma melatonin rhythms in weight-matched T2DM and non-diabetic individuals supports a possible role of melatonin in T2DM aetiology. However, neither

  5. Male fertility and obesity: are ghrelin, leptin and glucagon-like peptide-1 pharmacologically relevant?

    Science.gov (United States)

    Alves, Marco G; Jesus, Tito T; Sousa, Mário; Goldberg, Erwin; Silva, Branca M; Oliveira, Pedro F

    2016-01-01

    Obesity is rising to unprecedented numbers, affecting a growing number of children, adolescents and young adult men. These individuals face innumerous health problems, including subfertility or even infertility. Overweight and obese men present severe alterations in their body composition and hormonal profile, particularly in ghrelin, leptin and glucagon-like peptide-1 (GLP-1) levels. It is well known that male reproductive health is under the control of the individual's nutritional status and also of a tight network of regulatory signals, particularly hormonal signaling. However, few studies have been focused on the effects of ghrelin, leptin and GLP-1 in male reproduction and how energy homeostasis and male reproductive function are linked. These hormones regulate body glucose homeostasis and several studies suggest that they can serve as targets for anti-obesity drugs. In recent years, our understanding of the mechanisms of action of these hormones has grown significantly. Curiously, their effect on male reproductive potential, that is highly dependent of the metabolic cooperation established between testicular cells, remains a matter of debate. Herein, we review general concepts of male fertility and obesity, with a special focus on the effects of ghrelin, leptin and GLP-1 on male reproductive health. We also discuss the possible pharmacological relevance of these hormones to counteract the fertility problems that overweight and obese men face.

  6. Glucocorticoid inhibition of leptin- and lipopolysaccharide-induced interleukin-6 production in obesity.

    Science.gov (United States)

    Huang, Chun-Jung; Acevedo, Edmund O; Mari, David C; Randazzo, Christopher; Shibata, Yoshimi

    2014-01-01

    Obesity is considered a chronic inflammatory condition that enhances the risk of numerous inflammatory diseases, including diabetes and cardiovascular disease. Glucocorticoids (GCs) and synthetic therapeutic GCs are anti-inflammatory agents, but the exact functions of GCs in obesity-related inflammation are unknown. Therefore, the objective of this study was to examine the inhibitory effect of an exogenous GC (dexamethasone, DEX) on leptin- and lipopolysaccharide (LPS)-induced IL-6 production by peripheral blood mononuclear cells (PBMCs) ex vivo in obese subjects compared to normal-weight subjects. Blood samples were drawn from 14 obese (BMI>30 kg/m(2)) and 14 normal-weight (BMIobese subjects showed greater leptin- and LPS-induced IL-6 production compared to normal-weight subjects. The suppressive effect of DEX on leptin- and LPS-induced IL-6 production (IC50) was not different between the two groups. However, the IC50 of DEX for LPS-induced was correlated with BMI, waist circumference, and hip circumference. These findings suggest that reduced GC sensitivity may be an important mechanism in the up-regulation of selected obese inflammation. Published by Elsevier Inc.

  7. The correlation between leptin and highly sensitive C-reactive protein levels in obese children aged 9-15 years

    Directory of Open Access Journals (Sweden)

    Sarah M. Warouw

    2011-02-01

    Full Text Available Background Obesity is a low level and chronic inflammatory condition predominantly affecting white adipose tissue, where macrophage infiltration is found. Leptin is one of many molecules relating obesity to cardiovascular disease. Leptin can increase cytokine production in macrophages and monocytes, and increase oxidative stress on endothelial cells. Pro-inflammatory cytokines, in turn, may trigger the release of C-reactive protein. Objective To examine the correlation between leptin and hsCRP in obese children aged 9-15 years. Methods This cross-sectional study was done in Manado from May to December 2009, on elementary and junior high school children. Subjects were obese children aged 9-15 years, with nutritional status detennined by Body Mass Index and converted into z-score. Physical examination, blood pressure, and blood examinations for  fasting blood sugar (FBS, lipid profile, leptin, and hsCRP were perfonned. Data were analyzed with appropriate statistical methods. Results The mean leptin level in obese children was 34,009.2 pgiL (SD 18,224.79, higher than that of the control, 7,760.9 pgiL (SD 8,859.55 (P<0.0001. The mean hsCRP level in obese children was 3.6 mgiL (SD 3.60, higher than that of the control, 0.7 mgiL (SD 1.32 (<0.0001. There was a significant positive correlation between leptin and hsCRP levels in obese children (r 0.355; P<0.0001. Conclusions There is significant positive correlation between leptin and hsCRP levels in obese children aged 9-15 years. Increased leptin and hsCRP levels indicate a low degree of chronic inflammation. Thus, intervention is needed to decrease the body weight of obese children.

  8. Leptin is associated with exaggerated brain reward and emotion responses to food images in adolescent obesity.

    Science.gov (United States)

    Jastreboff, Ania M; Lacadie, Cheryl; Seo, Dongju; Kubat, Jessica; Van Name, Michelle A; Giannini, Cosimo; Savoye, Mary; Constable, R Todd; Sherwin, Robert S; Caprio, Sonia; Sinha, Rajita

    2014-11-01

    In the U.S., an astonishing 12.5 million children and adolescents are now obese, predisposing 17% of our nation's youth to metabolic complications of obesity, such as type 2 diabetes (T2D). Adolescent obesity has tripled over the last three decades in the setting of food advertising directed at children. Obese adults exhibit increased brain responses to food images in motivation-reward pathways. These neural alterations may be attributed to obesity-related metabolic changes, which promote food craving and high-calorie food (HCF) consumption. It is not known whether these metabolic changes affect neural responses in the adolescent brain during a crucial period for establishing healthy eating behaviors. Twenty-five obese (BMI 34.4 kg/m2, age 15.7 years) and fifteen lean (BMI 20.96 kg/m2, age 15.5 years) adolescents underwent functional MRI during exposure to HCF, low-calorie food (LCF), and nonfood (NF) visual stimuli 2 h after isocaloric meal consumption. Brain responses to HCF relative to NF cues increased in obese versus lean adolescents in striatal-limbic regions (i.e., putamen/caudate, insula, amygdala) (P < 0.05, family-wise error [FWE]), involved in motivation-reward and emotion processing. Higher endogenous leptin levels correlated with increased neural activation to HCF images in all subjects (P < 0.05, FWE). This significant association between higher circulating leptin and hyperresponsiveness of brain motivation-reward regions to HCF images suggests that dysfunctional leptin signaling may contribute to the risk of overconsumption of these foods, thus further predisposing adolescents to the development of obesity and T2D. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  9. Plaqueta e leptina em adolescentes com obesidade Platelet and leptin in obese adolescents

    Directory of Open Access Journals (Sweden)

    Denis Foschini

    2008-12-01

    Full Text Available OBJETIVOS: Analisar a influência de obesidade na contagem de células imunológicas e na concentração dos hormônios cortisol e leptina, a fim de estabelecer uma relação entre as variáveis analisadas. MÉTODOS: Foram recrutados 27 adolescentes obesos [índice de massa corporal (IMC ≥ percentil 95[ e 21 não-obesos (IMC ≤ percentil 75, de ambos os sexos, com idade entre 15 e 19 anos, na fase pós-púbere. O IMC foi calculado através da divisão do peso pela altura ao quadrado e a composição corporal foi estimada por pletismografia no sistema Bod PodTM. Amostras de sangue foram colhidas para análise de leucócitos, neutrófilos, linfócitos, monócitos, plaquetas, cortisol e leptina. O teste de Kolmogorov-Smirnov foi utilizado, seguido pelo teste t de Student independente supondo distribuição normal. O nível de significância estabelecido foi p OBJECTIVE: To analyze the influence of obesity status on immune cell count and concentration of the hormones cortisol and leptin, in order to establish a relationship among the variables analyzed. METHODS: We recruited 27 obese [body mass index (BMI ≥ 95th percentile[ and 21 non-obese (BMI ≤ 75th percentile adolescent boys and girls, aged 15-19 years at the post-pubertal stage. BMI was calculated as body weight divided by height squared, and body composition was estimated by plethysmography in the Bod PodTM system. Blood samples were collected to analyze leukocytes, neutrophils, lymphocytes, monocytes, platelets, cortisol, and leptin. The Kolmogorov-Smirnov test was performed, followed by the independent Student t test in case of normal distribution. Significance values were set at p < 0.05 and expressed as means ± standard deviation. The statistical package SPSS for Windows version 12.0 was used. RESULTS: There was no difference between obese and non-obese adolescents in terms of leukocyte, neutrophil, lymphocyte, monocyte and cortisol serum concentrations. The group of obese

  10. Whole-Body and Hepatic Insulin Resistance in Obese Children

    Science.gov (United States)

    Ibarra-Reynoso, Lorena del Rocío; Pisarchyk, Liudmila; Pérez-Luque, Elva Leticia; Garay-Sevilla, Ma. Eugenia; Malacara, Juan Manuel

    2014-01-01

    Background Insulin resistance may be assessed as whole body or hepatic. Objective To study factors associated with both types of insulin resistance. Methods Cross-sectional study of 182 obese children. Somatometric measurements were registered, and the following three adiposity indexes were compared: BMI, waist-to-height ratio and visceral adiposity. Whole-body insulin resistance was evaluated using HOMA-IR, with 2.5 as the cut-off point. Hepatic insulin resistance was considered for IGFBP-1 level quartiles 1 to 3 (HOMA-IR was negatively associated with IGFBP-1 and positively associated with BMI, triglycerides, leptin and mother's BMI. Girls had increased HOMA-IR. IGFBP-1 was negatively associated with waist-to-height ratio, age, leptin, HOMA-IR and IGF-I. We did not find HOMA-IR or IGFBP-1 associated with fatty liver. Conclusion In school-aged children, BMI is the best metric to predict whole-body insulin resistance, and waist-to-height ratio is the best predictor of hepatic insulin resistance, indicating that central obesity is important for hepatic insulin resistance. The reciprocal negative association of IGFBP-1 and HOMA-IR may represent a strong interaction of the physiological processes of both whole-body and hepatic insulin resistance. PMID:25411786

  11. The relationship between obesity, leptin, adiponectin and the ...

    African Journals Online (AJOL)

    Objectives: Obesity prevalence is increasing worldwide. In South Africa, older and urbanised African women have significantly higher rates of obesity. Limited information is available on the relationship between anthropometric parameters, adipokines and metabolic health status of African women. This study investigated the ...

  12. Relationship between obesity and leptin serum among low socioeconomic primary school children aged 5-7 years

    Directory of Open Access Journals (Sweden)

    Soenarto Soenarto

    2010-06-01

    Full Text Available Background Obesity has become a major health problem globally, indicates as an epidemic problem by World Health Organization (WHO. Adiposity rebound period may represent critical period for the development of adiposity. Recent data suggest that, in industrialized countries, people of low socioeconomic group are more likely to be obese than their high socioeconomic counterparts. Level of serum leptin was reported to be higher in obese subjects. There has been lack of data regarding leptin serum level in Indonesian obese children. Objective This study aimed to investigate leptin serum level in low socioeconomic obese children.  Methods This was a cross sectional study perfonned in Tuminting District, Manado. Obesity was defined based on body mass index for AsiaPacific condition, i.e., grade I obesity (BMI 25/29.9 kg/ mL, grade II (BM] 30-40 kg/ml, and grade III (BM] > 40 kg/m2 Low socioeconomic status was detennined based on Government's program Cash Direct Aid Program. loBod sample was obtained from inclusion subjects, consisted of leptin serum. Results Fiftytwo low socioeconomic obese children were eligible \\\\lith age ranged between 5 to 7 years. They were divided into grade ] obesity (43 or 82.7%, and grade II (9 or 17.3%. The lowest leptin blood level was 10,291 pg/mL, while the highest was 41,500 pg/dL. All girls had nonnal serum leptin level; in contrast all boys had increased serum leptin level.  Conclusions Leprin level increased in those subjects whose BMI increased.

  13. The Association of Polymorphisms in Leptin/Leptin Receptor Genes and Ghrelin/Ghrelin Receptor Genes With Overweight/Obesity and the Related Metabolic Disturbances: A Review.

    Science.gov (United States)

    Ghalandari, Hamid; Hosseini-Esfahani, Firoozeh; Mirmiran, Parvin

    2015-07-01

    Leptin and ghrelin are two important appetite and energy balance-regulating peptides. Common polymorphisms in the genes coding these peptides and their related receptors are shown to be associated with body weight, different markers of obesity and metabolic abnormalities. This review article aims to investigate the association of common polymorphisms of these genes with overweight/obesity and the metabolic disturbances related to it. The keywords leptin, ghrelin, polymorphism, single-nucleotide polymorphism (SNP), obesity, overweight, Body Mass Index, metabolic syndrome, and type 2 diabetes mellitus (T2DM) (MeSH headings) were used to search in the following databases: Pubmed, Sciencedirect (Elsevier), and Google scholar. Overall, 24 case-control studies, relevant to our topic, met the criteria and were included in the review. The most prevalent leptin/leptin receptor genes (LEP/LEPR) and ghrelin/ghrelin receptor genes (GHRL/GHSR) single nucleotide polymorphisms studied were LEP G-2548A, LEPR Q223R, and Leu72Met, respectively. Nine studies of the 17 studies on LEP/LEPR, and three studies of the seven studies on GHRL/GHSR showed significant relationships. In general, our study suggests that the association between LEP/LEPR and GHRL/GHSR with overweight/obesity and the related metabolic disturbances is inconclusive. These results may be due to unidentified gene-environment interactions. More investigations are needed to further clarify this association.

  14. The Association of Polymorphisms in Leptin/Leptin Receptor Genes and Ghrelin/Ghrelin Receptor Genes With Overweight/Obesity and the Related Metabolic Disturbances: A Review

    OpenAIRE

    Ghalandari; Hosseini-Esfahani; Mirmiran

    2015-01-01

    Context Leptin and ghrelin are two important appetite and energy balance-regulating peptides. Common polymorphisms in the genes coding these peptides and their related receptors are shown to be associated with body weight, different markers of obesity and metabolic abnormalities. This review article aims to investigate the association of common polymorphisms of these genes with overweight/obesity and the metabolic disturbances related to it. E...

  15. Leptin and variables of body adiposity, energy balance, and insulin resistance in a population-based study. The Hoorn Study

    NARCIS (Netherlands)

    Ruige, J B; Dekker, J M; Blum, W F; Stehouwer, C D; Nijpels, G; Mooy, J; Kostense, P J; Bouter, L M; Heine, R J

    OBJECTIVE: Leptin is thought to play a key role in the control of body weight. There is a complex interrelationship between leptin and insulin or insulin resistance, but it is unknown how leptin is regulated. We therefore explored, in a large population-based study of 2,484 Caucasian subjects aged

  16. Association of leptin/receptor and TNF-α gene variants with adolescent obesity in Malaysia.

    Science.gov (United States)

    Ng, Zoe Yi; Veerapen, Muthu Kumar; Hon, Wei Min; Lim, Renee Lay Hong

    2014-10-01

    Leptin (LEP) G-2548A (rs7799039), leptin receptor (LEPR) Q223R (rs1137101) and tumor necrosis factor (TNF)-α G-308A (rs1800629) gene variants have been reported to be associated with obesity, although results for subjects from different countries have been controversial. The aim of this study was to determine the prevalence of overweight and obesity in Malaysian adolescents and the association of these polymorphisms with overweight and obese or over-fat adolescents. A total of 613 adolescents (241 Malay, 219 Chinese, 153 Indian) were enrolled. Anthropometric measurements of body mass index (BMI) and body fat percentage were used to classify subjects as controls (non-overweight/obese or normal fat) or as cases (overweight/obese or over-fat). Genomic DNA was extracted from oral buccal mucosa cells for genotyping using polymerase chain reaction-restriction fragment length polymorphism and data obtained were statistically analyzed. A total of 23.3% of subjects were overweight/obese whereas 11.4% were over-fat; there were significantly more overweight/obese and over-fat Indian and Malay adolescents compared to Chinese (P obesity (P = 0.025; odds ratio, 3.64; 95% confidence interval: 1.15-11.54). Despite the lack of association observed for LEPR Q223R and TNF-α G-308A, Indian and Chinese subjects with AA risk genotype for LEPR Q223R/LEP G-2548A and TNF-α G-308A/LEP G-2548A, respectively, had increased mean BMI (P = 0.049, P = 0.016). Genotype distribution and association of these polymorphisms with overweight/obesity vary between ethnic groups and genders. Nevertheless, the LEP G-2548A risk allele may be associated with overweight/obese Indian male adolescents in Malaysia. © 2014 Japan Pediatric Society.

  17. The cerebrospinal fluid/serum leptin ratio during pharmacological therapy for obesity.

    Science.gov (United States)

    Rodrigues, Adriane Maria; Radominski, Rosana Bento; Suplicy, Henrique de Lacerda; De Almeida, Sergio Monteiro; Niclewicz, Patricia Artigas; Boguszewski, Cesar Luiz

    2002-04-01

    The aim of the present study was to evaluate the cerebrospinal fluid (CSF)/serum leptin ratio during pharmacological therapy for obesity with centrally and peripherally acting drugs. Thirty-one obese women (mean age, 32.3 +/- 10 yr; body mass index, 38.2 +/- 5.2 kg/m(2); body fat, 43.3 +/- 5.4%) were studied before and 2 months after a weight loss program consisting of a balanced diet (1200 kcal/d) plus drug therapy. The patients were randomly assigned into three study groups: group I, fenproporex 25 mg/d (n = 10); group II, sibutramine 10 mg/d (n = 10); and group III, orlistat 120 mg tid (n = 11). Body fat, measured by dual-energy x-ray absorptiometry, and serum and CSF concentrations of leptin were examined at baseline and 2 months after therapy. At baseline, clinical and biochemical characteristics of the groups were similar. All of the women lost weight, approximately 7.0% of their initial body weight, and the reduction was not different among the groups. Serum leptin fell significantly after 2 months in all groups, and the decline was proportional to the reduction in body fat, because leptin levels adjusted for body fat did not change after treatment. CSF leptin levels showed a significant decrease after 2 months in all groups, and this decline was higher on group III compared with group I (P = 0.006). After therapy, the CSF/serum leptin ratio did not change in group I (1.57 +/- 0.3 to 1.72 +/- 0.62%) and group II (1.78 +/- 1.01 to 1.69 +/- 1.27%), whereas it declined significantly in group III (1.65 +/- 0.43 to 1.09 +/- 0.47%; P obese women treated during 2 months with orlistat, whereas this ratio did not change in this period of time in obese women treated with fenproporex and sibutramine.

  18. The relationship between obesity, leptin, adiponectin and the ...

    African Journals Online (AJOL)

    This study investigated the relationship between obesity, adipokines and the components of ... women between adiponectin and age, BMI and fasting blood glucose, and positive .... or medians. Correlations between continuous variables were.

  19. Prenatal programming of postnatal obesity: fetal nutrition and the regulation of leptin synthesis and secretion before birth.

    Science.gov (United States)

    McMillen, I C; Muhlhausler, B S; Duffield, J A; Yuen, B S J

    2004-08-01

    Exposure to either an increased or decreased level of intrauterine nutrition can result in an increase in adiposity and in circulating leptin concentrations in later life. In animals such as the sheep and pig in which fat is deposited before birth, leptin is synthesised in fetal adipose tissue and is present in the fetal circulation throughout late gestation. In the sheep a moderate increase or decrease in the level of maternal nutrition does not alter fetal plasma leptin concentrations, but there is evidence that chronic fetal hyperglycaemia and hyperinsulinaemia increase fetal fat mass and leptin synthesis within fetal fat depots. Importantly, there is a positive relationship between the relative mass of the 'unilocular' component of fetal perirenal and interscapular adipose tissue and circulating fetal leptin concentrations in the sheep. Thus, as in the neonate and adult, circulating leptin concentrations may be a signal of fat mass in fetal life. There is also evidence that leptin can act to regulate the lipid storage, leptin synthetic capacity and potential thermogenic functions of fat before birth. Thus, leptin may act as a signal of energy supply and have a 'lipostatic' role before birth. Future studies are clearly required to determine whether the intrauterine and early postnatal nutrient environment programme the endocrine feedback loop between adipose tissue and the central and peripheral neuroendocrine systems that regulate energy balance, resulting in an enhanced risk of obesity in adult life.

  20. Obesity genes and insulin resistance.

    Science.gov (United States)

    Belkina, Anna C; Denis, Gerald V

    2010-10-01

    The exploding prevalence of insulin resistance and Type 2 diabetes (T2D) linked to obesity has become an alarming public health concern. Worldwide, approximately 171 million people suffer from obesity-induced diabetes and public health authorities expect this situation to deteriorate rapidly. An interesting clinical population of 'metabolically healthy but obese' (MHO) cases is relatively protected from T2D and its associated cardiovascular risk. The molecular basis for this protection is not well understood but is likely to involve reduced inflammatory responses. The inflammatory cells and pathways that respond to overnutrition are the primary subject matter for this review. The chance discovery of a genetic mutation in the Brd2 gene, which is located in the class II major histocompatibility complex and makes mice enormously fat but protects them from diabetes, offers revolutionary new insights into the cellular mechanisms that link obesity to insulin resistance and T2D. These Brd2-hypomorphic mice have reduced inflammation in fat that is normally associated with insulin resistance, and resemble MHO patients, suggesting novel therapeutic pathways for obese patients at risk for T2D. Deeper understanding of the functional links between genes that control inflammatory responses to diet-induced obesity is crucial to the development of therapies for obese, insulin-resistant patients.

  1. Voluntary exercise improves high-fat diet-induced leptin resistance independent of adiposity.

    Science.gov (United States)

    Krawczewski Carhuatanta, Kimberly A; Demuro, Giovanna; Tschöp, Matthias H; Pfluger, Paul T; Benoit, Stephen C; Obici, Silvana

    2011-07-01

    The efficacy of exercise as primary prevention of obesity is the subject of intense investigation. Here, we show that voluntary exercise in a mouse strain susceptible to diet-induced obesity (C57B6J) decreases fat mass and increases energy expenditure. In addition, exercise attenuates obesity in mice fed a high-fat diet (HFD). Using FosB immunoreactivity as a marker of chronic neuronal activation, we found that exercise activates leptin receptor-positive neurons in the ventromedial hypothalamic nucleus, involved in homeostatic control of energy balance. FosB immunoreactivity in the ventromedial hypothalamic nucleus is decreased in sedentary mice exposed to HFD but is increased in exercised mice independent of adiposity. To determine whether the antiobesity effects of voluntary exercise improve central nervous system (CNS) leptin action, we measured the anorectic and weight reducing effects of intracerebroventricular (ICV) leptin in sedentary and exercised mice exposed to HFD (EH), as well as in sedentary mice that have been calorie restricted (SR) to match the fat mass of EH mice. ICV leptin was ineffective in lowering food intake and body weight (BW) in sedentary mice exposed to HFD mice. The anorectic potency of leptin was partially restored in EH and SR groups. However, ICV leptin significantly lowered BW in EH but not SR mice. Thus, exercise leads to the maintenance of a lower BW and leaner composition, as well as to improved CNS leptin action, independent of fat mass. These results support the notion that physical exercise directly influences the responsiveness of the CNS circuits involved in energy homeostasis by allowing the defense of a lowered BW.

  2. Higher Leptin but Not Human Milk Macronutrient Concentration Distinguishes Normal-Weight from Obese Mothers at 1-Month Postpartum.

    Science.gov (United States)

    De Luca, Arnaud; Frasquet-Darrieux, Marine; Gaud, Marie-Agnès; Christin, Patricia; Boquien, Clair-Yves; Millet, Christine; Herviou, Manon; Darmaun, Dominique; Robins, Richard J; Ingrand, Pierre; Hankard, Régis

    2016-01-01

    Exclusively breastfed infants born to obese mothers have previously been shown to gain less weight by 1-month postpartum than infants of normal-weight mothers. Our hypothesis is that human milk composition and volume may differ between obese and normal-weight mothers. To compare human milk leptin, macronutrient concentration, and volume in obese and normal-weight mothers. Mother and infant characteristics were studied as secondary aims. This cross-sectional observational study compared 50 obese mothers matched for age, parity, ethnic origin, and educational level with 50 normal-weight mothers. Leptin, macronutrient human milk concentration, and milk volume were determined at 1 month in exclusively breastfed infants. Mother characteristics and infant growth were recorded. Human milk leptin concentration was higher in obese mothers than normal-weight mothers (4.8±2.7 vs. 2.5±1.5 ng.mL-1, pobese and normal-weight mothers in protein, lipid, carbohydrate content, and volume, nor in infant weight gain. Leptin concentration was higher in the milk of obese mothers than that of normal-weight mothers, but macronutrient concentration was not. It remains to be established whether the higher leptin content impacts on infant growth beyond the 1-month of the study period.

  3. Leptin Increases Striatal Dopamine D2 Receptor Binding in Leptin-Deficient Obese (ob/ob) Mice

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    Pfaffly, J.; Michaelides, M.; Wang, G-J.; Pessin, J.E.; Volkow, N.D.; Thanos, P.K.

    2010-06-01

    Peripheral and central leptin administration have been shown to mediate central dopamine (DA) signaling. Leptin-receptor deficient rodents show decreased DA D2 receptor (D2R) binding in striatum and unique DA profiles compared to controls. Leptin-deficient mice show increased DA activity in reward-related brain regions. The objective of this study was to examine whether basal D2R-binding differences contribute to the phenotypic behaviors of leptin-deficient ob/ob mice, and whether D2R binding is altered in response to peripheral leptin treatment in these mice. Leptin decreased body weight, food intake, and plasma insulin concentration in ob/ob mice but not in wild-type mice. Basal striatal D2R binding (measured with autoradiography [{sup 3}H] spiperone) did not differ between ob/ob and wild-type mice but the response to leptin did. In wild-type mice, leptin decreased striatal D2R binding, whereas, in ob/ob mice, leptin increased D2R binding. Our findings provide further evidence that leptin modulates D2R expression in striatum and that these effects are genotype/phenotype dependent.

  4. Leptin modulates human Sertoli cells acetate production and glycolytic profile: a novel mechanism of obesity-induced male infertility?

    Science.gov (United States)

    Martins, Ana D; Moreira, Ana C; Sá, Rosália; Monteiro, Mariana P; Sousa, Mário; Carvalho, Rui A; Silva, Branca M; Oliveira, Pedro F; Alves, Marco G

    2015-09-01

    Human feeding behavior and lifestyle are gradually being altered, favoring the development of metabolic diseases, particularly type 2 diabetes and obesity. Leptin is produced by the adipose tissue acting as a satiety signal. Its levels have been positively correlated with fat mass and hyperleptinemia has been proposed to negatively affect male reproductive function. Nevertheless, the molecular mechanisms by which this hormone affects male fertility remain unknown. Herein, we hypothesize that leptin acts on human Sertoli cells (hSCs), the "nurse cells" of spermatogenesis, altering their metabolism. To test our hypothesis, hSCs were cultured without or with leptin (5, 25 and 50ng/mL). Leptin receptor was identified by qPCR and Western blot. Protein levels of glucose transporters (GLUT1, GLUT2 and GLUT3), phosphofructokinase, lactate dehydrogenase (LDH) and monocarboxylate transporter 4 (MCT4) were determined by Western Blot. LDH activity was assessed and metabolite production/consumption determined by proton nuclear magnetic resonance. Oxidative damage was evaluated by assessing lipid peroxidation, protein carbonilation and nitration. Our data shows that leptin receptor is expressed in hSCs. The concentration of leptin found in lean, healthy patients, upregulated GLUT2 protein levels and concentrations of leptin found in lean and obese patients increased LDH activity. Of note, all leptin concentrations decreased hSCs acetate production illustrating a novel mechanism for this hormone action. Moreover, our data shows that leptin does not induce or protect hSCs from oxidative damage. We report that this hormone modulates the nutritional support of spermatogenesis, illustrating a novel mechanism that may be linked to obesity-induced male infertility. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Leptin as a Marker of Body Fat and Hyperinsulinemia in College Students

    Science.gov (United States)

    Kempf, Angela M.; Strother, Myra L.; Li, Chaoyang; Kaur, Harsohena; Huang, Terry T-K.

    2006-01-01

    Little is known about obesity and insulin resistance in college students. Leptin is a hormone secreted by fat cells and has been shown to strongly correlate with both obesity and insulin resistance in children and adults. We investigated associations of leptin with insulin secretion and action in 119 normal-weight students aged 18-24 years. Leptin…

  6. The impact of leptin on perinatal development and psychopathology.

    Science.gov (United States)

    Valleau, Jeanette C; Sullivan, Elinor L

    2014-11-01

    Leptin has long been associated with metabolism as it is a critical regulator of both food intake and energy expenditure, but recently, leptin dysregulation has been proposed as a mechanism of psychopathology. This review discusses the evidence supporting a role for leptin in mental health disorders and describes potential mechanisms that may underlie this association. Leptin plays a critical role in pregnancy and in fetal growth and development. Leptin's role and profile during development is examined in available human studies, and the validity of applying studies conducted in animal models to the human population are discussed. Rodents experience a postnatal leptin surge, which does not occur in humans or larger animal models. This suggests that further research using large mammal models, which have a leptin profile across pregnancy and development similar to humans, are of high importance. Maternal obesity and hyperleptinemia correlate with increased leptin levels in the umbilical cord, placenta, and fetus. Leptin levels are thought to impact fetal brain development; likely by activating proinflammatory cytokines that are known to impact many of the neurotransmitter systems that regulate behavior. Leptin is likely involved in behavioral regulation as leptin receptors are widely distributed in the brain, and leptin influences cortisol release, the mesoaccumbens dopamine pathway, serotonin synthesis, and hippocampal synaptic plasticity. In humans, both high and low levels of leptin are reported to be associated with psychopathology. This inconsistency is likely due to differences in the metabolic state of the study populations. Leptin resistance, which occurs in the obese state, may explain how both high and low levels of leptin are associated with psychopathology, as well as the comorbidity of obesity with numerous mental illnesses. Leptin resistance is likely to influence disorders such as depression and anxiety where high leptin levels have been correlated

  7. Obesity, Inflammation and Acute Myocardial Infarction - Expression of leptin, IL-6 and high sensitivity-CRP in Chennai based population

    Directory of Open Access Journals (Sweden)

    Rajendran Karthick

    2012-08-01

    Full Text Available Abstract Background Obesity, characterised by increased fat mass and is currently regarded as a pro-inflammatory state and often associated with increased risk of cardiovascular diseases (CVD including Myocardial infarction. There is an upregulation of inflammatory markers such as interleukin-6, interleukin-6 receptor and acute phase protein CRP in Acute Myocardial Infarction (AMI patients but the exact mechanism linking obesity and inflammation is not known. It is of our interest to investigate if serum leptin (ob gene product is associated with AMI and correlated with inflammatory proteins namely Interleukin-6 (IL-6 and high sensitivity - C reactive protein (hs-CRP. Results Serum leptin levels were significantly higher in AMI patients when compared to Non-CVD controls. IL-6 and hs-CRP were also elevated in the AMI group and leptin correlated positively with IL-6 and hs-CRP. Incidentally this is the first report from Chennai based population, India. Conclusions The strong correlation between serum levels of leptin and IL-6 implicates an involvement of leptin in the upregulation of inflammatory cytokines during AMI. We hypothesise that the increase in values of IL-6, hs-CRP and their correlation to leptin in AMI patients could be due to participation of leptin in the signaling cascade after myocardial ischemia.

  8. Obesity, Inflammation and Acute Myocardial Infarction - Expression of leptin, IL-6 and high sensitivity-CRP in Chennai based population.

    Science.gov (United States)

    Rajendran, Karthick; Devarajan, Nalini; Ganesan, Manohar; Ragunathan, Malathi

    2012-08-14

    Obesity, characterised by increased fat mass and is currently regarded as a pro-inflammatory state and often associated with increased risk of cardiovascular diseases (CVD) including Myocardial infarction. There is an upregulation of inflammatory markers such as interleukin-6, interleukin-6 receptor and acute phase protein CRP in Acute Myocardial Infarction (AMI) patients but the exact mechanism linking obesity and inflammation is not known. It is of our interest to investigate if serum leptin (ob gene product) is associated with AMI and correlated with inflammatory proteins namely Interleukin-6 (IL-6) and high sensitivity - C reactive protein (hs-CRP). Serum leptin levels were significantly higher in AMI patients when compared to Non-CVD controls. IL-6 and hs-CRP were also elevated in the AMI group and leptin correlated positively with IL-6 and hs-CRP. Incidentally this is the first report from Chennai based population, India. The strong correlation between serum levels of leptin and IL-6 implicates an involvement of leptin in the upregulation of inflammatory cytokines during AMI. We hypothesise that the increase in values of IL-6, hs-CRP and their correlation to leptin in AMI patients could be due to participation of leptin in the signaling cascade after myocardial ischemia.

  9. Analysis of the relationship of leptin, high-sensitivity C-reactive protein, adiponectin, insulin, and uric acid to metabolic syndrome in lean, overweight, and obese young females.

    Science.gov (United States)

    Abdullah, Abdul Ridha; Hasan, Haydar A; Raigangar, Veena L

    2009-02-01

    Over the last decade there has been a steady rise in obesity and co-morbidity, but little is known about the rate of metabolic dysfunction among young adults in the United Arab Emirates. Various factors have been implicated as biomarkers of metabolic syndrome. The objective of this study was to analyze the relationships of leptin, C-reactive protein (CRP), adiponectin, insulin, and uric acid to the metabolic syndrome components in lean, overweight, and obese young females. This was a cross-sectional study of 69 apparently healthy young females, who were classified according to their body mass index (BMI) (kg/m(2)) into three groups: lean (25 and or=30). Estimated biomarkers were: leptin, insulin, adiponectin, high-sensitivity [hs]-CRP, uric acid, blood sugar, high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol, and triglycerides (TG). Anthropometric measures, blood pressure, and homeostasis model assessment-insulin resistance (HOMA-IR) were also measured. Serum leptin, hs-CRP, insulin, and uric acid increased significantly (p syndrome components was found in lean subjects (leptin vs. waist circumference r = 0.48) as opposed to six in the obese group (hs-CRP vs. waist circumference and systolic blood pressure [SBP], r = 0.45 and r = -0.41, respectively; insulin vs. diastolic blood pressure [DBP], r = 0.47; adiponectin vs. blood sugar, r = -0.44; and uric acid vs. waist circumference and TG, r = 0.5 and r = 0.51, respectively). Estimation of the levels of studied biomarkers could be an important tool for early detection of metabolic syndrome before the appearance of its frank components. Uric acid seems to be the most reliable biomarker to identify obese subjects with metabolic syndrome.

  10. [Association between feeding behavior, and genetic polymorphism of leptin and its receptor in obese Chilean children].

    Science.gov (United States)

    Valladares, Macarena; Obregón, Ana María; Weisstaub, Gerardo; Burrows, Raquel; Patiño, Ana; Ho-Urriola, Judith; Santos, José Luis

    2014-09-12

    Leptin (LEP) is mainly produced in adipose tissue and acts in the hypothalamus to regulate energy intake. Mutations in the LEP gene or its receptor (LEPR) that produce monogenic obesity are infrequent. However, LEP and LEPR polymorphisms have been associated with obesity multifactorial, due to the association found with body weight and eating behavior. Measure the association between LEP and LEPR polymorphisms with childhood obesity and eating behavior. 221 Chilean obese children (BMI above the 95th percentile) were recruited. Parents of 134 of these children were also recruited to determine the association between LEP and LEPR polymorphisms with obesity in a case study-parent trio. Eating behavior was measured through the questionnaire of three factors progenitors' version (TFEQ-P19) and eating behavior in children (CEBQ). No significant difference between the studied polymorphisms and childhood obesity, after correction for multiple comparisons, was observed. The dimensions; "Slow eating", "emotional eating", "enjoyment of food" and "uncontrolling eating" were significant associated with certain polymorphisms of LEP and LEPR. There would be an association between polymorphisms of the LEP and LEPR genes with eating behavior in Chilean obese children. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  11. Melatonin Efficacy in Obese Leptin-Deficient Mice Heart

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    Alessandra Stacchiotti

    2017-12-01

    Full Text Available Cardiomyocytes are particularly sensitive to oxidative damage due to the link between mitochondria and sarcoplasmic reticulum necessary for calcium flux and contraction. Melatonin, important indoleamine secreted by the pineal gland during darkness, also has important cardioprotective properties. We designed the present study to define morphological and ultrastructural changes in cardiomyocytes and mainly in mitochondria of an animal model of obesity (ob/ob mice, when treated orally or not with melatonin at 100 mg/kg/day for 8 weeks (from 5 up to 13 week of life. We observed that ob/ob mice mitochondria in sub-sarcolemmal and inter-myofibrillar compartments are often devoid of cristae with an abnormally large size, which are called mega-mitochondria. Moreover, in ob/ob mice the hypertrophic cardiomyocytes expressed high level of 4hydroxy-2-nonenal (4HNE, a marker of lipid peroxidation but scarce degree of mitofusin2, indicative of mitochondrial sufferance. Melatonin oral supplementation in ob/ob mice restores mitochondrial cristae, enhances mitofusin2 expression and minimizes 4HNE and p62/SQSTM1, an index of aberrant autophagic flux. At pericardial fat level, adipose tissue depot strictly associated with myocardium infarction, melatonin reduces adipocyte hypertrophy and inversely regulates 4HNE and adiponectin expressions. In summary, melatonin might represent a safe dietary adjuvant to hamper cardiac mitochondria remodeling and the hypoxic status that occur in pre-diabetic obese mice at 13 weeks of life.

  12. Association of leptin and insulin resistance in PCOS: A case-controlled study.

    Science.gov (United States)

    Namavar Jahromi, Bahia; Dabaghmanesh, Mohammad Hassan; Parsanezhad, Mohammad Ebrahim; Fatehpoor, Faranak

    2017-07-01

    Endocrine abnormalities related to polycystic ovary Syndrome (PCOS) are important problems. To compare serum leptin levels between infertile women with and without PCOS. To rank sensitivity of six indirect methods for detection of insulin resistance (IR) and to evaluate the association between leptin and IR in PCOS group. This Case-controlled study performed on 189 infertile women referred to Shiraz Mother and Child Hospital during 2012-2015. Ninety-nine PCOS cases according to Rotterdam criteria were compared to 90 cases without PCOS. Serum leptin, body mass index (BMI), several hormones, and their correlation coefficients with leptin were compared. IR in PCOS women was measured by indirect methods, including fasting blood sugar (FBS), fasting insulin (FI), glucose/insulin, homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and MacAuley index. Association between IR and leptin was evaluated. Independent sample t-test and Pearson's test were used. Infertile women with PCOS had higher BMI (26.47±3.62 vs. 24.82±5.18 kg/m 2 ) and serum leptin levels (41.79±187.89 vs. 19.38±12.57 ng/mL). Leptin showed significant association with weight and BMI in both groups (pPCOS group. HOMA-IR showed the highest rate of IR followed by FI and QUICKI methods. The mean leptin levels had positive association with IR assessed by HOMA-IR (pPCOS infertile women. HOMA-IR followed by FI and QUICKI is the most sensitive test for detection of IR.

  13. High Leptin Level Attenuates Embryo Development in Overweight/Obese Infertile Women by Inhibiting Proliferation and Promotes Apoptosis in Granule Cell.

    Science.gov (United States)

    Lin, Xian-Hua; Wang, Hui; Wu, Dan-Dan; Ullah, Kamran; Yu, Tian-Tian; Ur Rahman, Tanzil; Huang, He-Feng

    2017-07-01

    Obesity appears to be associated with female reproductive dysfunction and infertility. Women with obesity undergoing in vitro fertilization (IVF) had poor oocyte quality, decreased embryo development, and poor pregnancy outcome. However, the mechanism linking obesity to poor reproductive outcomes is still unclear. Obesity is frequently accompanied with elevated leptin levels. Here we aimed to evaluate the effect of high leptin level in follicular fluid (FF) on the proliferation and apoptosis in granule cells and correlate these findings with poor reproductive outcomes in infertile women with overweight or obesity who underwent IVF treatment. We investigated clinical and ongoing pregnancy rates in 189 infertile women who underwent IVF. Leptin levels were quantified in peripheral blood and FF as well. In vitro cell model was used to explore the potential effect of high leptin on the proliferation and apoptosis in granulosa cells. Results showed reduced clinical and ongoing pregnancy rates in overweight/obesity women who underwent IVF compared to control with normal BMI. On the other hand, leptin levels presented significant increase in peripheral blood and FF in overweight/obese women. Leptin level in FF was negatively correlated to good quality embryo rate. Importantly, in vitro study showed that leptin inhibited cells proliferation and promoted apoptosis by upregulation of caspase-3 and downregulation of Bcl-2 in granulosa cells in a dose dependent manner. These observations suggest that leptin may acts as a local mediator to attenuate embryo development and reduce fertility in obese patients. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Influence of Antioxidants on Leptin Metabolism and its Role in the Pathogenesis of Obesity.

    Science.gov (United States)

    Mangge, Harald; Ciardi, Christian; Becker, Kathrin; Strasser, Barbara; Fuchs, Dietmar; Gostner, Johanna M

    2017-01-01

    Obesity is associated with low-grade inflammation. Leptin, a hormone made by fat cells regulates appetite and hunger and thus food intake behavior. Interestingly, , food preservatives like sodium sulfite and sodium benzoate and also natural colorant and spice compounds such as curcumin were found to decrease the release of leptin in murine 3T3-L1 adipocytes, after co-incubation with LPS, which was added to mimic the pro-inflammatory status in obesity. Several of these compounds are well known food antioxidants.Whilst reducing oxidation events is beneficial in states of elevated oxidative stress, overexposure to food antioxidant can lead to adverse effects. There are hints from in vivo data, that antioxidant stress in younger age plays a role in the development of adiposity in later life. The insufficient exposure to oxidizing compounds like reactive oxygen species (ROS) cannot only cause an insufficient burning of calories but there is also a link to the regulation of food intake behavior. If the in vitro findings can be extrapolated to the in vivo situation, consumption of antioxidant supplemented food could lead to decreased leptin release and contribute to an obesogenic environment. This aspect sheds some new critical light on the potential role of an antioxidant-enriched nutrition in the obesity epidemic during the past few centuries. Doing sports could represent not only a proper strategy to initiate physiological ROS production and burning of calories, but also may shift the hormone milieu towards a reduction of hunger feelings and thus reduce appetite and food intake.

  15. [Cardiovascular exercise on obese women: effects on adiponectine, leptine, and tumour necrosis factor-alpha].

    Science.gov (United States)

    Landeros-Olvera, Erick; López-Alvarenga, Juan Carlos; Nava-González, Edna J; Gallegos-Cabriales, Esther; Lavalle-González, Fernando; Bastarrachea, Raúl A; Salazar González, Bertha Cecilia

    2014-01-01

    The relationship of hormones adiponectin, leptin and tumor necrosis factor-alpha in adipose tissue on the atherogenic process is one of the most promising models in preventive medicine. The numerous tests performed to identify the effect of exercise on these hormones have not been clear on the type of exercise routine and physical effort calculated to contribute to changing plasma concentrations in obese women. Analyze controlledcardiovascular exercise effect on serum level of adiponectin, leptin, and tumournecrosis factor-alpha in obese young women. A simple blind clinical essay. The intervention covered a 10-week controlled, cardiovascular exercise program by 34 women (cases n=17, controls n=17) with a body mass index>27kg/m(2). Molecular analysis was performed by immune-fluorescence. Following the intervention, cases and controls means were as follows: adiponectin 19.0 vs. 12.2μ/ml (P=.008); leptin 20.0 vs. 28.0μ/L (P=.02); and tumour necrosis factor-alpha 4.7 vs. 5.1pg/ml (P=.05). The established exercise (5 sessions a week of exercise of 40min each for 10 weeks with a heart rate reserve of 40 to 80%) improved plasma concentrations of these hormones in the expected direction. This finding highlights an unpublished amount of exercise, controlled by the reserve cardiac frequency that might contribute the cardiovascular and metabolic protection to obese women. Copyright © 2013 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

  16. Leptin and reproduction: a review.

    Science.gov (United States)

    Moschos, Stergios; Chan, Jean L; Mantzoros, Christos S

    2002-03-01

    To review recent advances in understanding the role of leptin in the physiology and pathophysiology of reproduction, with a focus on relevant clinical situations. A MEDLINE computer search was performed to identify relevant articles. Leptin, an adipocyte hormone important in regulating energy homeostasis, interacts with the reproductive axis at multiple sites, with stimulatory effects at the hypothalamus and pituitary and inhibitory actions at the gonads. More recently, leptin has been shown to play a role in other target reproductive organs, such as the endometrium, placenta, and mammary gland, with corresponding influences on important physiologic processes such as menstruation, pregnancy, and lactation. As a marker of whether nutritional stores are adequate, leptin may act in concert with gonadotropins and the growth hormone axis to initiate the complex process of puberty. Conditions in which nutritional status is suboptimal, such as eating disorders, exercise-induced amenorrhea, and functional hypothalamic amenorrhea, are associated with low serum leptin levels; and conditions with excess energy stores or metabolic disturbances, such as obesity and polycystic ovarian syndrome, often have elevated serum or follicular fluid leptin levels, raising the possibility that relative leptin deficiency or resistance may be at least partly responsible for the reproductive abnormalities that occur with these conditions. Leptin may act as the critical link between adipose tissue and the reproductive system, indicating whether adequate energy reserves are present for normal reproductive function. Future interventional studies involving leptin administration are expected to further clarify this role of leptin and may provide new therapeutic options for the reproductive dysfunction associated with states of relative leptin deficiency or resistance.

  17. Appetite Response among Those Susceptible or Resistant to Obesity

    Directory of Open Access Journals (Sweden)

    Rachel C. Brown

    2014-01-01

    Full Text Available An alternative approach in determining cause, treatment, and prevention of obesity is to study those who appear resistant to the obesogenic environment. We examined appetite responses in 33 obesity resistant individuals (ORI versus 28 obesity susceptible individuals (OSI. Fingerprick blood samples to measure ghrelin, total peptide YY (PYY, leptin, glucose, and insulin along with appetite ratings were collected at baseline and 15, 30, 60, 120, and 180 min following consumption of a standardized meal. Fasting, area under the curve (AUC, peak/nadir, and time to peak/nadir were compared. Participants completed the three factor eating questionnaire (TFEQ. No significant differences were observed for ghrelin or PYY. Higher leptin concentrations in the OSI disappeared after controlling for percent body fat (%BF. Significant differences in appetite ratings included a lower hunger nadir among OSI compared with ORI (P=0.017. Dietary restraint (P<0.001 and disinhibition (P<0.001 were lower in ORI compared with OSI, with and without adjustment for %BF. Given the differential body weight of the study groups, similar observed ghrelin concentrations were unexpected, perhaps indicating OSI and ORI respond differently to the same ghrelin concentration. Also ORI response to hunger appears different as they exhibit lower levels of dietary restraint and disinhibition compared with OSI.

  18. ROLE OF LEPTIN ON CYTOCHROME P-450 AND SOME LIVER MICROSOMAL ENZYMES ACTIVITIES IN THE OBESE AND LEAN MICE

    International Nuclear Information System (INIS)

    HEBEISHY, M.I.A.; MAZEN, G.M.A.; SHAHIN, M.I

    2008-01-01

    Leptin is a hormone that is secreted by adipocytes and regulates body weight through its effect on satiety and energy metabolism. The obese mouse is deficient in this protein and is characterized by obesity and other metabolic disorders. This study investigated the alterations of several hepatic cytochrome P 4 -5 0 (CYP), conjugation and antioxidant enzymes in lean and obese mice and the role of leptin in the modulation of these enzymes. Lean and obese male mice were injected with leptin (100 μg / rat) for 15 days. The obtained results revealed that administration of leptin to lean mice caused a significant elevation in the level of blood glucose, serum insulin, 6α, 6β, 16α- hydroxylation of testosterone, the activity of CYP 1 A 1 , CYP 4 A and GSH reductase in liver microsomes while serum corticosterone and the activity of total GSH were significantly decreased when compared to lean control mice. Moreover, obese mice treated with leptin recorded significant reduction in body weight, blood glucose concentration, serum levels of insulin and corticosterone, 7α and 16α- hydroxylation of testosterone, the activity of CYP 1A 1, CYP 2 B 1 and CYP 4 A and GST in liver microsomes. On the other hand, 6α, 6β-hydroxylation of testosterone, the activity of CYP 2 E 1 and GSH reductase in liver microsome were significantly increased when compared to obese control mice. The mechanism for the observed alterations may be due to direct leptin effects or via indirect alterations in insulin, corticosterone and/or growth hormone

  19. Leptin level correlates with obesity and health related quality of life in obstructive sleep apnea syndrome patients.

    Science.gov (United States)

    Dubey, Abhishek; Kant, Surya; Tiwari, Sunita; Agarwal, Sarita; Mahdi, Abbas Ali

    2015-04-01

    Leptin takes part in regulation of energy balance, neuronal functions, pain and mood. It may act as intermediary marker for various components of HRQOL in patients of obstructive sleep apnea syndrome. To document the correlation among leptin levels, obesity and HRQoL in OSAS patients. A tertiary care hospital based cross-sectional study was done in 224 subjects aged 18-65 years, after taking informed consent. Subjects with previous history of smoking, Liver disease, COPD, CHD, T2 DM, asthma, cancer, end stage renal disease, heart failure, any endocrine disorder including Cushing syndrome, thyroid, on systemic steroid or any continuous medication for last 6 months, on dieting or suffering from any disability condition (other than obesity and OSAS) affecting their HRQoL were excluded from the study. All subjects underwent Polysomnography. Leptin assay was done by ELISA method. Hindi version of HRQoL tool SF-36 was used to evaluate HRQoL. SPSS 20 was used to analyse data. Three groups (AHI 15) were compared. Significant differences were observed in BMI, NC, WC, WHR and ESS. Differences were not significant in sleep architecture and Leptin level. SF-36 HRQoL, scores were observed decreased with increase in severity of disease. Leptin level was found significantly correlated with "Role limitations due to physical health problems", "Social functioning", Hypopnea and obesity indices. In these subjects Obesity indices are the most important correlates of Leptin level. Oxygen desaturation indices with exception of Hypopnea and HRQoL may not be exclusively correlated to leptin levels. Copyright © 2015 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

  20. Leptin in humans: lessons from translational research.

    Science.gov (United States)

    Blüher, Susann; Mantzoros, Christos S

    2009-03-01

    Leptin has emerged over the past decade as a key hormone in not only the regulation of food intake and energy expenditure but also in the regulation of neuroendocrine and immune function as well as the modulation of glucose and fat metabolism as shown by numerous observational and interventional studies in humans with (complete) congenital or relative leptin deficiency. These results have led to proof-of-concept studies that have investigated the effect of leptin administration in subjects with complete (congenital) leptin deficiency caused by mutations in the leptin gene as well as in humans with relative leptin deficiency, including states of lipoatrophy or negative energy balance and neuroendocrine dysfunction, as for instance seen with hypothalamic amenorrhea in states of exercise-induced weight loss. In those conditions, most neuroendocrine, metabolic, or immune disturbances can be restored by leptin administration. Leptin replacement therapy is thus a promising approach in several disease states, including congenital complete leptin deficiency, states of energy deprivation, including anorexia nervosa or milder forms of hypothalamic amenorrhea, as well as syndromes of insulin resistance seen in conditions such as congenital or acquired lipodystrophy. In contrast, states of energy excess such as garden-variety obesity are associated with hyperleptinemia that reflects either leptin tolerance or leptin resistance. For those conditions, development of leptin sensitizers is currently a focus of pharmaceutical research. This article summarizes our current understanding of leptin's role in human physiology and its potential role as a novel therapeutic option in human disease states associated with a new hormone deficiency, ie, leptin deficiency.

  1. Lipopolysaccharide-binding protein and leptin are associated with stress-induced interleukin-6 cytokine expression ex vivo in obesity.

    Science.gov (United States)

    Huang, Chun-Jung; Stewart, Jennifer K; Shibata, Yoshimi; Slusher, Aaron L; Acevedo, Edmund O

    2015-05-01

    Obesity is associated with enhanced inflammation and mental stress, but limited information has addressed the potential additive effect of psychological stress on obesity-associated inflammation. This study examined whether obese subjects would elicit a greater host immune response (IL-6 mRNA and cytokine) to lipopolysaccharide (LPS) in response to mental stress. Blood samples for LPS-stimulated IL-6 mRNA and cytokine were collected prior to and following mental stress. Results showed that obese subjects elicited a greater LPS-induced IL-6 along with its mRNA expression following mental stress compared to normal-weight subjects. Stress-induced IL-6 cytokine response to LPS was correlated with the baseline levels of plasma LPS binding protein (LBP) and leptin. These findings are consistent with the idea that endogenous inflammatory agents (e.g., LBP and leptin), often elevated with obesity, enhance inflammatory responses to psychological stress. © 2014 Society for Psychophysiological Research.

  2. Adiponectin and Leptin Synovial Fluid Concentration as a Marker for the Severity of Knee Osteoarthritis in Obese Patients

    Directory of Open Access Journals (Sweden)

    Eddy Mart Salim

    2015-12-01

    Full Text Available Purpose: Osteoarthritis (OA is a chronic degenerative joint disorder of the synovial joint characterized by loss of articular cartilage, osteophyte formation, and alterations of subchondral bone. An increase of weight bearing affect on knee joint biomechanically and alter concentration of adipokines, such as adiponectin and leptin. Herein we reported a correlation between adiponectin and leptin synovial fluid concentration with the severity of knee OA in obese patients. Material and Methods: Totally 45 patients were included in this research. ELISA was used to determine adiponectin and leptin concentrations of synovial fluid. The severity of knee OA was classified by Kellgren-Lawrence grading scale. Data analysis was conducted using SPSS for windows. Results: Based on the leptin measurement, it was shown that leptin concentrations were correlated positively with the severity of knee OA. Vice versa, adiponectin concentrations were correlated negative. Conclusion: Our study was support the biomarker function of adiponectin and leptin concentration on synovial fluids, in which those concentrations were related with the severity of OA. Those results also suggested the function of leptin and adiponectin on OA. [Cukurova Med J 2015; 40(4.000: 746-756

  3. Leptin promoter variant G2548A is associated with serum leptin and HDL-C levels in a case control observational study in association with obesity in a Pakistani cohort.

    Science.gov (United States)

    Shabana, -; Hasnain, Shahida

    2016-06-01

    Leptin is a protein hormone synthesized by adipocytes and is involved in the regulation of food intake and energy expenditure. We hypothesized that any change in the promoter sequence can affect the expression of the gene and hence leptin protein levels in the serum. The aim of the current study was to investigate the relationship of such a promoter variant of the leptin gene, G-2548A polymorphism, with obesity and its effect on various anthropometric and metabolic parameters in a Pakistani cohort consisting of 250 obese and 225 non-obese control subjects. Body weight, height, waist circumference (WC), hip circumference (HC) and blood pressure (BP) were measured by standard methods and levels of fasting blood glucose (FBG), total cholesterol, triglycerides, HDLC, LDLC, and leptin were determined. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results showed that the LEP G-2548A polymorphism showed significant association with obesity in Pakistan. In addition, the polymorphism showed association with weight, height, BMI, WC, HDLC and serum leptin levels. The findings suggest that the leptin promoter G-2548A variant may play its part in the progression to obesity by not only affecting the body's fat distribution but also by changing the serum leptin and HDLC levels.

  4. Leptin and leptin-related gene polymorphisms, obesity, and influenza A/H1N1 vaccine-induced immune responses in older individuals.

    Science.gov (United States)

    Ovsyannikova, Inna G; White, Sarah J; Larrabee, Beth R; Grill, Diane E; Jacobson, Robert M; Poland, Gregory A

    2014-02-07

    Obesity is a risk factor for complicated influenza A/H1N1 disease and poor vaccine immunogenicity. Leptin, an adipocyte-derived hormone/cytokine, has many immune regulatory functions and therefore could explain susceptibility to infections and poor vaccine outcomes. We recruited 159 healthy adults (50-74 years old) who were immunized with inactivated TIV influenza vaccine that contained A/California/7/2009/H1N1 virus. We found a strong correlation between leptin concentration and BMI (r=0.55, pGHRL genes that were associated with leptin levels and four SNPs in the PTPN1/LEPR/STAT3 genes associated with peripheral blood TREC levels (p<0.05). Heterozygosity of the synonymous variant rs2230604 in the PTPN1 gene was associated with a significantly lower (531 vs. 259, p=0.005) TREC level, as compared to the homozygous major variant. We also found eight SNPs in the LEP/PPARG/CRP genes associated with variations in influenza-specific HAI and B-cell responses (p<0.05). Our results suggest that specific allelic variations in the leptin-related genes may influence adaptive immune responses to influenza vaccine. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Serum leptin levels in female patients with niddm

    International Nuclear Information System (INIS)

    Haque, Z.; Rahman, M.A.

    2003-01-01

    Objective: To compare serum leptin levels of diabetic and non-diabetic female subjects and also assess the relationship of hyperglycemia with serum insulin, C-peptide and leptin levels. Results: Serum leptin levels of obese diabetic and non-diabetic subjects were significantly higher as compared with lean diabetic patients and non-diabetic subjects (P<0.05). Leptin levels were positively correlated with serum insulin and C-peptide levels. Serum leptin increased with increase in body mass index and waist hip ratio was strongly related with insulin resistance in NIDDM. Conclusion: Leptin levels are increased in obesity and may play a role in development of insulin resistance and NIDDM. (author)

  6. [Plasma levels of insulin and leptin in patients with morbid obesity and anorexia nervosa after weight loss or gain, respectively].

    Science.gov (United States)

    Escobar, L; Freire, J M; Girón, J A; Vázquez, J M; Pajares, M; Ortego, J; Gavilán, I; Chover, A J; Carrasco, M; Epinosa, R; Marín, F; Aguilar, M

    2000-06-01

    The present study was conducted in order to analyze the relationship existing between leptin and insulin levels in massive weight loss and weight recovery. Thirteen patients with severe obesity, 14 patients with anorexia nervosa and 13 healthy control subjects were studied. The patients with severe obesity underwent a vertical banded gastroplasty followed by an 800 kcal/day diet for 12 weeks. They were evaluated prior to (body mass index [BMI] 51.2 +/- 8.8 Kg/m2) and after drastic weight loss (BMI 40.6 +/- 6.7 Kg/m2). Patients with anorexia nervosa were treated exclusively with nutritional therapy during 12 weeks, and they were evaluated at their lowest weight status (BMI 16.2 +/- 2.2 Kg/m2) and after weight recovery (BMI 17.9 +/- 2.3 Kg/m2). The BMI of the normal subjects was in the normal range of 20 to 27 Kg/m2 (average 22.8 +/- 2.6 Kg/m2). BMI, percentage of body fat, waist circumference, and serum levels of leptin, insulin, and C-peptide were determined in each patient and normal subject. In severely obese patients, serum leptin and insulin decreased significantly after drastic weight reduction (leptin: from 51.8 +/- 22.3 to 23.7 +/- 10.2 ng/ml; insulin: from 27.1 +/- 13.3 to 17.2 +/- 7.2 mU/ml). In patients with anorexia nervosa, the mean serum leptin levels were significantly higher after weight recovery (5.5 +/- 3.2 vs 7.6 +/- 6 ng/ml). Serum leptin in the severe obesity group correlated positively with BMI, percentage body fat and waist circumference before and after weight loss. In those patients suffering from anorexia nervosa, serum leptin correlated positively with the BMI, percentage of body fat, and waist circumference in the low weight state and after weight recovery. In addition, their serum insulin correlated with BMI and waist circumference after weight recovery. These data reveal that serum leptin concentration correlates significantly with the BMI and body fat content 1) in subjects with a range of weight and caloric intake, 2) in obese

  7. Leptin induces cardiac fibrosis through galectin-3, mTOR and oxidative stress: potential role in obesity.

    Science.gov (United States)

    Martínez-Martínez, Ernesto; Jurado-López, Raquel; Valero-Muñoz, María; Bartolomé, María Visitación; Ballesteros, Sandra; Luaces, María; Briones, Ana María; López-Andrés, Natalia; Miana, María; Cachofeiro, Victoria

    2014-05-01

    Leptin acts as a cardiac profibrotic factor. However, the mechanisms underlying this effect are unclear. Therefore, we sought to elucidate the mediators involved in this process and the potential role of leptin in cardiac fibrosis associated with obesity. Male Wistar rats were fed either a high-fat diet (HFD; 33.5% fat), or a standard diet (3.5% fat) for 6 weeks. HFD animals show cardiac hypertrophy, fibrosis and an increase in O2- production as evaluated by dihydroethidium. Echocardiographic parameters of cardiac structure and systolic function were similar in both groups. Cardiac levels of leptin, collagen I, galectin-3 and transforming growth factor β (TGF-β) were higher in HFD than in controls. In cardiac myofibroblasts, leptin (10-100 ng/ml) increased O2-, collagen I, galectin-3, TGF-β and connective tissue growth factor production (CTGF). These effects were prevented by the presence of either melatonin (10 mmol/l) or the inhibitor of mTOR, rapamycin (10 mmol/l). Blockage of galectin-3 activity by N-acetyllactosamine (LacNac 10 mmol/l) reduced both collagen I and O2(*-) production induced by leptin. The p70S6 kinase activation/phosphorylation, the downstream mediator of mTOR, induced by leptin was not modified by melatonin. Leptin reduced the metalloproteinase (MMP) 2 activity and the presence of melatonin, rapamycin or LacNac were unable to prevent it. The data suggest that leptin locally produced in the heart could participate in the fibrosis observed in HFD by affecting collagen turnover. Collagen synthesis induced by leptin seems to be mediated by the production of galectin-3, TGF-β and CTGF through oxidative stress increased by activation of mTOR pathway.

  8. [Leptin and the feedback regulation of body weight].

    Science.gov (United States)

    Wang, X; Ye, G; Sun, J

    1999-09-30

    Body weight may be controlled by a negative feedback loop. Recent studies have identified that the ob gene product, leptin, apparently and exclusively expressed in adipose tissue, is a part of the negative feedback loop. Leptin is proposed to act as an afferent signal in the negative feedback loop to hypothalamus that limiting food-intake, controlling energy homeostasis and regulating the mass of adipose tissue. The dificiency of or resistance to leptin causes severe obesity.

  9. Obesity and chronic stress are able to desynchronize the temporal pattern of serum levels of leptin and triglycerides.

    Science.gov (United States)

    de Oliveira, Carla; Scarabelot, Vanessa Leal; de Souza, Andressa; de Oliveira, Cleverson Moraes; Medeiros, Liciane Fernandes; de Macedo, Isabel Cristina; Marques Filho, Paulo Ricardo; Cioato, Stefania Giotti; Caumo, Wolnei; Torres, Iraci L S

    2014-01-01

    Disruption of the circadian system can lead to metabolic dysfunction as a response to environmental alterations. This study assessed the effects of the association between obesity and chronic stress on the temporal pattern of serum levels of adipogenic markers and corticosterone in rats. We evaluated weekly weight, delta weight, Lee index, and weight fractions of adipose tissue (mesenteric, MAT; subcutaneous, SAT; and pericardial, PAT) to control for hypercaloric diet-induced obesity model efficacy. Wistar rats were divided into four groups: standard chow (C), hypercaloric diet (HD), stress plus standard chow (S), and stress plus hypercaloric diet (SHD), and analyzed at three time points: ZT0, ZT12, and ZT18. Stressed animals were subjected to chronic stress for 1h per day, 5 days per week, during 80 days. The chronic exposure to a hypercaloric diet was an effective model for the induction of obesity and metabolic syndrome, increasing delta weight, Lee index, weight fractions of adipose tissue, and triglycerides and leptin levels. We confirmed the presence of a temporal pattern in the release of triglycerides, corticosterone, leptin, and adiponectin in naïve animals. Chronic stress reduced delta weight, MAT weight, and levels of triglycerides, total cholesterol, and leptin. There were interactions between chronic stress and obesity and serum total cholesterol levels, between time points and obesity and adiponectin and corticosterone levels, and between time points and chronic stress and serum leptin levels. In conclusion, both parameters were able to desynchronize the temporal pattern of leptin and triglyceride release, which could contribute to the development of metabolic diseases such as obesity and metabolic syndrome. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Mitofusin 2 in POMC neurons connects ER stress with leptin resistance and energy imbalance

    DEFF Research Database (Denmark)

    Schneeberger, Marc; Dietrich, Marcelo O; Sebastián, David

    2013-01-01

    Mitofusin 2 (MFN2) plays critical roles in both mitochondrial fusion and the establishment of mitochondria-endoplasmic reticulum (ER) interactions. Hypothalamic ER stress has emerged as a causative factor for the development of leptin resistance, but the underlying mechanisms are largely unknown....

  11. Leptin-induced endothelium-dependent vasorelaxation of peripheral arteries in lean and obese rats: role of nitric oxide and hydrogen sulfide.

    Directory of Open Access Journals (Sweden)

    Anna Jamroz-Wiśniewska

    Full Text Available Adipose tissue hormone leptin induces endothelium-dependent vasorelaxation mediated by nitric oxide (NO and endothelium-derived hyperpolarizing factors (EDHF. Previously it has been demonstrated that in short-term obesity the NO-dependent and the EDHF-dependent components of vascular effect of leptin are impaired and up-regulated, respectively. Herein we examined the mechanism of the EDHF-dependent vasodilatory effect of leptin and tested the hypothesis that alterations of acute vascular effects of leptin in obesity are accounted for by chronic hyperleptinemia. The study was performed in 5 groups of rats: (1 control, (2 treated with exogenous leptin for 1 week to induce hyperleptinemia, (3 obese, fed highly-palatable diet for 4 weeks, (4 obese treated with pegylated superactive rat leptin receptor antagonist (PEG-SRLA for 1 week, (5 fed standard chow and treated with PEG-SRLA. Acute effect of leptin on isometric tension of mesenteric artery segments was measured ex vivo. Leptin relaxed phenylephrine-preconstricted vascular segments in NO- and EDHF-dependent manner. The NO-dependent component was impaired and the EDHF-dependent component was increased in the leptin-treated and obese groups and in the latter group both these effects were abolished by PEG-SRLA. The EDHF-dependent vasodilatory effect of leptin was blocked by either the inhibitor of cystathionine γ-lyase, propargylglycine, or a hydrogen sulfide (H2S scavenger, bismuth (III subsalicylate. The results indicate that NO deficiency is compensated by the up-regulation of EDHF in obese rats and both effects are accounted for by chronic hyperleptinemia. The EDHF-dependent component of leptin-induced vasorelaxation is mediated, at least partially, by H2S.

  12. The integrative role of leptin, oestrogen and the insulin family in obesity-associated breast cancer: potential effects of exercise.

    Science.gov (United States)

    Schmidt, S; Monk, J M; Robinson, L E; Mourtzakis, M

    2015-06-01

    Obesity is an established risk factor for postmenopausal breast cancer. The mechanisms through which obesity influences the development and progression of breast cancer are not fully elucidated; however, several factors such as increased oestrogen, concentrations of various members of the insulin family and inflammation that are associated with adiposity are purported to be important factors in this relationship. Emerging research has also begun to focus on the role of adipokines, (i.e. adipocyte secreted factors), in breast cancer. Leptin secretion is directly related to adiposity and is believed to promote breast cancer directly and independently, as well as through involvement with the oestrogen and insulin signalling pathways. As leptin is secreted from white adipose tissue, any intervention that reduces adiposity may be favourable. However, it is also important to consider that energy expenditure through exercise, independent of fat loss, may improve leptin regulation. The purpose of this narrative review was to explore the role of leptin in breast cancer development and progression, identify key interactions with oestrogen and the insulin family, and distinguish the potential effects of exercise on these interactions. © 2015 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity.

  13. [Mechanism study on leptin resistance in lung cancer cachexia rats treated by Xiaoyan Decoction].

    Science.gov (United States)

    Zhang, Yun-Chao; Jia, Ying-Jie; Yang, Pei-Ying; Zhang, Xing; Li, Xiao-Jiang; Zhang, Ying; Zhu, Jin-Li; Sun, Yi-Yu; Chen, Jun; Duan, Hao-Guo; Guo, Hua; Li, Chao

    2014-12-01

    To study the leptin resistance mechanism of Xiaoyan Decoction (XD) in lung cancer cachexia (LCC) rats. An LCC rat model was established. Totally 40 rats were randomly divided into the normal control group, the LCC model group, the XD group, and the positive control group, 10 in each group. After LCC model was set up, rats in the LCC model group were administered with normal saline, 2 mL each time. Rats in the XD group were administered with XD at the daily dose of 2 mL. Those in the positive control group were administered with Medroxyprogesterone Acetate suspension (20 mg/kg) by gastrogavage at the daily dose of 2 mL. All medication lasted for 14 days. The general condition and tumor growth were observed. Serum levels of leptin and leptin receptor in the hypothalamus were detected using enzyme-linked immunosorbent assay. Contents of neuropeptide Y (NPY) and anorexia for genomic POMC were detected using real-time PCR technique. Serum leptin levels were lower in the LCC model group than in the normal control group with statistical significance (P XD group (P XD or Medroxyprogesterone Acetate could effectively reduce levels of leptin receptor with statistical significance (P XD group and the positive control group (P 0.05). There was statistical difference in POMC between the normal control group and the LCC model group (P XD group and the positive control group with statistical significance (P XD group (P XD could increase serum leptin levels and reduce leptin receptor levels in the hypothalamus. LCC could be improved by elevating NPY contents in the hypothalamus and reducing POMC contents, promoting the appetite, and increasing food intake from the periphery pathway and the central pathway.

  14. Genetic variation in the leptin receptor gene, leptin, and weight gain in young Dutch adults.

    Science.gov (United States)

    van Rossum, Caroline T M; Hoebee, Barbara; van Baak, Marleen A; Mars, Monica; Saris, Wim H M; Seidell, Jacob C

    2003-03-01

    To investigate the association between leptin levels, polymorphisms in the leptin receptor (LEPR) gene, and weight gain. From two large prospective cohorts in The Netherlands (n = 17,500), we compared the baseline leptin of 259 subjects who had gained an average of 12.6 kg (range 5.5 to 33 kg) with 277 subjects who kept stable weight (range -2.6 to 3.1 kg) after a mean follow-up of 6.8 years. Three polymorphisms in the LEPR gene (Lys109Arg, Gln223Arg, and Lys656Asn) were determined. Weight gainers had significantly higher baseline leptin levels than those who kept stable weight (odds ratio = 1.27, 95% confidence interval 1.1 to 1.5, per SD increase in log(e)-transformed leptin). Weight gainers with the Arg109 or the Arg223 alleles had higher leptin levels compared with the noncarriers of these alleles. Only among men, the association between leptin and weight gain tended to be stronger among those with an Arg223 allele compared with those without this mutation. Relatively high leptin levels predict weight gain, suggesting that leptin resistance plays a role in the development of obesity in the general population. Higher leptin levels for those with a Lys109Arg or Gln223Arg mutation (or a linked other marker) may imply that these subjects have a modified functional leptin receptor. However, the role of these mutations on weight gain is limited.

  15. Effects of aerobic training on leptin, tumor necrosis factor-α and interleukin-6 levels in obese and lean men

    Directory of Open Access Journals (Sweden)

    Vahdat Boghrabadi

    2009-10-01

    Full Text Available Introduction: Obesity results in some diseases such as of atherosclerosis diabetic and thereforeinfluence on the immune system, greatly. Given the undeniable role of sport in general health, the aim ofthis present study was to assay the effects of regular exercise on serum levels of immunoregulators factors(leptin, tumor necrosis factor- α (TNF- α and interleukin-6 in obese and lean men.Material and methods: 37 male subjects divided two groups of obese and lean with body compositionanalyzer. Blood samples were taken 48 h before starting the aerobic training program. Then, both groupsperformed the aerobic training program included running with 65-85% of individual maximum heart rateon treadmill for 3 sessions per week, 30 minutes per session and 2 consecutive months. Then anotherblood sample was taken following the training period. Serum levels of leptin, TNF- α and interleukin-6of all subjects before and after the training period were measured using standard biochemical methodsfrom all the subjects and all the parameters were measured in both groups again.Results: Our results showed that the aerobic training resulted in a significant decrease in leptin levelsin obese (p=0.000 and non obese (p=0.004 peoples and also a significant decrease in TNF- α (p=0.042in lean people. However, the aerobic training had no significant influence in the levels of interleukin-6 inboth groups.Conclusion: The results showed that regular and light aerobic exercises could decrase leptin levels inboth obese and lean men, but have differential effects on levels of TNF- α in both groups. These effectsmay influence functions of immune system and metabolism in obese and lean men in a different way.

  16. Repeated electroacupuncture in obese Zucker diabetic fatty rats: adiponectin and leptin in serum and adipose tissue.

    Science.gov (United States)

    Peplow, Philip V

    2015-04-01

    Fasted, male, obese, Zucker, diabetic fatty rats aged 10-16 weeks were anesthetized with 1% halothane in nitrous oxide-oxygen (3:1) on alternate weekdays over 2 weeks. Group 1 (n = 4) did not receive electroacupuncture (controls); Group 2 (n = 4) received electroacupuncture using the Zhongwan and the Guanyuan acupoints; Group 3 (n = 4) received electroacupuncture using the bilateral Zusanli acupoints; Group 4 (n = 6) received neither halothane in nitrous oxide:oxygen nor electroacupuncture. At the end of study, animals were injected with sodium pentobarbitone (60 mg/mL, i.p.), and blood and white adipose tissue were collected. Analysis of variance and Duncan's tests showed that the mean leptin in serum was significantly lower and the adiponectin:leptin ratio was significantly higher in Group 2 than in Group 1 (p  0.05). No significant differences in the serum or the adipose-tissue measurements between Groups 1 and 3 were observed (p > 0.05). Copyright © 2015. Published by Elsevier B.V.

  17. Differential hypothalamic leptin sensitivity in obese rat offspring exposed to maternal and postnatal intake of chocolate and soft drink.

    Science.gov (United States)

    Kjaergaard, M; Nilsson, C; Secher, A; Kildegaard, J; Skovgaard, T; Nielsen, M O; Grove, K; Raun, K

    2017-01-16

    Intake of high-energy foods and maternal nutrient overload increases the risk of metabolic diseases in the progeny such as obesity and diabetes. We hypothesized that maternal and postnatal intake of chocolate and soft drink will affect leptin sensitivity and hypothalamic astrocyte morphology in adult rat offspring. Pregnant Sprague-Dawley rats were fed ad libitum chow diet only (C) or with chocolate and high sucrose soft drink supplement (S). At birth, litter size was adjusted into 10 male offspring per mother. After weaning, offspring from both dietary groups were assigned to either S or C diet, giving four groups until the end of the experiment at 26 weeks of age. As expected, adult offspring fed the S diet post weaning became obese (body weight: Peffect of leptin than energy expenditure, suggesting differential programming of leptin sensitivity in ARC in SS offspring. Effects of the maternal S diet were normalized when offspring were fed a chow diet after weaning. Maternal intake of chocolate and soft drink had long-term consequences for the metabolic phenotype in the offspring if they continued on the S diet in postnatal life. These offspring displayed obesity despite lowered energy intake associated with alterations in hypothalamic leptin signalling.

  18. Metabolic syndrome and related variables, insulin resistance, leptin levels, and PPAR-γ2 and leptin gene polymorphisms in a pedigree of subjects with bipolar disorder

    Directory of Open Access Journals (Sweden)

    Trino Baptista

    2015-06-01

    Full Text Available Objective:Evidence points to a high prevalence of metabolic dysfunction in bipolar disorder (BD, but few studies have evaluated the relatives of subjects with BD. We conducted a cross-sectional study in an extended family of patients with BD type I.Methods:The available relatives of the same family were interviewed (DSM-IV-R and assessed in fasting conditions for body mass index, constituent variables of the metabolic syndrome (MS, leptin levels, insulin resistance index, and single nucleotide polymorphisms (SNPs for the leptin receptor and promoter and PPAR-γ2 genes. The frequency of MS was compared with that recorded in the local general population.Results:Ninety-three relatives of three adults with BD were evaluated (30 aged 18 years. The frequency of MS was similar to that of the general population. Significantly higher frequencies of abnormal glucose, total and low density cholesterol (LDL-c levels (all p < 0.05, waist circumference (p = 0.057, and leptin and insulin resistance values (in adults only were observed in the family. Adults with the QQ genotype of the leptin receptor displayed higher LDL-c levels than carriers of the R allele.Conclusions:The associations among BD consanguinity, familial hypercholesterolemia, and leptin receptor SNPs reported herein should be replicated and extended in other pedigrees.

  19. Longitudinal Analysis of Leptin Variation during Weight Regain after Weight Loss in Obese Children

    DEFF Research Database (Denmark)

    Holm, Jens-Christian; Gamborg, Michael; Ward, Leigh

    2009-01-01

    Objective: This study assessed if lower than predicted serum leptin concentrations seen during weight loss persisted during weight regain, with possible implications for weight control. Methods: 115 children were investigated during a 12-week weight loss program. 90 children completed the program....... Results: Children with the greatest increases in BMI standard deviation score (SDS) exhibited the largest leptin increments. The disproportionate reduction of leptin seen during weight loss recovered after weight loss. Leptin increases mirrored increases in BMI SDS during weight regain, and the leptin......-BMI SDS relationship seen during follow-up resembled the baseline leptin-BMI SDS relationship. Conclusion: Proportional increases of leptin and BMI SDS during weight regain suggests an intact leptin response during re-accumulation of fat. Following the pronounced reduction of leptin during weight loss...

  20. Differential hypothalamic leptin sensitivity in obese rat offspring exposed to maternal and postnatal intake of chocolate and soft drink

    DEFF Research Database (Denmark)

    Gerstenberg, Marina Kjærgaard; Nilsson, C; Secher, A

    2017-01-01

    Background/objective: Intake of high-energy foods and maternal nutrient overload increases the risk of metabolic diseases in the progeny such as obesity and diabetes. We hypothesized that maternal and postnatal intake of chocolate and soft drink will affect leptin sensitivity and hypothalamic...... for the metabolic phenotype in the offspring if they continued on the S diet in postnatal life. These offspring displayed obesity despite lowered energy intake associated with alterations in hypothalamic leptin signalling....... assigned to either S or C diet, giving four groups until the end of the experiment at 26 weeks of age. Results: As expected, adult offspring fed the S diet post weaning became obese (body weight: P

  1. Transport across the blood-brain barrier of pluronic leptin.

    Science.gov (United States)

    Price, Tulin O; Farr, Susan A; Yi, Xiang; Vinogradov, Serguei; Batrakova, Elena; Banks, William A; Kabanov, Alexander V

    2010-04-01

    Leptin is a peptide hormone produced primarily by adipose tissue that acts as a major regulator of food intake and energy homeostasis. Impaired transport of leptin across the blood-brain barrier (BBB) contributes to leptin resistance, which is a cause of obesity. Leptin as a candidate for the treatment of this obesity is limited because of the short half-life in circulation and the decreased BBB transport that arises in obesity. Chemical modification of polypeptides with amphiphilic poly(ethylene oxide)-poly(propylene oxide) block copolymers (Pluronic) is a promising technology to improve efficiency of delivery of polypeptides to the brain. In the present study, we determined the effects of Pluronic P85 (P85) with intermediate hydrophilic-lipophilic balance conjugated with leptin via a degradable SS bond [leptin(ss)-P85] on food intake, clearance, stability, and BBB uptake. The leptin(ss)-P85 exhibited biological activity when injected intracerebroventricularly after overnight food deprivation and 125I-leptin(ss)-P85 was stable in blood, with a half-time clearance of 32.3 min (versus 5.46 min for leptin). 125I-Leptin(ss)-P85 crossed the BBB [blood-to-brain unidirectional influx rate (K(i)) = 0.272 +/- 0.037 microl/g x min] by a nonsaturable mechanism unrelated to the leptin transporter. Capillary depletion showed that most of the 125I-leptin(ss)-P85 taken up by the brain reached the brain parenchyma. Food intake was reduced when 3 mg of leptin(ss)-P85 was administered via tail vein in normal body weight mice [0-30 min, p penetration by a mechanism-independent BBB leptin transporter.

  2. Searching for Evidence of an Anti-Inflammatory Diet in Children: A Systematic Review of Randomized Controlled Trials for Pediatric Obesity Interventions With a Focus on Leptin, Ghrelin, and Adiponectin.

    Science.gov (United States)

    Lewis, Kimberly A; Brown, Sharon A

    2017-10-01

    To address the complex phenomenon of pediatric obesity, one must understand the physiological mechanisms regulating energy intake and inflammation. The peptide hormones leptin, ghrelin, and adiponectin are involved in both, but their functions are dysregulated in obesity. The purpose of this systematic review is (1) to characterize studies of nutrition interventions for weight management in children who measure these peptides as outcomes, (2) to assess risk of bias in the studies, and (3) to determine the relationships between these peptides and body mass index (BMI). Eligibility Criteria: Peer-reviewed articles written in English, published in 2001-2016, and describing randomized controlled trials of pediatric interventions involving a nutrition component with the outcome measures leptin, ghrelin, and/or adiponectin were included. Articles were excluded if the intervention involved pharmaceuticals, supplements, infant formula, breastfeeding, or surgery. The 25 international studies represented 2,153 obese children. Ten diets were identified. Successful interventions included both structured exercise and hypocaloric dietary components, with or without counseling, resistance training, or medical components. Direct measures of adiposity were used in 69% of studies. Comparison group designs were disparate. Leptin levels decreased as BMI decreased. Evidence regarding the relationships of ghrelin and adiponectin with BMI was inconclusive. Despite known effects of maturation on hormones, studies did not consistently differentiate findings by maturational stage. Common anti-inflammatory and disease risk modification diets were missing or underrepresented. Studies that include children with comorbidities are needed. BMI and leptin levels have a positive relationship, but evidence on ghrelin and adiponectin was inconclusive.

  3. Some metabolic and anthropometric variables in obes children by measuring serum insulin, and leptin

    International Nuclear Information System (INIS)

    Nour Eldin, A.M.

    2004-01-01

    The present study aimed to assess serum leptin level in obese children to study its correlation with some metabolic variables as serum insulin and serum glucose. The study was conducted on 30 obese children of age from 9-14 years with body mass index (BMI) > 27.8 Kg/m 2 . All children were subjected to history taking, clinical examination, anthropometric measurements and laboratory investigations including fasting serum leptin, insulin and blood glucose. Serum leptin was significantly higher in obese children (102.3± 56.2 ng/ml) compared to non-obese ones (48.15±26.1 ng/ml). The relation between serum leptin and anthropometric measurements and laboratory investigations including fasting serum insulin and blood glucose. Serum leptin was significantly higher in obese children (102.3± 56.2 ng/ml)compared to non-obese ones (48.15±26.1 ng/ml). The relation between serum leptin and anthropometric variables was positively correlated with BMI r s = 0.68, (p s = 0.59.(p<0.01). It is concluded that serum leptin is increased in obesity and its concentration effects the size of the body. Moreover, the relation of leptin and insulin suggests a positive role of leptin in insulin resistance, which are common metabolic disorders associated with obesity

  4. Serum Neuropeptide Y and Leptin Levels compared between Non-pregnant and Pregnant Women in Overall, Non-obese, and Obese Subjects

    Directory of Open Access Journals (Sweden)

    Chantacha Sitticharoon, M.D., Ph.D.

    2018-05-01

    Full Text Available Objective: The primary objective of this study was to compare serum NPY and leptin levels between non-pregnant and pregnant women in overall, non-obese, and obese subjects. The secondary objective was to compare these peptides between non-obese and obese pregnant women. Methods: Fasting venous blood was collected from non-pregnant women before open abdominal surgery and from pregnant women when admitted to the delivery room during the latent phase of labor. Results: There were 12 non-obese and 14 obese subjects in the non-pregnant group and 9 non-obese and 30 obese subjects in the pregnant group. Systolic blood pressure (SBP was comparable, but heart rate (HR was higher in pregnant compared to non-pregnant women. Mean±S.E.M serum NPY levels were lower in the pregnant than in the non-pregnant group in overall (0.54±0.02 and 1.34±0.08, respectively, non-obese (0.53±0.05 and 1.23±0.14, respectively, and obese (0.54±0.03 and 1.43±0.09, respectively subjects (p<0.01 for all, but these were comparable between obese and non- obese pregnant subjects. Serum NPY was positively correlated with SBP (R=0.281, p<0.05, but negatively correlated with HR (R=-0.324, p<0.01. Serum leptin levels were not different between pregnant and non-pregnant groups, but were significantly higher in obese than non-obese pregnant subjects (p<0.001. Serum leptin levels were positively correlated with body weight, BMI, waist and hip circumferences in overall and pregnant subjects (p<0.001 all. Conclusion: In pregnancy, decreased NPY levels might be associated with inhibition of SBP rising as well as increased HR. Leptin levels might not be associated with pregnancy, but associated mainly with obesity.

  5. Effect of exogenous leptin on serum levels of lipids, glucose, renal and hepatic variables in both genders of obese and streptozotocin-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Parichehr Hayatdavoudi

    2015-11-01

    Full Text Available Objective(s: Leptin exerts various effects on appetite and body weight. Disruption of the obesitygene is precedent to fatness. Insulin or glucose elevates leptin, but streptozotocin reduces it. However, controversial data exist for the effects of leptin on diabetes and leptin level in each gender. Leptin can damage the kidney function but little evidence exists for its hepatic effects. The aim of this study was to investigate the probable sex-dependent differences in blood sugar levels, lipid profile, and renal and hepatic biochemical factors in the obesity and streptozotocin-induced diabetic rats after leptin administration. Materials and Methods: Wistar rats of both sexes were randomly divided into two groups, namely obese and diabetic rats. Each group was further divided into male and female subgroups. Extra fat and carbohydrate was added to the diet to induce obesity. Furthermore, streptozotocin (55 mg/kg, IP was injected to induce diabetes. The treatment groups received leptin (0.1 mg/kg SC for 10 days, and then, blood samples were taken from the orbital sinus for laboratory evaluations. Results: Leptin resulted in a significant weight loss in both sexes (P

  6. Response of Leptin and C-reactive Protein Serum Levels to 12 Weeks Moderate Intensity Aerobic Exercise in Obese Men

    Directory of Open Access Journals (Sweden)

    Sonia Ghiasi

    2017-01-01

    Full Text Available The aim of this study was to investigate the effect of 12 weeks moderate intensity aerobic exercise on leptin and C-reactive protein serum levels in obese men. The study was conducted in Urmia- Iran in 2015. Twenty-four obese men with an aged range 40-50 yrs. were enrolled into the study. Subjects were randomized to one of 2 groups exercise (n=12 and control groups (n=12. The exercise group performed aerobic exercise training up to 50-70 % heart rate reserve, three times a week for 12 weeks. Leptin and CRP serum level was measured by ELISA method before and after the 12 weeks. After 12 weeks exercise training, leptin and CRP serum level in the exercise group compared to the control group, were decreased significantly (P<0.05. To sum up, 12 weeks moderate intensity aerobic exercise in the reduction of CRP and leptin concentration had a prominent role that might be effective in reducing weight and improving cardiovascular risk factors.

  7. Deletion of skeletal muscle SOCS3 prevents insulin resistance in obesity

    DEFF Research Database (Denmark)

    Beck Jørgensen, Sebastian; O'Neill, Hayley M; Sylow, Lykke

    2013-01-01

    Obesity is associated with chronic low-grade inflammation that contributes to defects in energy metabolism and insulin resistance. Suppressor of cytokine signaling (SOCS)-3 expression is increased in skeletal muscle of obese humans. SOCS3 inhibits leptin signaling in the hypothalamus and insulin...... of hyperinsulinemia and insulin resistance because of enhanced skeletal muscle insulin receptor substrate 1 (IRS1) and Akt phosphorylation that resulted in increased skeletal muscle glucose uptake. These data indicate that skeletal muscle SOCS3 does not play a critical role in regulating muscle development or energy...... expenditure, but it is an important contributing factor for inhibiting insulin sensitivity in obesity. Therapies aimed at inhibiting SOCS3 in skeletal muscle may be effective in reversing obesity-related glucose intolerance and insulin resistance....

  8. Measurement of serum leptin levels in polycystic ovary syndrome with hyperandrogenemia and its significance

    International Nuclear Information System (INIS)

    Wang Yande; Zhang Zhiping; Lu Gen; Luo Beilei

    2002-01-01

    Objective: To investigate the serum leptin concentration in polycystic ovary syndrome (PCOS) with hyperandrogenemia (HA) and its relationship with testosterone (T) level and body mass index (BMI). Methods: Serum leptin levels were measured by radioimmunoassay in 53 patients with PCOS, in which 36 cases were of the in non-obesity group and 17 cases in obese group. 30 non-obese cases and 20 obese cases without PCOS served as controls. Results: The levels of leptin in PCOS with HA in obese and non-obese group were significantly higher than those in control group (all p < 0.01). There was a positive correlation between serum leptin levels and testosterone levels in both groups (r = 0.51, p < 0.01 and r = 0.58, p < 0.01). No correlation existed between serum leptin levels and body mass index (BMI) in PCOS patients of non-obese group but there was positive correlation in obesity group (r = 0.56, p < 0.01). Conclusion: High serum leptin levels is one of the characteristic in PCOS patients. The HA in PCOS patients is related to serum leptin levels and heavyweight or obese patients have the phenomenon of leptin resistance

  9. Melatonin Absence Leads to Long-Term Leptin Resistance and Overweight in Rats

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    Buonfiglio, Daniella; Parthimos, Rafaela; Dantas, Rosana; Cerqueira Silva, Raysa; Gomes, Guilherme; Andrade-Silva, Jéssica; Ramos-Lobo, Angela; Amaral, Fernanda Gaspar; Matos, Raphael; Sinésio, José; Motta-Teixeira, Lívia Clemente; Donato, José; Reiter, Russel J.; Cipolla-Neto, José

    2018-01-01

    Melatonin (Mel), a molecule that conveys photoperiodic information to the organisms, is also involved in the regulation of energy homeostasis. Mechanisms of action of Mel in the energy balance remain unclear; herein we investigated how Mel regulates energy intake and expenditure to promote a proper energy balance. Male Wistar rats were assigned to control, control + Mel, pinealectomized (PINX) and PINX + Mel groups. To restore a 24-h rhythm, Mel (1 mg/kg) was added to the drinking water exclusively during the dark phase for 13 weeks. After this treatment period, rats were subjected to a 24-h fasting test, an acute leptin responsiveness test and cold challenge. Mel treatment reduced food intake, body weight, and adiposity. When challenged to 24-h fasting, Mel-treated rats also showed reduced hyperphagia when the food was replaced. Remarkably, PINX rats exhibited leptin resistance; this was likely related to the capacity of leptin to affect body weight, food intake, and hypothalamic signal-transducer and activator of transcription 3 phosphorylation, all of which were reduced. Mel treatment restored leptin sensitivity in PINX rats. An increased hypothalamic expression of agouti-related peptide (Agrp), neuropeptide Y, and Orexin was observed in the PINX group while Mel treatment reduced the expression of Agrp and Orexin. In addition, PINX rats presented lower UCP1 protein levels in the brown adipose tissue and required higher tail vasoconstriction to get a proper thermogenic response to cold challenge. Our findings reveal a previously unrecognized interaction of Mel and leptin in the hypothalamus to regulate the energy balance. These findings may help to explain the high incidence of metabolic diseases in individuals exposed to light at night. PMID:29636725

  10. The Relationship among Smoking, Plasma Adiponectin, Leptin, Inflammatory Markers and Insulin Resistance

    International Nuclear Information System (INIS)

    Shousha, M.A.; Soliman, S.Et

    2012-01-01

    We aimed to study how smoking influences the relationship between fat mass ,soluble tumor necrosis factor-α, (TNF?) receptors 1 and 2 (sTNFR1 and sTNFR2),highly sensitive C-reactive protein(hs-CRP), adiponectin, leptin and insulin resistance.A total of 60 healthy men (age: 27-53 years, body mass index (BMI): 20-35 kg/m 2 ), 30 of whom were never-smokers and 30 smokers, matched for age, BMI and waist-to-hip ratio were included in this study. Those were subdivided into insulin resistant (IR) and insulin sensitive (IS) subgroups. Measures included circulating soluble fractions of the tumor necrosis factor α (TNF α) receptors (sTNFR1 and sTNFR2) and their relationship to fat mass, fasting plasma adiponectin, leptin, hs- CRP and insulin sensitivity index.Smokers had significantly lower fat mass, lower fasting glucose, insulin and leptin concentrations than nonsmokers. Despite lower fat mass, insulin and leptin, smokers showed significantly increased circulating sTNFR2 levels (3.7±0.8 vs. 2.9 ±0.8 ng/ml, π=0.03). Being either a smoker or having insulin resistance was independently associated with lower adiponectin concentrations (π = 0.046 and 0.001, respectively). No difference was detected in average hs- CRP concentrations between smokers and nonsmokers (π = 0.18) and between IR and IS subjects (π = 0.13).Both fat mass and smoking are related to increased activity of the TNFα axis. Plasma adiponectin concentrations are lower in smokers and IR subjects. These two mechanisms could be associated with increased cardiovascular risk in smokers

  11. The Relationship among Smoking, Plasma Adiponectin, Leptin, Inflammatory Markers and Insulin Resistance

    International Nuclear Information System (INIS)

    Shousha, M.A.; Soliman, S.Et.

    2011-01-01

    The study aimed to investigate how smoking influences the relationship between fat mass, soluble tumor necrosis factor-α , (TNFα ) receptors 1 and 2 (sTNFR1 and sTNFR2), highly sensitive C-reactive protein (hs-CRP), adiponectin, leptin and insulin resistance. A total of 60 healthy men (age: 27-53 years, body mass index (BMI): 20-35 kg/m2), 30 of whom were never-smokers and 30 smokers, matched for age, BMI and waist-to-hip ratio were included in this study. Those were subdivided into insulin resistant (IR) and insulin sensitive (IS) subgroups. Measures included circulating soluble fractions of the tumor necrosis factor α (TNFα ) receptors (sTNFR1 and sTNFR2) and their relationship to fat mass, fasting plasma adiponectin, leptin, hs-CRP and insulin sensitivity index. Smokers had significantly lower fat mass, lower fasting glucose, insulin and leptin concentrations than nonsmokers. Despite lower fat mass, insulin and leptin, smokers showed significantly increased circulating sTNFR2 levels (3.7±0.8 vs. 2.9±0.8 ng/ml, P=0.03). Being either a smoker or having insulin resistance was independently associated with lower adiponectin concentrations (P = 0.046 and 0.001, respectively). No difference was detected in average hs- CRP concentrations between smokers and nonsmokers (P = 0.18) and between IR and IS subjects (P = 0.13).Both fat mass and smoking are related to increased activity of the TNFα axis. Plasma adiponectin concentrations are lower in smokers and IR subjects. These two mechanisms could be associated with increased cardiovascular risk in smokers

  12. Preliminary evidence for obesity-associated insulin resistance in adolescents without elevations of inflammatory cytokines

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    Cohen Jessica I

    2012-06-01

    Full Text Available Abstract Background To ascertain whether the associations between obesity, inflammation, and insulin resistance established in human adult studies are found among adolescents. Methods We contrasted 36 obese and 24 lean youth on fasting glucose, insulin levels, lipid profile, hemoglobin A1C, markers of hepatic function, white blood cell count, C-reactive protein (CRP and fibrinogen levels. The cytokines IL-6, TNF-α, IFN-γ, IL-10 and IL-4 and the adipokines leptin, resistin, and adiponectin were also compared between the two groups. The fasting glucose and insulin values were used to estimate the degree of insulin resistance with the homeostatic model assessment of insulin resistance (HOMA-IR. T-tests and correlations were run to examine group differences and associations between groups. In addition, regression analyses were used to ascertain whether the markers of inflammation were predictive of the degree of insulin resistance. Results Although obese adolescents had clear evidence of insulin resistance, only CRP, fibrinogen and leptin were elevated; there were no group differences in pro- or anti-inflammatory cytokines nor adiponectin and resistin. Anthropometric measures of obesity and level of insulin resistance were highly correlated to the acute phase reactants CRP and fibrinogen; however, the degree of insulin resistance was not predicted by the pro- or anti-inflammatory cytokine markers. Obese adolescents had higher white blood cell counts. In addition they had higher circulating alanine aminotransferase concentrations and lower circulating albumin and total protein than lean adolescents, possibly as a result of hepatocyte damage from fatty liver. Conclusion Unlike rodent or adult studies, we found that wide-spread systemic inflammation is not necessarily associated with insulin resistance among adolescents. This finding does not support the current paradigm that the associations between obesity and insulin resistance are, to a

  13. 7A.06: MATERNAL OBESITY AND THE DEVELOPMENTAL PROGRAMMING OF HYPERTENSION: ALTERED LEPTIN SIGNALLING PATHWAY IN THE CENTRAL NERVOUS SYSTEM.

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    Lim, J; Burke, S; Head, G A

    2015-06-01

    The prevalence of obesity in women among child baring age is increasing and this has been parallel to the increase in obesity in general population around the world. We investigated the trans-generational 'programming' of leptin signalling in the central nervous system (CNS) to increase blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA) following a high fat diet (HFD)feeding in mothers. Female New Zealand White rabbits were fed a high fat (13%) diet (mHFD) or a control diet (mCD) prior mating and during pregnancy. Kittens from mCD rabbits were subdivided and fed HFD for 10days (mCD10dHFD) at 15 weeks of age. All rabbits received an intracerebroventricular (ICV) catheter into the lateral ventricle and a recording electrode on the left renal nerve. Experiments were conducted in conscious rabbits and BP, HR and RSNA was measured. Rabbits received an increasing doses of ICV Melanocortin receptor antagonist (SHU9119),alpha-Melanocortin stimulating hormone (alpha-MSH) and a single dose of Leptin antagonist. ICV SHU9119 reduced BP (-5.8 ± 0.7mmHg and -4.1 ± 0.9mmHg) and RSNA (-2.4 ± 0.3 nu and -0.7 ± 0.3 nu) in mHFD and mCD10dHFD rabbits (P fat was increased (50%) in all rabbits that had HFD. Obesity during pregnancy 'programs' leptin signalling pathway in the CNS of the offspring during development. Leptin via activation of melanocirtin pathway plays a key role in the CNS contributing to the pressor and tachycardic effects as well as renal sympathetic nerve activity in the pathophysiology of obesity.

  14. Leptin as well as Free Leptin Receptor Is Associated with Polycystic Ovary Syndrome in Young Women

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    Rizk, Nasser M.; Sharif, Elham

    2015-01-01

    Background and Aim. Leptin has two forms in the circulation: free and bound forms. The soluble leptin receptor (sOB-R) circulates in the blood and can bind to leptin. The aim of this study is to assess the concentrations of the leptin and the sOB-R in PCOS and its relation to adiposity, insulin resistance, and androgens. Methods. A cross-sectional study included 78 female students aged 17–25 years. Fasting serum leptin and sOB-R concentrations were measured. The anthropometric variables and the hormonal profile such as insulin, female and male sex hormones, and prolactin were assessed. Results. In PCOS, leptin level (ng/ml) and free leptin index (FLI) increased significantly while sOB-R (ng/ml) significantly decreased compared to control subjects. In age-matched subjects, obese PCOS had increased leptin level in ng/ml (median level with interquartile levels) of 45.67 (41.98–48.04) and decreased sOB-R in ng/ml 11.47 (7.59–16.44) compared to lean PCOS 16.97 (10.60–45.55) for leptin and 16.62 (11.61–17.96) for sOB-R with p values 0.013 and 0.042, respectively. However, body mass index (BMI) is significantly correlated with leptin and s-OBR, while no significant correlations with parameters of insulin resistance were detected. Conclusion. PCOS is associated with hyperleptinemia and increased free leptin index. Decreased sOB-R could be a compensatory mechanism for the defective action of leptin. PMID:26180527

  15. Leptin as well as Free Leptin Receptor Is Associated with Polycystic Ovary Syndrome in Young Women

    Directory of Open Access Journals (Sweden)

    Nasser M. Rizk

    2015-01-01

    Full Text Available Background and Aim. Leptin has two forms in the circulation: free and bound forms. The soluble leptin receptor (sOB-R circulates in the blood and can bind to leptin. The aim of this study is to assess the concentrations of the leptin and the sOB-R in PCOS and its relation to adiposity, insulin resistance, and androgens. Methods. A cross-sectional study included 78 female students aged 17–25 years. Fasting serum leptin and sOB-R concentrations were measured. The anthropometric variables and the hormonal profile such as insulin, female and male sex hormones, and prolactin were assessed. Results. In PCOS, leptin level (ng/ml and free leptin index (FLI increased significantly while sOB-R (ng/ml significantly decreased compared to control subjects. In age-matched subjects, obese PCOS had increased leptin level in ng/ml (median level with interquartile levels of 45.67 (41.98–48.04 and decreased sOB-R in ng/ml 11.47 (7.59–16.44 compared to lean PCOS 16.97 (10.60–45.55 for leptin and 16.62 (11.61–17.96 for sOB-R with p values 0.013 and 0.042, respectively. However, body mass index (BMI is significantly correlated with leptin and s-OBR, while no significant correlations with parameters of insulin resistance were detected. Conclusion. PCOS is associated with hyperleptinemia and increased free leptin index. Decreased sOB-R could be a compensatory mechanism for the defective action of leptin.

  16. Ingestion of carbohydrate-rich supplements during gestation programs insulin and leptin resistance but not body weight gain in adult rat offspring

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    Bernard eBeck

    2012-06-01

    Full Text Available Prenatal nutritional conditions can predispose to development of obesity and metabolic syndrome in adulthood. Gestation with its important hormonal status modification is a period of changes in usual feeding habits with pulses or avoidance for certain categories of food. We tried to mimic in an animal model some changes in food consumption patterns observed in pregnant women. For this purpose, Long-Evans female rats were fed during the dark period, their usual pre-gestational food quantity, and were allowed to complete their intake with either a control (Cr, high-fat (HF, or high-carbohydrate (HC diet available ad libitum during the light period. Dams fed a control diet ad libitum (Ca served as controls. Body weight and composition, food intake, and metabolic hormones (insulin, leptin were recorded in male offspring until 20 weeks after birth. Cr and HC females ate less than Ca females ( -16%; p<0.001 and their offspring presented a weight deficit from birth until 6 (HC group and 10 (Cr group weeks of age (p<0.05 or less. Plasma leptin corresponded to low body weight in Cr offspring, but was increased in HC offspring that in addition, had increased plasma insulin, blood glucose and subcutaneous adipose tissue mass. HF dams ate more than Ca dams (+13%;p<0.001, but plasma leptin and insulin were similar in their offspring. Hypothalamic Ob-Rb expression was increased in Cr, HC and HF offspring (+33-100% vs. Ca; p<0.05 or less. HC supplement ingestion during gestation leads therefore to insulin and leptin resistance in adult offspring independently of lower birth weight. These hormonal changes characterize obesity-prone animals. We therefore suggest to be heedful of the carbohydrate content in the diet during the last weeks (or months preceding delivery to limit development of later metabolic disorders in offspring.

  17. The p. N103K mutation of leptin (LEP gene and severe early onset obesity in Pakistan

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    Shabana

    Full Text Available BACKGROUND: Obesity is a complex disorder and has been increasing globally at alarming rates including Pakistan. However, there is scarce research on understanding obesity genetics in Pakistan. Leptin is a hormone secreted by adipocytes in response to satiety and correlates with body weight. Any mutations in the LEP gene have an adverse effect on energy regulation pathway and lead to severe, early onset obesity. To date, only eight mutations have been described in the LEP gene of which p. N103K is one. METHODS: We aimed to analyze the prevalence of this mutation in Pakistani subjects. A total of 475 subjects were genotyped by PCR-RFLP analysis and their serum profiling was done. RESULTS: Results showed that this mutation was present only in one male child with early onset obesity (10 year. He had very low serum leptin levels suggestive of functional impact of the mutation. The prevalence of such mutations is, however, low due to the drastic effects on the energy regulation. CONCLUSION: In conclusion, LEP gene mutations contribute significantly to the monogenic forms of obesity and are important due to the availability of treatment options. Such mutations may exert their effect by directly affecting energy regulation pathway and are more prominent in the early stages of life only.

  18. Leptin levels distribution and ethnic background in two populations from Chile: Caucasian and Mapuche groups.

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    Pérez-Bravo, F; Albala, C; Santos, J L; Yañez, M; Carrasco, E

    1998-10-01

    Leptin, the product of the human ob gene is increased in obese individuals, suggesting resistance to its effect. We examined the relationship of serum leptin levels with respect to obesity, gender and insulin levels in two populations with different ethnic compositions in Chile. Leptin and insulin levels were determined by radioimmunoassay (RIA) and correlated with body mass index (BMI), gender and ethnic background. 79 Caucasian subjects from Santiago and 65 Mapuche natives from the Araucania region, Chile, were included in this study. Leptin concentrations in obese subjects were significantly increased in both ethnic groups in relation to lean status: Caucasian and Mapuche obese 19.3 +/- 11.6 and 10.1 +/- 5.8 (P Mapuche lean 10.4 +/- 5.8 and 4.7 +/- 2.9 (P Mapuche and Caucasian groups, similar leptin levels were observed among the males of the two populations in both metabolic states (lean and obese). In contrast, the leptin level distributions between women showed a marked difference, having a minor value in the Mapuche women with a comparable value with the male group in this ethnic population. The leptin concentrations are associated with obesity in both ethnic groups in Chile. However, the leptin levels between the Mapuche natives were significantly decreased compared to the Caucasian group. The gender distribution does not seem to be important in the Mapuche natives. The ethnic composition seems to be important in the leptin distribution in the analysed populations.

  19. Clinical significance of determination of serum leptin levels in patients with type 2 diabetes mellitus

    International Nuclear Information System (INIS)

    Du Fuman; Hou Ying; Feng Kun; Zhu Wei; Yang Yuzhi

    2006-01-01

    Objective: To investigate the relationship between levels of serum leptin and levels of blood sugar, lipid as well as degree of obesity in patients with type 2 diabetes mellitus (DM2). Methods: Serum leptin levels were determined with RIA in 42 patients with DM2 and 38 controls. Results: The serum leptin levels in DM2 patients were significantly higher than those in controls (P <0.001) and were positively correlated with serum INS, TC, TG, LDL-C levels as well as BMI. Conclusion: High level of serum leptin was associated with obesity, high blood lipid levels and insulin resistance (IR). (authors)

  20. The clinical significance of serum Leptin in the pathogenesis of 2DM and obesity

    International Nuclear Information System (INIS)

    Liu Chunyu; Lu Kuan; Gao Yanyan

    2001-01-01

    Objective: To study the relationship between serum Leptin ad insulin, body fat distribution and testosterone in 2-DM patients. Methods: The fasting blood serum Leptin and insulin levels in 65 2DM patients and 42 controls were measured by radioimmunoassay. Abdominal subcutaneous adipose tissue volume (ASF) and abdominal visceral adipose tissue volume (AVF) were measured by spiral CT SSD soft-ware in 32 2DM patients. The authors also measured the Leptin before and 2h after a 75 g OGTT in 34 2DM patients and fasting plasma testosterone in 30 2DM males. Results: DM group and normal group had equal number of females and were matched in BMI. Baseline plasma Leptin concentrations were not significantly different between the groups (P 14 mmol/L) had lower Leptin levels (P < 0.05). Sex, BMI, ASF were important factors contributing to the serum Leptin. The Leptin concentrations were significantly positively correlated with BMI (r 0.57, P0.0001), ASF(r = 0.67 P0.025) and insulin (r = 0.47, P0.0013) and was negative correlated with the serum testosterone (r = -0.061, P0.025). Conclusion: There were no abnormal Leptin levels in 2DM implies, suggesting that Leptin might not be the main causing factor in 2DM. The poorly metabolic controlled patients might have lack of Leptin. The lower Leptin levels in men might be caused by testosterone, sex BMI, ASF were important factors contributing to the serum Leptin levels

  1. Correlation of insulin resistance with serum C-reactive protein, adiponectin and leptin levels in patients with type 2 diabetes

    International Nuclear Information System (INIS)

    Duan Yangqiang; Wang Zuobing; Yu Hui

    2012-01-01

    Objective: To explore the relationship between serum C-reactive protein (CRP), adiponectin (APN), leptin (Leptin) levels, insulin resistance index (HOMA-IR) and type 2 diabetes mellitus (T2DM) disease susceptibility. Methods: The plasma leptin and insulin (FINS) levels in the DM patients were determined by RIA, and the serum ANP levels were determined by ELSIA. The CRP, conventional serum fasting plasma glucose (FPG) levels were determine by automatic biochemistry analyzer. The insulin resistance index (HOMA-IR, FPG x FINS/22.5) was calculated. The result was analyzed with normal healthy control group. Results: The serum CRP and leptin, HOMA-IR levels in T2DM group were significantly higher than that of in control group (P< 0.01), and the serum ANP was significantly lower than in control group (P<0.01). The HOMA-IR in T2DM was positively correlated with serum CRP (r= 0.36, P<0.05) and leptin(r= 0.39, P<0.05), and was negatively correlated with serum APN (r=0.32, P<0.05). Conclusion: The high serum CRP and leptin and low APN levels hyperlipidaemia might be factors for diabetes, and their metabolic disorders may be closely related with insulin resistance in patients with type 2 diabetes. (authors)

  2. Leptin administration to overweight and obese subjects for 6 months increases free leptin concentrations but does not alter circulating hormones of the thyroid and IGF axes during weight loss induced by a mild hypocaloric diet.

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    Shetty, Greeshma K; Matarese, Giuseppe; Magkos, Faidon; Moon, Hyun-Seuk; Liu, Xiaowen; Brennan, Aoife M; Mylvaganam, Geetha; Sykoutri, Despina; Depaoli, Alex M; Mantzoros, Christos S

    2011-08-01

    Short-term energy deprivation reduces leptin concentrations and alters the levels of circulating hormones of the hypothalamic-pituitary-peripheral axis in lean subjects. Whether the reduction in leptin concentration during long-term weight loss in obese individuals is linked to the same neuroendocrine changes seen in lean, leptin-sensitive subjects remains to be fully clarified. In this study, 24 overweight and obese adults (16 women and eight men; body mass index (BMI): 27.5-38.0 kg/m(2)) were prescribed a hypocaloric diet (-500 kcal/day) and were randomized to receive recombinant methionyl leptin (n=18, metreleptin, 10 mg/day self-injected s.c.) or placebo (n=6, same volume and time as metreleptin) for 6 months. Metreleptin administration did not affect weight loss beyond that induced by hypocaloric diet alone (P for interaction=0.341) but increased the serum concentrations of total leptin by six- to eight-fold (Phypocaloric diet in overweight and obese subjects.

  3. Effects of n-3 Polyunsaturated Fatty Acid Supplementation on Serum Leptin Levels, Appetite Sensations, and Intake of Energy and Macronutrients in Obese People: A Randomized Clinical Trial.

    Science.gov (United States)

    Payahoo, L; Ostadrahimi, A; Farrin, N; Khaje-Bishak, Y

    2017-10-05

    Obesity is a common health problem. Appetite is one of the main obesity-controlling factors that can be influenced by leptin. Leptin reduces food intake and accelerates energy expenditure. Leptin levels can be affected by dietary factors such as fats, special amino acids, and fructose. This study aimed to determine the effects of polyunsaturated fatty acid n-3 (PUFA n-3) supplementation on serum leptin levels, appetite sensations, and dietary intakes in obese people. This study was performed on 60 obese individuals with body mass index (BMI) 30 (kg/m 2 ) and above in 2012 in Tabriz, Iran. The participants were randomly allocated to the intervention (consumed two capsules containing 1 g/day n-3 fatty acids [180 mg EPA, 120 mg DHA] for 4 weeks) and control groups. Serum leptin levels were assessed by ELISA method, and visual analogue scale (VAS) questionnaire was completed for evaluating appetite sensations. The mean caloric [before = 1,575.39 (600), after = 1,236.14 (448.40)] and macronutrient intakes were decreased significantly in the intervention group (p macronutrient intakes, probably through the modulating of satiety. The short period of study caused the nonsignificant changes in BMI and circulatory leptin. Further studies are needed to confirm these results.

  4. What fans the fire: insights into mechanisms of leptin in metabolic syndrome-associated heart diseases.

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    Dong, Maolong; Ren, Jun

    2014-01-01

    Obesity and metabolic syndrome are one of the most devastating risk factors for cardiovascular diseases. The obesity gene product leptin plays a central role in the regulation of food intake and energy expenditure. The physiological and pathophysiological roles of leptin in cardiovascular system have been investigated extensively since its discovery in 1994. In addition to its well-established metabolic effects, more recent evidence have depicted a rather pivotal role of leptin in inflammation, oxidative stress, endoplasmic reticulum stress, apoptosis and tissue remodeling en route to the pathogenesis of type 2 diabetes mellitus, hypertension, atherosclerosis, and insulin resistance. Under physiological condition, leptin is known to reduce appetite, promote energy expenditure, increase sympathetic activity, facilitate glucose utilization and improve insulin sensitivity. In addition, leptin may regulate cardiac and vascular function through a nitric oxide-dependent mechanism. However, hyperleptinemia usually occurs with progressively increased body weight and metabolic syndrome development, leading to a state of global or selective leptin resistance. Both central and peripheral leptin resistance may be present under pathophysiological conditions such as inflammation, insulin resistance, hyperlipidemia and a cadre of other cardiovascular diseases including hypertension, atherosclerosis, obesity, ischemic heart disease and heart failure. In this review, we will discuss cardiovascular actions of leptin related to various components of metabolic syndrome. Particular emphasis will be given to insights derived from therapeutic interventions with lifestyle modification, cardiovascular drugs, anti-diabetic and anti-obesity drugs.

  5. Fatty Acids, Obesity and Insulin Resistance

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    Peter Arner

    2015-04-01

    Full Text Available Objective: Although elevated free fatty acid (FFA levels in obesity have been considered to be of importance for insulin resistance, a recent meta-analysis suggested normal FFA levels in obese subjects. We investigated fasting circulating FFA and glycerol levels in a large cohort of non-obese and obese subjects. Methods: Subjects recruited for a study on obesity genetics were investigated in the morning after an overnight fast (n = 3,888. Serum FFA (n = 3,306, plasma glycerol (n = 3,776, and insulin sensitivity index (HOMA-IR,n = 3,469 were determined. Obesity was defined as BMI ≥ 30 kg/m2 and insulin resistance as HOMA-IR ≥ 2.21. Results: In obese subjects, circulating FFA and glycerol levels were higher than in non-obese individuals (by 26% and 47%, respectively; both p Conclusion: Circulating FFA and glycerol levels are markedly elevated in obesity but only marginally influenced by insulin resistance and type 2 diabetes. Whether these differences persist during diurnal variations in circulating FFA/glycerol, remains to be established.

  6. Insulin resistance in obese children and adolescents

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    Monica Cristina dos Santos Romualdo

    2014-11-01

    Conclusion: The results confirmed that insulin resistance is present in many obese children and adolescents, and that this condition is associated with alterations that represent an increased risk for developing metabolic disorders in adulthood.

  7. [D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3, small molecule synthetic peptide leptin mimetics, improve glycemic control in diet-induced obese (DIO) mice.

    Science.gov (United States)

    Wang, Anke; Anderson, Brian M; Novakovic, Zachary M; Grasso, Patricia

    2018-03-01

    We have previously shown that following oral delivery in dodecyl maltoside (DDM), [D-Leu-4]-OB3 and its myristic acid conjugate, MA-[D-Leu-4]-OB3, improved energy balance and glucose homeostasis in genetically obese/diabetic mouse models. More recently, we have provided immunohistochemical evidence indicating that these synthetic peptide leptin mimetics cross the blood-brain barrier and concentrate in the area of the arcuate nucleus of the hypothalamus in normal C57BL/6J and Swiss Webster mice, in genetically obese ob/ob mice, and in diet-induced obese (DIO) mice. In the present study, we describe the effects of oral delivery of [D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3 on glycemic control in diet-induced (DIO) mice, a non-genetic rodent model of obesity and its associated insulin resistance, which more closely recapitulates common obesity and diabetes in humans. Male C57BL/6J and DIO mice, 17, 20, and 28 weeks of age, were maintained on a low-fat or high-fat diet and given vehicle (DDM) alone or [D-Leu-4]-OB3 or MA-[D-Leu-4]-OB3 in DDM by oral gavage for 12 or 14 days. Body weight gain, food and water intake, fasting blood glucose, oral glucose tolerance, and serum insulin levels were measured. Our data indicate that (1) [D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3 restore glucose tolerance in male DIO mice maintained on a high-fat diet to levels comparable to those of non-obese C57BL/6J wild-type mice of the same age and sex maintained on a low-fat diet; and (2) the influence of [D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3 on glycemic control appears to be independent of their effects on energy balance. These results suggest that [D-Leu-4]-OB3 and/or MA-[D-Leu-4]-OB3 may have application to the management of the majority of cases of common obesity in humans, a state characterized at least in part, by leptin resistance resulting from a defect in leptin transport across the blood-brain barrier. They further suggest that these small molecule synthetic peptide leptin mimetics, through their

  8. Bilirubin Increases Insulin Sensitivity in Leptin-Receptor Deficient and Diet-Induced Obese Mice Through Suppression of ER Stress and Chronic Inflammation

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    Dong, Huansheng; Huang, Hu; Yun, Xinxu; Kim, Do-sung; Yue, Yinan; Wu, Hongju; Sutter, Alton; Chavin, Kenneth D.; Otterbein, Leo E.; Adams, David B.; Kim, Young-Bum

    2014-01-01

    Obesity-induced endoplasmic reticulum (ER) stress causes chronic inflammation in adipose tissue and steatosis in the liver, and eventually leads to insulin resistance and type 2 diabetes (T2D). The goal of this study was to understand the mechanisms by which administration of bilirubin, a powerful antioxidant, reduces hyperglycemia and ameliorates obesity in leptin-receptor-deficient (db/db) and diet-induced obese (DIO) mouse models. db/db or DIO mice were injected with bilirubin or vehicle ip. Blood glucose and body weight were measured. Activation of insulin-signaling pathways, expression of inflammatory cytokines, and ER stress markers were measured in skeletal muscle, adipose tissue, and liver of mice. Bilirubin administration significantly reduced hyperglycemia and increased insulin sensitivity in db/db mice. Bilirubin treatment increased protein kinase B (PKB/Akt) phosphorylation in skeletal muscle and suppressed expression of ER stress markers, including the 78-kDa glucose-regulated protein (GRP78), CCAAT/enhancer-binding protein (C/EBP) homologous protein, X box binding protein (XBP-1), and activating transcription factor 4 in db/db mice. In DIO mice, bilirubin treatment significantly reduced body weight and increased insulin sensitivity. Moreover, bilirubin suppressed macrophage infiltration and proinflammatory cytokine expression, including TNF-α, IL-1β, and monocyte chemoattractant protein-1, in adipose tissue. In liver and adipose tissue of DIO mice, bilirubin ameliorated hepatic steatosis and reduced expression of GRP78 and C/EBP homologous protein. These results demonstrate that bilirubin administration improves hyperglycemia and obesity by increasing insulin sensitivity in both genetically engineered and DIO mice models. Bilirubin or bilirubin-increasing drugs might be useful as an insulin sensitizer for the treatment of obesity-induced insulin resistance and type 2 diabetes based on its profound anti-ER stress and antiinflammatory properties. PMID

  9. Dietary fat and insulin resistance: a connection through leptin and PPARγ activation

    Directory of Open Access Journals (Sweden)

    Doaa Nader Al-Jada

    2016-06-01

    Full Text Available Insulin resistance refers to reduced insulin action in peripheral tissues and impaired suppression of endogenous glucose production, a state which is critical for maintaining normal glucose homeostasis. Insulin resistance is partly explained by genetic factors and is strongly influenced by the individual's habitual lifestyle. Investigating factors that may influence the development of insulin resistance and their mechanisms of action is highly significant; one of these factors include dietary fat. Both quantitative and qualitative terms of dietary fat have been known to play an important role in the development of insulin resistance, although the mechanism underlying this effect is not fully understood. In this regard, the classical view has been that dietary fat quality mainly affects cell membrane fatty acid composition and consequently the membrane function. Recently, the relationship between dietary fat and insulin resistance has entered an advanced level due to the discovery that different fatty acids can regulate gene expression, transcriptional activity and adipocytokines secretion. In essence, this provides new mechanisms by which fatty acids exert their cellular effects. The present review critically assesses the effect of dietary fat quality on the development of insulin resistance in relation to the adipocytokine, leptin and the activation of the transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ. It is evident that fat quality influences the development of insulin resistance and has a more important role than quantity. Leptin and PPARγ prove to be potential candidates linking dietary fat with insulin resistance. However, the exact role or mechanism of action of various types of dietary fat in the development of insulin resistance is still uncertain. Further well-controlled studies in humans are necessary to establish better evidence-based dietary fat recommendations for diabetes prevention and its

  10. Leptin receptor blockade reduces intrahepatic vascular resistance and portal pressure in an experimental model of rat liver cirrhosis.

    Science.gov (United States)

    Delgado, María Gabriela; Gracia-Sancho, Jordi; Marrone, Giusi; Rodríguez-Vilarrupla, Aina; Deulofeu, Ramon; Abraldes, Juan G; Bosch, Jaume; García-Pagán, Juan Carlos

    2013-10-01

    Increased hepatic vascular resistance mainly due to elevated vascular tone and to fibrosis is the primary factor in the development of portal hypertension in cirrhosis. Leptin, a hormone associated with reduction in nitric oxide bioavailability, vascular dysfunction, and liver fibrosis, is increased in patients with cirrhosis. We aimed at evaluating whether leptin influences the increased hepatic resistance in portal hypertension. CCl4-cirrhotic rats received the leptin receptor-blocker ObR antibody, or its vehicle, every other day for 1 wk. Hepatic and systemic hemodynamics were measured in both groups. Hepatic nitric oxide production and bioavailability, together with oxidative stress, nitrotyrosinated proteins, and liver fibrosis, were evaluated. In cirrhotic rats, leptin-receptor blockade significantly reduced portal pressure without modifying portal blood flow, suggesting a reduction in the intrahepatic resistance. Portal pressure reduction was associated with increased nitric oxide bioavailability and with decreased O2(-) levels and nitrotyrosinated proteins. No changes in systemic hemodynamics and liver fibrosis were observed. In conclusion, the present study shows that blockade of the leptin signaling pathway in cirrhosis significantly reduces portal pressure. This effect is probably due to a nitric oxide-mediated reduction in the hepatic vascular tone.

  11. Influence of the metabolic syndrome on leptin and leptin receptor in breast cancer.

    Science.gov (United States)

    Carroll, Paul A; Healy, Laura; Lysaght, Joanne; Boyle, Terry; Reynolds, John V; Kennedy, M John; Pidgeon, Graham; Connolly, Elizabeth M

    2011-08-01

    Obesity and its associated metabolic syndrome (MetS) are recognized risk factors for breast cancer. The molecular basis for this association remains largely unknown. Adipokines, in particular leptin and adiponectin, are thought to form part of the mechanism linking obesity with cancer through their altered expression/production either systemically (endocrine pathway) or locally (paracrine/autocrine pathway). Using quantitative PCR, mRNA expression of adiponectin (AdipoQ) and leptin (Ob) in mammary adipose tissue (MAT), intratumoral leptin and associated ligand receptors (ObR, AdipoR1, and AdipoR2) was examined in 77 patients with complete anthropomorphic and serological data. Expression of Ob in MAT, and ObR in matched tumor tissue was significantly higher in patients with MetS compared to obese only or normal weight cancer patients (P < 0.005). There was no difference in intratumoral leptin adiponectin or its ligand receptors in the same groups. Individual features of MetS correlated with Ob and ObR expression, but not obesity markers (BMI, waist circumference). mRNA expression of leptin (Ob) and ObR, in adipose tissue and matched tumor samples, respectively, appear to be associated with obesity status in breast cancer. Increasing insulin resistance is a predominant feature of this higher Ob/ObR expression observed. These novel data indicate that the MetS may be an amenable risk factor for breast cancer. Copyright © 2011 Wiley-Liss, Inc.

  12. Time course and determinants of leptin decline during weight loss in obese boys and girls

    DEFF Research Database (Denmark)

    Holm, Jens-Christian; Gamborg, Michael; Kaas-Ibsen, Karsten

    2007-01-01

    OBJECTIVE: To investigate whether changes in leptin concentrations during weight loss can be explained by gender, puberty, baseline adiposity and changes in adiposity, body composition, rate of weight loss, physical activity and insulin concentrations. DESIGN: A longitudinal study with 9 repeated......, puberty, baseline adiposity or concomitant changes in BMI SDS, fat mass percentage, rate of weight loss, physical activity scores or insulin concentrations. CONCLUSION: The biphasic leptin decline, which exceeded the level expected, was independent of puberty, baseline adiposity and changes in adiposity...... size, physical activity scores, blood leptin (ng/ml) and insulin concentrations (pmol/l) were measured at baseline, and except for Tanner stage and testicular size, repeated regularly during the programme. RESULTS: The weight loss was accompanied by a steep decline in leptin concentrations during...

  13. Leptine: an hormone secreted by adipose tissue. First study in Uruguayan population sample

    International Nuclear Information System (INIS)

    Pisabarro, Raul; Irrazabal, Ernesto; Recalde, Alicia; Barrios, Enrique; Arocena, Beatriz; Garcia Loriente, Jose Maria; Lorenzo Bonifazio, Juan

    1999-01-01

    The recent discovery of leptine, an hormone secreted by adipose tissue which modulates the energetic expenditure has signified a gigantic advance in studying obesity facts. In spite of a recent description of absence of leptine in humans, the obesity human model answers to leptine resistance. In this paper, we revise the actual concepts and show leptine values of a sample of 101 middle aged uruguayans, male and female, of normal weight and over weighted (table 1), correlated with corporal mass index (CMI) as an indirect measure of total body fat and waist diameter as an indirect measure of visceral fat, and hips (periferical fat). Bioimpedance studies were carried out to get the corporal composition. Results: good correlation between corporal fat and leptine, but fat distribution was not found representative. All in all, this data set confirms the correlation between leptine and total body fat mass

  14. Diet-induced obesity, exogenous leptin-, and MADB106 tumor cell challenge affect tissue leukocyte distribution and serum levels of cytokines in F344 rats.

    Science.gov (United States)

    Behrendt, Patrick; Buchenauer, Tobias; Horn, Rüdiger; Brabant, Georg; Jacobs, Roland; Bode, Felix; Stephan, Michael; Nave, Heike

    2010-08-01

    The adipocyte-derived catabolic protein leptin alters cell-mediated immunity and cytokine crosstalk. This may provide new insights into the altered immune response, seen in obese individuals. Therefore, we determined the tissue distribution of immune cells in diet-induced obese (dio) and normal weight F344 rats challenged with MADB106 tumor cells or leptin. Immune cell distribution in blood (by FACS analysis) and tissues (NK cells in spleen and liver, immunohistologically) as well as pro-inflammatory cytokines (IL-6, TNF-α; by flow cytometry) were investigated in 28 normal weight and 28 dio rats (n = 4-6/group). Pro-inflammatory cytokines were increased 3-fold for IL-6 and 7-fold for TNF-α in obese animals. Higher numbers of blood monocytes and NK cells were found in obese as compared to normal weight animals. In dio rats challenged with leptin and MADB106 tumor cells, monocyte numbers were decreased as compared to the obese control animals. Immunohistochemistry revealed an altered NK cell distribution in a compartment-, treatment-, and bodyweight-specific manner. In conclusion, our data reveal a distinct distribution pattern of monocytes and NK cells in dio rats as compared to normal weight littermates and an additional modulatory effect of a leptin- and MADB106 tumor cell challenge.

  15. Leptin deficiency-induced obesity exacerbates ultraviolet B radiation-induced cyclooxygenase-2 expression and cell survival signals in ultraviolet B-irradiated mouse skin

    International Nuclear Information System (INIS)

    Sharma, Som D.; Katiyar, Santosh K.

    2010-01-01

    Obesity has been implicated in several inflammatory diseases and in different types of cancer. Chronic inflammation induced by exposure to ultraviolet (UV) radiation has been implicated in various skin diseases, including melanoma and nonmelanoma skin cancers. As the relationship between obesity and susceptibility to UV radiation-caused inflammation is not clearly understood, we assessed the role of obesity on UVB-induced inflammation, and mediators of this inflammatory response, using the genetically obese (leptin-deficient) mouse model. Leptin-deficient obese (ob/ob) mice and wild-type counterparts (C57/BL6 mice) were exposed to UVB radiation (120 mJ/cm 2 ) on alternate days for 1 month. The mice were then euthanized and skin samples collected for analysis of biomarkers of inflammatory responses using immunohistochemistry, western blotting, ELISA and real-time PCR. Here, we report that the levels of inflammatory responses were higher in the UVB-exposed skin of the ob/ob obese mice than those in the UVB-exposed skin of the wild-type non-obese mice. The levels of UVB-induced cyclooxygenase-2 expression, prostaglandin-E 2 production, proinflammatory cytokines (i.e., tumor necrosis factor-α, interleukin-1β, interleukin-6), and proliferating cell nuclear antigen and cell survival signals (phosphatidylinositol-3-kinase and p-Akt-Ser 473 ) were higher in the skin of the ob/ob obese mice than the those in skin of their wild-type non-obese counterparts. Compared with the wild-type non-obese mice, the leptin-deficient obese mice also exhibited greater activation of NF-κB/p65 and fewer apoptotic cells in the UVB-irradiated skin. Our study suggests for the first time that obesity in mice is associated with greater susceptibility to UVB-induced inflammatory responses and, therefore, obesity may increase susceptibility to UVB-induced inflammation-associated skin diseases, including the risk of skin cancer.

  16. Obesity and risk of incident heart failure in older men with and without pre-existing coronary heart disease: does leptin have a role?

    Science.gov (United States)

    Wannamethee, S Goya; Shaper, A Gerald; Whincup, Peter H; Lennon, Lucy; Sattar, Naveed

    2011-10-25

    We examined the relationship between body mass index (BMI), waist circumference, and incident HF in men with and without pre-existing coronary heart disease (CHD) and assessed the contribution of plasma leptin concentration to these associations. Leptin has been proposed as a potential link between obesity and heart failure (HF). This was a prospective study of 4,080 men age 60 to 79 years with no diagnosed HF followed for a mean period of 9 years, in whom there were 228 incident HF cases. Increased BMI was associated with significantly increased risk of HF in men with and without pre-existing CHD (myocardial infarction or angina) after adjustment for cardiovascular risk factors including C-reactive protein. The adjusted hazard ratios (HRs) associated with a 1-SD increase in BMI were 1.37 (95% confidence interval [CI]: 1.09 to 1.72) and 1.18 (95% CI: 1.00 to 1.39) in men with and without CHD, respectively. Increased leptin was significantly associated with an increased risk of HF in men without pre-existing CHD, independent of BMI and potential mediators (adjusted HR for a 1-SD increase in log leptin: 1.30 [95% CI: 1.06 to 1.61]; p = 0.01). However, no association was seen in those with pre-existing CHD (corresponding HR: 1.06 [95% CI: 0.77 to 1.45]; p = 0.72). Adjustment for leptin abolished the association between BMI and HF in men with no CHD; in those with CHD, the association between BMI and HF remained significant (p = 0.03). Similar patterns were seen for waist circumference. In the absence of established CHD, the association between obesity and HF may be mediated by plasma leptin. In those with CHD, obesity appears to increase the risk of HF independent of leptin. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  17. Leptin and adiponectin in the female life course

    Directory of Open Access Journals (Sweden)

    S.B. Lecke

    2011-05-01

    Full Text Available Adipose tissue secretes a variety of adipokines, including leptin and adiponectin, which are involved in endocrine processes regulating glucose and fatty metabolism, energy expenditure, inflammatory response, immunity, cardiovascular function, and reproduction. The present article describes the fluctuations in circulating leptin and adiponectin as well as their patterns of secretion in women from birth to menopause. During pregnancy, leptin and adiponectin seem to act in an autocrine/paracrine fashion in the placenta and adipose tissue, playing a role in the maternal-fetal interface and contributing to glucose metabolism and fetal development. In newborns, adiponectin levels are two to three times higher than in adults. Full-term newborns have significantly higher leptin and adiponectin levels than preterms, whereas small-for-gestational-age infants have lower levels of these adipokines than adequate-for-gestational-age newborns. However, with weight gain, leptin concentrations increase significantly. Children between 5 and 8 years of age experience an increase in leptin and a decrease in adiponectin regardless of body mass index, with a reversal of the newborn pattern for adiponectin: plasma adiponectin levels at age five are inversely correlated with percentage of body fat. In puberty, leptin plays a role in the regulation of menstrual cycles. In adults, it has been suggested that obese individuals exhibit both leptin resistance and decreased serum adiponectin levels. In conclusion, a progressive increase in adiposity throughout life seems to influence the relationship between leptin and adiponectin in women.

  18. Children with classic congenital adrenal hyperplasia have elevated serum leptin concentrations and insulin resistance: potential clinical implications.

    Science.gov (United States)

    Charmandari, Evangelia; Weise, Martina; Bornstein, Stefan R; Eisenhofer, Graeme; Keil, Margaret F; Chrousos, George P; Merke, Deborah P

    2002-05-01

    Leptin is secreted by the white adipose tissue and modulates energy homeostasis. Nutritional, neural, neuroendocrine, paracrine, and autocrine factors, including the sympathetic nervous system and the adrenal medulla, have been implicated in the regulation of leptin secretion. Classic congenital adrenal hyperplasia (CAH) is characterized by a defect in cortisol and aldosterone secretion, impaired development and function of the adrenal medulla, and adrenal hyperandrogenism. To examine leptin secretion in patients with classic CAH in relation to their adrenomedullary function and insulin and androgen secretion, we studied 18 children with classic CAH (12 boys and 6 girls; age range 2-12 yr) and 28 normal children (16 boys and 12 girls; age range 5-12 yr) matched for body mass index (BMI). Serum leptin concentrations were significantly higher in patients with CAH than in control subjects (8.1 +/- 2.0 vs. 2.5 +/- 0.6 ng/ml, P = 0.01), and this difference persisted when leptin values were corrected for BMI. When compared with their normal counterparts, children with CAH had significantly lower plasma epinephrine (7.1 +/- 1.3 vs. 50.0 +/- 4.2, P fasting serum insulin (10.6 +/- 1.4 vs. 3.2 +/- 0.2 microU/ml, P Insulin resistance determined by the homeostasis model assessment method was significantly greater in children with classic CAH than in normal children (2.2 +/- 0.3 vs. 0.7 +/- 0.04, P patients and controls. Gender predicted serum leptin concentrations in controls but not in patients with classic CAH. No association was found between the dose of hydrocortisone and serum leptin (r = -0.17, P = 0.5) or insulin (r = 0.24, P = 0.3) concentrations in children with CAH. Our findings indicate that children with classic CAH have elevated fasting serum leptin and insulin concentrations, and insulin resistance. These most likely reflect differences in long-term adrenomedullary hypofunction and glucocorticoid therapy. Elevated leptin and insulin concentrations in patients

  19. The gut microbiota, obesity and insulin resistance.

    Science.gov (United States)

    Shen, Jian; Obin, Martin S; Zhao, Liping

    2013-02-01

    The human gut is densely populated by commensal and symbiotic microbes (the "gut microbiota"), with the majority of the constituent microorganisms being bacteria. Accumulating evidence indicates that the gut microbiota plays a significant role in the development of obesity, obesity-associated inflammation and insulin resistance. In this review we discuss molecular and cell biological mechanisms by which the microbiota participate in host functions that impact the development and maintenance of the obese state, including host ingestive behavior, energy harvest, energy expenditure and fat storage. We additionally explore the diverse signaling pathways that regulate gut permeability and bacterial translocation to the host and how these are altered in the obese state to promote the systemic inflammation ("metabolic endotoxemia") that is a hallmark of obesity and its complications. Fundamental to our discussions is the concept of "crosstalk", i.e., the biochemical exchange between host and microbiota that maintains the metabolic health of the superorganism and whose dysregulation is a hallmark of the obese state. Differences in community composition, functional genes and metabolic activities of the gut microbiota appear to distinguish lean vs obese individuals, suggesting that gut 'dysbiosis' contributes to the development of obesity and/or its complications. The current challenge is to determine the relative importance of obesity-associated compositional and functional changes in the microbiota and to identify the relevant taxa and functional gene modules that promote leanness and metabolic health. As diet appears to play a predominant role in shaping the microbiota and promoting obesity-associated dysbiosis, parallel initiatives are required to elucidate dietary patterns and diet components (e.g., prebiotics, probiotics) that promote healthy gut microbiota. How the microbiota promotes human health and disease is a rich area of investigation that is likely to generate

  20. Prevalence of the insulin resistance syndrome in obesity

    OpenAIRE

    Viner, R; Segal, T; Lichtarowicz-Kryn..., E; Hindmarsh, P

    2005-01-01

    Aims: To assess prevalence of the insulin resistance syndrome (IRS: obesity, abnormal glucose homoeostasis, dyslipidaemia, and hypertension) in obese UK children and adolescents of different ethnicities and to assess whether fasting data is sufficient to identify IRS in childhood obesity.

  1. The obesity paradox in men with coronary heart disease and heart failure: the role of muscle mass and leptin.

    Science.gov (United States)

    Wannamethee, S Goya; Shaper, A Gerald; Whincup, Peter H; Lennon, Lucy; Papacosta, Olia; Sattar, Naveed

    2014-01-15

    We have investigated the role of muscle mass, natriuretic peptides and adipokines in explaining the obesity paradox. The obesity paradox relates to the association between obesity and increased survival in patients with coronary heart disease (CHD) or heart failure (HF). Prospective study of 4046 men aged 60-79 years followed up for a mean period of 11 years, during which 1340 deaths occurred. The men were divided according to the presence of doctor diagnosed CHD and HF: (i) no CHD or HF ii), with CHD (no HF) and (iii) with HF. Overweight (BMI 25-9.9 kg/m(2)) and obesity (BMI ≥ 30 kg/m(2)) were associated with lower mortality risk compared to men with normal weight (BMI 18.5-24.9 kg/m(2)) in those with CHD [hazards ratio (HR) 0.71 (0.56,0.91) and 0.77 (0.57,1.04); p=0.04 for trend] and in those with HF [HR 0.57 (0.28,1.16) and 0.41 (0.16,1.09; p=0.04 for trend). Adjustment for muscle mass and NT-proBNP attenuated the inverse association in those with CHD (no HF) [HR 0.78 (0.61,1.01) and 0.96 (0.68,1.36) p=0.60 for trend) but made minor differences to those with HF [p=0.05]. Leptin related positively to mortality in men without HF but inversely to mortality in those with HF; adjustment for leptin abolished the BMI mortality association in men with HF [HR 0.82 (0.31,2.20) and 0.99 (0.27,3.71); p=0.98 for trend]. The lower mortality risk associated with excess weight in men with CHD without HF may be due to higher muscle mass. In men with HF, leptin (possibly reflecting cachexia) explain the inverse association. Copyright © 2013. Published by Elsevier Ireland Ltd.

  2. The photo biological effect of low level laser therapy on serum level of leptin, cholesterol and triglycerides in overweight and obese females

    International Nuclear Information System (INIS)

    Salem, E.S.; Tawfik, M.S.; Youssef, S.S.; Serry, Z.M.; Aboel magd, H.F.

    2013-01-01

    The use of low level laser for body contouring and weight reduction depends on the photochemical non thermal effect of laser light on the adipose tissue. LLLT was reported to liquefy or release stored fat in adipocytes by the opening of specialized yet not identified cell membrane-associated pores after a brief treatment The concentration of leptin in adipose tissue and serum closely parallel the mass of adipose tissue and adipocyte size and triglycerides content. Thus, leptin increases in obesity and falls with weight loss. The current study was conducted to evaluate the effect of the low level laser therapy (LLLT) on leptin hormone, Cholesterol and triglyceride in both overweight and obese females. Twenty women were included in this study. Their ages ranged from 30-40 years. They were divided into two equal groups. Group A (Overweight group): included 10 females with BMI between 25 and 29.9 Kg/m2 -Group B (Obese group): included 10 females with BMI . 30. Both groups received LLL to the abdomen using laser scanner for uniform distribution of the beam above and below the umbilicus. Duration of treatment was 30 minutes, 2 times per week for 8 weeks as a total period of treatment. Serum level of leptin was estimated by radioimmunoassay (RIA). As regards serum cholesterol and triglyceride they were determined by enzymatic colorimetric test. Biochemical assessments were done before and after treatment. Results of the present study showed that in the overweight group laser treatment resulted in highly significant reduction in leptin serum level accompanied by highly significant increase in serum triglycerides level. Meanwhile, the increase in cholesterol level was insignificant. As regards the obese group, alteration in serum leptin level caused by laser treatment was not significant. In this group the increase in triglycerides and cholesterol serum levels after treatment were highly significant

  3. Comparative Study of Serum Leptin and Insulin Resistance Levels Between Korean Postmenopausal Vegetarian and Non-vegetarian Women.

    Science.gov (United States)

    Kim, Mi-Hyun; Bae, Yun-Jung

    2015-07-01

    The present study was conducted to compare serum leptin and insulin resistance levels between Korean postmenopausal long-term semi-vegetarians and non-vegetarians. Subjects of this study belonged to either a group of postmenopausal vegetarian women (n = 54), who maintained a semi-vegetarian diet for over 20 years or a group of non-vegetarian controls. Anthropometric characteristics, serum leptin, serum glucose, serum insulin, insulin resistance (HOMA-IR; Homeostasis Model Assessment of Insulin Resistance), and nutrient intake were compared between the two groups. The vegetarians showed significantly lower body weight (p vegetarians. The HOMA-IR of the vegetarians was significantly lower than that of the non-vegetarians (p vegetarian diet might be related to lower insulin resistance independent of the % of body fat in postmenopausal women.

  4. Reprogramming the body weight set point by a reciprocal interaction of hypothalamic leptin sensitivity and Pomc gene expression reverts extreme obesity

    Directory of Open Access Journals (Sweden)

    Kavaljit H. Chhabra

    2016-10-01

    Conclusions: Pomc reactivation in previously obese, calorie-restricted ArcPomc−/− mice normalized energy homeostasis, suggesting that their body weight set point was restored to control levels. In contrast, massively obese and hyperleptinemic ArcPomc−/− mice or those weight-matched and treated with PASylated leptin to maintain extreme hyperleptinemia prior to Pomc reactivation converged to an intermediate set point relative to lean control and obese ArcPomc−/− mice. We conclude that restoration of hypothalamic leptin sensitivity and Pomc expression is necessary for obese ArcPomc−/− mice to achieve and sustain normal metabolic homeostasis; whereas deficits in either parameter set a maladaptive allostatic balance that defends increased adiposity and body weight.

  5. Leptin as a Potential Regulator of FGF21

    Directory of Open Access Journals (Sweden)

    Mohamed Asrih

    2016-03-01

    Full Text Available Background/Aims: Fibroblast growth factor 21 (FGF21, a potent metabolic regulator, has been shown to improve insulin sensitivity in animal models of insulin resistance. Several studies have focused on identifying mediators of FGF21 effects. However, the identification of factors involved in FGF21 regulation is far from complete. As leptin is a potent metabolic modulator as well, we aimed at characterizing whether leptin may regulate FGF21. Methods: We investigated a potential regulation of FGF21 by leptin in vivo in Wistar rats and in vitro using human derived hepatocarcinoma HepG2 cells. This model was chosen as the liver is considered the main FGF21 expression site. Results: We found that leptin injections increased plasma FGF21 levels in adult Wistar rats. This was confirmed in vitro, as leptin increased FGF21 expression in HepG2 cells. We also showed that the leptin effect on FGF21 expression was mediated by STAT3 activation in HepG2 cells. Conclusion: New findings regarding a leptin-STAT3-FGF21 axis were provided in this study, although investigating the exact mechanisms linking leptin and FGF21 are still needed. These results are of great interest in the context of identifying potential new clinical approaches to treat metabolic diseases associated with insulin resistance, such as obesity and type 2 diabetes.

  6. Narrative review: the role of leptin in human physiology: emerging clinical applications.

    Science.gov (United States)

    Kelesidis, Theodore; Kelesidis, Iosif; Chou, Sharon; Mantzoros, Christos S

    2010-01-19

    Leptin is a hormone secreted by adipose tissue in direct proportion to amount of body fat. The circulating leptin levels serve as a gauge of energy stores, thereby directing the regulation of energy homeostasis, neuroendocrine function, and metabolism. Persons with congenital deficiency are obese, and treatment with leptin results in dramatic weight loss through decreased food intake and possible increased energy expenditure. However, most obese persons are resistant to the weight-reducing effects of leptin. Recent studies suggest that leptin is physiologically more important as an indicator of energy deficiency, rather than energy excess, and may mediate adaptation by driving increased food intake and directing neuroendocrine function to converse energy, such as inducing hypothalamic hypogonadism to prevent fertilization. Current studies investigate the role of leptin in weight-loss management because persons who have recently lost weight have relative leptin deficiency that may drive them to regain weight. Leptin deficiency is also evident in patients with diet- or exercise-induced hypothalamic amenorrhea and lipoatrophy. Replacement of leptin in physiologic doses restores ovulatory menstruation in women with hypothalamic amenorrhea and improves metabolic dysfunction in patients with lipoatrophy, including lipoatrophy associated with HIV or highly active antiretroviral therapy. The applications of leptin continue to grow and will hopefully soon be used therapeutically.

  7. Mechanisms of insulin resistance in obesity

    Science.gov (United States)

    Ye, Jianping

    2014-01-01

    Obesity increases the risk for type 2 diabetes through induction of insulin resistance. Treatment of type 2 diabetes has been limited by little translational knowledge of insulin resistance although there have been several well-documented hypotheses for insulin resistance. In those hypotheses, inflammation, mitochondrial dysfunction, hyperinsulinemia and lipotoxicity have been the major concepts and have received a lot of attention. Oxidative stress, endoplasmic reticulum (ER) stress, genetic background, aging, fatty liver, hypoxia and lipodystrophy are active subjects in the study of these concepts. However, none of those concepts or views has led to an effective therapy for type 2 diabetes. The reason is that there has been no consensus for a unifying mechanism of insulin resistance. In this review article, literature is critically analyzed and reinterpreted for a new energy-based concept of insulin resistance, in which insulin resistance is a result of energy surplus in cells. The energy surplus signal is mediated by ATP and sensed by adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Decreasing ATP level by suppression of production or stimulation of utilization is a promising approach in the treatment of insulin resistance. In support, many of existing insulin sensitizing medicines inhibit ATP production in mitochondria. The effective therapies such as weight loss, exercise, and caloric restriction all reduce ATP in insulin sensitive cells. This new concept provides a unifying cellular and molecular mechanism of insulin resistance in obesity, which may apply to insulin resistance in aging and lipodystrophy. PMID:23471659

  8. Longitudinal Analysis of Leptin Variation during Weight Regain after Weight Loss in Obese Children

    DEFF Research Database (Denmark)

    Jens-Christian, Holm; Michael, Gamborg; Leigh, Ward

    2009-01-01

    , and 68 children entered a follow-up program spanning 28 months. Measurements were performed at baseline and day 82 as well as at months 10, 16, and 28. Height, weight, body composition, Tanner stages, testicular size, and serum concentrations of leptin, and insulin were measured at all time points...

  9. Fasting leptin and glucose in normal weight, over weight and obese men and women diabetes patients with and without clinical depression.

    Science.gov (United States)

    Haleem, Darakhshan Jabeen; Sheikh, Shehnaz; Fawad, Asher; Haleem, Muhammad A

    2017-06-01

    A large number of diabetes patients suffer from major depression and are at high risk of mortality. In view of a role of leptin in diabetes, depression and energy homeostasis, the present study concerns circulating levels of leptin in different BMI groups of un-depressed and depressed diabetes patients. Six hundred thirty male and female patients with a primary diagnosis of diabetes were grouped according to BMI and with or without clinical symptoms of depression. Age matched healthy, normal weight male and female volunteers without clinical symptoms of depression or diabetes were taken as controls. Blood samples were obtained after an overnight fast of 12 h. Serum was stored for the determination of leptin and glucose. We found that there were more female than male diabetes patients with comorbid depression. Fasting leptin was higher in normal weight non-diabetes women than men; but comparable in normal weight men and women diabetes patients. Fasting glucose levels were higher in diabetes than non diabetes groups; values were comparable in men and women. Depression was associated with a decrease and increase in leptin respectively in normal-overweight and obese men and women diabetes patients. Glucose levels were also higher in obese depressed than un-depressed diabetes patients. The results suggested that the female gender is at greater risk to comorbid diabetes with depression. Adipo-insular axis plays an important role in diabetes, associated depression and in the greater risk of the female gender to comorbid diabetes with depression.

  10. [Relationship between leptin and body mass and metabolic syndrome in an adult population].

    Science.gov (United States)

    Martins, Maria do Carmo; Lima Faleiro, Luís; Fonseca, Aidil

    2012-11-01

    To analyze the relationship between leptin and obesity expressed as body mass index (BMI) and certain components of the metabolic syndrome (MS) in an adult population. The study included 103 subjects, 42 men and 61 women, aged over 30 years, clinically defined as non-diabetic but with personal or family history of cardiovascular disease. All subjects underwent fasting blood measurements of leptin, insulin, glucose, glucose after ingestion of 75g glucose, HDL cholesterol and triglycerides, and insulin resistance (IR) and BMI were calculated. BMI as an index of overall adiposity was strongly associated with serum leptin. BMI rose as serum leptin levels increased from the first to the third tertile; the correlation between leptin and BMI was strong, r=0.524 in men and r=0.603 in women, with high statistical significance (pcorrelations between leptin and IR, and leptin and insulinemia, were strong in both sexes. With regard to MS components, increased serum levels of the study variables were observed as leptin concentrations rose from the first to the third tertile (with the exception of HDL cholesterol, which decreased). Elevated serum leptin, particularly in obese individuals, should be taken as a warning sign of energy imbalance, poor diet, hyperinsulinemia, insulin resistance, or changes in other metabolic risk factors that are strongly associated with cardiovascular disease and type 2 diabetes. Copyright © 2011 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  11. Association of leptin with cardiometabolic factors in schoolchildren and adolescents with congenital adrenal hyperplasia.

    Science.gov (United States)

    Zurita-Cruz, Jessie Nallely; Villasís-Keever, Miguel Ángel; Damasio-Santana, Leticia; Manuel-Apolinar, Leticia; Ferrusca-Ceja, Rosalba; Nishimura-Meguro, Elisa; Rivera-Hernández, Aleida de J; Garrido-Magaña, Eulalia

    2018-01-01

    In congenital adrenal hyperplasia (CAH), obesity, hyperinsulinemia and leptin levels are increased. To identify the frequency of cardiometabolic risk factors (CRF) in children and adolescents with CAH and to explore the relationship with leptin levels. Cross-sectional study of 40 patients who underwent anthropometric measurements and had fasting glucose, insulin, triglycerides, 17-hidroxyprogesterone, leptin, HDL and LDL-cholesterol assessed. The patients were classified according to the number of CRFs, and leptin levels were analyzed with the Kruskal-Wallis test. Pearson's correlation was applied between leptin, body mass index (BMI) z-score and body fat percentage. Fifty percent of the patients had obesity and overweight, 59% had hypertriglyceridemia, 40%, hypoalphalipoproteinemia, 27.5%, high LDL-cholesterol and 22.5% insulin resistance. There was positive correlation between leptin and body fat percentage (r = 0.64), BMI z-score (r = 0.55) and the number of CRFs (r = 0.65). In the obesity-adjusted multivariate analysis, leptin levels were associated with the number of CRFs. CAH had a high frequency of CRFs and leptin appeared to be associated with a more adverse cardiometabolic profile in subjects with obesity and overweight. Copyright: © 2018 SecretarÍa de Salud.

  12. Short-term effects of a hypocaloric diet with low glycemic index and low glycemic load on body adiposity, metabolic variables, ghrelin, leptin, and pregnancy rate in overweight and obese infertile women: a randomized controlled trial.

    Science.gov (United States)

    Becker, Geórgia F; Passos, Eduardo P; Moulin, Cileide C

    2015-12-01

    Obesity is related to hormonal disorders that affect the reproductive system. Low-glycemic index (LGI) diets seem to exert a positive effect on weight loss and on metabolic changes that result from obesity. We investigated the effects of a hypocaloric diet with an LGI and low glycemic load on anthropometric and metabolic variables, ghrelin and leptin concentrations, and the pregnancy rate in overweight and obese infertile women who were undergoing in vitro fertilization (IVF). The study was a randomized block-design controlled trial in which we analyzed 26 overweight or obese infertile women. Patients were assigned to a hypocaloric LGI-diet group or a control group and followed the protocol for 12 wk. Body weight, body mass index (BMI), percentage of body fat, glucose, insulin, homeostasis model assessment of insulin resistance, serum lipids, reproductive hormones, leptin, acylated ghrelin, number of oocytes retrieved in the IVF cycle, and pregnancy rate were determined. There were greater reductions in body mass, BMI, percentage of body fat, waist:hip ratio, and leptin in the LGI-diet group than in the control group (P diet group had 85.4% more oocytes retrieved than did the control group (7.75 ± 1.44 and 4.18 ± 0.87, respectively; P = 0.039) in the IVF cycle. Three patients (21.4%) in the LGI group experienced a spontaneous pregnancy during the follow-up, which generated 3 live births. The hypocaloric LGI diet promoted a decrease in BMI, percentage of body fat, and leptin concentrations, which improved oocyte development and pregnancy rate. These results support the clinical recommendation to advise overweight and obese women to lose weight through a balanced diet before being submitted for treatment with assisted reproduction technologies. A hypocaloric diet combined with LGI foods seems to be beneficial for these patients, but additional studies are required before this treatment is recommended. This trial was registered at clinicaltrials.gov as NCT02416960

  13. Bioactive leptin is stronger related to parameters of fat mass and distribution than conventionally measured leptin: Findings from a longitudinal study in obese children participating in a lifestyle intervention.

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    Niklowitz, Petra; Rothermel, Juliane; Lass, Nina; Barth, Andre; Reinehr, Thomas

    2018-05-01

    This study analyzed the relationships between bioactive leptin, conventionally measured leptin, and parameters of fat mass and distribution in obese children before and after weight reduction. We determined bioactive leptin (bioLep), conventional measured leptin (conLep), weight, height, body fat based on skinfold measurements and bioimpedance analyses, waist circumference (wc), and pubertal stage in 88 obese children participating in a lifestyle intervention at baseline and one year later. We identified no child with homozygous or heterozygous status for bioinactive leptin mutations. The baseline associations between bioLep and BMI (r = 0.53), BMI-SDS (r = 0.48), body fat (bioimpedance: r = 0.61, skinfold thickness: r = 0.49), wc (r = 0.42), and waist to height ratio (whr) (r = 0.39) were stronger than the associations between conLep and BMI (r = 0.50), BMI-SDS (r = 0.44), body fat (bioimpedance: r = 0.57, skinfold thickness: r = 0.41), wc (r = 0.41), and whr (r = 0.37). The changes of bioLep were stronger related to changes of BMI-SDS (r = 0.54), body fat (bioimpedance r = 0.59, skinfold thickness: r = 0.37), wc (r = 0.22), and whr (r = 0.21) than the associations between changes of conLep and changes of BMI-SDS (r = 0.48), body fat (bioimpedance: r = 0.56, skinfold thickness: r = 0.43), wc (r = 0.20), and whr (r = 0.20). The same findings were observed in multiple linear regression analyses adjusted to multiple confounders. In contrast to changes of conLep (r = 0.22), the changes of bioLep during intervention were not related to weight regain after the end of intervention. BioLep concentrations did not differ between prepubertal girls and boys, but were higher in pubertal girls compared to pubertal boys (p = 0.031). Bioactive leptin was stronger related to fat mass and distribution compared to conventionally measured leptin. Copyright © 2018 Elsevier B.V. All rights

  14. Leptin-Aldosterone-Neprilysin Axis: Identification of Its Distinctive Role in the Pathogenesis of the Three Phenotypes of Heart Failure in People With Obesity.

    Science.gov (United States)

    Packer, Milton

    2018-04-10

    Obesity (especially visceral adiposity) can be associated with 3 different phenotypes of heart failure: heart failure with a reduced ejection fraction, heart failure with a preserved ejection fraction, and high-output heart failure. All 3 phenotypes are characterized by an excessive secretion of aldosterone and sodium retention. In addition, obesity is accompanied by increased signaling through the leptin receptor, which can promote activation of both the sympathetic nervous system and the renin-angiotensin system and can directly stimulate the secretion of aldosterone. The deleterious interaction of leptin and aldosterone is potentiated by the simultaneous action of adiposity and the renal sympathetic nerves to cause overactivity of neprilysin; the loss of the counterbalancing effects of natriuretic peptides is exacerbated by an additional effect of both obesity and heart failure to interfere with adiponectin signaling. This intricate neurohormonal interplay leads to plasma volume expansion as well as to adverse ventricular remodeling and cardiac fibrosis. Furthermore, the activity of aldosterone and neprilysin is not only enhanced by obesity, but these mechanisms can also promote adipogenesis and adipocyte dysfunction, thereby enhancing the positive feedback loop. Last, in elderly obese women, changes in quantity and biology of epicardial adipose tissue further enhances the release of leptin and other proinflammatory adipokines, thereby leading to cardiac and systemic inflammation, end-organ fibrosis, and multiple comorbidities. Regardless of the phenotypic expression, activation of the leptin-aldosterone-neprilysin axis appears to contribute importantly to the evolution and progression of heart failure in people with obesity. Efforts to interfere with the detrimental interactions of this distinctive neurohormonal ecosystem with existing or novel therapeutic agents are likely to yield unique clinical benefits. © 2018 American Heart Association, Inc.

  15. The gut microbiota reduces leptin sensitivity and the expression of the obesity-suppressing neuropeptides proglucagon (Gcg) and brain-derived neurotrophic factor (Bdnf) in the central nervous system.

    Science.gov (United States)

    Schéle, Erik; Grahnemo, Louise; Anesten, Fredrik; Hallén, Anna; Bäckhed, Fredrik; Jansson, John-Olov

    2013-10-01

    The gut microbiota contributes to fat mass and the susceptibility to obesity. However, the underlying mechanisms are not completely understood. To investigate whether the gut microbiota affects hypothalamic and brainstem body fat-regulating circuits, we compared gene expression of food intake-regulating neuropeptides between germ-free and conventionally raised (CONV-R) mice. We found that CONV-R mice had decreased expression of the antiobesity neuropeptide glucagon-like peptide-1 (GLP-1) precursor proglucagon (Gcg) in the brainstem. Moreover, in both the hypothalamus and the brainstem, CONV-R mice had decreased expression of the antiobesity neuropeptide brain-derived neurotrophic factor (Bdnf). CONV-R mice had reduced expression of the pro-obesity peptides neuropeptide-Y (Npy) and agouti-related protein (Agrp), and increased expression of the antiobesity peptides proopiomelanocortin (Pomc) and cocaine- and amphetamine-regulated transcript (Cart) in the hypothalamus. The latter changes in neuropeptide expression could be secondary to elevated fat mass in CONV-R mice. Leptin treatment caused less weight reduction and less suppression of orexigenic Npy and Agrp expression in CONV-R mice compared with germ-free mice. The hypothalamic expression of leptin resistance-associated suppressor of cytokine signaling 3 (Socs-3) was increased in CONV-R mice. In conclusion, the gut microbiota reduces the expression of 2 genes coding for body fat-suppressing neuropeptides, Gcg and Bdnf, an alteration that may contribute to fat mass induction by the gut microbiota. Moreover, the presence of body fat-inducing gut microbiota is associated with hypothalamic signs of Socs-3-mediated leptin resistance, which may be linked to failed compensatory body fat reduction.

  16. High fat diet blunts the effects of leptin on ventilation and on carotid body activity.

    Science.gov (United States)

    Ribeiro, Maria J; Sacramento, Joana F; Gallego-Martin, Teresa; Olea, Elena; Melo, Bernardete F; Guarino, Maria P; Yubero, Sara; Obeso, Ana; Conde, Silvia V

    2017-12-22

    Leptin plays a role in the control of breathing, acting mainly on central nervous system; however, leptin receptors have been recently shown to be expressed in the carotid body (CB), and this finding suggests a physiological role for leptin in the regulation of CB function. Leptin increases minute ventilation in both basal and hypoxic conditions in rats. It increases the frequency of carotid sinus nerve discharge in basal conditions, as well as the release of adenosine from the CB. However, in a metabolic syndrome animal model, the effects of leptin in ventilatory control, carotid sinus nerve activity and adenosine release by the CB are blunted. Although leptin may be involved in triggering CB overactivation in initial stages of obesity and dysmetabolism, resistance to leptin signalling and blunting of responses develops in metabolic syndrome animal models. Leptin plays a role in the control of breathing, acting mainly on central nervous system structures. Leptin receptors are expressed in the carotid body (CB) and this finding has been associated with a putative physiological role of leptin in the regulation of CB function. Since, the CBs are implicated in energy metabolism, here we tested the effects of different concentrations of leptin administration on ventilatory parameters and on carotid sinus nerve (CSN) activity in control and high-fat (HF) diet fed rats, in order to clarify the role of leptin in ventilation control in metabolic disease states. We also investigated the expression of leptin receptors and the neurotransmitters involved in leptin signalling in the CBs. We found that in non-disease conditions, leptin increases minute ventilation in both basal and hypoxic conditions. However, in the HF model, the effect of leptin in ventilatory control is blunted. We also observed that HF rats display an increased frequency of CSN discharge in basal conditions that is not altered by leptin, in contrast to what is observed in control animals. Leptin did not

  17. Cannabinoid CB2 receptor potentiates obesity-associated inflammation, insulin resistance and hepatic steatosis.

    Directory of Open Access Journals (Sweden)

    Vanessa Deveaux

    Full Text Available BACKGROUND: Obesity-associated inflammation is of critical importance in the development of insulin resistance and non-alcoholic fatty liver disease. Since the cannabinoid receptor CB2 regulates innate immunity, the aim of the present study was to investigate its role in obesity-induced inflammation, insulin resistance and fatty liver. METHODOLOGY: Murine obesity models included genetically leptin-deficient ob/ob mice and wild type (WT mice fed a high fat diet (HFD, that were compared to their lean counterparts. Animals were treated with pharmacological modulators of CB2 receptors. Experiments were also performed in mice knock-out for CB2 receptors (Cnr2 -/-. PRINCIPAL FINDINGS: In both HFD-fed WT mice and ob/ob mice, Cnr2 expression underwent a marked induction in the stromal vascular fraction of epididymal adipose tissue that correlated with increased fat inflammation. Treatment with the CB2 agonist JWH-133 potentiated adipose tissue inflammation in HFD-fed WT mice. Moreover, cultured fat pads isolated from ob/ob mice displayed increased Tnf and Ccl2 expression upon exposure to JWH-133. In keeping, genetic or pharmacological inactivation of CB2 receptors decreased adipose tissue macrophage infiltration associated with obesity, and reduced inductions of Tnf and Ccl2 expressions. In the liver of obese mice, Cnr2 mRNA was only weakly induced, and CB2 receptors moderately contributed to liver inflammation. HFD-induced insulin resistance increased in response to JWH-133 and reduced in Cnr2 -/- mice. Finally, HFD-induced hepatic steatosis was enhanced in WT mice treated with JWH-133 and blunted in Cnr2 -/- mice. CONCLUSION/SIGNIFICANCE: These data unravel a previously unrecognized contribution of CB2 receptors to obesity-associated inflammation, insulin resistance and non-alcoholic fatty liver disease, and suggest that CB2 receptor antagonists may open a new therapeutic approach for the management of obesity-associated metabolic disorders.

  18. Response of osteocalcin and insulin resistance after a hypocaloric diet in obese patients.

    Science.gov (United States)

    de Luis, D A; Perez Castrillon, J L; Aller, R; Izaola, O; Bachiller, C

    2015-06-01

    Osteocalcin is a hormone with a complex cross-talk between adipose tissue and the skeleton. The aim of the present study was to explore the change of osteocalcin, insulin resistance, and adipocytokines after hypocaloric diet in obese patients. A population of 178 obese patients was analyzed. At basal time and 2 months after the dietary intervention, weight, fat mass, body mass index, basal glucose, insulin, insulin resistance (HOMA), total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, leptin, adiponectin, IL-6, TNF alpha and osteocalcin levels were measured. After dietary treatment, BMI, weight, fat mass, waist circumference, waist to hip ratio, systolic pressure, glucose, HOMA, triglycerides, total cholesterol, leptin and LDL cholesterol decreased significantly. Osteocalcin levels have a significant decrease after weight loss (Osteocalcin (ng/ml); 9.76 ± 5.3 vs 9.31 ± 4.1: p < 0.05). In correlation analysis, a negative association was detected among osteocalcin and age, BMI, fat mass, glucose, C reactive protein, interleukin-6. In the linear regression with age-, sex-, BMI, fat mass- and insulin- adjusted, only C reactive protein concentrations are related with osteocalcin levels -0.21 (CI 95%: -0.40 -0.009). Osteocalcin decreased after a weight loss treatment. Moreover, osteocalcin levels, before and after treatment, were related in a negative way with CRP fat mass, body mass index, age and glucose levels.

  19. Hormonal and adiposity state of women with polycystic ovary syndrome: implication of adiponectin and leptin

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    Aleksandra Atanasova Boshku

    2016-12-01

    Full Text Available Obesity and insulin resistance are frequently seen comorbidities in patients with polycystic ovary syndrome (PCOS, affecting the already disturbed metabolism of these patients. Disturbed secretion of adiponectin and leptin could be one of the contributing factors of obesity and insulin resistance in patients with PCOS. The aim of this study was to determine the levels of adiponectin and leptin in PCOS patients, as well as their association with other components of the syndrome. This cross-sectional study determined clinical, hormonal, and biochemical markers in 61 women with PCOS and 56 controls. There was a statistically significant difference in adiponectin and leptin between the groups (p>0.001. There was a significant negative correlation between adiponectin, body mass index (BMI, and waist circumference (r= -0.478; -0.452, p<0.001 and a negative correlation with testosterone, free androgen index (FAI, insulin, and the homeostasis model assessment for insulin resistance (HOMA-IR. A positive correlation between adiponectin, sex hormone binding globulin (SHGB, and fasting glucose levels was present. Correlation analysis of leptin with other metabolic parameters showed a positive correlation with BMI, waist circumference, insulin, and HOMA-IR. A significant inverse correlation was present between leptin and SHGB. In conclusion, adiponectin and leptin may serve as potential biomarkers of insulin resistance. Determining levels of adiponectin and leptin in the early course of this syndrome may enable earlier diagnosis of insulin resistance, or even early prevention in PCOS patients.

  20. Insulin resistance in obese children and adolescents.

    Science.gov (United States)

    Romualdo, Monica Cristina dos Santos; Nóbrega, Fernando José de; Escrivão, Maria Arlete Meil Schimith

    2014-01-01

    To evaluate the presence of insulin resistance and its association with other metabolic abnormalities in obese children and adolescents. Retrospective study of 220 children and adolescents aged 5-14 years. Anthropometric measurements were performed (weight, height, and waist circumference) and clinical (gender, age, pubertal stage, and degree of obesity) and biochemical (glucose, insulin, total cholesterol, and fractions, triglycerides) data were analyzed. Insulin resistance was identified by the homeostasis model assessment for insulin resistance (HOMA-IR) index. The analysis of the differences between the variables of interest and the HOMA-IR quartiles was performed by ANOVA or Kruskal-Wallis tests. Insulin resistance was diagnosed in 33.20% of the sample. It was associated with low levels of high-density lipoprotein cholesterol (HDL-C; p=0.044), waist circumference measurement (p=0.030), and the set of clinical and metabolic (p=0.000) alterations. Insulin-resistant individuals had higher mean age (p=0.000), body mass index (BMI; p=0.000), abdominal circumference (p=0.000), median triglycerides (p=0.001), total cholesterol (p≤0.042), and low-density lipoprotein cholesterol (LDL-C; p≤0.027); and lower HDL-C levels (p=0.005). There was an increase in mean BMI (p=0.000), abdominal circumference (p=0.000), and median triglycerides (p=0.002) as the values of HOMA -IR increased, with the exception of HDL-C, which decreased (p=0.001). Those with the highest number of simultaneous alterations were between the second and third quartiles of the HOMA-IR index (p=0.000). The results confirmed that insulin resistance is present in many obese children and adolescents, and that this condition is associated with alterations that represent an increased risk for developing metabolic disorders in adulthood. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  1. Mexico City normal weight children exposed to high concentrations of ambient PM2.5 show high blood leptin and endothelin-1, vitamin D deficiency, and food reward hormone dysregulation versus low pollution controls. Relevance for obesity and Alzheimer disease.

    Science.gov (United States)

    Calderón-Garcidueñas, Lilian; Franco-Lira, Maricela; D'Angiulli, Amedeo; Rodríguez-Díaz, Joel; Blaurock-Busch, Eleonore; Busch, Yvette; Chao, Chih-kai; Thompson, Charles; Mukherjee, Partha S; Torres-Jardón, Ricardo; Perry, George

    2015-07-01

    Millions of Mexico, US and across the world children are overweight and obese. Exposure to fossil-fuel combustion sources increases the risk for obesity and diabetes, while long-term exposure to fine particulate matter (PM2.5) and ozone (O3) above US EPA standards is associated with increased risk of Alzheimer's disease (AD). Mexico City Metropolitan Area children are chronically exposed to PM2.5 and O3 concentrations above the standards and exhibit systemic, brain and intrathecal inflammation, cognitive deficits, and Alzheimer disease neuropathology. We investigated adipokines, food reward hormones, endothelial dysfunction, vitamin D and apolipoprotein E (APOE) relationships in 80 healthy, normal weight 11.1±3.2 year olds matched by age, gender, BMI and SES, low (n: 26) versus high (n:54) PM2.5 exposures. Mexico City children had higher leptin and endothelin-1 (pMexico City APOE 4 versus 3 children had higher glucose (p=0.009). Serum 25-hydroxyvitamin DMexico City children. Leptin is strongly positively associated to PM 2.5 cumulative exposures. Residing in a high PM2.5 and O3 environment is associated with 12h fasting hyperleptinemia, altered appetite-regulating peptides, vitamin D deficiency, and increases in ET-1 in clinically healthy children. These changes could signal the future trajectory of urban children towards the development of insulin resistance, obesity, type II diabetes, premature cardiovascular disease, addiction-like behavior, cognitive impairment and Alzheimer's disease. Increased efforts should be made to decrease pediatric PM2.5 exposures, to deliver health interventions prior to the development of obesity and to identify and mitigate environmental factors influencing obesity and Alzheimer disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Metabolic syndrome, leptin-insulin resistance and uric acid: a trinomial foe for Algerian city-dweller adolescents' health.

    Science.gov (United States)

    Bouhenni, Hamida; Daoudi, Hadjer; Djemai, Haidar; Rouabah, Abdelkader; Vitiello, Damien; Rouabah, Leila

    2018-03-28

    Background Adolescence is one of the critical periods where increased risk for long-term obesity-related complications is an important health concern. This highlights the need to perform early diagnostics based on precise biomarkers to decrease the risk of complications in adolescents with obesity. Objective To determine the relationships between serum levels of uric acid (UA), leptin and insulin with metabolic syndrome (MS) components in Algerian adolescents. Subjects Nondiabetic adolescents (n = 204). Methods Blood pressure (BP) and anthropometric measurements were performed using standardized techniques. Blood samples were taken for determination of glycemia, triglyceridemia, uricemia, cholesterolemia, leptinemia and insulinemia. Results The rate of MS among an excess weight group was 17.4% [95% confidence interval (CI)]. Serum levels of UA, leptin and insulin were significantly higher in the excess weight group compared to a normal weight group (279.4 ± 86.05 vs. 204.9 ± 50.34 μmol/L and 25.65 ± 14.01 vs. 4.09 ± 2.60 μg/L, p < 0.001; 24.58 ± 13.85 vs. 13.34 ± 6.41 μIU/L, p < 0.05). Serum levels of UA, leptin and insulin were significantly higher in adolescents with MS compared to those without MS (304.86 ± 111.41 vs. 224.72 ± 77.81 μmol/L, 30.26 ± 12.46 vs. 16.93 ± 14.97 μg/L and 30.91 ± 17.30 vs. 18.71 ± 10.14 μIU/L, p < 0.05, respectively). Significant correlations were found between UA and leptin with waist circumference (r = 0.50 and 0.76), diastolic blood pressure (r = 0.58 and 0.43), triglycerides (r = 0.42 and 0.35) and high-density lipoprotein-cholesterol (r = -0.36 and -0.35). Conclusion Serum levels of UA and leptin may be useful biomarkers for early diagnosis of the risk of MS in our Algerian adolescent population.

  3. Excessive Refined Carbohydrates and Scarce Micronutrients Intakes Increase Inflammatory Mediators and Insulin Resistance in Prepubertal and Pubertal Obese Children Independently of Obesity

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    Mardia López-Alarcón

    2014-01-01

    Full Text Available Background. Low-grade inflammation is the link between obesity and insulin resistance. Because physiologic insulin resistance occurs at puberty, obese pubertal children are at higher risk for insulin resistance. Excessive diets in refined carbohydrates and saturated fats are risk factors for insulin resistance, but calcium, magnesium, vitamin-D, and the omega-3 fatty acids likely protect against inflammation and insulin resistance. Objective. To analyze interactions among dietary saturated fat, refined carbohydrates, calcium, magnesium, vitamin D, and omega-3 fatty acids on the risk of inflammation and insulin resistance in a sample of prepubertal and pubertal children. Methods. A sample of 229 children from Mexico City was analyzed in a cross-sectional design. Anthropometric measurements, 24 h recall questionnaires, and blood samples were obtained. Serum insulin, glucose, calcium, magnesium, 25-OHD3, C-reactive protein, leptin, adiponectin, and erythrocytes fatty acids were measured. Parametric and nonparametric statistics were used for analysis. Results. While mean macronutrients intake was excessive, micronutrients intake was deficient (P<0.01. Inflammation determinants were central obesity and magnesium-deficient diets. Determinants of insulin resistance were carbohydrates intake and circulating magnesium and adiponectin. Conclusions. Magnesium-deficient diets are determinants of inflammation, while high intake of refined carbohydrates is a risk factor for insulin resistance, independently of central adiposity.

  4. Protein quantitative trait locus study in obesity during weight-loss identifies a leptin regulator

    DEFF Research Database (Denmark)

    Carayol, Jérôme; Chabert, Christian; Di Cara, Alessandro

    2017-01-01

    of an organism. Proteome analysis especially can provide new insights into the molecular mechanisms of complex traits like obesity. The role of genetic variation in determining protein level variation has not been assessed in obesity. To address this, we design a large-scale protein quantitative trait locus (p...

  5. Retinol binding protein 4, obesity, and insulin resistance in adolescents

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    Ronaldi Noor

    2017-02-01

    Full Text Available Background Obesity is a global problem. Even in poor and developing countries, obesity has reached alarming levels. In childhood, obesity may lead to insulin resistance. Retinol binding protein (RBP4, secreted primarily by liver and adipose tissues, was recently proposed as a link between obesity and insulin resistance. The role of RBP4 in pediatric obesity and its relationship with insulin resistance have not been well elucidated. Objective To compare RBP4 levels in obese and lean adolescents and to assess for a relationship between RBP4 levels and insulin resistance. Method This cross-sectional study was conducted in three senior high schools in Padang, West Sumatera, Indonesia. Subjects were adolescents aged 14-18 years, who were obese or normal weight (n=56. We measured subjects’ body mass index (BMI and serum RBP4 concentrations. Insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR index. Results Similar RBP4 levels were found in the obese and normoweight groups (P>0.05. Higher RBP4 levels were found in the insulin resistant compared to the non-insulin resistant group, but the difference was not significant (P > 0.05. Conclusion There is no significant difference in mean RBP4 levels in obese adolescents compared to normoweight adolescents. Nor are mean RBP4 levels significantly different between obese adolescents with and without insulin resistance.

  6. Maternal Western diet increases adiposity even in male offspring of obesity-resistant rat dams: early endocrine risk markers.

    Science.gov (United States)

    Frihauf, Jennifer B; Fekete, Éva M; Nagy, Tim R; Levin, Barry E; Zorrilla, Eric P

    2016-12-01

    Maternal overnutrition or associated complications putatively mediate the obesogenic effects of perinatal high-fat diet on developing offspring. Here, we tested the hypothesis that a Western diet developmental environment increases adiposity not only in male offspring from obesity-prone (DIO) mothers, but also in those from obesity-resistant (DR) dams, implicating a deleterious role for the Western diet per se. Selectively bred DIO and DR female rats were fed chow (17% kcal fat) or Western diet (32%) for 54 days before mating and, thereafter, through weaning. As intended, despite chow-like caloric intake, Western diet increased prepregnancy weight gain and circulating leptin levels in DIO, but not DR, dams. Yet, in both genotypes, maternal Western diet increased the weight and adiposity of preweanlings, as early as in DR offspring, and increased plasma leptin, insulin, and adiponectin of weanlings. Although body weight normalized with chow feeding during adolescence, young adult Western diet offspring subsequently showed decreased energy expenditure and, in DR offspring, decreased lipid utilization as a fuel substrate. By mid-adulthood, maternal Western diet DR offspring ate more chow, weighed more, and were fatter than controls. Thus, maternal Western diet covertly programmed increased adiposity in childhood and adulthood, disrupted relations of energy regulatory hormones with body fat, and decreased energy expenditure in offspring of lean, genetically obesity-resistant mothers. Maternal Western diet exposure alone, without maternal obesity or overnutrition, can promote offspring weight gain. Copyright © 2016 Frihauf et al.

  7. Long-Term Consumption of Platycodi Radix Ameliorates Obesity and Insulin Resistance via the Activation of AMPK Pathways

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    Chae Eun Lee

    2012-01-01

    Full Text Available This study was designed to evaluate the effects and mechanism of Platycodi radix, having white balloon flower (Platycodon grandiflorum for. albiflorum (Honda H. Hara on obesity and insulin resistance. The extracts of Platycodi radix with white balloon flower were tested in cultured cells and administered into mice on a high-fat diet. The Platycodi radix activated the AMPK/ACC phosphorylation in C2C12 myotubes and also suppressed adipocyte differentiation in 3T3-L1 cells. In experimental animal, it suppressed the weight gain of obese mice and ameliorated obesity-induced insulin resistance. It also reduced the elevated circulating mediators, including triglyceride (TG, T-CHO, leptin, resistin, and monocyte chemotactic protein (MCP-1 in obesity. As shown in C2C12 myotubes, the administration of Platycodi radix extracts also recovered the AMPK/ACC phosphorylation in the muscle of obese mice. These results suggest that Platycodi radix with white balloon flower ameliorates obesity and insulin resistance in obese mice via the activation of AMPK/ACC pathways and reductions of adipocyte differentiation.

  8. Gestational hypoxia disrupts the neonatal leptin surge and programs hyperphagia and obesity in male offspring in the Sprague-Dawley rat.

    Science.gov (United States)

    Vargas, Vladimir E; Gurung, Sunam; Grant, Benjamin; Hyatt, Kimberly; Singleton, Krista; Myers, Sarah M; Saunders, Debra; Njoku, Charity; Towner, Rheal; Myers, Dean A

    2017-01-01

    The effect of gestational hypoxia on the neonatal leptin surge, development of hypothalamic arcuate nuclei (ARH) projections and appetite that could contribute to the programming of offspring obesity is lacking. We examined the effect of 12% O2 from gestational days 15-19 in the Sprague-Dawley rat on post-weaning appetite, fat deposition by MRI, adipose tissue cytokine expression, the neonatal leptin surge, ARH response to exogenous leptin, and αMSH projections to the paraventricular nucleus (PVN) in response to a high fat (HFD) or control diet (CD) in male offspring. Normoxia (NMX) and Hypoxia (HPX) offspring exhibited increased food intake when fed a HFD from 5-8 weeks post-birth; HPX offspring on the CD had increased food intake from weeks 5-7 vs. NMX offspring on a CD. HPX offspring on a HFD remained hyperphagic through 23 weeks. Body weight were the same between offspring from HPX vs. NMX dams from 4-12 weeks of age fed a CD or HFD. By 14-23 weeks of age, HPX offspring fed the CD or HFD as well as male NMX offspring fed the HFD were heavier vs. NMX offspring fed the CD. HPX offspring fed a CD exhibited increased abdominal adiposity (MRI) that was amplified by a HFD. HPX offspring fed a HFD exhibited the highest abdominal fat cytokine expression. HPX male offspring had higher plasma leptin from postnatal day (PN) 6 through 14 vs. NMX pups. HPX offspring exhibited increased basal c-Fos labeled cells in the ARH vs. NMX pups on PN16. Leptin increased c-Fos staining in the ARH in NMX but not HPX offspring at PN16. HPX offspring had fewer αMSH fibers in the PVN vs. NMX offspring on PN16. In conclusion, gestational hypoxia impacts the developing ARH resulting in hyperphagia contributing to adult obesity on a control diet and exacerbated by a HFD.

  9. Obesity in BSB mice is correlated with expression of genes foriron homeostasis and leptin

    Energy Technology Data Exchange (ETDEWEB)

    Farahani, Poupak; Chiu, Sally; Bowlus, Christopher L.; Boffelli,Dario; Lee, Eric; Fisler, Janis S.; Krauss, Ronald M.; Warden, Craig H.

    2003-04-01

    Obesity is a complex disease. To date, over 100 chromosomal loci for body weight, body fat, regional white adipose tissue weight, and other obesity-related traits have been identified in humans and in animal models. For most loci, the underlying genes are not yet identified; some of these chromosomal loci will be alleles of known obesity genes, whereas many will represent alleles of unknown genes. Microarray analysis allows simultaneous multiple gene and pathway discovery. cDNA and oligonucleotide arrays are commonly used to identify differentially expressed genes by surveys of large numbers of known and unnamed genes. Two papers previously identified genes differentially expressed in adipose tissue of mouse models of obesity and diabetes by analysis of hybridization to Affymetrix oligonucleotide chips.

  10. Obesity and Postmenopausal Breast Cancer: Leptin-Estrogen Cross-Talk

    National Research Council Canada - National Science Library

    Surmacz, Eva

    2004-01-01

    Obesity is a risk factor for breast cancer development in postmenopausal women and correlates with shorter disease-free and overall survival in breast cancer patients, regardless of menopausal status...

  11. The Homeostasis Model Assessment-adiponectin (HOMA-AD) is the most sensitive predictor of insulin resistance in obese children.

    Science.gov (United States)

    Makni, Emna; Moalla, Wassim; Lac, Gérard; Aouichaoui, Chirine; Cannon, Daniel; Elloumi, Mohamed; Tabka, Zouhair

    2012-02-01

    The aim of this study was to examine the efficacy of three indices i.e. adiponectin/leptin ratio, HOMA-IR and HOMA-AD in assessing insulin resistance among obese children. One hundred and twenty-two obese children (57 girls, 65 boys): mean age 13.7±1.3 years, BMI 30.1±4.5kg/m(2), eight tanner stage I, 48 tanner stage II-III, 66 tanner stage IV-V, participated in this study. They were classified into four groups according to sex and the presence of metabolic syndrome characteristics: with metabolic syndrome (MS; 21 girls and 36 boys) and controls without metabolic syndrome (CON, 36 girls and 29 boys). The correlations between these three indices of insulin resistance and the MS criteria were analyzed using linear and multiple regressions and receiver operating characteristics (ROC) curves analysis. The majority of anthropometric and biological parameters as well as adiponectin/leptin ratio, HOMA-IR and HOMA-AD were significantly different between MS and CON in both sexes. Both HOMA-AD and HOMA-IR were significantly correlated with the majority of metabolic syndrome components than was the adiponectin/leptin ratio in MS of both sexes. In boys and girls with and without MS, multiple regression analyses highlighted that both HOMA-AD and adiponectin/leptin ratio (r=-0.99 and r=-0.54 for MS girls and boys respectively, 0.05HOMA-AD and HOMA-IR (r=0.66 and r=0.31 for MS girls and boys respectively, 0.05HOMA-IR. Additionally, the area under the ROC curves for predicting insulin resistance were 0.69 (CI 95%, 0.60-0.77), 0.68 (CI 95%, 0.59-0.76) and 0.71 (CI 95%, 0.62-0.79) for adiponectin/leptin ratio, HOMA-IR and HOMA-AD, respectively. The current study strengthens the validity of the HOMA-AD as an adequate tool for determining insulin resistance among obese children with MS. Copyright © 2012. Published by Elsevier Masson SAS.

  12. Insulin and Leptin Signaling Interact in the Mouse Kiss1 Neuron during the Peripubertal Period.

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    Xiaoliang Qiu

    Full Text Available Reproduction requires adequate energy stores for parents and offspring to survive. Kiss1 neurons, which are essential for fertility, have the potential to serve as the central sensors of metabolic factors that signal to the reproductive axis the presence of stored calories. Paradoxically, obesity is often accompanied by infertility. Despite excess circulating levels of insulin and leptin, obese individuals exhibit resistance to both metabolic factors in many neuron types. Thus, resistance to insulin or leptin in Kiss1 neurons could lead to infertility. Single deletion of the receptors for either insulin or the adipokine leptin from Kiss1 neurons does not impair adult reproductive dysfunction. However, insulin and leptin signaling pathways may interact in such a way as to obscure their individual functions. We hypothesized that in the presence of genetic or obesity-induced concurrent insulin and leptin resistance, Kiss1 neurons would be unable to maintain reproductive function. We therefore induced a chronic hyperinsulinemic and hyperleptinemic state in mice lacking insulin receptors in Kiss1 neurons through high fat feeding and examined the impact on fertility. In an additional, genetic model, we ablated both leptin and insulin signaling in Kiss1 neurons (IR/LepRKiss mice. Counter to our hypothesis, we found that the addition of leptin insensitivity did not alter the reproductive phenotype of IRKiss mice. We also found that weight gain, body composition, glucose and insulin tolerance were normal in mice of both genders. Nonetheless, leptin and insulin receptor deletion altered pubertal timing as well as LH and FSH levels in mid-puberty in a reciprocal manner. Our results confirm that Kiss1 neurons do not directly mediate the critical role that insulin and leptin play in reproduction. However, during puberty kisspeptin neurons may experience a critical window of susceptibility to the influence of metabolic factors that can modify the onset of

  13. Comparative measurement of ghrelin, leptin, adiponectin, EGF and IGF-1 in breast milk of mothers with overweight/obese and normal-weight infants.

    Science.gov (United States)

    Khodabakhshi, A; Ghayour-Mobarhan, M; Rooki, H; Vakili, R; Hashemy, S-I; Mirhafez, S R; Shakeri, M-T; Kashanifar, R; Pourbafarani, R; Mirzaei, H; Dahri, M; Mazidi, M; Ferns, G; Safarian, M

    2015-05-01

    Obese infants are more susceptible to develop adulthood obesity and its related comorbidities. Previous studies have shown the presence of hormones and growth factors in maternal breast milk that may influence infant adiposity. The aim of this study was to investigate differences in concentrations of three hormones and two growth factors in the breast milk of mothers with obese and non-obese infants. In this cross-sectional study, 40 mothers with overweight or obese infants (weight for length percentile >97) and 40 age-matched mothers with normal-weight infant (-10 milk concentrations of ghrelin and adiponectin, leptin, epithelial growth factor (EGF) and insulin-like growth factor-1 (IGF-1) were measured using enzyme-linked immunosorbent assay methods. The mean breast milk concentration of ghrelin was higher in mothers with normal-weight infants, 137.50 pg/ml, than in mothers with obese infants, 132.00 pg/ml (P=0.001). This was also true regarding the concentration of EGF in mothers with (0/04 ng/ml) and without (0/038 ng/ml) normal-weight infants (P=0.01). No significant differences were observed in concentrations of leptin, adiponectin and IGF-1 between two groups (P > 0.05). There was also a significant positive correlation between EGF and ghrelin in both groups. This study revealed that there was a correlation between ghrelin and EGF level in breast milk of mothers with obese and non-obese infants, suggesting a possible regulatory effect of these two hormones on weight in infants.

  14. Branched Chain Amino Acids Are Associated with Insulin Resistance Independent of Leptin and Adiponectin in Subjects with Varying Degrees of Glucose Tolerance

    NARCIS (Netherlands)

    Connelly, Margery A.; Wolak-Dinsmore, Justyna; Dullaart, Robin P. F.

    Background: Branched chain amino acids (BCAA) may be involved in the pathogenesis of insulin resistance and are associated with type 2 diabetes mellitus (T2DM) development. Adipokines such as leptin and adiponectin influence insulin resistance and reflect adipocyte dysfunction. We examined the

  15. Hyperleptinaemia rather than fasting hyperinsulinaemia is associated with obesity following hypothalamic damage in children.

    Science.gov (United States)

    Shaikh, M Guftar; Grundy, Richard G; Kirk, Jeremy M W

    2008-12-01

    Obesity following hypothalamic damage is often severe and resistant to lifestyle changes. Disruption of hypothalamic feedback mechanisms that maintain energy homeostasis may be responsible for this intractable obesity. Adipocytokines including insulin and leptin are also known to be important regulators of appetite and weight. To investigate the role of insulin, leptin, adiponectin and resistin in the aetiology of hypothalamic obesity (HO). This was a cross-sectional study of three groups of children, those with HO, congenital hypopituitarism (CH) and simple obesity (SO). A total of 69 children (HO=28, CH=18, SO=23) had leptin, resistin, adiponectin and insulin measured. Although fasting hyperinsulinaemia and insulin resistance were demonstrated, no differences in insulin or insulin resistance were seen between the groups. The HO group, however, had higher levels of leptin, adiponectin and resistin, which persisted even after adjusting for fat mass, compared with the other groups (Pfasting hyperinsulinaemia or insulin resistance were seen between the groups; however, leptin levels are elevated, even after adjusting for fat mass, suggesting that an element of leptin resistance is associated with HO. This is consistent with the inability of leptin to act on the hypothalamus, either due to transport across the blood-brain barrier or dysfunctional receptors. The lack of response to leptin may be more important in the development of obesity in these individuals, and the fasting hyperinsulinaemia is a result of the increased adipose tissue rather than the cause of the weight gain.

  16. Influence of FTO rs9939609 polymorphism on appetite, ghrelin, leptin, IL6, TNFα levels, and food intake of women with morbid obesity.

    Science.gov (United States)

    Magno, Fernanda Cristina Carvalho Mattos; Guaraná, Helena Chrispim; Fonseca, Ana Carolina Proença; Cabello, Giselda Maria Kalil; Carneiro, João Régis Ivar; Pedrosa, Aline Pereira; Ximenes, Ana Carolina; Rosado, Eliane Lopes

    2018-01-01

    The fat mass and obesity-related ( FTO ) gene has a strong relationship with obesity, extreme obesity and inflammatory state, and may also be associated with food intake regulation. The aim of the present study was to evaluate the influence of the rs9939609 single-nucleotide polymorphism of the FTO gene on appetite, ghrelin, leptin, interleukin 6 (IL6), tumor necrosis factor α (TNFα) levels and food intake of morbidly obese women. The study comprised 70 women, aged between 20 and 48 years, from Rio de Janeiro, Brazil. The participants were selected according to the body mass index between 40 and 60 kg/m 2 . Anthropometric and biochemical data were measured during fasting. Hormones and inflammatory data were measured before and after the participants ate an isocaloric meal. Dietary records were calculated and analyzed using a nutritional assessment program. Visual analog scales were used for behaviors of the sensations of appetite and food preferences. The FTO rs9939609 variant was genotyped using real-time polymerase chain reaction. Participants with the AA genotype had lower values of ghrelin and IL6 and higher values of leptin than those with TT and TA in the postprandial period. Comparing the plasma concentrations of ghrelin, insulin, IL6 and TNFα intragenotypes, it was observed that those with TT had decreased leptin and increased IL6 at the postprandial period. Subjects with TA showed increased postprandial IL6, and those with AA had decreased postprandial ghrelin. There was no difference in TNFα intra- and intergenotypes. The postprandial sensations of hunger were lower in AA than those with TT. There were differences between genotypes regarding ingested grams of protein by weight, cholesterol, B3, B5, B6 and B12 vitamins, and selenium potassium and sodium minerals. These findings suggest that genetics may exert an influence on physiologic factors and might alter eating behavior.

  17. An acute bout of whole body passive hyperthermia increases plasma leptin, but does not alter glucose or insulin responses in obese type 2 diabetics and healthy adults.

    Science.gov (United States)

    Rivas, Eric; Newmire, Dan E; Crandall, Craig G; Hooper, Philip L; Ben-Ezra, Vic

    2016-07-01

    Acute and chronic hyperthermic treatments in diabetic animal models repeatedly improve insulin sensitivity and glycemic control. Therefore, the purpose of this study was to test the hypothesis that an acute 1h bout of hyperthermic treatment improves glucose, insulin, and leptin responses to an oral glucose challenge (OGTT) in obese type 2 diabetics and healthy humans. Nine obese (45±7.1% fat mass) type 2 diabetics (T2DM: 50.1±12y, 7.5±1.8% HbA1c) absent of insulin therapy and nine similar aged (41.1±13.7y) healthy non-obese controls (HC: 33.4±7.8% fat mass, Pwhole body passive hyperthermia treatment via head-out hot water immersion (1h resting in 39.4±0.4°C water) that increased internal temperature above baseline by ∆1.6±0.4°C or a control resting condition. Twenty-four hours post treatments, a 75g OGTT was administered to evaluate changes in plasma glucose, insulin, C-peptide, and leptin concentrations. Hyperthermia itself did not alter area under the curve for plasma glucose, insulin, or C-peptide during the OGTT in either group. Fasting absolute and normalized (kg·fat mass) plasma leptin was significantly increased (P<0.01) only after the hyperthermic exposure by 17% in T2DM and 24% in HC groups (P<0.001) when compared to the control condition. These data indicate that an acute hyperthermic treatment does not improve glucose tolerance 24h post treatment in moderate metabolic controlled obese T2DM or HC individuals. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

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    Yea Eun Kang

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

  19. Branched Chain Amino Acids Are Associated with Insulin Resistance Independent of Leptin and Adiponectin in Subjects with Varying Degrees of Glucose Tolerance.

    Science.gov (United States)

    Connelly, Margery A; Wolak-Dinsmore, Justyna; Dullaart, Robin P F

    2017-05-01

    Branched chain amino acids (BCAA) may be involved in the pathogenesis of insulin resistance and are associated with type 2 diabetes mellitus (T2DM) development. Adipokines such as leptin and adiponectin influence insulin resistance and reflect adipocyte dysfunction. We examined the extent to which the association of BCAA with insulin resistance is attributable to altered leptin and adiponectin levels in individuals with varying degrees of glucose tolerance. BCAA were measured by nuclear magnetic resonance, whereas leptin and adiponectin were measured by immunoassay, in subjects with normal fasting glucose (n = 30), impaired fasting glucose (n = 25), and T2DM (n = 15). Insulin resistance was estimated by homeostasis model assessment (HOMAir). BCAA were higher in men than in women (P BCAA were correlated with HOMAir (r = 0.46; P  0.05). Multivariable linear regression analysis, adjusting for age, sex, T2DM, and body mass index (BMI), demonstrated that BCAA were positively associated with HOMAir (β = 0.242, P = 0.023). When BCAA, leptin, and adiponectin were included together, the positive relationship of HOMAir with BCAA (β = 0.275, P = 0.012) remained significant. Insulin resistance was associated with BCAA. This association remained after adjusting for age, sex, T2DM, BMI, as well as leptin and adiponectin. It is unlikely that the relationship of insulin resistance with BCAA is to a major extent attributable to effects of leptin and adiponectin.

  20. Serum leptin and its relationship with metabolic variables in Arabs with type 2 diabetes mellitus

    International Nuclear Information System (INIS)

    Al-Shoumer, Kamal A.; Doi, Suhail A.; Vasanthy, Bagavathy A.; Al-Asousi, Adnan A.

    2008-01-01

    Most studies on serum leptin in type 2 diabetes mellitus have focused on white populations. We studied serum leptin concentrations and parameters related to glycemic control and the association between leptin levels and anthropometric and metabolic factors in Arab patients with type 2 diabetes and in Arab control subjects. Ninety-two patients (65 females and 27 males) with type 2 diabetes and 69 matched normal and control subjects (48 females and 21 males) were included. Anthropometric measures (including body mass index (BMI) and waist: hip ratio) were assessed in all subjects. After an overnight fast, blood was collected for serum leptin assay. Other metabolic parameters include glucose, insulin, C-peptide, intact proinsulin, insulin resistance index (HOMA-IR), insulin-like growth factor 1 (IGF-1), lipids and hemoglobin A 1c (HbA) were determined. Fasting serum leptin levels, IGF-1 and high-density lipoprotein (HDL) cholesterol were similar in patients with type 2 diabetes and control subjects. When obese subjects (BMI>-30kg/m2) were analyzed separately, serum levels of leptin were significantly lower in patients compared to controls. In contrast, patients had higher fasting glucose, insulin, C-peptide, intact proinsulin, insulin resistance, total cholesterol, triglycerides, HbA, and a larger waist circumference and waist-to-hip ratio than controls. Serum leptin correlated positively with BM, negatively with waist-to-hip ratio, and demonstrated no relationship to other parameters. Patients with type 2 diabetes in an Arab ethnic population showed evidence of an unfavorable metabolic profile despite having leptin levels similar to controls. Obesity influences serum leptin levels more significantly in type 2 diabetes, in which leptin levels tends to be low. (author)

  1. Metabolic Profiles in Obese Children and Adolescents with Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Marko Kostovski

    2018-03-01

    CONCLUSION: Higher percentage of insulin-resistant participants was of female gender and was adolescents. In general, insulin resistant obese children and adolescents tend to have a worse metabolic profile in comparison to individuals without insulin resistance. It is of note that the highest insulin resistance was also linked with the highest concentrations of triglycerides.

  2. Novel Insights into How Overnutrition Disrupts the Hypothalamic Actions of Leptin

    Directory of Open Access Journals (Sweden)

    Stefanie Fruhwürth

    2018-03-01

    Full Text Available Obesity has become a worldwide health problem, but we still do not understand the molecular mechanisms that contribute to overeating and low expenditure of energy. Leptin has emerged as a major regulator of energy balance through its actions in the hypothalamus. Importantly, obese people exhibit high circulating levels of leptin, yet the hypothalamus no longer responds normally to this hormone to suppress appetite or to increase energy expenditure. Several well-known hypotheses have been proposed to explain impaired central responsiveness to the effects of leptin in obesity, including defective transit across the blood–brain barrier at the arcuate nucleus, hypothalamic endoplasmic reticulum stress, maladaptive sterile inflammation in the hypothalamus, and overexpression of molecules that may inhibit leptin signaling. We also discuss a new explanation that is based on our group’s recent discovery of a signaling pathway that we named “NSAPP” after its five main protein components. The NSAPP pathway consists of an oxide transport chain that causes a transient, targeted burst in intracellular hydrogen peroxide (H2O2 to inactivate redox-sensitive members of the protein tyrosine phosphatase gene family. The NSAPP oxide transport chain is required for full activation of canonical leptin signaling in neurons but fails to function normally in states of overnutrition. Remarkably, leptin and insulin both require the NSAPP oxide transport chain, suggesting that a defect in this pathway could explain simultaneous resistance to the appetite-suppressing effects of both hormones in obesity.

  3. The association of cysteine with obesity, inflammatory cytokines and insulin resistance in Hispanic children and adolescents.

    Directory of Open Access Journals (Sweden)

    Amany K Elshorbagy

    Full Text Available Plasma total cysteine (tCys independently relates to fat mass in adults. Dietary cyst(eine promotes adiposity and decreases glucose tolerance in some rodent models, but alleviates insulin resistance in others.To investigate whether the association of tCys with body fat extends to children at particular risk of obesity, and whether tCys is associated with insulin resistance and obesity-associated inflammation.We explored the cross-sectional relations of fasting plasma tCys and related metabolites with body composition measured by dual-energy X-ray absorptiometry in 984 Hispanic children and adolescents aged 4-19 years from the Viva La Familia Study. Linear and logistic regression and dose-response curves were used to evaluate relations of tCys with obesity, insulin resistance and inflammatory markers including interleukin-6 (IL-6, tumor necrosis factor-alpha (TNF-α, monocyte chemoattractant protein-1 (MCP-1 and C-reactive protein (CRP.tCys, methionine and total homocysteine (tHcy increased with age. Upper tCys quartile was independently associated with a 5-fold increased risk of obesity (95% CI 3.5-8.0, P<0.001, and 2-fold risk of insulin resistance (95% CI: 1.6-5.0, P<0.001; adjusted for body fat%. Within the overweight/obese subgroup, but not in normal-weight children, tCys accounted for 9% of the variability in body fat% (partial r = 0.30, P<0.001; adjusted for age and gender. tCys correlated positively with serum non-esterified fatty acids and leptin, partly independent of body fat, but was not associated with serum IL-6, TNF-α or MCP-1. A positive correlation with CRP disappeared after adjustment for BMI.tCys is independently associated with obesity and insulin resistance in Hispanic children and adolescents, highlighting a previously underappreciated link between the sulfur amino acid metabolic pathway and obesity and cardiometabolic risk.

  4. Insulin and leptin levels in overweight and normal-weight Iranian adolescents: The CASPIAN-III study

    Directory of Open Access Journals (Sweden)

    Ehsan Bahrami

    2014-01-01

    Full Text Available Background: In this study, we aim to compare insulin and leptin levels in adolescents with or without excess weight and in those with or without abdominal obesity. Materials and Methods : This case-control study was conducted among 486 samples. We randomly selected 243 overweight and an equal number of normal-weight adolescents from among participants of the third survey of a national surveillance program entitled "Childhood and Adolescence Surveillance and PreventIon of Adult Non-communicable diseases study." Serum insulin and leptin were compared between two groups and their correlation was determined with other variables. Results: The mean age and body mass index (BMI of participants were 14.10 ± 2.82 years and 22.12 ± 6.49 kg/m 2 , respectively. Leptin and insulin levels were higher in overweight than in normal-weight adolescents (P < 0.05. Leptin level was higher in children with abdominal obesity than in their other counterparts (P < 0.001. Leptin level was correlated with age, fasting blood glucose, BMI, and insulin level. Conclusion: Insulin and leptin levels were higher among overweight and obese children, which may reflect insulin and leptin-resistance. Given the complications of excess weight from early life, prevention and controlling childhood obesity should be considered as a health priority.

  5. Maternal serum leptin concentration in gestational diabetes

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    Sedigheh Soheilykhah

    2011-06-01

    Conclusion: Our data showed that serum leptin level was higher in GDM and had a positive correlation with insulin resistance. Our findings suggest that high leptin levels might be a risk factor for GDM and IGT in pregnant women.

  6. Effects of high-fat diet and/or body weight on mammary tumor leptin and apoptosis signaling pathways in MMTV-TGF-α mice

    Science.gov (United States)

    Dogan, Soner; Hu, Xin; Zhang, Yan; Maihle, Nita J; Grande, Joseph P; Cleary, Margot P

    2007-01-01

    Introduction Obesity is a risk factor for postmenopausal breast cancer and is associated with shortened mammary tumor (MT) latency in MMTV-TGF-α mice with dietary-induced obesity. One link between obesity and breast cancer is the adipokine, leptin. Here, the focus is on diet-induced obesity and MT and mammary fat pad (MFP) leptin and apoptotic signaling proteins. Methods MMTV-TGF-α mice were fed low-fat or high-fat diets from 10 to 85 weeks of age. High-Fat mice were divided into Obesity-Prone and Obesity-Resistant groups based on final body weights. Mice were followed to assess MT development and obtain serum, MFP, and MT. Results Incidence of palpable MTs was significantly different: Obesity-Prone > Obesity-Resistant > Low-Fat. Serum leptin was significantly higher in Obesity-Prone compared with Obesity-Resistant and Low-Fat mice. Low-Fat mice had higher MFP and MT ObRb (leptin receptor) protein and Jak2 (Janus kinase 2) protein and mRNA levels in comparison with High-Fat mice regardless of body weight. Leptin (mRNA) and pSTAT3 (phosphorylated signal transducer and activator of transcription 3) (mRNA and protein) also were higher in MTs from Low-Fat versus High-Fat mice. Expression of MT and MFP pro-apoptotic proteins was higher in Low-Fat versus High-Fat mice. Conclusion These results confirm a connection between body weight and MT development and between body weight and serum leptin levels. However, diet impacts MT and MFP leptin and apoptosis signaling proteins independently of body weight. PMID:18162139

  7. Assessment of insulin sensitivity/resistance and their relations with leptin concentrations and anthropometric measures in a pregnant population with and without gestational diabetes mellitus.

    Science.gov (United States)

    Yilmaz, Ozgur; Kucuk, Mert; Ilgin, Aydin; Dagdelen, Muride

    2010-01-01

    Fifty-six pregnant women with gestational diabetes mellitus (GDM) and 42 normal glucose tolerant (NGT) pregnant women between 26 and 36 gestational weeks were included in the study prospectively. The body fat percentage (BFP) was calculated using the Siri formula from skinfold thickness (SFT) measurements. Both groups were comparable for gestational age, height, weight, and body mass index (P>.05). Insulin resistance assessed by homeostasis model assessment for insulin resistance (HOMA-IR) method was significantly higher in GDM patients compared to their NGT weight-matched control group. In contrast, the insulin sensitivity calculated from quantitative insulin sensitivity check index (QUICKI-IS) equation was significantly lower in GDM group. Calculated lean body mass was found to be similar in between both groups. Body fat percentage derived from SFT parameters was significantly higher in women with GDM. Women with GDM had significantly higher levels of serum insulin and leptin concentrations when compared with the NGT group. All SFT measurements were higher in GDM group when compared to those in NGT women. We did not find any correlation between leptin levels and insulin resistance; we found negative correlation between leptin levels and insulin sensitivity. Thus, we observed that leptin may contribute development of GDM by decreasing insulin sensitivity but not increasing insulin resistance. Also, we observed that the BFP estimated by the Siri formula from SFT measurements correlated significantly with HOMA-IR and QUICKI-IS and leptin concentrations in pregnant women. We suggest that by simply evaluating SFT, we may hold a view about BFP and leptin concentrations and insulin sensitivity in pregnant women.

  8. Study of genetic variation in the STAT3 on obesity and insulin resistance in male adults.

    Science.gov (United States)

    Gianotti, Tomas F; Sookoian, Silvia; Gemma, Carolina; Burgueño, Adriana L; González, Claudio D; Pirola, Carlos J

    2008-07-01

    Signal transducer and activator of transcription 3 (STAT3) plays an important role in hepatic glucose homeostasis and carbohydrate metabolism and has been implicated in the leptin-mediated energy homeostasis. We explored whether STAT3 gene variants are associated with obesity and insulin resistance in a well-characterized sample of 984 adult men (aged 34.4+/-8.6 years) of self-reported European ancestry from a population-based study. We analyzed three tagging single-nucleotide polymorphisms (tagSNPs), two intronic (rs2293152 and rs6503695) and one located in a noncoding region near the gene promoter (rs9891119). These variants were not associated with either obesity (in which 488 lean individuals were compared to 496 overweight/obese subjects) (P values: 0.68, 0.49, and 0.9 for rs2293152, rs6503695, and rs9891119, respectively) or BMI as a continuous trait (P values: 0.85, 0.73, and 0.58 for rs2293152, rs6503695, and rs9891119, respectively). We found no significant association between the three tagSNPs and fasting plasma glucose and insulin. Likewise, no association was observed between the homeostasis model assessment (HOMA) index and any of the tagSNPs. A significant association was observed with total cholesterol and rs6503695 (nominal P value 0.019), but after correcting for multiple testing by Bonferroni correction, the significance becomes marginal (P=0.057). In conclusion, although STAT3 is an excellent candidate gene for assessing obesity and insulin resistance susceptibility alleles, our results do not support a major role for STAT3 variants in BMI and insulin resistance in our male population.

  9. HOMA, BMI, and Serum Leptin Levels Variations during Antiviral Treatment Suggest Virus-Related Insulin Resistance in Noncirrhotic, Nonobese, and Nondiabetic Chronic Hepatitis C Genotype 1 Patients

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    Alessandro Grasso

    2015-01-01

    Full Text Available Objective. To investigate the relationship between insulin resistance and viral load decay in nondiabetic and noncirrhotic genotype 1 chronic HCV patients during peginterferon and ribavirin treatment and the possible influence of BMI and leptin as metabolic confounders. Methods. 75 consecutive noncirrhotic, nonobese, and nondiabetic patients with genotype 1 chronic hepatitis C treated with peginterferon alpha 2a plus ribavirin were evaluated. HOMA-IR, serum leptin, and BMI were measured in all patients at baseline and at weeks 12 and 48, whereas viral load was measured at the same time points and then 24 weeks after the end of treatment. Results. HOMA-IR was significantly associated with both BMI and leptin at baseline. During peginterferon plus ribavirin treatment, there was a significant reduction of HOMA-IR at weeks 12 and 48 from baseline (P=0.033 and 0.048, resp. in patients who achieved an early viral load decay (EVR, a trend not observed in patients who not achieved EVR. No variations during treatment were observed regarding BMI and leptin irrespective of EVR. Conclusion. The early reduction of HOMA-IR but not of BMI and leptin during antiviral treatment in noncirrhotic, chronic hepatitis C genotype 1 patients who achieved EVR suggests a viral genesis of insulin resistance in patients with nonmetabolic phenotype.

  10. HOMA, BMI, and Serum Leptin Levels Variations during Antiviral Treatment Suggest Virus-Related Insulin Resistance in Noncirrhotic, Nonobese, and Nondiabetic Chronic Hepatitis C Genotype 1 Patients.

    Science.gov (United States)

    Grasso, Alessandro; Malfatti, Federica; Andraghetti, Gabriella; Marenco, Simona; Mazzucchelli, Chiara; Labanca, Sara; Cordera, Renzo; Testa, Roberto; Picciotto, Antonino

    2015-01-01

    Objective. To investigate the relationship between insulin resistance and viral load decay in nondiabetic and noncirrhotic genotype 1 chronic HCV patients during peginterferon and ribavirin treatment and the possible influence of BMI and leptin as metabolic confounders. Methods. 75 consecutive noncirrhotic, nonobese, and nondiabetic patients with genotype 1 chronic hepatitis C treated with peginterferon alpha 2a plus ribavirin were evaluated. HOMA-IR, serum leptin, and BMI were measured in all patients at baseline and at weeks 12 and 48, whereas viral load was measured at the same time points and then 24 weeks after the end of treatment. Results. HOMA-IR was significantly associated with both BMI and leptin at baseline. During peginterferon plus ribavirin treatment, there was a significant reduction of HOMA-IR at weeks 12 and 48 from baseline (P = 0.033 and 0.048, resp.) in patients who achieved an early viral load decay (EVR), a trend not observed in patients who not achieved EVR. No variations during treatment were observed regarding BMI and leptin irrespective of EVR. Conclusion. The early reduction of HOMA-IR but not of BMI and leptin during antiviral treatment in noncirrhotic, chronic hepatitis C genotype 1 patients who achieved EVR suggests a viral genesis of insulin resistance in patients with nonmetabolic phenotype.

  11. Greater effects of high- compared with moderate-intensity interval training on cardio-metabolic variables, blood leptin concentration and ratings of perceived exertion in obese adolescent females

    OpenAIRE

    Racil, G; Coquart, JB; Elmontassar, W; Haddad, M; Goebel, R; Chaouachi, A; Amri, M; Chamari, K

    2016-01-01

    This study examined the effects of high- vs. moderate-intensity interval training on cardiovascular fitness, leptin levels and ratings of perceived exertion (RPE) in obese female adolescents. Forty-seven participants were randomly assigned to one of three groups receiving either a 1:1 ratio of 15 s of effort comprising moderate-intensity interval training (MIIT at 80% maximal aerobic speed: MAS) or high-intensity interval training (HIIT at 100% MAS), with matched 15 s recovery at 50% MAS, thr...

  12. miRNA Signatures of Insulin Resistance in Obesity.

    Science.gov (United States)

    Jones, Angela; Danielson, Kirsty M; Benton, Miles C; Ziegler, Olivia; Shah, Ravi; Stubbs, Richard S; Das, Saumya; Macartney-Coxson, Donia

    2017-10-01

    Extracellular microRNAs (miRNAs) represent functional biomarkers for obesity and related disorders; this study investigated plasma miRNAs in insulin resistance phenotypes in obesity. One hundred seventy-five miRNAs were analyzed in females with obesity (insulin sensitivity, n = 11; insulin resistance, n = 19; type 2 diabetes, n = 15) and without obesity (n = 12). Correlations between miRNA level and clinical parameters and levels of 15 miRNAs in a murine obesity model were investigated. One hundred six miRNAs were significantly (adjusted P ≤ 0.05) different between controls and at least one obesity phenotype, including miRNAs with the following attributes: previously reported roles in obesity and altered circulating levels (e.g., miR-122, miR-192); known roles in obesity but no reported changes in circulating levels (e.g., miR-378a); and no current reported role in, or association with, obesity (e.g., miR-28-5p, miR-374b, miR-32). The miRNAs in the latter group were found to be associated with extracellular vesicles. Forty-eight miRNAs showed significant correlations with clinical parameters; stepwise regression retained let-7b, miR-144-5p, miR-34a, and miR-532-5p in a model predictive of insulin resistance (R 2  = 0.57, P = 7.5 × 10 -8 ). Both miR-378a and miR-122 were perturbed in metabolically relevant tissues in a murine model of obesity. This study expands on the role of extracellular miRNAs in insulin-resistant phenotypes of obesity and identifies candidate miRNAs not previously associated with obesity. © 2017 The Obesity Society.

  13. Association of insulin resistance with obesity in children

    International Nuclear Information System (INIS)

    Siddiqui, S.A.; Bashir, S.; Shabbir, I.; Sherwani, M.K.; Aasim, M.

    2011-01-01

    Background: Insulin resistance is the primary metabolic disorder associated with obesity. Little is known about its role as a determinant of the metabolic syndrome in obese children. Objectives: To assess the association of insulin resistance with metabolic syndrome in obese and non obese children. Study type and settings: Cross sectional analytical study conducted among children of ten Municipal Corporation high schools of Data Ganj Buksh Town Lahore. Subjects and Methods: A total of 46 obese and 49 non obese children with consent were recruited for the study. Fasting blood glucose, serum insulin, high density lipoprotein in cholesterol, triglycerides, cholesterol, non HDL-cholesterol LDL-cholesterol were measured using standard methods. Data were analyzed by using statistical software SPSS-Version 15. Results: A total of 95 children 49 obese and 46 non obese were recruited for the study. A significant association of serum triglyceride(p<0.001), high density lipoprotein cholesterol(p<0.001), fasting blood glucose(p<0.001), and insulin levels (p<0.001) , was seen between the two groups. For each component of metabolic syndrome, when insulin resistance increased so did odds ratios for cardio metabolic risk factors. Conclusions: Insulin resistance was seen in 34.7% children. Metabolic syndrome was found in 31.6% children reflecting that obese children are at high risk for metabolic syndrome and have low HDL-cholesterol and high triglycerides levels. (author)

  14. Maternal obesity programs increased leptin gene expression in rat male offspring via epigenetic modifications in a depot-specific manner

    Directory of Open Access Journals (Sweden)

    Simon Lecoutre

    2017-08-01

    Conclusions: Consistent with the DOHaD hypothesis, persistent epigenetic remodeling occurs at regulatory regions especially within intergenic sequences, linked to higher leptin gene expression in adult HF offspring in a depot-specific manner.

  15. Positive correlation of serum leptin with estradiol levels in patients with polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Mendonça H.C.

    2004-01-01

    Full Text Available Patients with polycystic ovary syndrome (PCOS usually are obese, insulin resistant and hyperinsulinemic. The known association between leptin, obesity andinsulin action suggests that leptin may have a role in PCOS but this has only been addressed peripherally. This study was designed to assess the relationship between serum leptin and the anthropometric, metabolic and endocrine variables of obese (body mass index, BMI ³30 kg/m² and non-obese (BMI <30 kg/m² PCOS patients. Twenty-eight PCOS patients and 24 control women subdivided into obese and non-obese groups were evaluated. Leptin, androgens, lipids, gonadotrophins and insulin-glucose response to the oral glucose tolerance test were measured by radioimmunoassay in all participants. The assays were done all in one time. The areas under the insulin curve (AUC-I and the glycemia curve were calculated to identify patients with insulin resistance. Mean leptin levels were not significantly higher in patients with PCOS compared to the control group (21.2 ± 10.2 vs 27.3 ± 12.4 ng/ml. Leptin levels were found to be significantly higher in the obese subgroups both in patients with PCOS (26.9 ± 9.3 vs 14.1 ± 7.0 ng/ml and in the control group (37.3 ± 15.5 vs 12.9 ± 5.8 ng/ml. The leptin of the PCOS group was correlated with BMI (r = 0.74; P < 0.0001 and estradiol (r = 0.48; P < 0.008 and tended to be correlated with the AUC-I (r = 0.36; P = 0.05. Of the parameters which showed a correlation with leptin in PCOS, only estradiol and probably insulinemia (AUC-I did not show a significant correlation with BMI, suggesting that the other parameters were correlated with leptin due to their correlation with BMI. Estradiol correlated with leptin in PCOS patients regardless of their weight.

  16. Leptin: A cardiovascular perspective | Schutte | Journal of ...

    African Journals Online (AJOL)

    The development of obesity, as well as resultant type 2 diabetes, hypertension and cardiovascular disease, is causing concern in South Africa. Following the discovery of leptin in 1994, hopes were raised that the manipulation of the leptin axis might yield successful therapy for obesity. Although hope still remains, the role of ...

  17. Insulin resistance in obesity can be reliably identified from fasting plasma insulin

    NARCIS (Netherlands)

    ter Horst, K. W.; Gilijamse, P. W.; Koopman, K. E.; de Weijer, B. A.; Brands, M.; Kootte, R. S.; Romijn, J. A.; Ackermans, M. T.; Nieuwdorp, M.; Soeters, M. R.; Serlie, M. J.

    2015-01-01

    Insulin resistance is the major contributor to cardiometabolic complications of obesity. We aimed to (1) establish cutoff points for insulin resistance from euglycemic hyperinsulinemic clamps (EHCs), (2) identify insulin-resistant obese subjects and (3) predict insulin resistance from routinely

  18. Distinct Roles for JNK and IKK Activation in Agouti-Related Peptide Neurons in the Development of Obesity and Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Eva Tsaousidou

    2014-11-01

    Full Text Available Activation of c-Jun N-terminal kinase 1 (JNK1- and inhibitor of nuclear factor kappa-B kinase 2 (IKK2-dependent signaling plays a crucial role in the development of obesity-associated insulin and leptin resistance not only in peripheral tissues but also in the CNS. Here, we demonstrate that constitutive JNK activation in agouti-related peptide (AgRP-expressing neurons of the hypothalamus is sufficient to induce weight gain and adiposity in mice as a consequence of hyperphagia. JNK activation increases spontaneous action potential firing of AgRP cells and causes both neuronal and systemic leptin resistance. Similarly, activation of IKK2 signaling in AgRP neurons also increases firing of these cells but fails to cause obesity and leptin resistance. In contrast to JNK activation, IKK2 activation blunts insulin signaling in AgRP neurons and impairs systemic glucose homeostasis. Collectively, these experiments reveal both overlapping and nonredundant effects of JNK- and IKK-dependent signaling in AgRP neurons, which cooperate in the manifestation of the metabolic syndrome.

  19. Leptin/HER2 crosstalk in breast cancer: in vitro study and preliminary in vivo analysis

    International Nuclear Information System (INIS)

    Fiorio, Elena; Bonetti, Franco; Giordano, Antonio; Cetto, Gian Luigi; Surmacz, Eva; Mercanti, Anna; Terrasi, Marianna; Micciolo, Rocco; Remo, Andrea; Auriemma, Alessandra; Molino, Annamaria; Parolin, Veronica; Di Stefano, Bruno

    2008-01-01

    Obesity in postmenopausal women is associated with increased breast cancer risk, development of more aggressive tumors and resistance to certain anti-breast cancer treatments. Some of these effects might be mediated by obesity hormone leptin, acting independently or modulating other signaling pathways. Here we focused on the link between leptin and HER2. We tested if HER2 and the leptin receptor (ObR) can be coexpressed in breast cancer cell models, whether these two receptors can physically interact, and whether leptin can transactivate HER2. Next, we studied if leptin/ObR can coexist with HER2 in breast cancer tissues, and if presence of these two systems correlates with specific clinicopathological features. Expression of ObR, HER2, phospo-HER2 was assessed by immonoblotting. Physical interactions between ObR and HER2 were probed by immunoprecipitation and fluorescent immunostaining. Expression of leptin and ObR in breast cancer tissues was detected by immunohistochemistry (IHC). Associations among markers studied by IHC were evaluated using Fisher's exact test for count data. HER2 and ObR were coexpressed in all studied breast cancer cell lines. In MCF-7 cells, HER2 physically interacted with ObR and leptin treatment increased HER2 phosphorylation on Tyr 1248. In 59 breast cancers, the presence of leptin was correlated with ObR (the overall association was about 93%). This result was confirmed both in HER2-positive and in HER2-negative subgroups. The expression of leptin or ObR was numerically more frequent in larger (> 10 mm) tumors. Coexpression of HER2 and the leptin/ObR system might contribute to enhanced HER2 activity and reduced sensitivity to anti-HER2 treatments

  20. Consumption of a liquid high-fat meal increases triglycerides but decreases high-density lipoprotein cholesterol in abdominally obese subjects with high postprandial insulin resistance.

    Science.gov (United States)

    Wang, Feng; Lu, Huixia; Liu, Fukang; Cai, Huizhen; Xia, Hui; Guo, Fei; Xie, Yulan; Huang, Guiling; Miao, Miao; Shu, Guofang; Sun, Guiju

    2017-07-01

    Abdominal obesity is associated with an increased risk of insulin resistance, which may be a potential contributor to dyslipidemia. However, the relationship between postprandial insulin resistance and lipid metabolism in abdominally obese subjects remains unknown. We hypothesized that postprandial dyslipidemia would be exaggerated in abdominally obese subjects with high postprandial insulin resistance. To test this hypothesis, serum glucose, insulin, triglycerides, total cholesterol, high-density lipoprotein cholesterol, and apolipoprotein B were measured at baseline and postprandial state at 0.5, 1, 2, 4, 6, and 8 hours after a liquid high-fat meal in non-abdominally obese controls (n=44) and abdominally obese subjects with low (AO-LPIR, n=40), middle (n=40), and high postprandial insulin resistance (AO-HPIR, n=40) based on the tertiles ratio of the insulin to glucose areas under the curve (AUC). Their serum adipokines were tested at baseline only. Fasting serum leptin was higher (Pinsulin resistance and controls. The present study indicated that the higher degree of postprandial insulin resistance, the more adverse lipid profiles in abdominally obese subjects, which provides insight into opportunity for screening in health. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Leptin and Adiponectin Levels in Patients with Chronic Hepatitis C with Carbohydrate and Lipid Metabolism Disorders

    Directory of Open Access Journals (Sweden)

    T. V. Antonova

    2014-01-01

    Full Text Available Aim: to analyze leptin and adiponectin serum levels in patients with chronic hepatitis C in comparison with metabolic syndrome components, biochemical features and stage of hepatitis.Materials and methods: In 93 patients with chronic HCV in age 20-55 with a few symptomatic HCV-infection and minimal liver fibrosis stage serum leptin and adiponectin was measured. Associations between leptin, adiponectin and metabolic abnormalities, biochemical features, and hepatic fibrosis were determined.Results: Abdominal obesity was revealed at 40% patients, overweight – at 41%, insulin resistance – at 36,6% cases. The leptin and adiponectin levels were within normal limits range at most patients. Patients with minimal liver fibrosis had higher index of leptin by comparison to patients with moderate and severe fibrosis (r= – 0,402, р= 0,018. In patients with HCV genotype 3a the adiponectin level was below, than in HCV genotype 1b. Patients with abdominal obesity and overweight had higher leptin and lower adiponectin indexes by comparison to patients without these metabolic abnormalities. Direct cross-correlation between the leptin level and body mass index (r=0,358, p=0,001, waist circumference (r=0,292, p=0,01; negative cross-correlation between the adiponectin level and body mass index (r=- 0,435, р <0,021, waist circumference (r=- 0,386, р =0,001 were displayed.Conclusion: Leptin and adiponectin blood levels in HCVpatientis associated with abdominal obesity and overweight. The connection of leptin level and liver fibrosis stage was revealed. Difference of adiponectin level in HCV-patients with 3a and 1b genotypes of virus was found.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Neuronal Rap1 Regulates Energy Balance, Glucose Homeostasis, and Leptin Actions.

    Science.gov (United States)

    Kaneko, Kentaro; Xu, Pingwen; Cordonier, Elizabeth L; Chen, Siyu S; Ng, Amy; Xu, Yong; Morozov, Alexei; Fukuda, Makoto

    2016-09-13

    The CNS contributes to obesity and metabolic disease; however, the underlying neurobiological pathways remain to be fully established. Here, we show that the small GTPase Rap1 is expressed in multiple hypothalamic nuclei that control whole-body metabolism and is activated in high-fat diet (HFD)-induced obesity. Genetic ablation of CNS Rap1 protects mice from dietary obesity, glucose imbalance, and insulin resistance in the periphery and from HFD-induced neuropathological changes in the hypothalamus, including diminished cellular leptin sensitivity and increased endoplasmic reticulum (ER) stress and inflammation. Furthermore, pharmacological inhibition of CNS Rap1 signaling normalizes hypothalamic ER stress and inflammation, improves cellular leptin sensitivity, and reduces body weight in mice with dietary obesity. We also demonstrate that Rap1 mediates leptin resistance via interplay with ER stress. Thus, neuronal Rap1 critically regulates leptin sensitivity and mediates HFD-induced obesity and hypothalamic pathology and may represent a potential therapeutic target for obesity treatment. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Neuronal Rap1 Regulates Energy Balance, Glucose Homeostasis, and Leptin Actions

    Directory of Open Access Journals (Sweden)

    Kentaro Kaneko

    2016-09-01

    Full Text Available The CNS contributes to obesity and metabolic disease; however, the underlying neurobiological pathways remain to be fully established. Here, we show that the small GTPase Rap1 is expressed in multiple hypothalamic nuclei that control whole-body metabolism and is activated in high-fat diet (HFD-induced obesity. Genetic ablation of CNS Rap1 protects mice from dietary obesity, glucose imbalance, and insulin resistance in the periphery and from HFD-induced neuropathological changes in the hypothalamus, including diminished cellular leptin sensitivity and increased endoplasmic reticulum (ER stress and inflammation. Furthermore, pharmacological inhibition of CNS Rap1 signaling normalizes hypothalamic ER stress and inflammation, improves cellular leptin sensitivity, and reduces body weight in mice with dietary obesity. We also demonstrate that Rap1 mediates leptin resistance via interplay with ER stress. Thus, neuronal Rap1 critically regulates leptin sensitivity and mediates HFD-induced obesity and hypothalamic pathology and may represent a potential therapeutic target for obesity treatment.

  5. Chronic blood pressure and appetite responses to central leptin infusion in rats fed a high fat diet.

    Science.gov (United States)

    Dubinion, John H; da Silva, Alexandre A; Hall, John E

    2011-04-01

    Obesity has been suggested to induce selective leptin resistance whereby leptin's anorexic effects are attenuated, whereas the effects to increase sympathetic nervous system activity and blood pressure remain intact. Most studies, however, have tested only the acute responses to leptin administration. This study tested whether feeding a high-fat diet causes resistance to the appetite and cardiovascular responses to chronic central leptin infusion. Sprague-Dawley rats were fed high-fat diet (40% kcal from fat, n=5) or normal-fat diet (13% kcal from fat, n=5) for a year. Radiotelemeters were implanted for continuous monitoring of mean arterial pressure (MAP) and heart rate (HR). A 21G steel cannula was implanted in the lateral cerebral ventricle [intracerebroventricular (ICV)]. After recovery, leptin was infused ICV at 0.02 μg/kg per min for 10 days. High-fat rats were heavier than normal-fat rats (582±12 vs. 511±19 g) and exhibited significantly higher MAP (114±3 vs. 96±7 mmHg). Although the acute (24 h) effects of leptin were attenuated in high-fat rats, chronic ICV leptin infusion decreased caloric intake in both groups similarly (50±8 vs. 40±10%) by day 5. Despite decreased food intake and weight loss, leptin infusion significantly increased MAP and HR in both high-fat and normal-fat rats (7±2 and 5±1 mmHg; 18±11 and 21±10 b.p.m., respectively). These results suggest that obesity induced by feeding a high-fat diet blunts the acute anorexic effects of leptin but does not cause significant resistance to the chronic central nervous system effects of leptin on appetite, MAP, or HR.

  6. Obesity, insulin resistance, and type 1 diabetes mellitus.

    Science.gov (United States)

    Polsky, Sarit; Ellis, Samuel L

    2015-08-01

    To summarize recent studies about obesity, insulin resistance, and type 1 diabetes mellitus (T1DM). Overweight and obesity continue to be prevalent among individuals with T1DM. Obesity rates appear to have reached a plateau among children with T1DM in some parts of the world. The risk for development of T1DM is increased by obesity and may occur at an earlier age among obese individuals with a predisposition. Obesity increases the risk for comorbidities among individuals with T1DM, especially metabolic syndrome, and microvascular and macrovascular diseases. Metformin, glucagon-like peptide-1 agonist therapy, sodium glucose cotransporter-2 inhibitor therapy, and bariatric surgery may be beneficial therapies for glucose control, comorbidity management, and obesity among adults with T1DM. Insulin resistance may be improved among obese individuals with T1DM by biguanides (metformin) and glucagon-like peptide-1 agonists (exenatide). We review the last 18 months of literature on obesity, insulin resistance, and T1DM to highlight new epidemiologic results and treatments.

  7. The Gene-Lifestyle Interaction on Leptin Sensitivity and Lipid Metabolism in Adults: A Population Based Study.

    Science.gov (United States)

    Luglio, Harry Freitag; Sulistyoningrum, Dian Caturini; Huriyati, Emy; Lee, Yi Yi; Wan Muda, Wan Abdul Manan

    2017-07-07

    Obesity has been associated with leptin resistance and this might be caused by genetic factors. The aim of this study was to investigate the gene-lifestyle interaction between -866G/A UCP2 (uncoupling protein 2) gene polymorphism, dietary intake and leptin in a population based study. This is a cross sectional study conducted in adults living at urban area of Yogyakarta, Indonesia. Data of adiposity, lifestyle, triglyceride, high density lipoprotein (HDL) cholesterol, leptin and UCP2 gene polymorphism were obtained in 380 men and female adults. UCP2 gene polymorphism was not significantly associated with adiposity, leptin, triglyceride, HDL cholesterol, dietary intake and physical activity (all p > 0.05). Leptin was lower in overweight subjects with AA + GA genotypes than those with GG genotype counterparts ( p = 0.029). In subjects with AA + GA genotypes there was a negative correlation between leptin concentration ( r = -0.324; p correlation was not seen in GG genotype ( r = -0.111; p = 0.188). In summary, we showed how genetic variation in -866G/A UCP2 affected individual response to leptin production. AA + GA genotype had a better leptin sensitivity shown by its response in dietary intake and body mass index (BMI) and this explained the protective effect of A allele to obesity.

  8. The Gene-Lifestyle Interaction on Leptin Sensitivity and Lipid Metabolism in Adults: A Population Based Study

    Directory of Open Access Journals (Sweden)

    Harry Freitag Luglio

    2017-07-01

    Full Text Available Background: Obesity has been associated with leptin resistance and this might be caused by genetic factors. The aim of this study was to investigate the gene-lifestyle interaction between −866G/A UCP2 (uncoupling protein 2 gene polymorphism, dietary intake and leptin in a population based study. Methods: This is a cross sectional study conducted in adults living at urban area of Yogyakarta, Indonesia. Data of adiposity, lifestyle, triglyceride, high density lipoprotein (HDL cholesterol, leptin and UCP2 gene polymorphism were obtained in 380 men and female adults. Results: UCP2 gene polymorphism was not significantly associated with adiposity, leptin, triglyceride, HDL cholesterol, dietary intake and physical activity (all p > 0.05. Leptin was lower in overweight subjects with AA + GA genotypes than those with GG genotype counterparts (p = 0.029. In subjects with AA + GA genotypes there was a negative correlation between leptin concentration (r = −0.324; p < 0.0001 and total energy intake and this correlation was not seen in GG genotype (r = −0.111; p = 0.188. Conclusions: In summary, we showed how genetic variation in −866G/A UCP2 affected individual response to leptin production. AA + GA genotype had a better leptin sensitivity shown by its response in dietary intake and body mass index (BMI and this explained the protective effect of A allele to obesity.

  9. Association of cocaine- and amphetamine-related transcript, leptin and leptin receptor gene polymorphisms with anthropometric obesity phenotype indicators in South African learners.

    Science.gov (United States)

    Yako, Y Y; Fanampe, B L; Hassan, M S; Erasmus, R T; van der Merwe, L; van Rensburg, S J; Matsha, T E

    2011-01-01

    Obesity has increased rapidly in South African children and adolescents. Genes involved in appetite regulation have been extensively studied worldwide, but their role in the obesity phenotype in South African Black and mixed-ancestry school adolescents is unknown. Seven common polymorphisms in LEP, GHRL, CART and LEPR were analysed for genotype and haplotype association with anthropometric obesity phenotype indicators in South African Black and mixed-ancestry adolescent school learners. The CART c.517A→G polymorphism was significantly associated with obesity susceptibility. The LEPR Lys(109)Arg G allele was associated with an average reduction of 2.36 kg/m(2) in body mass index (BMI), 5.66 cm in waist circumference (WC) and 1.61 cm in mid-upper-arm circumference (MUAC). This was confirmed by haplotype analysis. Additionally, a haplotype of the LEP polymorphisms significantly increased BMI, MUAC and hip circumference, while LEPR haplotypes were associated with differences in MUAC. Our findings suggest that c.517A→G and Lys(109)Arg contribute to the variation in anthropometric obesity phenotype indicators observed among Black African and mixed-ancestry South African learners. Furthermore, haplotypes of LEP, LEPR and GHRL polymorphisms were associated with varying measurements of weight, BMI and WC. Further studies are required to confirm our results in a larger and homogeneous study population group. Copyright © 2011 S. Karger AG, Basel.

  10. Influence of FTO rs9939609 polymorphism on appetite, ghrelin, leptin, IL6, TNFα levels, and food intake of women with morbid obesity

    Directory of Open Access Journals (Sweden)

    Magno FCCM

    2018-05-01

    Full Text Available Fernanda Cristina Carvalho Mattos Magno,1 Helena Chrispim Guaraná,1 Ana Carolina Proença Fonseca,2 Giselda Maria Kalil Cabello,2 João Régis Ivar Carneiro,3 Aline Pereira Pedrosa,1 Ana Carolina Ximenes,1 Eliane Lopes Rosado1 1Institute of Nutrition, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil; 2Oswaldo Cruz Foundation (FIOCRUZ, Oswaldo Cruz Institute (IOC, Human Genetics Laboratory, Rio de Janeiro, RJ, Brazil; 3Federal University of Rio de Janeiro, University Hospital Clementino Fraga Filho, Service of Nutrology, Rio de Janeiro, RJ, Brazil Background: The fat mass and obesity-related (FTO gene has a strong relationship with obesity, extreme obesity and inflammatory state, and may also be associated with food intake regulation.Objective: The aim of the present study was to evaluate the influence of the rs9939609 single-nucleotide polymorphism of the FTO gene on appetite, ghrelin, leptin, interleukin 6 (IL6, tumor necrosis factor α (TNFα levels and food intake of morbidly obese women.Materials and methods: The study comprised 70 women, aged between 20 and 48 years, from Rio de Janeiro, Brazil. The participants were selected according to the body mass index between 40 and 60 kg/m2. Anthropometric and biochemical data were measured during fasting. Hormones and inflammatory data were measured before and after the participants ate an isocaloric meal. Dietary records were calculated and analyzed using a nutritional assessment program. Visual analog scales were used for behaviors of the sensations of appetite and food preferences. The FTO rs9939609 variant was genotyped using real-time polymerase chain reaction.Results: Participants with the AA genotype had lower values of ghrelin and IL6 and higher values of leptin than those with TT and TA in the postprandial period. Comparing the plasma concentrations of ghrelin, insulin, IL6 and TNFα intragenotypes, it was observed that those with TT had decreased leptin and increased IL6

  11. Running from Disease: Molecular Mechanisms Associating Dopamine and Leptin Signaling in the Brain with Physical Inactivity, Obesity, and Type 2 Diabetes.

    Science.gov (United States)

    Ruegsegger, Gregory N; Booth, Frank W

    2017-01-01

    Physical inactivity is a primary contributor to diseases such as obesity, cardiovascular disease, and type 2 diabetes. Accelerometry data suggest that a majority of US adults fail to perform substantial levels of physical activity needed to improve health. Thus, understanding the molecular factors that stimulate physical activity, and physical inactivity, is imperative for the development of strategies to reduce sedentary behavior and in turn prevent chronic disease. Despite many of the well-known health benefits of physical activity being described, little is known about genetic and biological factors that may influence this complex behavior. The mesolimbic dopamine system regulates motivating and rewarding behavior as well as motor movement. Here, we present data supporting the hypothesis that obesity may mechanistically lower voluntary physical activity levels via dopamine dysregulation. In doing so, we review data that suggest mesolimbic dopamine activity is a strong contributor to voluntary physical activity behavior. We also summarize findings suggesting that obesity leads to central dopaminergic dysfunction, which in turn contributes to reductions in physical activity that often accompany obesity. Additionally, we highlight examples in which central leptin activity influences physical activity levels in a dopamine-dependent manner. Future elucidation of these mechanisms will help support strategies to increase physical activity levels in obese patients and prevent diseases caused by physical inactivity.

  12. Running from Disease: Molecular Mechanisms Associating Dopamine and Leptin Signaling in the Brain with Physical Inactivity, Obesity, and Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Gregory N. Ruegsegger

    2017-05-01

    Full Text Available Physical inactivity is a primary contributor to diseases such as obesity, cardiovascular disease, and type 2 diabetes. Accelerometry data suggest that a majority of US adults fail to perform substantial levels of physical activity needed to improve health. Thus, understanding the molecular factors that stimulate physical activity, and physical inactivity, is imperative for the development of strategies to reduce sedentary behavior and in turn prevent chronic disease. Despite many of the well-known health benefits of physical activity being described, little is known about genetic and biological factors that may influence this complex behavior. The mesolimbic dopamine system regulates motivating and rewarding behavior as well as motor movement. Here, we present data supporting the hypothesis that obesity may mechanistically lower voluntary physical activity levels via dopamine dysregulation. In doing so, we review data that suggest mesolimbic dopamine activity is a strong contributor to voluntary physical activity behavior. We also summarize findings suggesting that obesity leads to central dopaminergic dysfunction, which in turn contributes to reductions in physical activity that often accompany obesity. Additionally, we highlight examples in which central leptin activity influences physical activity levels in a dopamine-dependent manner. Future elucidation of these mechanisms will help support strategies to increase physical activity levels in obese patients and prevent diseases caused by physical inactivity.

  13. Interleukin-6 induces impairment in human subcutaneous adipogenesis in obesity-associated insulin resistance.

    Science.gov (United States)

    Almuraikhy, Shamma; Kafienah, Wael; Bashah, Moataz; Diboun, Ilhame; Jaganjac, Morana; Al-Khelaifi, Fatima; Abdesselem, Houari; Mazloum, Nayef A; Alsayrafi, Mohammed; Mohamed-Ali, Vidya; Elrayess, Mohamed A

    2016-11-01

    A subset of obese individuals remains insulin sensitive by mechanisms as yet unclear. The hypothesis that maintenance of normal subcutaneous (SC) adipogenesis accounts, at least partially, for this protective phenotype and whether it can be abrogated by chronic exposure to IL-6 was investigated. Adipose tissue biopsies were collected from insulin-sensitive (IS) and insulin-resistant (IR) individuals undergoing weight-reduction surgery. Adipocyte size, pre-adipocyte proportion of stromal vascular fraction (SVF)-derived cells, adipogenic capacity and gene expression profiles of isolated pre-adipocytes were determined, along with local in vitro IL-6 secretion. Adipogenic capacity was further assessed in response to exogenous IL-6 application. Despite being equally obese, IR individuals had significantly lower plasma leptin and adiponectin levels and higher IL-6 levels compared with age-matched IS counterparts. Elevated systemic IL-6 in IR individuals was associated with hyperplasia of adipose tissue-derived SVF cells, despite higher frequency of hypertrophied adipocytes. SC pre-adipocytes from these tissues exhibited lower adipogenic capacity accompanied by downregulation of PPARγ (also known as PPARG) and CEBPα (also known as CEBPA) and upregulation of GATA3 expression. Impaired adipogenesis in IR individuals was further associated with increased adipose secretion of IL-6. Treatment of IS-derived SC pre-adipocytes with IL-6 reduced their adipogenic capacity to levels of the IR group. Obesity-associated insulin resistance is marked by impaired SC adipogenesis, mediated, at least in a subset of individuals, by elevated local levels of IL-6. Understanding the molecular mechanisms underlying reduced adipogenic capacity in IR individuals could help target appropriate therapeutic strategies aimed at those at greatest risk of insulin resistance and type 2 diabetes mellitus.

  14. The gut microbiota, obesity and insulin resistance

    Science.gov (United States)

    The human gut is densely populated by commensal and symbiotic microbes (the "gut microbiota"), with the majority of the constituent microorganisms being bacteria. Accumulating evidence indicates that the gut microbiota plays a significant role in the development of obesity, obesity-associated inflam...

  15. Role of sympathetic nervous system and neuropeptides in obesity hypertension

    Directory of Open Access Journals (Sweden)

    J.E. Hall

    2000-06-01

    Full Text Available Obesity is the most common cause of human essential hypertension in most industrialized countries. Although the precise mechanisms of obesity hypertension are not fully understood, considerable evidence suggests that excess renal sodium reabsorption and a hypertensive shift of pressure natriuresis play a major role. Sympathetic activation appears to mediate at least part of the obesity-induced sodium retention and hypertension since adrenergic blockade or renal denervation markedly attenuates these changes. Recent observations suggest that leptin and its multiple interactions with neuropeptides in the hypothalamus may link excess weight gain with increased sympathetic activity. Leptin is produced mainly in adipocytes and is believed to regulate energy balance by acting on the hypothalamus to reduce food intake and to increase energy expenditure via sympathetic activation. Short-term administration of leptin into the cerebral ventricles increases renal sympathetic activity, and long-term leptin infusion at rates that mimic plasma concentrations found in obesity raises arterial pressure and heart rate via adrenergic activation in non-obese rodents. Transgenic mice overexpressing leptin also develop hypertension. Acute studies suggest that the renal sympathetic effects of leptin may depend on interactions with other neurochemical pathways in the hypothalamus, including the melanocortin-4 receptor (MC4-R. However, the role of this pathway in mediating the long-term effects of leptin on blood pressure is unclear. Also, it is uncertain whether there is resistance to the chronic renal sympathetic and blood pressure effects of leptin in obese subjects. In addition, leptin also has other cardiovascular and renal actions, such as stimulation of nitric oxide formation and improvement of insulin sensitivity, which may tend to reduce blood pressure in some conditions. Although the role of these mechanisms in human obesity has not been elucidated, this

  16. Evidence of early alterations in adipose tissue biology and function and its association with obesity-related inflammation and insulin resistance in children.

    Science.gov (United States)

    Landgraf, Kathrin; Rockstroh, Denise; Wagner, Isabel V; Weise, Sebastian; Tauscher, Roy; Schwartze, Julian T; Löffler, Dennis; Bühligen, Ulf; Wojan, Magdalena; Till, Holger; Kratzsch, Jürgen; Kiess, Wieland; Blüher, Matthias; Körner, Antje

    2015-04-01

    Accumulation of fat mass in obesity may result from hypertrophy and/or hyperplasia and is frequently associated with adipose tissue (AT) dysfunction in adults. Here we assessed early alterations in AT biology and function by comprehensive experimental and clinical characterization of 171 AT samples from lean and obese children aged 0 to 18 years. We show an increase in adipocyte size and number in obese compared with lean children beginning in early childhood. These alterations in AT composition in obese children were accompanied by decreased basal lipolytic activity and significantly enhanced stromal vascular cell proliferation in vitro, potentially underlying the hypertrophy and hyperplasia seen in obese children, respectively. Furthermore, macrophage infiltration, including the formation of crown-like structures, was increased in AT of obese children from 6 years on and was associated with higher hs-CRP serum levels. Clinically, adipocyte hypertrophy was not only associated with leptin serum levels but was highly and independently correlated with HOMA-IR as a marker of insulin resistance in children. In summary, we show that adipocyte hypertrophy is linked to increased inflammation in AT in obese children, thereby providing evidence that obesity-associated AT dysfunction develops in early childhood and is related to insulin resistance. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  17. Endocrine and metabolic effects of consuming fructose- and glucose-sweetened beverages with meals in obese men and women: influence of insulin resistance on plasma triglyceride responses.

    Science.gov (United States)

    Teff, Karen L; Grudziak, Joanne; Townsend, Raymond R; Dunn, Tamara N; Grant, Ryan W; Adams, Sean H; Keim, Nancy L; Cummings, Bethany P; Stanhope, Kimber L; Havel, Peter J

    2009-05-01

    Compared with glucose-sweetened beverages, consumption of fructose-sweetened beverages with meals elevates postprandial plasma triglycerides and lowers 24-h insulin and leptin profiles in normal-weight women. The effects of fructose, compared with glucose, ingestion on metabolic profiles in obese subjects has not been studied. The objective of the study was to compare the effects of fructose- and glucose-sweetened beverages consumed with meals on hormones and metabolic substrates in obese subjects. The study had a within-subject design conducted in the clinical and translational research center. Participants included 17 obese men (n = 9) and women (n = 8), with a body mass index greater than 30 kg/m(2). Subjects were studied under two conditions involving ingestion of mixed nutrient meals with either glucose-sweetened beverages or fructose-sweetened beverages. The beverages provided 30% of total kilocalories. Blood samples were collected over 24 h. Area under the curve (24 h AUC) for glucose, lactate, insulin, leptin, ghrelin, uric acid, triglycerides (TGs), and free fatty acids was measured. Compared with glucose-sweetened beverages, fructose consumption was associated with lower AUCs for insulin (1052.6 +/- 135.1 vs. 549.2 +/- 79.7 muU/ml per 23 h, P glucose consumption. Increases of TGs were augmented in obese subjects with insulin resistance, suggesting that fructose consumption may exacerbate an already adverse metabolic profile present in many obese subjects.

  18. [Role of leptin in human reproduction (anorexia, bulimia)].

    Science.gov (United States)

    Pilka, L; Rumpík, D; Pilka, R

    2012-12-01

    Leptin may act as the critical link between adipose tissue and the reproductive system, indicating whether adequate energy reserves are presenting for normal reproductive functions. Future interventional studies involving leptin administration are excepted to further clarify this role of leptin and may provide new therapeutic options for the reproductive dysfunctions associated with states of relative leptin deficiency or resistance.

  19. Improved leptin sensitivity as a potential candidate responsible for the spontaneous food restriction of the Lou/C rat.

    Directory of Open Access Journals (Sweden)

    Christelle Veyrat-Durebex

    Full Text Available The Lou/C rat, an inbred strain of Wistar origin, was described as a model of resistance to age- and diet-induced obesity. Although such a resistance involves many metabolic parameters described in our previous studies, Lou/C rats also exhibit a spontaneous food restriction due to decreased food consumption during the nocturnal period. We then attempted to delineate the leptin sensitivity and mechanisms implicated in this strain, using different protocols of acute central and peripheral leptin administration. A first analysis of the meal patterns revealed that Lou/C rats eat smaller meals, without any change in meal number compared to age-matched Wistar animals. Although the expression of the recognized leptin transporters (leptin receptors and megalin measured in the choroid plexus was normal in Lou/C rats, the decreased triglyceridemia observed in these animals is compatible with an increased leptin transport across the blood brain barrier. Improved hypothalamic leptin signaling in Lou/C rats was also suggested by the higher pSTAT3/STAT3 (signal transducer and activator of transcription 3 ratio observed following acute peripheral leptin administration, as well as by the lower hypothalamic mRNA expression of the suppressor of cytokine signaling 3 (SOCS3, known to downregulate leptin signaling. To conclude, spontaneous hypophagia of Lou/C rats appears to be related to improved leptin sensitivity. The main mechanism underlying such a phenomenon consists in improved leptin signaling through the Ob-Rb leptin receptor isoform, which seems to consequently lead to overexpression of brain-derived neurotrophic factor (BDNF and thyrotropin-releasing hormone (TRH.

  20. Chronic sleep fragmentation during the sleep period induces hypothalamic endoplasmic reticulum stress and PTP1b-mediated leptin resistance in male mice.

    Science.gov (United States)

    Hakim, Fahed; Wang, Yang; Carreras, Alba; Hirotsu, Camila; Zhang, Jing; Peris, Eduard; Gozal, David

    2015-01-01

    Sleep fragmentation (SF) is highly prevalent and may constitute an important contributing factor to excessive weight gain and the metabolic syndrome. Increased endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) leading to the attenuation of leptin receptor signaling in the hypothalamus leads to obesity and metabolic dysfunction. Mice were exposed to SF and sleep control (SC) for varying periods of time during which ingestive behaviors were monitored. UPR pathways and leptin receptor signaling were assessed in hypothalami. To further examine the mechanistic role of ER stress, changes in leptin receptor (ObR) signaling were also examined in wild-type mice treated with the ER chaperone tauroursodeoxycholic acid (TUDCA), as well as in CHOP-/+ transgenic mice. Fragmented sleep in male mice induced increased food intake starting day 3 and thereafter, which was preceded by increases in ER stress and activation of all three UPR pathways in the hypothalamus. Although ObR expression was unchanged, signal transducer and activator of transcription 3 (STAT3) phosphorylation was decreased, suggesting reduced ObR signaling. Unchanged suppressor of cytokine signaling-3 (SOCS3) expression and increases in protein-tyrosine phosphatase 1B (PTP1B) expression and activity emerged with SF, along with reduced p-STAT3 responses to exogenous leptin. SF-induced effects were reversed following TUDCA treatment and were absent in CHOP -/+ mice. SF induces hyperphagic behaviors and reduced leptin signaling in hypothalamus that are mediated by activation of ER stress, and ultimately lead to increased PTP1B activity. ER stress pathways are therefore potentially implicated in SF-induced weight gain and metabolic dysfunction, and may represent a viable therapeutic target. © 2014 Associated Professional Sleep Societies, LLC.

  1. Increased 4E-BP1 Expression Protects against Diet-Induced Obesity and Insulin Resistance in Male Mice

    Directory of Open Access Journals (Sweden)

    Shih-Yin Tsai

    2016-08-01

    Full Text Available Obesity is a major risk factor driving the global type II diabetes pandemic. However, the molecular factors linking obesity to disease remain to be elucidated. Gender differences are apparent in humans and are also observed in murine models. Here, we link these differences to expression of eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1, which, upon HFD feeding, becomes significantly reduced in the skeletal muscle and adipose tissue of male but not female mice. Strikingly, restoring 4E-BP1 expression in male mice protects them against HFD-induced obesity and insulin resistance. Male 4E-BP1 transgenic mice also exhibit reduced white adipose tissue accumulation accompanied by decreased circulating levels of leptin and triglycerides. Importantly, transgenic 4E-BP1 male mice are also protected from aging-induced obesity and metabolic decline on a normal diet. These results demonstrate that 4E-BP1 is a gender-specific suppressor of obesity that regulates insulin sensitivity and energy metabolism.

  2. Obesity, insulin resistance and Polycystic Ovary Syndrome

    OpenAIRE

    Joham, Anju Elizabeth

    2017-01-01

    Polycystic Ovary Syndrome (PCOS) affects 12 to 21% of Australian reproductive-aged women and is a major public health concern (1-5). Whilst reproductive features (anovulation, infertility) are prominent, PCOS also has major metabolic [obesity, metabolic syndrome, type 2 diabetes (T2DM), cardiovascular disease risk factors] and psychological features (6-8). Obesity is a major chronic disease, with rising prevalence and diverse health impacts. The interplay between PCOS and weight contributes t...

  3. Therapeutic potential of flurbiprofen against obesity in mice.

    Science.gov (United States)

    Hosoi, Toru; Baba, Sachiko; Ozawa, Koichiro

    2014-06-20

    Obesity is associated with several diseases including diabetes, nonalcoholic steatohepatitis (NASH), hypertension, cardiovascular disease, and cancer. Therefore, anti-obesity drugs have the potential to prevent these diseases. In the present study, we demonstrated that flurbiprofen, a nonsteroidal anti-inflammatory drug (NSAID), exhibited therapeutic potency against obesity. Mice were fed a high-fat diet (HFD) for 6 months, followed by a normal-chow diet (NCD). The flurbiprofen treatment simultaneously administered. Although body weight was significantly decreased in flurbiprofen-treated mice, growth was not affected. Flurbiprofen also reduced the HFD-induced accumulation of visceral fat. Leptin resistance, which is characterized by insensitivity to the anti-obesity hormone leptin, is known to be involved in the development of obesity. We found that one of the possible mechanisms underlying the anti-obesity effects of flurbiprofen may have been mediated through the attenuation of leptin resistance, because the high circulating levels of leptin in HFD-fed mice were decreased in flurbiprofen-treated mice. Therefore, flurbiprofen may exhibit therapeutic potential against obesity by reducing leptin resistance. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Leptin and zinc relation : In regulation of food intake and immunity

    Directory of Open Access Journals (Sweden)

    Abdulkerim Kasim Baltaci

    2012-01-01

    Full Text Available Leptin is synthesized and released by the adipose tissue. Leptin, which carries the information about energy reserves of the body to the brain, controls food intake by acting on neuropeptide Y (NPY, which exercises a food-intake-increasing effect through relevant receptors in the hypothalamus. Zinc deficiency is claimed to result in anorexia, weight loss, poor food efficiency, and growth impairment. The fact that obese individuals have low zinc and high leptin levels suggests that there is a relation between zinc and nutrition, and consequently also between zinc and leptin. Leptin deficiency increases the predisposition to infections and this increase is associated with the impairments in the production of cytokines. Zinc has a key role in the sustenance of immune resistance against infections. Dietary zinc deficiency negatively affects CD +4 cells, Th functions, and consequently, cell-mediated immunity by causing a decrease in the production of IL-2, IF-γ, and TNF-α, which are Th1 products. The relation between zinc and the concerned cytokines in particular, and the fact that leptin has a part in the immune responses mediated by these cytokines demonstrate that an interaction among cellular immunity, leptin and zinc is inevitable. An overall evaluation of the information presented above suggests that there are complex relations among food intake, leptin and zinc on one hand and among cellular immunity, leptin and zinc on the other. The aim of the present review was to draw attention to the possible relation between zinc and leptin in dietary regulation and cellular immunity.

  5. Greater effects of high- compared with moderate-intensity interval training on cardio-metabolic variables, blood leptin concentration and ratings of perceived exertion in obese adolescent females.

    Science.gov (United States)

    Racil, G; Coquart, J B; Elmontassar, W; Haddad, M; Goebel, R; Chaouachi, A; Amri, M; Chamari, K

    2016-06-01

    This study examined the effects of high- vs. moderate-intensity interval training on cardiovascular fitness, leptin levels and ratings of perceived exertion (RPE) in obese female adolescents. Forty-seven participants were randomly assigned to one of three groups receiving either a 1:1 ratio of 15 s of effort comprising moderate-intensity interval training (MIIT at 80% maximal aerobic speed: MAS) or high-intensity interval training (HIIT at 100% MAS), with matched 15 s recovery at 50% MAS, thrice weekly, or a no-training control group. The HIIT and MIIT groups showed improved (p HIIT group showed decreased waist circumference (WC) (p = 0.017). The effect of exercise on maximal oxygen uptake (VO2max) was significant (p = 0.019, ES = 0.48 and p = 0.010, ES = 0.57, HIIT and MIIT, respectively). The decrease of rate-pressure product (RPP) (p HIIT and MIIT, respectively) followed the positive changes in resting heart rate and blood pressures. Blood glucose, insulin level and the homeostasis model assessment index for insulin decreased (p HIIT and MIIT, respectively. In the post-intervention period, blood leptin was strongly associated with %BF (p HIIT and MIIT groups, respectively, while RPE was strongly associated with BM (p HIIT group. The results suggest that high-intensity interval training may produce more positive effects on health determinants in comparison with the same training mode at a moderate intensity.

  6. The Correlation of Plasma Levels of Apelin-13 with Insulin Resistance Index and Plasma Leptin of Diabetic Male Rats after 8-Week Aerobic Exercise

    Directory of Open Access Journals (Sweden)

    Fahimeh Kazemi

    2015-09-01

    Full Text Available Abstract Background: The physiological role of apelin, an adipokine secreted by adipose tissue, in insulin resistance and type 2 diabetes has been identified. The aim of this study was to determine the correlation of plasma levels of apelin-13 with insulin resistance index (HOMA-IR and plasma leptin of diabetic male rats after 8-week aerobic exercise. Materials and Methods: Peresent study was an experimental study with animal model. Twenty eight diabetic male Wistar rats were divided into 3 groups: Non-diabetic (n=9, control diabetic (n=9 and trained diabetic (n=10. Type 2 diabetes was induced by intraperitoneal injection of nicotinamide and streptozotocin. The trained diabetic rat ran 8-week on treadmill progressively. After the training period, plasma levels of glucose, insulin, leptin and apelin-13 were measured and HOMA-IR was calculated. One-way analysis of variance (ANOVA and Pearson’s correlation were used for analyzing data. p<0.05 was considered to be statistically significant. Results: A significant decrease in plasma levels of glucose, insulin and leptin and HOMA-IR in trained diabetic vs control diabetic rats, a significant increase in plasma levels of apelin in trained diabetic vs non-diabetic and control diabetic rats and a significant negative correlation of plasma levels of apelin with HOMA-IR and plasma leptin in trained diabetic rats was observed. Conclusion: In present study, 8-week aerobic training by improvement of insulin sensitivity (decrease of HOMA-IR and plasma leptin increased plasma levels of apelin-13 in diabetic male rats.

  7. Central leptin gene therapy ameliorates diabetes type 1 and 2 through two independent hypothalamic relays

    Science.gov (United States)

    Kalra, Satya P.

    2009-01-01

    Although its role in energy homeostasis is firmly established, the evidence accumulated over a decade linking the adipocyte leptin -hypothalamus axis in the pathogenesis of diabetes mellitus has received little attention in the contemporary thinking. In this context various lines of evidence are collated here to show that (1) under the direction of leptin two independent relays emanating from the hypothalamus restrain insulin secretion from the pancreas and mobilize peripheral organs - liver, skeletal muscle and brown adipose tissue - to upregulate glucose disposal, and (2), leptin insufficiency in the hypothalamus produced by either leptinopenia or restriction of leptin transport across the blood brain barrier due to hyperleptinemia of obesity and aging, initiate antecedent pathophysiological sequalae of diabetes type 1 and 2. Further, we document here the efficacy of leptin replenishment in vivo, especially by supplying it to the hypothalamus with the aid of gene therapy, in preventing the antecedent pathophysiological sequalae-hyperinsulinemia, insulin resistance and hyperglycemia - in various animal models and clinical paradigms of diabetes type 1 and 2 with or without attendant obesity. Overall, the new insights on the long-lasting antidiabetic potential of two independent hypothalamic relays engendered by central leptin gene therapy and the preclinical safety indicators in rodents warrant further validation in subhuman primates and humans. PMID:19647774

  8. Midkine, a potential link between obesity and insulin resistance.

    Directory of Open Access Journals (Sweden)

    Nengguang Fan

    Full Text Available Obesity is associated with increased production of inflammatory mediators in adipose tissue, which contributes to chronic inflammation and insulin resistance. Midkine (MK is a heparin-binding growth factor with potent proinflammatory activities. We aimed to test whether MK is associated with obesity and has a role in insulin resistance. It was found that MK was expressed in adipocytes and regulated by inflammatory modulators (TNF-α and rosiglitazone. In addition, a significant increase in MK levels was observed in adipose tissue of obese ob/ob mice as well as in serum of overweight/obese subjects when compared with their respective controls. In vitro studies further revealed that MK impaired insulin signaling in 3T3-L1 adipocytes, as indicated by reduced phosphorylation of Akt and IRS-1 and decreased translocation of glucose transporter 4 (GLUT4 to the plasma membrane in response to insulin stimulation. Moreover, MK activated the STAT3-suppressor of cytokine signaling 3 (SOCS3 pathway in adipocytes. Thus, MK is a novel adipocyte-secreted factor associated with obesity and inhibition of insulin signaling in adipocytes. It may provide a potential link between obesity and insulin resistance.

  9. Monomeric tartrate resistant acid phosphatase induces insulin sensitive obesity.

    Directory of Open Access Journals (Sweden)

    Pernilla Lång

    2008-03-01

    Full Text Available Obesity is associated with macrophage infiltration of adipose tissue, which may link adipose inflammation to insulin resistance. However, the impact of inflammatory cells in the pathophysiology of obesity remains unclear. Tartrate resistant acid phosphatase (TRAP is an enzyme expressed by subsets of macrophages and osteoclasts that exists either as an enzymatically inactive monomer or as an active, proteolytically processed dimer.Using mice over expressing TRAP, we show that over-expression of monomeric, but not the dimeric form in adipose tissue leads to early onset spontaneous hyperplastic obesity i.e. many small fat cells. In vitro, recombinant monomeric, but not proteolytically processed TRAP induced proliferation and differentiation of mouse and human adipocyte precursor cells. In humans, monomeric TRAP was highly expressed in the adipose tissue of obese individuals. In both the mouse model and in the obese humans the source of TRAP in adipose tissue was macrophages. In addition, the obese TRAP over expressing mice exhibited signs of a low-grade inflammatory reaction in adipose tissue without evidence of abnormal adipocyte lipolysis, lipogenesis or insulin sensitivity.Monomeric TRAP, most likely secreted from adipose tissue macrophages, induces hyperplastic obesity with normal adipocyte lipid metabolism and insulin sensitivity.

  10. O papel dos hormônios leptina e grelina na gênese da obesidade The role of leptin and ghrelin on the genesis of obesity

    Directory of Open Access Journals (Sweden)

    Carla Eduarda Machado Romero

    2006-02-01

    Full Text Available A prevalência da obesidade está aumentando e estudos prospectivos mostram que, em 2025, o Brasil será o quinto país do mundo a apresentar problemas de obesidade em sua população. A etiologia da obesidade não é de fácil identificação, uma vez que a mesma é caracterizada como uma doença multifatorial, ou seja, diversos fatores estão envolvidos em sua gênese, incluindo fatores genéticos, psicológicos, metabólicos e ambientais. Pesquisas recentes na área de metabolismo mostram que o adipócito é capaz de sintetizar várias substâncias e, diferentemente do que se supunha anteriormente, o tecido adiposo não é apenas um sítio de armazenamento de triglicérides, é hoje considerado um órgão endócrino. Dentre as diversas substâncias sintetizadas pelo adipócito, destacam-se a adiponectina, a angiotensina e a leptina. A leptina é um petídeo que desempenha importante papel na regulação da ingestão alimentar e no gasto energético, gerando um aumento na queima de energia e diminuindo a ingestão alimentar. Além dos avanços no estudo da célula adiposa, um novo hormôrnio relacionado ao metabolismo foi descoberto recentemente, a grelina. A grelina é um peptídeo produzido nas células do estômago, e está diretamente envolvida na regulação do balanço energético a curto prazo. Assim, este artigo abordará o papel da leptina e da grelina no controle do peso corporal e as limitações que ainda existem para tratar a obesidade em humanos.The prevalence of obesity is rising around the world and prospective studies show that in 2025, Brazil will be the fifth country in the world to have obesity problems. Multifactorial factors are involved in the genesis of obesity including genetic, psychological, metabolic and environmental factors. Recently, adipocytes have been considered an endocrine tissue capable of producing several substances, including adiponectin, angiotensin and leptin. Leptin is the main peptide produced by

  11. Leptin deficiency: clinical implications and opportunities for therapeutic interventions.

    Science.gov (United States)

    Blüher, Susan; Shah, Sunali; Mantzoros, Christos S

    2009-10-01

    The discovery of leptin has significantly advanced our understanding of the metabolic importance of adipose tissue and has revealed that both leptin deficiency and leptin excess are associated with severe metabolic, endocrine, and immunological consequences. We and others have shown that a prominent role of leptin in humans is to mediate the neuroendocrine adaptation to energy deprivation. Humans with genetic mutations in the leptin and leptin receptor genes have deregulated food intake and energy expenditure leading to a morbidly obese phenotype and a disrupted regulation in neuroendocrine and immune function and in glucose and fat metabolism. Observational and interventional studies in humans with (complete) congenital leptin deficiency caused by mutations in the leptin gene or with relative leptin deficiency as seen in states of negative energy balance such as lipoatrophy, anorexia nervosa, or exercise-induced hypothalamic and neuroendocrine dysfunction have contributed to the elucidation of the pathophysiological role of leptin in these conditions and of the clinical significance of leptin administration in these subjects. More specifically, interventional studies have demonstrated that several neuroendocrine, metabolic, or immune disturbances in these states could be restored by leptin administration. Leptin replacement therapy is currently available through a compassionate use program for congenital complete leptin deficiency and under an expanded access program to subjects with leptin deficiency associated with congenital or acquired lipoatrophy. In addition, leptin remains a potentially forthcoming treatment for several other states of energy deprivation including anorexia nervosa or milder forms of hypothalamic amenorrhea pending appropriate clinical trials.

  12. Polymorphism rs3123554 in the cannabinoid receptor gene type 2 (CNR2) reveals effects on body weight and insulin resistance in obese subjects.

    Science.gov (United States)

    de Luis, Daniel Antonio; Izaola, Olatz; Primo, David; de la Fuente, Beatriz; Aller, Rocio

    2017-10-01

    Few studies assessing the relationship between single nucleotide polymorphisms in CNR2 and obesity or its related metabolic parameters are available. To investigate the influence of polymorphism rs3123554 in the CNR2 receptor gene on obesity anthropometric parameters, insulin resistance, and adipokines in subjects with obesity. The study population consisted of 1027 obese subjects, who were performed bioelectrical impedance analyses, blood pressure measurements, serial assessments of dietary intake during three days, and biochemical tests. Genotypes GG, GA, and AA were found in 339 (33.0%), 467 (45.5%), and 221 (21.5%) respectively. Body mass index, weight, fat mass, waist circumference, insulin, HOMA-IR, and triglyceride and leptin levels were higher in A-allele carriers as compared to non A-allele carriers. No differences were seen in these parameters between the GA and AA genotypes. There were no statistical differences in dietary intake. The main study finding was the association of the minor allele of the SNP rs3123554 in the CNR2 gene with body weight and triglyceride, HOMA-IR, insulin, and leptin levels. Copyright © 2017 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Correlation between maternal and cord blood leptin and fetal growth

    African Journals Online (AJOL)

    SERVER

    2007-09-05

    Sep 5, 2007 ... IL -2 and growth hormone. The long form of the leptin receptor functions similarly to cytokine ... regulation of leptin synthesis and the risk for obesity in the offspring. In species such as the human and sheep, ..... Hormonal regulation of leptin levels in the fetus and neonate might be different from the endocrine ...

  14. Leptin promotes wound healing in the skin.

    Directory of Open Access Journals (Sweden)

    Susumu Tadokoro

    Full Text Available Leptin, a 16 kDa anti-obesity hormone, exhibits various physiological properties. Interestingly, skin wound healing was proven to delay in leptin-deficient ob/ob mice. However, little is known on the mechanisms of this phenomenon. In this study, we attempted to elucidate a role of leptin in wound healing of skin.Immunohistochemical analysis was performed to confirm the expression of the leptin receptor (Ob-R in human and mouse skin. Leptin was topically administered to chemical wounds created in mouse back skin along with sustained-release absorbable hydrogel. The process of wound repair was histologically observed and the area of ulceration was measured over time. The effect of leptin on the proliferation, differentiation and migration of human epidermal keratinocytes was investigated.Ob-R was expressed in epidermal cells of human and mouse skin. Topical administration of leptin significantly promoted wound healing. Histological analysis showed more blood vessels in the dermal connective tissues in the leptin-treated group. The proliferation, differentiation/function and migration of human epidermal keratinocytes were enhanced by exogenous leptin.Topically administered leptin was proven to promote wound healing in the skin by accelerating proliferation, differentiation/function and migration of epidermal keratinocytes and enhancing angiogenesis around the wounded area. These results strongly suggest that topical administration of leptin may be useful as a treatment to promote wound healing in the skin.

  15. Downregulation of leptin and resistin expression in blood following bariatric surgery.

    Science.gov (United States)

    Edwards, Claire; Hindle, A Katharine; Fu, Sidney; Brody, Fredrick

    2011-06-01

    Type 2 diabetes (T2D) resolves rapidly after bariatric surgery, even before substantial weight is lost. However, the molecular pathways underlying this phenomenon remain unclear. Microarray data has shown that numerous genes are differentially expressed in blood after bariatric surgery, including resistin and leptin. Resistin and leptin are circulating hormones derived from adipose tissue, which are associated with obesity and insulin resistance. This study examined expression of these genes before and after bariatric surgery in diabetic and nondiabetic obese patients. The study included 16 obese patients who underwent bariatric surgery, either Roux-en-Y gastric bypass (RYGB) or adjustable gastric banding. Eight patients had T2D. Preoperative blood samples were collected in PAXgene tubes to stabilize mRNA. Postoperative samples were collected 3 months after surgery. Total RNA was isolated and cDNA was synthesized. Real-time quantitative PCR was used to quantify mRNA. Results were analyzed using Student's t test with a P<0.05 considered significant. Postoperatively, five diabetic patients had discontinued hypoglycemic medications and one showed improved glycemic control. Both leptin and resistin mRNA levels were elevated in the diabetic group but decreased after surgery to levels near those of the nondiabetic group. Greater downregulation of resistin and leptin expression occurred in patients who lost more excess body weight (EBW), while patients who lost less than 10% EBW had a mean increase in expression of the two genes. Downregulation of both genes was more pronounced after RYGB compared to gastric banding. Downregulation of resistin and leptin gene expression after bariatric surgery may play a role in normalizing obesity-associated insulin resistance. Interestingly, downregulation is greater after RYGB and in patients who lose a greater proportion of EBW. Targeted therapies for obesity and diabetes may be developed by understanding the pathways by which these

  16. [Leptin--an interim evaluation].

    Science.gov (United States)

    Bodner, J; Ebenbichler, C F; Lechleitner, M; Ritsch, A; Sandhofer, A; Gander, R; Wolf, H J; Huter, O; Patsch, J R

    1998-03-27

    The discovery of leptin, the product of the obese (ob)-gene, has broadened the horizons of research on energy balance. This hormone, produced and secreted by adipose tissue and some placental cells, finds its way to the hypothalamus, where it binds to the leptin receptors and signals satiety through the neuroendocrine axis. The fact that adipose tissue is not merely a storage depot, but also an important endocrine tissue, has revived the interest in the "lipostatic" theory of body fat regulation and has initiated many research efforts in the field of obesity, anorexia nervosa, bulimia, reproduction and haematology.

  17. Presence and distribution of leptin and leptin receptor in the canine gallbladder.

    Science.gov (United States)

    Lee, Sungin; Lee, Aeri; Kweon, Oh-Kyeong; Kim, Wan Hee

    2016-09-01

    The hormone leptin is produced by mature adipocytes and plays an important role in regulating food intake and energy metabolism through its interaction with the leptin receptor. In addition to roles in obesity and obesity-related diseases, leptin has been reported to affect the components and secretion of bile in leptin-deficient mice. Furthermore, gallbladder diseases such as cholelithiasis are known to be associated with serum leptin concentrations in humans. We hypothesized that the canine gallbladder is a source of leptin and that the leptin receptor may be localized in the gallbladder, where it plays a role in regulating the function of this organ. The aim of this study was to demonstrate the presence and expression patterns of leptin and its receptors in normal canine gallbladders using reverse transcriptase-PCR (RT-PCR) and immunohistochemistry. Clinically normal gallbladder tissue samples were obtained from four healthy beagle dogs with similar body condition scores. RT-PCR and sequencing of the amplified PCR products revealed the presence of leptin mRNA and its receptors in the gallbladder. Immunohistochemical investigations demonstrated the expression of leptin and its receptors in the luminal single columnar and tubuloalveolar glandular epithelial cells. In conclusion, the results of this study demonstrated the presence of leptin and its receptors in the gallbladders of dogs. Leptin and its receptor were both localized throughout the cytoplasm of luminal and glandular epithelial cells. These results suggested that the gallbladder is not only a source of leptin, but also a target of leptin though autocrine/paracrine mechanisms. The results of this study could increase the understanding of both the normal physiological functions of the gallbladder and the pathophysiological mechanisms of gallbladder diseases characterized by leptin system dysfunction. Copyright © 2016 The Authors. Published by Elsevier GmbH.. All rights reserved.

  18. Physical Training Improves Insulin Resistance Syndrome Markers in Obese Adolescents.

    Science.gov (United States)

    Kang, Hyun-Sik; Gutin, Bernard; Barbeau, Paule; Owens, Scott; Lemmon, Christian R.; Allison, Jerry; Litaker, Mark S.; Le, Ngoc-Anh

    2002-01-01

    Tested the hypothesis that physical training (PT), especially high-intensity PT, would favorably affect components of the insulin resistance syndrome (IRS) in obese adolescents. Data on teens randomized into lifestyle education (LSE) alone, LSE plus moderate -intensity PT, and LSE plus high-intensity PT indicated that PT, especially high-intensity…

  19. Alteration of brain insulin and leptin signaling promotes energy homeostasis impairment and neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Taouis Mohammed

    2011-09-01

    Full Text Available The central nervous system (CNS controls vital functions, by efficiently coordinating peripheral and central cascades of signals and networks in a coordinated manner. Historically, the brain was considered to be an insulin-insensitive tissue. But, new findings demonstrating that insulin is present in different regions of themammalian brain, in particular the hypothalamus and the hippocampus. Insulin acts through specific receptors and dialogues with numerous peptides, neurotransmitters and adipokines such as leptin. The cross-talk between leptin and insulin signaling pathways at the hypothalamic level is clearly involved in the control of energy homeostasis. Both hormones are anorexigenic through their action on hypothalamic arcuate nucleus by inducing the expression of anorexigenic neuropetides such as POMC (pro-opiomelanocortin, the precursor of aMSH and reducing the expression of orexigenic neuropeptide such as NPY (Neuropeptide Y. Central defect of insulin and leptin signaling predispose to obesity (leptin-resistant state and type-2 diabetes (insulin resistant state. Obesity and type-2 diabetes are associated to deep alterations in energy homeostasis control but also to other alterations of CNS functions as the predisposition to neurodegenerative diseases such as Alzheimer’s disease (AD. AD is a neurodegenerative disorder characterized by distinct hallmarks within the brain. Postmortem observation of AD brains showed the presence of parenchymal plaques due to the accumulation of the amyloid beta (AB peptide and neurofibrillary tangles. These accumulations result from the hyperphosphorylation of tau (a mictrotubule-interacting protein. Both insulin and leptin have been described to modulate tau phosphorylation and therefore in leptin and insulin resistant states may contribute to AD. The concentrations of leptin and insulin cerebrospinal fluid are decreased type2 diabetes and obese patients. In addition, the concentration of insulin in the

  20. Therapeutic effects of the allosteric protein tyrosine phosphatase 1B inhibitor KY-226 on experimental diabetes and obesity via enhancements in insulin and leptin signaling in mice

    Directory of Open Access Journals (Sweden)

    Yuma Ito

    2018-05-01

    Full Text Available The anti-diabetic and anti-obesity effects of the allosteric protein tyrosine phosphatase 1B (PTP1B inhibitor 4-(biphenyl-4-ylmethylsulfanylmethyl-N-(hexane-1-sulfonylbenzoylamide (KY-226 were pharmacologically evaluated. KY-226 inhibited human PTP1B activity (IC50 = 0.28 μM, but did not exhibit peroxisome proliferator-activated receptor γ (PPARγ agonist activity. In rodent preadipocytes (3T3-L1, KY-226 up to 10 μM had no effects on adipocyte differentiation, whereas pioglitazone, a PPARγ agonist, markedly promoted it. In human hepatoma-derived cells (HepG2, KY-226 (0.3–10 μM increased the phosphorylated insulin receptor (pIR produced by insulin. In db/db mice, the oral administration of KY-226 (10 and 30 mg/kg/day, 4 weeks significantly reduced plasma glucose and triglyceride levels as well as hemoglobin A1c values without increasing body weight gain, while pioglitazone exerted similar effects with increases in body weight gain. KY-226 attenuated plasma glucose elevations in the oral glucose tolerance test. KY-226 also increased pIR and phosphorylated Akt in the liver and femoral muscle. In high-fat diet-induced obese mice, the oral administration of KY-226 (30 and 60 mg/kg/day, 4 weeks decreased body weight gain, food consumption, and fat volume gain with increases in phosphorylated STAT3 in the hypothalamus. In conclusion, KY-226 exerted anti-diabetic and anti-obesity effects by enhancing insulin and leptin signaling, respectively. Keywords: PTP1B inhibitor, Diabetes, Obesity, Allosteric inhibitor, db/db mouse

  1. Mother and Infant Body Mass Index, Breast Milk Leptin and Their Serum Leptin Values.

    Science.gov (United States)

    Savino, Francesco; Sardo, Allegra; Rossi, Lorenza; Benetti, Stefania; Savino, Andrea; Silvestro, Leandra

    2016-06-21

    This study investigates correlations between mother and infant Body Mass Index (BMI), their serum leptin values and breast milk leptin concentration in early infancy. We determined serum leptin values in 58 healthy infants and leptin values in their mothers' breast milk, using radioimmunoassay (RIA). Infant and maternal anthropometrics were measured. Median leptin concentration was 3.9 ng/mL (interquartile range (IQR): 2.75) in infant serum, 4.27 ng/mL (IQR: 5.62) in maternal serum and 0.89 ng/mL (IQR: 1.32) in breast milk. Median maternal BMI and weight were 24 kg/m² (IQR: 4.41) and 64 kg (IQR: 15). Median infant BMI was 15.80 kg/cm² (IQR: 4.02), while average weight was 5.130 kg (IQR: 1.627). Infants serum leptin values positively correlated with infants' BMI (p = 0.001; r = 0.213) and breast milk leptin (p = 0.03; r = 0.285). Maternal serum leptin values positively correlated with maternal BMI (p = 0.000, r = 0.449) and breast milk leptin ones (p = 0.026; r = 0.322). Breast milk leptin and maternal BMI could influence infant serum leptin values. Further studies are needed to better elucidate the role of genetics and environment on infant leptin production and risk of obesity later in life.

  2. Obesity and kidney disease

    Directory of Open Access Journals (Sweden)

    Geraldo Bezerra da Silva Junior

    Full Text Available Abstract Obesity has been pointed out as an important cause of kidney diseases. Due to its close association with diabetes and hypertension, excess weight and obesity are important risk factors for chronic kidney disease (CKD. Obesity influences CKD development, among other factors, because it predisposes to diabetic nephropathy, hypertensive nephrosclerosis and focal and segmental glomerulosclerosis. Excess weight and obesity are associated with hemodynamic, structural and histological renal changes, in addition to metabolic and biochemical alterations that lead to kidney disease. Adipose tissue is dynamic and it is involved in the production of "adipokines", such as leptin, adiponectin, tumor necrosis factor-α, monocyte chemoattractant protein-1, transforming growth factor-β and angiotensin-II. A series of events is triggered by obesity, including insulin resistance, glucose intolerance, dyslipidemia, atherosclerosis and hypertension. There is evidence that obesity itself can lead to kidney disease development. Further studies are required to better understand the association between obesity and kidney disease.

  3. Childhood obesity and insulin resistance: how should it be managed?

    Science.gov (United States)

    Ho, Mandy; Garnett, Sarah P; Baur, Louise A

    2014-12-01

    Concomitant with the rise in global pediatric obesity in the past decades, there has been a significant increase in the number of children and adolescents with clinical signs of insulin resistance. Given insulin resistance is the important link between obesity and the associated metabolic abnormalities and cardiovascular risk, clinicians should be aware of high risk groups and treatment options. As there is no universally accepted biochemical definition of insulin resistance in children and adolescents, identification and diagnosis of insulin resistance usually relies on clinical features such as acanthosis nigricans, polycystic ovary syndrome, hypertension, dyslipidemia, and nonalcoholic fatty liver disease. Treatment for reducing insulin resistance and other obesity-associated comorbidities should focus on changes in health behaviors to achieve effective weight management. Lifestyle interventions incorporating dietary change, increased physical activity, and decreased sedentary behaviors, with the involvement of family and adoption of a developmentally appropriate approach, should be used as the first line treatment. Current evidence suggests that the primary objective of dietary interventions should be to reduce total energy intake and a combination of aerobic and resistance training should be encouraged. Metformin can be used in conjunction with a lifestyle intervention program in obese adolescents with clinical insulin resistance to achieve weight loss and to improve insulin sensitivity. Ongoing evaluation and research are required to explore optimal protocol and long-term effectiveness of lifestyle interventions, as well as to determine whether the improvements in insulin sensitivity induced by lifestyle interventions and weight loss will lead to a clinical benefit including reduced cardiovascular morbidity and mortality.

  4. Hypoxic Living and Exercise Training Alter Adipose Tissue Leptin/Leptin Receptor in Rats

    Directory of Open Access Journals (Sweden)

    Yingli Lu

    2016-11-01

    Full Text Available Background: Hypobaric hypoxia results in weight loss in obese individuals, and exercise training is advocated for the treatment of obesity and its related metabolic dysfunctions. The purpose of this study was to investigate the effects of hypoxic living and exercise training on obesity and adipose tissue leptin/leptin receptor in dietary-induced obese rats. Methods: One hundred and thirty high-fat diet fed Sprague-Dawley rats were assigned into one of the following groups (n=10 each: control, sedentary hypoxic living for 1 to 4 weeks (SH1, SH2, SH3, and SH4, living and exercise training in normoxic conditions for 1 to 4 weeks (TN1, TN2, TN3, and TN4, and living and exercise training in hypoxic conditions for 1 to 4 weeks (TN1, TN2, TN3, and TN4. Epididymal adipose tissue expression levels of leptin and leptin receptor were determined. Results: Compared to hypoxic living and living and exercise training in normoxic conditions, living and exercise training in hypoxic conditions for 3-4 weeks resulted in lower Lee index (P<0.05 to P<0.01, and higher expression of leptin and leptin receptor (P<0.05 to P<0.01 in adipose tissue. Conclusion: In a rodent model of altitude training, living and exercise training in hypoxic conditions resulted in greater alterations in obesity and adipose tissue leptin/leptin receptor than hypoxic living alone and living and exercise training in normoxic conditions.

  5. Relationship of serum resistin with insulin resistance and obesity

    International Nuclear Information System (INIS)

    Zaidi, S.I.Z.

    2015-01-01

    Background: Adipokines have been implicated in the modulation of insulin sensitivity and glucose tolerance and have thus gained importance in the study of Type 2 diabetes mellitus (T2DM). Resistin, a unique signalling molecule, is being proposed as a significant factor in the pathogenesis of obesity-related insulin resistance. However, its relevance to human diabetes mellitus remains uncertain and controversial. This study was therefore planned to compare and correlate the potential role of resistin in obese patients with T2DM and obese non-diabetic controls and also to evaluate the correlation between resistin and marker of obesity and glycaemic parameters. Method: Fasting serum resistin, glucose and insulin were measured in forty obese diabetics (mean±SD BMI 35±5 kg/m2) and forty obese non-diabetics (mean±SD BMI 33±3 kg/m2). Insulin resistance was assessed using the HOMA-IR formula derived from fasting insulin and glucose levels. Results: Serum resistin levels (38±8 ng/ml) were significantly higher in type 2 diabetic patients as compared with the controls. Fasting blood glucose (164±46 mg/dl), serum insulin (37±7 μU/ml) and insulin resistance (19±8), were considerably higher among the studied diabetics than in the controls. Pearson's correlation analysis revealed positive correlation between serum resistin and BMI (p=0.001) and HOMA-IR (p=0.561) in diabetic subjects. Similarly, a correlation also existed between serum resistin and BMI (p=0.016) and HOMA-IR (p=0.307) in control obese subjects. However, it was highly significant in diabetics as compared to non-diabetic controls. Conclusion: A significant BMI-dependent association exists between resistin and insulin resistance in patients with T2DM. It appears that resistin may play a role in the pathogenesis of obesity and insulin resistance and that both of these may contribute to the development of T2DM. (author)

  6. Loss of stearoyl-CoA desaturase 1 rescues cardiac function in obese leptin-deficient mice.

    Science.gov (United States)

    Dobrzyn, Pawel; Dobrzyn, Agnieszka; Miyazaki, Makoto; Ntambi, James M

    2010-08-01

    The heart of leptin-deficient ob/ob mice is characterized by pathologic left ventricular hypertrophy along with elevated triglyceride (TG) content, increased stearoyl-CoA desaturase (SCD) activity, and increased myocyte apoptosis. In the present study, using an ob/ob;SCD1(-/-) mouse model, we tested the hypothesis that lack of SCD1 could improve steatosis and left ventricle (LV) function in leptin deficiency. We show that disruption of the SCD1 gene improves cardiac function in ob/ob mice by correcting systolic and diastolic dysfunction without affecting levels of plasma TG and FFA. The improvement is associated with reduced expression of genes involved in FA transport and lipid synthesis in the heart, as well as reduction in cardiac FFA, diacylglycerol, TG, and ceramide levels. The rate of FA beta-oxidation is also significantly lower in the heart of ob/ob;SCD1(-/-) mice compared with ob/ob controls. Moreover, SCD1 deficiency reduces cardiac apoptosis in ob/ob mice due to increased expression of antiapoptotic factor Bcl-2 and inhibition of inducible nitric oxide synthase and caspase-3 activities. Reduction in myocardial lipid accumulation and inhibition of apoptosis appear to be one of the main mechanisms responsible for improved LV function in ob/ob mice caused by SCD1 deficiency.

  7. Skeletal muscle inflammation and insulin resistance in obesity

    Science.gov (United States)

    Wu, Huaizhu; Ballantyne, Christie M.

    2017-01-01

    Obesity is associated with chronic inflammation, which contributes to insulin resistance and type 2 diabetes mellitus. Under normal conditions, skeletal muscle is responsible for the majority of insulin-stimulated whole-body glucose disposal; thus, dysregulation of skeletal muscle metabolism can strongly influence whole-body glucose homeostasis and insulin sensitivity. Increasing evidence suggests that inflammation occurs in skeletal muscle in obesity and is mainly manifested by increased immune cell infiltration and proinflammatory activation in intermyocellular and perimuscular adipose tissue. By secreting proinflammatory molecules, immune cells may induce myocyte inflammation, adversely regulate myocyte metabolism, and contribute to insulin resistance via paracrine effects. Increased influx of fatty acids and inflammatory molecules from other tissues, particularly visceral adipose tissue, can also induce muscle inflammation and negatively regulate myocyte metabolism, leading to insulin resistance. PMID:28045398

  8. Greater effects of high- compared with moderate-intensity interval training on cardio-metabolic variables, blood leptin concentration and ratings of perceived exertion in obese adolescent females

    Directory of Open Access Journals (Sweden)

    G Racil

    2016-04-01

    Full Text Available This study examined the effects of high- vs. moderate-intensity interval training on cardiovascular fitness, leptin levels and ratings of perceived exertion (RPE in obese female adolescents. Forty-seven participants were randomly assigned to one of three groups receiving either a 1:1 ratio of 15 s of effort comprising moderate-intensity interval training (MIIT at 80% maximal aerobic speed: MAS or high-intensity interval training (HIIT at 100% MAS, with matched 15 s recovery at 50% MAS, thrice weekly, or a no-training control group. The HIIT and MIIT groups showed improved (p˂0.05 body mass (BM, BMI Z-score, and percentage of body fat (%BF. Only the HIIT group showed decreased waist circumference (WC (p=0.017. The effect of exercise on maximal oxygen uptake (VO2max was significant (p=0.019, ES=0.48 and p=0.010, ES=0.57, HIIT and MIIT, respectively. The decrease of rate-pressure product (RPP (p<0.05, ES=0.53 and ES=0.46, HIIT and MIIT, respectively followed the positive changes in resting heart rate and blood pressures. Blood glucose, insulin level and the homeostasis model assessment index for insulin decreased (p<0.05 in both training groups. Significant decreases occurred in blood leptin (p=0.021, ES=0.67 and p=0.011, ES=0.73 and in RPE (p=0.001, ES=0.76 and p=0.017, ES=0.57 in HIIT and MIIT, respectively. In the post-intervention period, blood leptin was strongly associated with %BF (p<0.001 and VO2max (p<0.01 in the HIIT and MIIT groups, respectively, while RPE was strongly associated with BM (p<0.01 in the HIIT group. The results suggest that high-intensity interval training may produce more positive effects on health determinants in comparison with the same training mode at a moderate intensity.

  9. The role of leptin in human lipid and glucose metabolism: the effects of acute recombinant human leptin infusion in young healthy males

    DEFF Research Database (Denmark)

    Wolsk, Emil; Mygind, Helene; Grøndahl, Thomas S

    2011-01-01

    Obese and lean humans treated with leptin have not experienced convincing weight-loss results compared with the dramatic weight losses observed in obese rodents.......Obese and lean humans treated with leptin have not experienced convincing weight-loss results compared with the dramatic weight losses observed in obese rodents....

  10. Metabolic syndrome and insulin resistance in obese adolescents

    Directory of Open Access Journals (Sweden)

    Amanda Oliva Gobato

    2014-03-01

    Full Text Available Objective: To verify the prevalence of metabolic syndrome and insulin resistance in obese adolescents and its relationship with different body composition indicators. Methods: A cross-sectional study comprising 79 adolescents aged ten to 18 years old. The assessed body composition indicators were: body mass index (BMI, body fat percentage, abdominal circumference, and subcutaneous fat. The metabolic syndrome was diagnosed according to the criteria proposed by Cook et al. The insulin resistance was determined by the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR index for values above 3.16. The analysis of ROC curves was used to assess the BMI and the abdominal circumference, aiming to identify the subjects with metabolic syndrome and insulin resistance. The cutoff point corresponded to the percentage above the reference value used to diagnose obesity. Results: The metabolic syndrome was diagnosed in 45.5% of the patients and insulin resistance, in 29.1%. Insulin resistance showed association with HDL-cholesterol (p=0.032 and with metabolic syndrome (p=0.006. All body composition indicators were correlated with insulin resistance (p<0.01. In relation to the cutoff point evaluation, the values of 23.5 and 36.3% above the BMI reference point allowed the identification of insulin resistance and metabolic syndrome. The best cutoff point for abdominal circumference to identify insulin resistance was 40%. Conclusions: All body composition indicators, HDL-cholesterol and metabolic syndrome showed correlation with insulin resistance. The BMI was the most effective anthropometric indicator to identify insulin resistance.

  11. Combined aerobic and resistance exercise is effective for achieving weight loss and reducing cardiovascular risk factors without deteriorating bone health in obese young adults

    Directory of Open Access Journals (Sweden)

    Jung Sub Lim

    2013-03-01

    Full Text Available PurposeWeight loss reduces cardiovascular risk factors in the obese. However, weight reduction through diet negatively affects long-term bone health. The aim of study was to determine the ability of combined aerobic and resistance exercise (CE to reduce weight and cardiovascular risk without diminishing bone health.MethodsTwenty-five young adults participated in an 8-week weight loss CE program. Subjects were allocated to an obese group or a control group by body mass index (BMI. Body weight, BMI, body composition, and bone mineral density (BMD of the lumbar spine and total hip were measured before and after the CE trial. Serum levels of metabolic markers, including adipokines and bone markers, were also evaluated.ResultsWeight loss was evident in the obese group after the 8 weeks CE trial. Fat mass was significantly reduced in both groups. Fasting insulin, homeostatic model assessment-insulin resistance (HOMA-IR, leptin and aminotransferases level were significantly reduced from baseline only in the obese group. High density lipoprotein cholesterol increased in both groups. Hip BMD increased in the obese group. In all study subjects, BMI changes were correlated with HOMA-IR, leptin, and HDL changes. BMI decreases were correlated with lumbar spine BMD increases, lumbar spine BMD increases were positively correlated with osteocalcin changes, and lumbar spine bone mineral content increases were correlated negatively with C-terminal telopeptide of type 1 collagen changes.ConclusionThese findings suggest that CE provides effective weight loss and improves cardiovascular risk factors without diminishing BMD. Furthermore, they indicate that lumbar spine BMD might be maintained by increasing bone formation and decreasing bone resorption.

  12. Prevalence of the metabolic syndrome, insulin resistance index, leptin and thyroid hormone levels in the general population of Merida (Venezuela).

    Science.gov (United States)

    Uzcátegui, Euderruh; Valery, Lenin; Uzcátegui, Lilia; Gómez Pérez, Roald; Marquina, David; Baptista, Trino

    2015-06-01

    The metabolic syndrome (MetSyn) is a significant risk factor for cardiovascular events, but scarce information exists about its frequency in Venezuela. In this cross-sectional study, we quantified the prevalence of the MetSyn in a probabilistic, stratified sample of 274 subjects aged > or =18 years from the Libertador district in Merida, Venezuela. Secondary outcomes were the measurement of thyroid hormones (free T4 and TSH), leptin levels, and insulin resistance index (HOMA2-IR). The frequency of MetSyn (percentage +/- 95% confidence interval) according to several diagnostic criteria was as follows: National Cholesterol Education Panel (NCEP, original): 27.4% (22.1-32.7); modified NCEP: 31.8% (26.3-37.3); International Diabetes Federation: 40.9% (35.1-46.7); Latin American Diabetes Association: 27% (21.7-32.3), and Venezuelan criteria: 31.8% (26.3-37.3). The MetSyn was more frequent in males than in females with most diagnostic criteria. The estimated prevalence of type 2 diabetes mellitus was 2.9% either according to the patients' self reports or to fasting glucose level found to be above 126 mg/dL. Abnormal HOMA2-IR index, free T4 and TSH (above the 95th percentile) were detected in 4.5%, 4.4% and 5.1% of the sample, respectively. Free T4 and TSH levels below the 5th percentile were detected in 4.4% and 4.7% of subjects respectively. These values are presented for comparisons with forthcoming studies in specific clinical populations. While studies are being conducted about the different definitions of the MetSyn in Venezuela, we recommend analyzing and publishing local research data with all the available criteria so as to allow comparisons with the results already reported in the literature.

  13. Evidence for Resistance Training as a Treatment Therapy in Obesity

    Directory of Open Access Journals (Sweden)

    Barbara Strasser

    2011-01-01

    Full Text Available Over the last decade, investigators have paid increasing attention to the effects of resistance training (RT on several metabolic syndrome variables. Evidence suggests that skeletal muscle is responsible for up to 40% of individuals' total body weight and may be influential in modifying metabolic risk factors via muscle mass development. Due to the metabolic consequences of reduced muscle mass, it is understood that normal aging and/or decreased physical activity may lead to a higher prevalence of metabolic disorders. The purpose of this review is to (1 evaluate the potential clinical effectiveness and biological mechanisms of RT in the treatment of obesity and (2 provide up-to-date evidence relating to the impact of RT in reducing major cardiovascular disease risk factors (including dyslipidaemia and type 2 diabetes. A further aim of this paper is to provide clinicians with recommendations for facilitating the use of RT as therapy in obesity and obesity-related metabolic disorders.

  14. Total antioxidant and oxidant status in obese children without insulin resistance

    OpenAIRE

    Ayşegül Doğan Demir; Ufuk Erenberk; İlker Tolga Özgen; Emin Özkaya; Aysel Vahapoğlu Türkmen; M. Ruşen Dündaröz; Özcan Erel

    2014-01-01

    Objective: Oxidative stress in obese children may lead in adulthood serious conditions such as coronary heart diseases or type 2 diabetes mellitus. In childhood oxidative stress is associated with insulin resistance or extreme obesity. In this study, we aimed to evaluate oxidative stress status in moderately obese children without insulin resistance. Methods: A total of 38 obese children (21 male, 17 female) without insulin resistance, mean aged 9.4±3.8 years) and 51 normal weight children...

  15. Leptin in pediatrics: A hormone from adipocyte that wheels several functions in children

    Directory of Open Access Journals (Sweden)

    Ashraf T Soliman

    2012-01-01

    Full Text Available The protein leptin, a pleiotropic hormone regulates appetite and energy balance of the body and plays important roles in controlling linear growth, pubertal development, cardiovascular function, and immunity. Recent findings in the understanding of the structure, functional roles, and clinical significance of conditions with increased and decreased leptin secretion are summarized. Balance between leptin and other hormones is significantly regulated by nutritional status. This balance influences many organ systems, including the brain, liver, and skeletal muscle, to mediate the essential adaptation process. The aim of this review is to summarize the possible physiological functions of leptin and its signaling pathways during childhood and adolescence including control of food intake, energy regulation, growth and puberty, and immunity. Moreover, its secretion and possible roles in the adaptation process during different disease states (obesity, malnutrition, eating disorders, delayed puberty, congenital heart diseases and hepatic disorders are discussed. The clinical manifestations and the successful management of patients with genetic leptin deficiency and the application of leptin therapy in other diseases including lipodystrophy, states with severe insulin resistance, and diabetes mellitus are discussed.

  16. Leptin in pediatrics: A hormone from adipocyte that wheels several functions in children

    Science.gov (United States)

    Soliman, Ashraf T.; Yasin, Mohamed; Kassem, Ahmed

    2012-01-01

    The protein leptin, a pleiotropic hormone regulates appetite and energy balance of the body and plays important roles in controlling linear growth, pubertal development, cardiovascular function, and immunity. Recent findings in the understanding of the structure, functional roles, and clinical significance of conditions with increased and decreased leptin secretion are summarized. Balance between leptin and other hormones is significantly regulated by nutritional status. This balance influences many organ systems, including the brain, liver, and skeletal muscle, to mediate the essential adaptation process. The aim of this review is to summarize the possible physiological functions of leptin and its signaling pathways during childhood and adolescence including control of food intake, energy regulation, growth and puberty, and immunity. Moreover, its secretion and possible roles in the adaptation process during different disease states (obesity, malnutrition, eating disorders, delayed puberty, congenital heart diseases and hepatic disorders) are discussed. The clinical manifestations and the successful management of patients with genetic leptin deficiency and the application of leptin therapy in other diseases including lipodystrophy, states with severe insulin resistance, and diabetes mellitus are discussed. PMID:23565493

  17. Cytokines and their association with insulin resistance in obese pregnant women with different levels of physical activity.

    Science.gov (United States)

    Nayak, Minakshi; Eekhoff, Marelise E W; Peinhaupt, Miriam; Heinemann, Akos; Desoye, Gernot; van Poppel, Mireille N M

    2016-01-01

    Cytokines contribute to insulin resistance in pregnancy, but the role of distinct cytokines is not fully understood. To study whether cytokines produced by tissues other than skeletal muscle are associated with glucose and insulin metabolism activity in overweight and obese women and to study whether these associations can be modified by physical activity. A longitudinal study with 44 overweight and obese pregnant women was conducted. Changes in cytokines levels (IFN-γ, IP-10, IL1-α, MIP1-α, adiponectin and leptin) and ICAM1 from early (15wk) to late (32wk) pregnancy were determined. Physical activity was measured objectively with accelerometers. In linear regression models, the associations between (changes in) cytokine levels and fasting glucose, fasting insulin and HOMA-IR were studied. Both IFN-γ and IP-10 levels increased from early to late pregnancy, and adiponectin levels decreased. IFN-γ and IP-10 were positively associated with fasting glucose, whereas IL-1α, ICAM1 and adiponectin were inversely associated with insulin and insulin resistance. The association of IL-1α with insulin and insulin resistance was only found in women with low levels of physical activity. IFN-γ, IP-10, IL1-α, ICAM1, and adiponectin may play a role in glucose and insulin metabolism in pregnancy. The relationship of IL-1α with insulin and insulin resistance might be moderated by levels of physical activity. Further studies are required to confirm the role of these cytokines in glucose and insulin metabolism in obese pregnant women. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Weight-loss changes PPAR expression, reduces atherosclerosis and improves cardiovascular function in obese insulin-resistant mice

    Energy Technology Data Exchange (ETDEWEB)

    Verreth, Wim; Verhamme, Peter; Pelat, Michael; Ganame, Javier; Bielicki, John K.; Mertens, Ann; Quarck, Rozenn; Benhabiles, Nora; Marguerie, Gerard; Mackness, Bharti; Mackness, Mike; Ninio, Ewa; Herregods, Marie-Christine; Balligand, Jean-Luc; Holvoet, Paul

    2003-09-01

    Weight-loss in obese insulin-resistant, but not in insulin-sensitive, persons reduces CHD risk. It is not known to what extent changes in the adipose gene expression profile are important for reducing CHD risk. We studied the effect of diet restriction-induced weight-loss on gene expression in adipose tissue, atherosclerosis and cardiovascular function in mice with combined leptin and LDL-receptor deficiency. Obesity, hypertriglyceridemia and insulin-resistance are associated with hypertension, impaired left ventricle function and accelerated atherosclerosis in those mice. Diet restriction during 12 weeks caused a 45% weight-loss and changes in the gene expression in adipose tissue of PPARa and PPAR? and of key genes regulating glucose transport and insulin sensitivity, lipid metabolism, oxidative stress and inflammation, most of which are under the transcriptional control of PPARs. These changes were associated with increased insulin-sensitivity, decreased hypertriglyceridemia, reduced mean 24-hour blood pressure and heart rate, restored circadian variations of blood pressure and heart rate, increased ejection fraction, and reduced atherosclerosis. Thus, induction of PPARa and PPAR? in adipose tissue is a key mechanism for reducing atherosclerosis and improving cardiovascular function resulting from weight-loss. Our observations point to the critical role of PPARs in the pathogenesis of cardiovascular features of the metabolic syndrome.

  19. Leptin and insulin pathways in POMC and AgRP neurons that modulate energy balance and glucose homeostasis

    Science.gov (United States)

    Varela, Luis; Horvath, Tamas L

    2012-01-01

    With the steady rise in the prevalence of obesity and its associated diseases, research aimed at understanding the mechanisms that regulate and control whole body energy homeostasis has gained new interest. Leptin and insulin, two anorectic hormones, have key roles in the regulation of body weight and energy homeostasis, as highlighted by the fact that several obese patients develop resistance to these hormones. Within the brain, the hypothalamic proopiomelanocortin and agouti-related protein neurons have been identified as major targets of leptin and insulin action. Many studies have attempted to discern the individual contributions of various components of the principal pathways that mediate the central effects of leptin and insulin. The aim of this review is to discuss the latest findings that might shed light on, and lead to a better understanding of, energy balance and glucose homeostasis. In addition, recently discovered targets and mechanisms that mediate hormonal action in the brain are highlighted. PMID:23146889

  20. Leptin and bone mineral density

    DEFF Research Database (Denmark)

    Morberg, Cathrine M.; Tetens, Inge; Black, Eva

    2003-01-01

    Leptin has been suggested to decrease bone mineral density (BMD). This observational analysis explored the relationship between serum leptin and BMD in 327 nonobese men (controls) (body mass index 26.1 +/- 3.7 kg/m(2), age 49.9 +/- 6.0 yr) and 285 juvenile obese men (body mass index 35.9 +/- 5.9 kg...... males, but it also stresses the fact that the strong covariation between the examined variables is a shortcoming of the cross-sectional design....

  1. Role of leptin in reverse epidemiology in chronic kidney disease

    DEFF Research Database (Denmark)

    Scholze, Alexandra; Tepel, Martin

    2007-01-01

    Leptin is mainly produced by adipocytes and metabolized in the kidney. Leptin is taken up into the central nervous system by a saturable transport system, and controls appetite in rodents and in healthy subjects. Leptin acts on peripheral tissue and increases the inflammatory response by stimulat......Leptin is mainly produced by adipocytes and metabolized in the kidney. Leptin is taken up into the central nervous system by a saturable transport system, and controls appetite in rodents and in healthy subjects. Leptin acts on peripheral tissue and increases the inflammatory response......, indicating leptin resistance. In healthy subjects increased leptin concentration constitutes a biomarker for increased cardiovascular risk. On the other hand, a recent prospective long-term study in patients with chronic kidney disease stage 5 on hemodialysis therapy showed that reduced serum leptin...... concentration is an independent risk factor for mortality in these patients....

  2. Can low-level laser therapy (LLLT) associated with an aerobic plus resistance training change the cardiometabolic risk in obese women? A placebo-controlled clinical trial.

    Science.gov (United States)

    Duarte, Fernanda Oliveira; Sene-Fiorese, Marcela; de Aquino Junior, Antonio Eduardo; da Silveira Campos, Raquel Munhoz; Masquio, Deborah Cristina Landi; Tock, Lian; Garcia de Oliveira Duarte, Ana Claudia; Dâmaso, Ana Raimunda; Bagnato, Vanderlei Salvador; Parizotto, Nivaldo Antonio

    2015-12-01

    Obesity is one of the most important link factors to coronary artery disease development mainly due to the pro-inflammatory and pro-thrombotic states favoring atherosclerosis progression. The LLLT acts in the cellular metabolism and it is highly effective to improve inflammation. The same occur in response to different kinds of exercise. However, we have not known the associate effects using LLLT therapies with aerobic plus resistance training as strategy specifically with target at human obesity control and its comorbidities. Investigate the effects of the LLLT associated with aerobic plus resistance training on cardiometabolic risk factors in obese women. Women aged 20-40 years (BMI ≥ 30 kg/m(2)), were divided into 2 groups: Phototherapy (PHOTO) and Placebo. They were trained aerobic plus resistance exercises (in a concurrent mode), 1h, 3 times/week during 16 weeks. Phototherapy was applied after each exercise session for 16 min, with infrared laser, wavelength 808 nm, continuous output, power 100 mW, and energy delivery 50 J. The body composition was measured with bioimpedance. Inflammatory mark concentrations were measured using a commercially available multiplex. LLLT associated with aerobic plus resistance training was effective in decrease neck (P=0.0003) and waist circumferences (P=0.02); percentual of fat (P=0.04); visceral fat area (P=0.02); HOMA-IR (P=0.0009); Leptin (P=0.03) and ICAM (P=0.03). Also, the reduction in leptin (P=0.008) and ICAM-1 (0, 05) was much more expressive in the phototherapy group in comparison to placebo group when analyzed by delta values. LLLT associated with concurrent exercise (aerobic plus resistance training) potentiates the exercise effects of decreasing the cardiometabolic risk factors in obese woman. These results suggest the LLLT associated with exercises as a new therapeutic tool in the control of obesity and its comorbidities for obese people, targeting to optimize the strategies to control the cardiometabolic risk

  3. Leptin, immune responses and autoimmune disease. Perspectives on the use of leptin antagonists.

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    Peelman, F; Iserentant, H; Eyckerman, S; Zabeau, L; Tavernier, J

    2005-01-01

    The pivotal role of leptin in regulating body weight and energy homeostasis is very well established. More recently, leptin also emerged as an important regulator of T-cell-dependent immunity. Reduced leptin levels, as observed during periods of starvation, correlate with an impaired cellular immune response, whereby especially the T(H)1 pro-inflammatory immune response appears to be affected. Physiologically, this could reflect the high energy demand of such processes, which are suppressed in animals or people with nutrient shortage. Several autoimmune diseases are T(H)1 T-cell dependent. In line with a pro-inflammatory role for leptin, animal models of leptin deficiency are markedly resistant to a variety of T-cell dependent autoimmune diseases. Here, we review the role of leptin in immune responses, with emphasis on autoimmune diseases. The design and potential use of leptin antagonists is also discussed.

  4. Reduced anorexigenic efficacy of leptin, but not of the melanocortin receptor agonist melanotan-II, predicts diet-induced obesity in rats

    NARCIS (Netherlands)

    van Dijk, G; de Vries, K; Nyakas, C; Buwalda, B; Adage, T; Kuipers, F; Kas, M.J.H.; Adan, RAH; Wilkinson, CW; Thiele, TE; Scheurink, AJW

    2005-01-01

    Leptin gains access to the central nervous system where it influences activity of neuronal networks involved in ingestive behavior, neuroendocrine activity, and metabolism. In particular, the brain melanocortin (MC) system is important in leptin signaling and maintenance of energy balance. Although

  5. Central infusion of leptin improves insulin resistance and suppresses beta-cell function, but not beta-cell mass, primarily through the sympathetic nervous system in a type 2 diabetic rat model.

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    Park, Sunmin; Ahn, Il Sung; Kim, Da Sol

    2010-06-05

    We investigated whether hypothalamic leptin alters beta-cell function and mass directly via the sympathetic nervous system (SNS) or indirectly as the result of altered insulin resistant states. The 90% pancreatectomized male Sprague Dawley rats had sympathectomy into the pancreas by applying phenol into the descending aorta (SNSX) or its sham operation (Sham). Each group was divided into two sections, receiving either leptin at 300ng/kgbw/h or artificial cerebrospinal fluid (aCSF) via intracerebroventricular (ICV) infusion for 3h as a short-term study. After finishing the infusion study, ICV leptin (3mug/kg bw/day) or ICV aCSF (control) was infused in rats fed 30 energy % fat diets by osmotic pump for 4weeks. At the end of the long-term study, glucose-stimulated insulin secretion and islet morphometry were analyzed. Acute ICV leptin administration in Sham rats, but not in SNSX rats, suppressed the first- and second-phase insulin secretion at hyperglycemic clamp by about 48% compared to the control. Regardless of SNSX, the 4-week administration of ICV leptin improved glucose tolerance during oral glucose tolerance tests and insulin sensitivity at hyperglycemic clamp, compared to the control, while it suppressed second-phase insulin secretion in Sham rats but not in SNSX rats. However, the pancreatic beta-cell area and mass were not affected by leptin and SNSX, though ICV leptin decreased individual beta-cell size and concomitantly increased beta-cell apoptosis in Sham rats. Leptin directly decreases insulin secretion capacity mainly through the activation of SNS without modulating pancreatic beta-cell mass.

  6. Insulin resistance and endocrine-metabolic abnormalities in polycystic ovarian syndrome: Comparison between obese and non-obese PCOS patients.

    Science.gov (United States)

    Layegh, Parvin; Mousavi, Zohreh; Farrokh Tehrani, Donya; Parizadeh, Seyed Mohammad Reza; Khajedaluee, Mohammad

    2016-04-01

    Insulin resistance has an important role in pathophysiology of polycystic ovarian syndrome (PCOS). Yet there are certain controversies regarding the presence of insulin resistance in non-obese patients. The aim was to compare the insulin resistance and various endocrine and metabolic abnormalities in obese and non-obese PCOS women. In this cross-sectional study which was performed from 2007-2010, 115 PCOS patients, aged 16-45 years were enrolled. Seventy patients were obese (BMI ≥25) and 45 patients were non-obese (BMI 2.3) between two groups (p=0.357). Waist circumference (pPCOS patients. There was no significant difference in total testosterone (p=0.634) and androstenedione (p=0.736) between groups whereas Dehydroepiandrotendione sulfate (DHEAS) was significantly higher in non-obese PCOS women (p=0.018). There was no case of fatty liver and metabolic syndrome in non-obese patients, whereas they were seen in 31.3% and 39.4% of obese PCOS women, respectively. Our study showed that metabolic abnormalities are more prevalent in obese PCOS women, but adrenal axis activity that is reflected in higher levels of DHEAS was more commonly pronounced in our non-obese PCOS patients.

  7. [Endocrine function in obesity].

    Science.gov (United States)

    Álvarez-Castro, Paula; Sangiao-Alvarellos, Susana; Brandón-Sandá, Iria; Cordido, Fernando

    2011-10-01

    Obesity is associated to significant disturbances in endocrine function. Hyper insulinemia and insulin resistance are the best known changes in obesity, but their mechanisms and clinical significance are not clearly established. Adipose tissue is considered to be a hormone-secreting endocrine organ; and increased leptin secretion from the adipocyte, a satiety signal, is a well-established endocrine change in obesity. In obesity there is a decreased GH secretion. Impairment of somatotropic function in obesity is functional and may be reversed in certain circumstances. The pathophysiological mechanism responsible for low GH secretion in obesity is probably multifactorial. There are many data suggesting that a chronic state of somatostatin hypersecretion results in inhibition of GH release. Increased FFA levels, as well as a deficient ghrelin secretion, probably contribute to the impaired GH secretion. In women, abdominal obesity is associated to hyperandrogenism and low sex hormone-binding globulin levels. Obese men, particularly those with morbid obesity, have decreased testosterone and gonadotropin levels. Obesity is associated to an increased cortisol production rate, which is compensated for by a higher cortisol clearance, resulting in plasma free cortisol levels that do not change when body weight increases. Ghrelin is the only known circulating orexigenic factor, and has been found to be decreased in obese people. In obesity there is also a trend to increased TSH and free T3 levels. Copyright © 2011 SEEN. Published by Elsevier Espana. All rights reserved.

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

    Science.gov (United States)

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

    2017-06-01

    There are insufficient data regarding the changes in adipokine levels after laparoscopic adjustable gastric banding (LAGB) in diabetic and non-diabetic patients and their effects on insulin resistance and type 2 diabetes remission. To assess leptin, adiponectin, and insulin resistance changes after LAGB in diabetic and non-diabetic morbidly obese patients. One hundred and three patients (37 with and 66 without type 2 diabetes) underwent LAGB from January 2009 to January 2010. Glycated hemoglobin, insulin, adipokine levels and insulin resistance were evaluated preoperatively, and 1 and 4 years after LAGB. The mean patient age was 45.9 ±11.7 years and mean preoperative body mass index was 47.5 ±7.3 kg/m 2 . A total of 80 of 103 patients (77.6%) completed the 4-year follow-up. After 4 years the mean excess weight loss was 38.8% and 39.5% in diabetic and non-diabetic patients respectively. Leptin levels decreased significantly in both groups at 1 year, but after 4 years this was noted only in non-diabetic patients. After 1 year adiponectin levels increased significantly only in non-diabetic patients (p = 0.003) and remained almost the same at 4 years. A significant decrease in insulin resistance was noted in both groups 1 year after LAGB and diabetes remission was observed in 23 (62.1%) patients. There was a negative correlation between preoperative insulin resistance and adiponectin levels throughout the follow-up period. Leptin levels positively correlated with BMI throughout the study period (baseline r = 0.45; p < 0.001; after 1 year r = 0.71; p < 0.001; after 4 years r = 0.68; p < 0.001). There was no significant correlation between leptin and adiponectin concentrations preoperatively or after 1 year; however, at 4 years it was significant (r = 0.27; p < 0.02). The most significant metabolic changes occurred within 1 year after LAGB. The 4-year follow-up revealed stabilization in metabolic indices rather than significant improvement.

  9. Self-administered nicotine differentially impacts body weight gain in obesity-prone and obesity-resistant rats.

    Science.gov (United States)

    Rupprecht, Laura E; Smith, Tracy T; Donny, Eric C; Sved, Alan F

    2017-07-01

    Obesity and tobacco smoking represent the largest challenges to public health, but the causal relationship between nicotine and obesity is poorly understood. Nicotine suppresses body weight gain, a factor impacting smoking initiation and the failure to quit, particularly among obese smokers. The impact of nicotine on body weight regulation in obesity-prone and obesity-resistant populations consuming densely caloric diets is unknown. In the current experiment, body weight gain of adult male rats maintained on a high energy diet (31.8% kcal from fat) distributed into obesity-prone (OP), obesity-resistant (OR) and an intermediate group, which was placed on standard rodent chow (Chow). These rats were surgically implanted with intravenous catheters and allowed to self-administer nicotine (0 or 60μg/kg/infusion, a standard self-administration dose) in 1-h sessions for 20 consecutive days. Self-administered nicotine significantly suppressed body weight gain but not food intake in OP and Chow rats. Self-administered nicotine had no effect on body weight gain in OR rats. These data suggest that: 1) OR rats are also resistant to nicotine-induced suppression of body weight gain; and 2) nicotine may reduce levels of obesity in a subset of smokers prone to obesity. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. The Effects of Leptin on Breastfeeding Behaviour

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    Anna M. Cannon

    2015-09-01

    Full Text Available Breastfed infants have a reduced risk of becoming overweight and/or obese later in life. This protective effect has been partly attributed to leptin present in breastmilk. This study investigated 24-h variations of skim milk leptin and its relationship with breastmilk macronutrients and infant breastfeeding patterns. Exclusive breastfeeding mothers of term singletons (n = 19; age 10 ± 5 weeks collected pre- and post-feed breastmilk samples for every breastfeed over a 24-h period and test-weighed their infants to determine milk intake at every breastfeed over a 24-h period. Samples (n = 454 were analysed for leptin, protein, lactose and fat content. Skim milk leptin concentration did not change with feeding (p = 0.184. However, larger feed volumes (>105 g were associated with a decrease in post-feed leptin levels (p = 0.009. There was no relationship between the change in leptin levels and change in protein (p = 0.313 or lactose levels (p = 0.587 between pre- and post-feed milk, but there was a trend for a positive association with changes in milk fat content (p = 0.056. Leptin concentration significantly increased at night (p < 0.001 indicating a possible 24-h pattern. Leptin dose (ng was not associated with the time between feeds (p = 0.232. Further research should include analysis of whole breastmilk and other breastmilk fractions to extend these findings.

  11. Efeitos do exercício crônico sobre a concentração circulante da leptina e grelina em ratos com obesidade induzida por dieta Effects of the chronic exercise on the circulating concentration of leptin and ghrelin in rats With diet-induced obesity

    Directory of Open Access Journals (Sweden)

    Ricardo Eguchi

    2008-06-01

    Full Text Available A obesidade vem se tornando uma das maiores epidemias mundiais, dessa forma, conhecer sua etiologia e mecanismos que regulam seu desenvolvimento é de grande relevância para o seu Tratamento. Portanto, o objetivo do presente estudo foi avaliar os efeitos da obesidade exógena induzida pela dieta de cafeteria e da atividade física crônica em ratos, sobre a adiposidade e a concentração sérica dos hormônios reguladores do balanço energético (leptina e grelina. Foram utilizados 32 ratos Wistar machos, divididos em quatro grupos: Sedentário alimentado com dieta padrão (SN, sedentário alimentado com dieta de cafeteria (SC, treinado alimentado com dieta padrão (TN e treinado alimentado com dieta de cafeteria (TC. A dieta de cafeteria aumentou significativamente a adiposidade central (RET e visceral (EPI (pObesity is becoming one of the biggest worldwide epidemics. Therefore, knowing its etiology and mechanisms that regulate its development is of great relevance for its treatment. Thus, the aim of the present study was to evaluate the effects of obesity induced by the palatable hyperlipidic diet and of the chronic physical activity in rats, on the adiposity and the serum concentration of regulating hormones of the energy balance (leptin and ghrelin. 32 male Wistar rats were divided in four groups: Sedentary fed with chow diet (SN, sedentary fed with cafeteria diet (SC, trained fed with chow diet (TN and trained fed with cafeteria diet (TC. The cafeteria diet led to a significant increase of central (RET and visceral (EPI adiposity (p<0.05. Conversely,the exercise training minimized the effect of the cafeteria diet, diminishing the central and visceral adiposity. Leptin was also increased in the groups fed with the cafeteria diet, suggesting increase of the resistance to the action of this hormone. Chronic physical activity did not hinder the development of hyperleptinemia. Reduction in the serum ghrelin concentration was observed only in

  12. Resistant starch lowers postprandial glucose and leptin in overweight adults consuming a moderate-to-high-fat diet: a randomized-controlled trial.

    Science.gov (United States)

    Maziarz, Mindy Patterson; Preisendanz, Sara; Juma, Shanil; Imrhan, Victorine; Prasad, Chandan; Vijayagopal, Parakat

    2017-02-21

    High-amylose maize resistant starch type 2 (HAM-RS2) stimulates gut-derived satiety peptides and reduces adiposity in animals. Human studies have not supported these findings despite improvements in glucose homeostasis and insulin sensitivity after HAM-RS2 intake which can lower adiposity-related disease risk. The primary objective of this study was to evaluate the impact of HAM-RS2 consumption on blood glucose homeostasis in overweight, healthy adults. We also examined changes in biomarkers of satiety (glucagon-like peptide-1 [GLP-1], peptide YY [PYY], and leptin) and body composition determined by anthropometrics and dual-energy x-ray absorptiometry, dietary intake, and subjective satiety measured by a visual analogue scale following HAM-RS2 consumption. Using a randomized-controlled, parallel-arm, double-blind design, 18 overweight, healthy adults consumed either muffins enriched with 30 g HAM-RS2 (n = 11) or 0 g HAM-RS2 (control; n = 7) daily for 6 weeks. The HAM-RS2 and control muffins were similar in total calories and available carbohydrate. At baseline, total PYY concentrations were significantly higher 120 min following the consumption of study muffins in the HAM-RS2 group than control group (P = 0.043). Within the HAM-RS2 group, the area under the curve (AUC) glucose (P = 0.028), AUC leptin (P = 0.022), and postprandial 120-min leptin (P = 0.028) decreased independent of changes in body composition or overall energy intake at the end of 6 weeks. Fasting total PYY increased (P = 0.033) in the HAM-RS2 group, but changes in insulin or total GLP-1 were not observed. Mean overall change in subjective satiety score did not correlate with mean AUC biomarker changes suggesting the satiety peptides did not elicit a satiation response or change in overall total caloric intake. The metabolic response from HAM-RS2 occurred despite the habitual intake of a moderate-to-high-fat diet (mean range 34.5% to 39.4% of total calories). Consuming 30

  13. Endothelial function and its relationship to leptin, homocysteine, and insulin resistance in lean and overweight eumenorrheic women and PCOS patients: a pilot study.

    Science.gov (United States)

    Mancini, Fulvia; Cianciosi, Arianna; Reggiani, Giulio Marchesini; Facchinetti, Fabio; Battaglia, Cesare; de Aloysio, Domenico

    2009-06-01

    To verify if patients with polycystic ovarian syndrome (PCOS), have an increased cardiovascular risk compared with healthy controls. Prospective case-control study. University-based practice. Twenty eumenorrheic controls (ten lean [group A] and ten overweight [group B]) and 24 PCOS women (14 lean [group C] and ten overweight [group D]). Cardiovascular risk markers and hormonal parameters were assessed. Androgens, fasting glucose, insulin, leptin, fibrinogen, homocysteine, endothelin-1 and flow-mediated dilatation of the brachial artery were measured to investigate their relationship to weight and to PCOS. The brachial artery diameter and the pulsatility index, after the reactive hyperemia, showed in group A the most intense vasodilatation compared with the other groups. Homocysteine levels did not differ among the groups. Endothelin-1 was significantly higher in group A compared with groups B and D. Leptin was significantly lower in groups A and C compared with groups B and D. Insulin resistance was higher in groups B and D. Group A had significantly higher glucose-insulin ratio compared with all of the other groups; group C had significantly higher glucose-insulin ratio only compared with group D. Weight and PCOS are two independent variables affecting the endothelial function.

  14. Taurine ameliorates hyperglycemia and dyslipidemia by reducing insulin resistance and leptin level in Otsuka Long-Evans Tokushima fatty (OLETF) rats with long-term diabetes

    Science.gov (United States)

    Oh, Da Hee; Kim, Jung Yeon; Lee, Bong Gn; You, Jeong Soon; Chang, Kyung Ja; Chung, Hyunju; Yoo, Myung Chul; Yang, Hyung-In; Kang, Ja-Heon; Hwang, Yoo Chul; Ahn, Kue Jeong; Chung, Ho-Yeon

    2012-01-01

    This study aimed to determine whether taurine supplementation improves metabolic disturbances and diabetic complications in an animal model for type 2 diabetes. We investigated whether taurine has therapeutic effects on glucose metabolism, lipid metabolism, and diabetic complications in Otsuka Long-Evans Tokushima fatty (OLETF) rats with long-term duration of diabetes. Fourteen 50-week-old OLETF rats with chronic diabetes were fed a diet supplemented with taurine (2%) or a non-supplemented control diet for 12 weeks. Taurine reduced blood glucose levels over 12 weeks, and improved OGTT outcomes at 6 weeks after taurine supplementation, in OLETF rats. Taurine significantly reduced insulin resistance but did not improve β-cell function or islet mass. After 12 weeks, taurine significantly decreased serum levels of lipids such as triglyceride, cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol. Taurine significantly reduced serum leptin, but not adiponectin levels. However, taurine had no therapeutic effect on damaged tissues. Taurine ameliorated hyperglycemia and dyslipidemia, at least in part, by improving insulin sensitivity and leptin modulation in OLETF rats with long-term diabetes. Additional study is needed to investigate whether taurine has the same beneficial effects in human diabetic patients. PMID:23114424

  15. Leptin regulates bone formation via the sympathetic nervous system

    Science.gov (United States)

    Takeda, Shu; Elefteriou, Florent; Levasseur, Regis; Liu, Xiuyun; Zhao, Liping; Parker, Keith L.; Armstrong, Dawna; Ducy, Patricia; Karsenty, Gerard

    2002-01-01

    We previously showed that leptin inhibits bone formation by an undefined mechanism. Here, we show that hypothalamic leptin-dependent antiosteogenic and anorexigenic networks differ, and that the peripheral mediators of leptin antiosteogenic function appear to be neuronal. Neuropeptides mediating leptin anorexigenic function do not affect bone formation. Leptin deficiency results in low sympathetic tone, and genetic or pharmacological ablation of adrenergic signaling leads to a leptin-resistant high bone mass. beta-adrenergic receptors on osteoblasts regulate their proliferation, and a beta-adrenergic agonist decreases bone mass in leptin-deficient and wild-type mice while a beta-adrenergic antagonist increases bone mass in wild-type and ovariectomized mice. None of these manipulations affects body weight. This study demonstrates a leptin-dependent neuronal regulation of bone formation with potential therapeutic implications for osteoporosis.

  16. Traumatic brain injury and obesity induce persistent central insulin resistance.

    Science.gov (United States)

    Karelina, Kate; Sarac, Benjamin; Freeman, Lindsey M; Gaier, Kristopher R; Weil, Zachary M

    2016-04-01

    Traumatic brain injury (TBI)-induced impairments in cerebral energy metabolism impede tissue repair and contribute to delayed functional recovery. Moreover, the transient alteration in brain glucose utilization corresponds to a period of increased vulnerability to the negative effects of a subsequent TBI. In order to better understand the factors contributing to TBI-induced central metabolic dysfunction, we examined the effect of single and repeated TBIs on brain insulin signalling. Here we show that TBI induced acute brain insulin resistance, which resolved within 7 days following a single injury but persisted until 28 days following repeated injuries. Obesity, which causes brain insulin resistance and neuroinflammation, exacerbated the consequences of TBI. Obese mice that underwent a TBI exhibited a prolonged reduction of Akt (also known as protein kinase B) signalling, exacerbated neuroinflammation (microglial activation), learning and memory deficits, and anxiety-like behaviours. Taken together, the transient changes in brain insulin sensitivity following TBI suggest a reduced capacity of the injured brain to respond to the neuroprotective and anti-inflammatory actions of insulin and Akt signalling, and thus may be a contributing factor for the damaging neuroinflammation and long-lasting deficits that occur following TBI. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  17. Treatment with constitutive androstane receptor ligand during pregnancy prevents insulin resistance in offspring from high-fat diet-induced obese pregnant mice.

    Science.gov (United States)

    Masuyama, Hisashi; Hiramatsu, Yuji

    2012-07-15

    The constitutive androstane receptor (CAR) has been reported to decrease insulin resistance even during pregnancy, while exposure to a high-fat diet (HFD) in utero in mice can induce a type 2 diabetes phenotype that can be transmitted to the progeny. Therefore, we examined whether treatment with a CAR ligand during pregnancy could prevent hypertension, insulin resistance, and hyperlipidemia in the offspring from HFD-induced obese pregnant mice (OH mice). We employed four groups of offspring from HFD-fed and control diet-fed pregnant mice with or without treatment with a CAR ligand. Treatment with a CAR ligand during pregnancy improved glucose tolerance and the levels of triglyceride and adipocytokine and restored the changes induced by HFD with amelioration of hypertension in the adult OH mice. This treatment also increased adiponectin mRNA expression, suppressed leptin expression in adipose tissues of OH mice, and abolished the effect of HFD on the epigenetic modifications of the genes encoding adiponectin and leptin in the offspring during immaturity and adulthood. Our data suggest that CAR might be a potential therapeutic target to prevent metabolic syndrome in adulthood of offspring exposed to an HFD in utero.

  18. Central leptin gene therapy ameliorates diabetes type 1 and 2 through two independent hypothalamic relays; a benefit beyond weight and appetite regulation.

    Science.gov (United States)

    Kalra, Satya P

    2009-10-01

    Although its role in energy homeostasis is firmly established, the evidence accumulated over a decade linking the adipocyte leptin-hypothalamus axis in the pathogenesis of diabetes mellitus has received little attention in the contemporary thinking. In this context various lines of evidence are collated here to show that (1) under the direction of leptin two independent relays emanating from the hypothalamus restrain insulin secretion from the pancreas and mobilize peripheral organs--liver, skeletal muscle and brown adipose tissue--to upregulate glucose disposal, and (2), leptin insufficiency in the hypothalamus produced by either leptinopenia or restriction of leptin transport across the blood brain barrier due to hyperleptinemia of obesity and aging, initiate antecedent pathophysiological sequalae of diabetes type 1 and 2. Further, we document here the efficacy of leptin replenishment in vivo, especially by supplying it to the hypothalamus with the aid of gene therapy, in preventing the antecedent pathophysiological sequalae--hyperinsulinemia, insulin resistance and hyperglycemia--in various animal models and clinical paradigms of diabetes type 1 and 2 with or without attendant obesity. Overall, the new insights on the long-lasting antidiabetic potential of two independent hypothalamic relays engendered by central leptin gene therapy and the preclinical safety indicators in rodents warrant further validation in subhuman primates and humans.

  19. Exposure to a high-fat diet alters leptin sensitivity and elevates renal sympathetic nerve activity and arterial pressure in rabbits.

    Science.gov (United States)

    Prior, Larissa J; Eikelis, Nina; Armitage, James A; Davern, Pamela J; Burke, Sandra L; Montani, Jean-Pierre; Barzel, Benjamin; Head, Geoffrey A

    2010-04-01

    The activation of the sympathetic nervous system through the central actions of the adipokine leptin has been suggested as a major mechanism by which obesity contributes to the development of hypertension. However, direct evidence for elevated sympathetic activity in obesity has been limited to muscle. The present study examined the renal sympathetic nerve activity and cardiovascular effects of a high-fat diet (HFD), as well as the changes in the sensitivity to intracerebroventricular leptin. New Zealand white rabbits fed a 13.5% HFD for 4 weeks showed modest weight gain but a 2- to 3-fold greater accumulation of visceral fat compared with control rabbits. Mean arterial pressure, heart rate, and plasma norepinephrine concentration increased by 8%, 26%, and 87%, respectively (Pdiet rabbits and was correlated to plasma leptin (r=0.87; Pfat accumulation through consumption of a HFD leads to marked sympathetic activation, which is related to increased responsiveness to central sympathoexcitatory effects of leptin. The paradoxical reduction in hypothalamic neuronal activation by leptin suggests a marked "selective leptin resistance" in these animals.

  20. Leptin and insulin up-regulate miR-4443 to suppress NCOA1 and TRAF4, and decrease the invasiveness of human colon cancer cells

    International Nuclear Information System (INIS)

    Meerson, Ari; Yehuda, Hila

    2016-01-01

    Obesity is a risk factor for colorectal cancer (CRC). Normal and tumor cells respond to metabolic hormones, such as leptin and insulin. Thus, obesity-associated resistance to these hormones likely leads to changes in gene expression and behavior of tumor cells. However, the mechanisms affected by leptin and insulin signaling in CRC cells remain mostly unknown. We hypothesized that microRNAs (miRNAs) are involved in the regulation of tumorigenesis-related gene expression in CRC cells by leptin and insulin. To test this hypothesis, miRNA levels in the CRC-derived cell lines HCT-116, HT-29 and DLD-1 were profiled, following leptin and insulin treatment. Candidate miRNAs were validated by RT-qPCR. Predicted miRNA targets with known roles in cancer, were validated by immunoblots and reporter assays in HCT-116 cells. Transfection of HCT-116 cells with candidate miRNA mimic was used to test in vitro effects on proliferation and invasion. Of ~800 miRNAs profiled, miR-4443 was consistently up-regulated by leptin and insulin in HCT-116 and HT-29, but not in DLD-1, which lacked normal leptin receptor expression. Dose response experiments showed that leptin at 100 ng/ml consistently up-regulated miR-4443 in HCT-116 cells, concomitantly with a significant decrease in cell invasion ability. Transfection with miR-4443 mimic decreased invasion and proliferation of HCT-116 cells. Moreover, leptin and miR-4443 transfection significantly down-regulated endogenous NCOA1 and TRAF4, both predicted targets of miR-4443 with known roles in cancer metastasis. miR-4443 was found to directly regulate TRAF4 and NCOA1, as validated by a reporter assay. The up-regulation of miR-4443 by leptin or insulin was attenuated by the inhibition of MEK1/2. Our findings suggest that miR-4443 acts in a tumor-suppressive manner by down-regulating TRAF4 and NCOA1 downstream of MEK-C/EBP-mediated leptin and insulin signaling, and that insulin and/or leptin resistance (e.g. in obesity) may suppress this pathway

  1. Leptin and its cardiovascular effects: Focus on angiogenesis

    Directory of Open Access Journals (Sweden)

    Zoya Tahergorabi

    2015-01-01

    Full Text Available Leptin is an endocrine hormone synthesized by adipocytes. It plays a key role in the energy homeostasis in central and peripheral tissues and has additional roles are attributed to it, such as the regulation of reproduction, immune function, bone homeostasis, and angiogenesis. The plasma concentration of leptin significantly increases in obese individuals. In the present review, we give an introduction concerning leptin, its receptors, signaling pathways, and its effect on cardiovascular system, especially on angiogenesis.

  2. Hypothalamic Leptin Gene Therapy Reduces Bone Marrow Adiposity in ob/ob Mice Fed Regular and High Fat Diets

    Directory of Open Access Journals (Sweden)

    Laurence B Lindenmaier

    2016-08-01

    Full Text Available Low bone mass is often associated with increased bone marrow adiposity. Since osteoblasts and adipocytes are derived from the same mesenchymal stem cell progenitor, adipocyte formation may increase at the expense of osteoblast formation. Leptin is an adipocyte-derived hormone known to regulate energy and bone metabolism. Genetic (e.g., leptin deficiency and high fat diet-induced (e.g., leptin resistance obesity are associated with increased marrow adipose tissue (MAT and reduced bone formation. Short-duration studies suggest that leptin treatment reduces MAT and increases bone formation in leptin-deficient ob/ob mice fed a regular diet. Here, we determined the long-duration impact of increased hypothalamic leptin on marrow adipocytes and osteoblasts in ob/ob mice using recombinant adeno-associated virus (rAAV gene therapy. In a first study, eight- to ten-week-old male ob/ob mice were randomized into 4 groups: (1 untreated, (2 rAAV-Lep, (3 rAAV-green fluorescent protein (rAAV-GFP, or (4 pair-fed to rAAV-Lep. For vector administration, mice were placed in a Kopf stereotaxic apparatus, and injected intracerebroventricularly with either rAAV-Lep or rAAV-GFP (9 × 107 particles in 1.5 µl. The mice were maintained for 30 weeks following vector administration. In a second study, the impact of increased hypothalamic leptin levels on MAT was determined in mice fed high fat diets. Eight- to ten-week-old male ob/ob mice were randomized into 2 groups and treated with either rAAV-Lep or rAAV-GFP. At 7 weeks post-vector administration, half the mice in each group were switched to a high fat diet for 8 weeks. Wild type (WT controls included age-matched mice fed regular or high fat diet. Hypothalamic leptin gene therapy increased osteoblast perimeter and osteoclast perimeter with minor change in cancellous bone architecture. The gene therapy decreased MAT levels in ob/ob mice fed regular or high fat diet to values similar to WT mice fed regular diet. These

  3. Insulin resistance in obesity can be reliably identified from fasting plasma insulin.

    Science.gov (United States)

    ter Horst, K W; Gilijamse, P W; Koopman, K E; de Weijer, B A; Brands, M; Kootte, R S; Romijn, J A; Ackermans, M T; Nieuwdorp, M; Soeters, M R; Serlie, M J

    2015-12-01

    Insulin resistance is the major contributor to cardiometabolic complications of obesity. We aimed to (1) establish cutoff points for insulin resistance from euglycemic hyperinsulinemic clamps (EHCs), (2) identify insulin-resistant obese subjects and (3) predict insulin resistance from routinely measured variables. We assembled data from non-obese (n=112) and obese (n=100) men who underwent two-step EHCs using [6,6-(2)H2]glucose as tracer (insulin infusion dose 20 and 60 mU m(-2) min(-1), respectively). Reference ranges for hepatic and peripheral insulin sensitivity were calculated from healthy non-obese men. Based on these reference values, obese men with preserved insulin sensitivity or insulin resistance were identified. Cutoff points for insulin-mediated suppression of endogenous glucose production (EGP) and insulin-stimulated glucose disappearance rate (Rd) were 46.5% and 37.3 μmol kg(-)(1) min(-)(1), respectively. Most obese men (78%) had EGP suppression within the reference range, whereas only 12% of obese men had Rd within the reference range. Obese men with Rd obese men in age, body mass index (BMI), body composition, fasting glucose or cholesterol, but did have higher fasting insulin (110±49 vs 63±29 pmol l(-1), Pobese men could be identified with good sensitivity (80%) and specificity (75%) from fasting insulin >74 pmol l(-1). Most obese men have hepatic insulin sensitivity within the range of non-obese controls, but below-normal peripheral insulin sensitivity, that is, insulin resistance. Fasting insulin (>74 pmol l(-1) with current insulin immunoassay) may be used for identification of insulin-resistant (or metabolically unhealthy) obese men in research and clinical settings.

  4. Hepatocyte Toll-like receptor 4 regulates obesity-induced inflammation and insulin resistance

    Science.gov (United States)

    Chronic low-grade inflammation is a hallmark of obesity and thought to contribute to the development of obesity-related insulin resistance. Toll-like receptor 4 (Tlr4) is a key mediator of pro-inflammatory responses. Mice lacking Tlr4s are protected from diet-induced insulin resistance and inflammat...

  5. 20 years of leptin: leptin and reproduction: past milestones, present undertakings, and future endeavors.

    Science.gov (United States)

    Chehab, Farid F

    2014-10-01

    The association between leptin and reproduction originated with the leptin-mediated correction of sterility in ob/ob mice and initiation of reproductive function in normal female mice. The uncovering of a central leptin pathway regulating food intake prompted the dissection of neuroendocrine mechanisms involving leptin in the metabolic control of reproduction. The absence of leptin receptors on GnRH neurons incited a search for intermediary neurons situated between leptin-responsive and GnRH neurons. This review addresses the most significant findings that have furthered our understanding of recent progress in this new field. The role of leptin in puberty was impacted by the discovery of neurons that co-express kisspeptin, neurokinin B, and dynorphin and these could act as leptin intermediates. Furthermore, the identification of first-order leptin-responsive neurons in the premammilary ventral nucleus and other brain regions opens new avenues to explore their relationship to GnRH neurons. Central to these advances is the unveiling that agouti-related protein/neuropeptide Y neurons project onto GnRH and kisspeptin neurons, allowing for a crosstalk between food intake and reproduction. Finally, while puberty is a state of leptin sensitivity, mid-gestation represents a state of leptin resistance aimed at building energy stores to sustain pregnancy and lactation. The mechanisms underlying leptin resistance in pregnancy have lagged; however, the establishment of this natural state is significant. Reproduction and energy balance are tightly controlled and backed up by redundant mechanisms that are critical for the survival of our species. It will be the goal of the following decade to shed new light on these complex and essential pathways. © 2014 Society for Endocrinology.

  6. Centrally administered urocortin 2 decreases gorging on high-fat diet in in both diet induced obesity-prone and -resistant rats

    Science.gov (United States)

    Cottone, Pietro; Sabino, Valentina; Nagy, Tim R.; Coscina, Donald V.; Levin, Barry E.; Zorrilla, Eric P.

    2013-01-01

    Objective Obesity is a costly, deadly public health problem for which new treatments are needed. Individual differences in meal pattern have been proposed to play a role in obesity risk. The present study tested the hypothesis that i) the microstructure of chronic high-fat diet intake differs between genetically selected Diet-Induced Obesity (DIO) and Diet Resistant (DR) rats, and ii) central administration of urocortin 2 (Ucn 2), a corticotropin-releasing factor type 2 (CRF2) agonist, decreases high-fat diet intake not only in lean DR rats, but also in obese DIO rats. Design Male, selectively bred DIO and DR rats (n=10/genotype) were chronically fed a high-fat diet. Food and water intake as well as ingestion microstructure were then compared under baseline conditions and following third intracerebroventricular injection of Ucn 2 (0, 0.1, 0.3, 1, 3 µg). Results Irrespective of genotype, Ucn 2 reduced nocturnal food intake with a minimum effective dose of 0.3 µg, suppressing high-fat diet intake by ~40% at the 3 µg dose. Ucn 2 also made rats of both genotypes eat smaller and briefer meals, including at doses that did not reduce drinking. Obese DIO rats ate fewer but larger meals than DR rats, which they ate more quickly and consumed with 2/3rd less water. Conclusions Unlike leptin and insulin, Ucn 2 retains its full central anorectic efficacy to reduce high-fat diet intake even in obese, genetically-prone DIO rats, which otherwise show a “gorging” meal pattern. These results open new opportunities of investigation towards treating some forms of diet-induced obesity. PMID:23478425

  7. Hypothalamic leptin action is mediated by histone deacetylase 5

    DEFF Research Database (Denmark)

    Kabra, Dhiraj G; Pfuhlmann, Katrin; García-Cáceres, Cristina

    2016-01-01

    Hypothalamic leptin signalling has a key role in food intake and energy-balance control and is often impaired in obese individuals. Here we identify histone deacetylase 5 (HDAC5) as a regulator of leptin signalling and organismal energy balance. Global HDAC5 KO mice have increased food intake and...

  8. Reversal of obesity and insulin resistance by a non-peptidic glucagon-like peptide-1 receptor agonist in diet-induced obese mice.

    Directory of Open Access Journals (Sweden)

    Min He

    Full Text Available BACKGROUND: Glucagon-like peptide-1 (GLP-1 is recognized as an important regulator of glucose homeostasis. Efforts to utilize GLP-1 mimetics in the treatment of diabetes have yielded clinical benefits. A major hurdle for an effective oral therapy has been the difficulty of finding a non-peptidic GLP-1 receptor (GLP-1R agonist. While its oral bioavailability still poses significant challenges, Boc5, one of the first such compounds, has demonstrated the attainment of GLP-1R agonism in diabetic mice. The present work was to investigate whether subchronic Boc5 treatment can restore glycemic control and induce sustainable weight loss in diet-induced obese (DIO mice, an animal model of human obesity and insulin resistance. METHODOLOGY/PRINCIPAL FINDINGS: DIO mice were treated three times a week with Boc5 (0.3, 1 and 3 mg for 12 weeks. Body weight, body mass index (BMI, food intake, fasting glucose, intraperitoneal glucose tolerance and insulin induced glucose clearance were monitored regularly throughout the treatment. Glucose-stimulated insulin secretion, β-cell mass, islet size, body composition, serum metabolic profiles, lipogenesis, lipolysis, adipose hypertrophy and lipid deposition in the liver and muscle were also measured after 12 weeks of dosing. Boc5 dose-dependently reduced body weight, BMI and food intake in DIO mice. These changes were associated with significant decreases in fat mass, adipocyte hypertrophy and peripheral tissue lipid accumulation. Boc5 treatment also restored glycemic control through marked improvement of insulin sensitivity and normalization of β-cell mass. Administration of Boc5 (3 mg reduced basal but enhanced insulin-mediated glucose incorporation and noradrenaline-stimulated lipolysis in isolated adipocytes from obese mice. Furthermore, circulating leptin, adiponectin, triglyceride, total cholesterol, nonesterified fatty acid and high-density lipoprotein/low-density lipoprotein ratio were normalized to various

  9. Adipocytokines, neuropeptide Y and insulin resistance in overweight women with gynoid and android type of adipose tissue distribution.

    Science.gov (United States)

    Orbetzova, Maria M; Koleva, Daniela I; Mitkov, Mitko D; Atanassova, Iliana B; Nikolova, Julia G; Atanassova, Pepa K; Genchev, Gencho D

    2012-01-01

    The AIM of the study was to compare the levels of certain adipose tissue hormones in women with the two main morphological types of obesity - android and gynoid obesity. The study included 2 groups of age- and weight-matched women with android (n = 32) and gynoid (n = 27) type of obesity, and a group of age-matched healthy women (n = 24) with normal weight and body constitution. Leptin, resistin, tumour necrosis factor alpha (TNFalpha), neuropeptide Y (NPY), glucose and insulin were measured. HOMA index was calculated. Leptin levels in the women with gynoid obesity did not differ significantly from those in the controls and the women with android obesity. The controls had significantly lower leptin levels compared with the android obesity women. NPY was significantly higher in the control women compared to the women with android obesity and did not differ significantly between the two groups of obese women. TNFalpha levels in all groups were very similar. Resistin did not show significant differences between all groups but tended to have the lowest levels in the controls. In the women with android obesity, insulin was significantly higher than that in the women with gynoid obesity and the controls. Insulin resistance was found in the women with android obesity only. Basal insulin and HOMA index in the women with gynoid obesity did not differ significantly from the values in the control group. The results from this study contribute to understanding the association of adipose tissue hormones and insulin resistance in obesity. When adipose tissue is predominantly distributed in the abdominal area at similar amount and percentage of body fats, leptin production is higher and insulin resistance develops. In the gynoid type of adipose tissue predisposition, overt insulin resistance is not found, leptin levels does not differ significantly from those in the control group.

  10. Expression of the central obesity and Type 2 Diabetes mellitus genes is associated with insulin resistance in young obese children.

    Science.gov (United States)

    Skoczen, S; Wojcik, M; Fijorek, K; Siedlar, M; Starzyk, J B

    2015-04-01

    The assessment of the health consequences associated with obesity in young children is challenging. The aims of this study were: (1) to compare insulin resistance indices derived from OGTT in obese patients and healthy control (2) to analyze central obesity and Type 2 Diabetes genes expression in obese children, with special attention to the youngest group (10 years old). The study included 49 children with obesity (median age 13.5 years old), and 25 healthy peers. Biochemical blood tests and expression of 11 central obesity and 33 Type 2 Diabetes genes was assessed. A significant difference in insulin resistance between obese and non-obese adolescents was observed in all studied indices (mean values of the insulin levels: 24.9 vs. 9.71 mIU/L in T0, 128 vs. 54.7 mIU/L in T60 and 98.7 vs. 41.1 mIU/L in T120 respectively; AUC: 217 vs. 77.2 ng/ml*h, mean values of B% (state beta cell function), S% (insulin sensitivity), and IR were 255 (±97) vs. 135 (±37.8), 46.6 (±37.3) vs. 84.2 (±29.6) and 3 (±1.55) vs. 1.36 (±0,56); HIS, WBIS and ISIBel median 3.89, 44.7, 0.73 vs. 8.57, 110, 2.25. All comparisons differed significantly p1). Moreover, insulin sensitivity was significantly better in the older obese group (>10 years old): median AUC 239 vs. 104 ng/ml*h, and HIS, WBIS and ISIBel 3.57, 38, 0.67 vs. 6.23, 75.6, 1.87 respectively in the obese older compared to the obese younger subgroup, pobesity genes and 70% of Type 2 Diabetes genes was higher in the obese compared to control groups. The differences were more pronounced in the younger obese group. Insulin resistance may develop in early stage of childhood obesity and in very young children may be associated with higher expression of the central obesity and Type 2 Diabetes genes. © Georg Thieme Verlag KG Stuttgart · New York.

  11. Adipocyte Versus Pituitary Leptin in the Regulation of Pituitary Hormones: Somatotropes Develop Normally in the Absence of Circulating Leptin

    Science.gov (United States)

    Odle, Angela K.; Haney, Anessa; Allensworth-James, Melody; Akhter, Noor

    2014-01-01

    Leptin is a cytokine produced by white fat cells, skeletal muscle, the placenta, and the pituitary gland among other tissues. Best known for its role in regulating appetite and energy expenditure, leptin is produced largely by and in proportion to white fat cells. Leptin is also important to the maintenance and function of the GH cells of the pituitary. This was shown when the deletion of leptin receptors on somatotropes caused decreased numbers of GH cells, decreased circulating GH, and adult-onset obesity. To determine the source of leptin most vital to GH cells and other pituitary cell types, we compared two different leptin knockout models with Cre-lox technology. The global Lep-null model is like the ob/ob mouse, whereby only the entire exon 3 is deleted. The selective adipocyte-Lep-null model lacks adipocyte leptin but retains pituitary leptin, allowing us to investigate the pituitary as a potential source of circulating leptin. Male and female mice lacking adipocyte leptin (Adipocyte-lep-null) did not produce any detectable circulating leptin and were infertile, suggesting that the pituitary does not contribute to serum levels. In the presence of only pituitary leptin, however, these same mutants were able to maintain somatotrope numbers and GH mRNA levels. Serum GH trended low, but values were not significant. However, hypothalamic GHRH mRNA was significantly reduced in these animals. Other serum hormone and pituitary mRNA differences were observed, some of which varied from previous results reported in ob/ob animals. Whereas pituitary leptin is capable of maintaining somatotrope numbers and GH mRNA production, the decreased hypothalamic GHRH mRNA and low (but not significant) serum GH levels indicate an important role for adipocyte leptin in the regulation of GH secretion in the mouse. Thus, normal GH secretion may require the coordinated actions of both adipocyte and pituitary leptin. PMID:25116704

  12. Clinical significance of changes of serum leptin and insulin levels in patients with polycystic ovary syndrome

    International Nuclear Information System (INIS)

    Chen Zhaojun; Zhang Lahong; Gao Ying; Ren Xiaohua

    2007-01-01

    Objective: To explore the relationship between the serum leptin, insulin levels and development of polycystic ovary syndrome (PCOS). Methods: Serum leptin and insulin levels (with RIA) were determined in 34 patients with PCOS and 30 controls. Results: The serum leptin and insulin levels in the 34 PCOS patients were significantly higher than those in controls (P<0. 01), and those in obese patients (n=22) were significantly higher than those in non-obese ones (n=12) too(P<0.01). Conclusion: Changes of serum leptin and insulin levels were closely related to the development of PCOS and leptin might be used as a diagnostic indicator for PCOS. (authors)

  13. Pivotal role of leptin in insulin effects

    Directory of Open Access Journals (Sweden)

    R.B. Ceddia

    1998-06-01

    Full Text Available The OB protein, also known as leptin, is secreted by adipose tissue, circulates in the blood, probably bound to a family of binding proteins, and acts on central neural networks regulating ingestive behavior and energy balance. The two forms of leptin receptors (long and short forms have been identified in various peripheral tissues, a fact that makes them possible target sites for a direct action of leptin. It has been shown that the OB protein interferes with insulin secretion from pancreatic islets, reduces insulin-stimulated glucose transport in adipocytes, and increases glucose transport, glycogen synthesis and fatty acid oxidation in skeletal muscle. Under normoglycemic and normoinsulinemic conditions, leptin seems to shift the flux of metabolites from adipose tissue to skeletal muscle. This may function as a peripheral mechanism that helps control body weight and prevents obesity. Data that substantiate this hypothesis are presented in this review.

  14. Effect of leptin level upon lipid metabolism in climacteric women

    International Nuclear Information System (INIS)

    Peng Lijing; Yan Ruming; Sun Enhua

    2005-01-01

    To observe the relationship between leptin and obesity of climacteric women with their lipid metabolism, 110 cases of climacteric women were chosen as observation group, consisting of 69 cases obese subgroup and 45 cases non-obese group, and 60 cases of normal reproduction- age women were arranged as control group. Blood levels of leptin, INS, LDL-C, TG, HDL-C, apoA1, apoB, LH, FSH, E-2, T, and P were detected and BMI was calculated. The results showed that blood levels of leptin and INS of obese subgroup were significantly higher than those of non-obese sub-group and control group(P<0.01), and that LDL-C(5.01 mmol/L), TG(2.21mmal/L) and apoB(0.89g/L) levels in obese subgroup were significantly higher than those of control group. Furthermore, an important observation was that in climacteric women group, blood leptin level was positively and significantly correlated with insulin, BMI and several atherogenic blood lipid parameters, including LDL-C, TG and apoB. Thus, a preliminary conclusion might be reached as that the high climacteric level of leptin is associated with abnormal lipid metabolism related to atherogenity, and so leptin and lipid metabolism as a whole should be paid more attention in climateric women, especially those with obesity. (authors)

  15. Structural changes of gut microbiota during berberine-mediated prevention of obesity and insulin resistance in high-fat diet-fed rats.

    Directory of Open Access Journals (Sweden)

    Xu Zhang

    Full Text Available Berberine, a major pharmacological component of the Chinese herb Coptis chinensis, which was originally used to treat bacterial diarrhea, has recently been demonstrated to be clinically effective in alleviating type 2 diabetes. In this study, we revealed that berberine effectively prevented the development of obesity and insulin resistance in high-fat diet (HFD-fed rats, which showed decreased food intake. Increases in the levels of serum lipopolysaccharide-binding protein, monocyte chemoattractant protein-1, and leptin and decrease in the serum level of adiponectin corrected for body fat in HFD-fed rats were also significantly retarded by the co-administration of berberine at 100 mg/kg body weight. Bar-coded pyrosequencing of the V3 region of 16S rRNA genes revealed a significant reduction in the gut microbiota diversity of berberine-treated rats. UniFrac principal coordinates analysis revealed a marked shift of the gut microbiota structure in berberine-treated rats away from that of the controls. Redundancy analysis identified 268 berberine-responding operational taxonomic units (OTUs, most of which were essentially eliminated, whereas a few putative short-chain fatty acid (SCFA-producing bacteria, including Blautia and Allobaculum, were selectively enriched, along with elevations of fecal SCFA concentrations. Partial least square regression models based on these 268 OTUs were established (Q(2>0.6 for predicting the adiposity index, body weight, leptin and adiponectin corrected for body fat, indicating that these discrete phylotypes might have a close association with the host metabolic phenotypes. Taken together, our findings suggest that the prevention of obesity and insulin resistance by berberine in HFD-fed rats is at least partially mediated by structural modulation of the gut microbiota, which may help to alleviate inflammation by reducing the exogenous antigen load in the host and elevating SCFA levels in the intestine.

  16. Structural changes of gut microbiota during berberine-mediated prevention of obesity and insulin resistance in high-fat diet-fed rats.

    Science.gov (United States)

    Zhang, Xu; Zhao, Yufeng; Zhang, Menghui; Pang, Xiaoyan; Xu, Jia; Kang, Chaoying; Li, Meng; Zhang, Chenhong; Zhang, Zhiguo; Zhang, Yifei; Li, Xiaoying; Ning, Guang; Zhao, Liping

    2012-01-01

    Berberine, a major pharmacological component of the Chinese herb Coptis chinensis, which was originally used to treat bacterial diarrhea, has recently been demonstrated to be clinically effective in alleviating type 2 diabetes. In this study, we revealed that berberine effectively prevented the development of obesity and insulin resistance in high-fat diet (HFD)-fed rats, which showed decreased food intake. Increases in the levels of serum lipopolysaccharide-binding protein, monocyte chemoattractant protein-1, and leptin and decrease in the serum level of adiponectin corrected for body fat in HFD-fed rats were also significantly retarded by the co-administration of berberine at 100 mg/kg body weight. Bar-coded pyrosequencing of the V3 region of 16S rRNA genes revealed a significant reduction in the gut microbiota diversity of berberine-treated rats. UniFrac principal coordinates analysis revealed a marked shift of the gut microbiota structure in berberine-treated rats away from that of the controls. Redundancy analysis identified 268 berberine-responding operational taxonomic units (OTUs), most of which were essentially eliminated, whereas a few putative short-chain fatty acid (SCFA)-producing bacteria, including Blautia and Allobaculum, were selectively enriched, along with elevations of fecal SCFA concentrations. Partial least square regression models based on these 268 OTUs were established (Q(2)>0.6) for predicting the adiposity index, body weight, leptin and adiponectin corrected for body fat, indicating that these discrete phylotypes might have a close association with the host metabolic phenotypes. Taken together, our findings suggest that the prevention of obesity and insulin resistance by berberine in HFD-fed rats is at least partially mediated by structural modulation of the gut microbiota, which may help to alleviate inflammation by reducing the exogenous antigen load in the host and elevating SCFA levels in the intestine.

  17. Leptin actions on food intake and body temperature are mediated by IL-1

    OpenAIRE

    Luheshi, Giamal N.; Gardner, Jason D.; Rushforth, David A.; Loudon, Andrew S.; Rothwell, Nancy J.

    1999-01-01

    Leptin regulates energy balance through its actions in the brain on appetite and energy expenditure and also shares properties with cytokines such as IL-1. We report here that leptin, injected into rats intracerebroventricularly or peripherally, induces significant dose-dependent increases in core body temperature as well as suppression of appetite. Leptin failed to affect food intake or body temperature in obese (fa/fa) Zucker rats, which posses a defective leptin receptor. Furthermore, inje...

  18. Increased tissue leptin hormone level and mast cell count in skin tags: A possible role of adipoimmune in the growth of benign skin growths

    Directory of Open Access Journals (Sweden)

    El Safoury Omar

    2010-01-01

    Full Text Available Background: Skin tags (ST are common tumors. They mainly consist of loose fibrous tissue and occur on the neck and major flexures as small, soft, pedunculated protrusions. Decrease in endocrine, hormone level and other factors are thought to play a role in the evolution of ST. Leptin is an adipocyte-derived hormone that acts as a major regulatory hormone for food intake and energy homeostasis. Leptin deficiency or resistance can result in profound obesity and diabetes in humans. A role of mast cell in the pathogenesis of ST is well recognized. Aims: To investigate the role of leptin in the pathogenesis of ST and to clarify whether there is a correlation between mast cell count and leptin level in ST. Methods: Forty-five skin biopsies were taken from 15 patients with ST. From each patient, a biopsy of a large ST (length >4 mm, a small ST (length <2 mm and a normal skin biopsy (as a control were taken. The samples were processed for leptin level. Skin biopsies were stained with hematoxylin and eosin and toluidine blue-uranyl nitrate metachromatic method for mast cell count was used. Results: There was a significant increased level of leptin in the ST compared to the normal skin. It was highly significant in small ST than in big ST (P = 0.0001 and it was highly significant in small and big ST compared to controls, P = 0.0001 and P = 0.001, respectively. There was a significant increase in mast cell count in the ST, which did not correlate with the increased levels of leptin. Conclusion: This is the first report to demonstrate that tissue leptin may play a role in the pathogenesis of ST. The significant increase in the levels of leptin and mast cell count in ST may indicate a possible role of adipoimmune in the benign skin growths.

  19. Obesity Resistance Promotes Mild Contractile Dysfunction Associated with Intracellular Ca{sup 2+} Handling

    Energy Technology Data Exchange (ETDEWEB)

    Sá, Felipe Gonçalves dos Santos de; Lima-Leopoldo, Ana Paula; Jacobsen, Bruno Barcellos; Ferron, Artur Junio Togneri; Estevam, Wagner Muller [Centro de Educação Física e Desportos - Departamento de Desportos - Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Campos, Dijon Henrique Salomé [Departamento de Clínica Médica - Faculdade de Medicina - Universidade Estadual Paulista, Botucatu, São Paulo (Brazil); Castardeli, Edson; Cunha, Márcia Regina Holanda da [Centro de Educação Física e Desportos - Departamento de Desportos - Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Cicogna, Antonio Carlos [Departamento de Clínica Médica - Faculdade de Medicina - Universidade Estadual Paulista, Botucatu, São Paulo (Brazil); Leopoldo, André Soares, E-mail: andresoaresleopoldo@gmail.com [Centro de Educação Física e Desportos - Departamento de Desportos - Universidade Federal do Espírito Santo, Vitória, ES (Brazil)

    2015-12-15

    Diet-induced obesity is frequently used to demonstrate cardiac dysfunction. However, some rats, like humans, are susceptible to developing an obesity phenotype, whereas others are resistant to that. To evaluate the association between obesity resistance and cardiac function, and the impact of obesity resistance on calcium handling. Thirty-day-old male Wistar rats were distributed into two groups, each with 54 animals: control (C; standard diet) and obese (four palatable high-fat diets) for 15 weeks. After the experimental protocol, rats consuming the high-fat diets were classified according to the adiposity index and subdivided into obesity-prone (OP) and obesity-resistant (OR). Nutritional profile, comorbidities, and cardiac remodeling were evaluated. Cardiac function was assessed by papillary muscle evaluation at baseline and after inotropic maneuvers. The high-fat diets promoted increase in body fat and adiposity index in OP rats compared with C and OR rats. Glucose, lipid, and blood pressure profiles remained unchanged in OR rats. In addition, the total heart weight and the weight of the left and right ventricles in OR rats were lower than those in OP rats, but similar to those in C rats. Baseline cardiac muscle data were similar in all rats, but myocardial responsiveness to a post-rest contraction stimulus was compromised in OP and OR rats compared with C rats. Obesity resistance promoted specific changes in the contraction phase without changes in the relaxation phase. This mild abnormality may be related to intracellular Ca2+ handling.

  20. Obesity Resistance Promotes Mild Contractile Dysfunction Associated with Intracellular Ca2+ Handling

    International Nuclear Information System (INIS)

    Sá, Felipe Gonçalves dos Santos de; Lima-Leopoldo, Ana Paula; Jacobsen, Bruno Barcellos; Ferron, Artur Junio Togneri; Estevam, Wagner Muller; Campos, Dijon Henrique Salomé; Castardeli, Edson; Cunha, Márcia Regina Holanda da; Cicogna, Antonio Carlos; Leopoldo, André Soares

    2015-01-01

    Diet-induced obesity is frequently used to demonstrate cardiac dysfunction. However, some rats, like humans, are susceptible to developing an obesity phenotype, whereas others are resistant to that. To evaluate the association between obesity resistance and cardiac function, and the impact of obesity resistance on calcium handling. Thirty-day-old male Wistar rats were distributed into two groups, each with 54 animals: control (C; standard diet) and obese (four palatable high-fat diets) for 15 weeks. After the experimental protocol, rats consuming the high-fat diets were classified according to the adiposity index and subdivided into obesity-prone (OP) and obesity-resistant (OR). Nutritional profile, comorbidities, and cardiac remodeling were evaluated. Cardiac function was assessed by papillary muscle evaluation at baseline and after inotropic maneuvers. The high-fat diets promoted increase in body fat and adiposity index in OP rats compared with C and OR rats. Glucose, lipid, and blood pressure profiles remained unchanged in OR rats. In addition, the total heart weight and the weight of the left and right ventricles in OR rats were lower than those in OP rats, but similar to those in C rats. Baseline cardiac muscle data were similar in all rats, but myocardial responsiveness to a post-rest contraction stimulus was compromised in OP and OR rats compared with C rats. Obesity resistance promoted specific changes in the contraction phase without changes in the relaxation phase. This mild abnormality may be related to intracellular Ca2+ handling

  1. The role of dietary fat in obesity-induced insulin resistance.

    Science.gov (United States)

    Lackey, Denise E; Lazaro, Raul G; Li, Pingping; Johnson, Andrew; Hernandez-Carretero, Angelina; Weber, Natalie; Vorobyova, Ivetta; Tsukomoto, Hidekazu; Osborn, Olivia

    2016-12-01

    Consumption of excess calories results in obesity and insulin resistance and has been intensively studied in mice and humans. The objective of this study was to determine the specific contribution of dietary fat rather than total caloric intake to the development of obesity-associated insulin resistance. We used an intragastric feeding method to overfeed excess calories from a low-fat diet (and an isocalorically matched high-fat diet) through a surgically implanted gastric feeding tube to generate obesity in wild-type mice followed by hyperinsulinemic-euglycemic clamp studies to assess the development of insulin resistance. We show that overfeeding a low-fat diet results in levels of obesity similar to high-fat diet feeding in mice. However, despite a similar body weight, obese high-fat diet-fed mice are more insulin resistant than mice fed an isocaloric low-fat diet. Therefore, increased proportion of calories from dietary fat further potentiates insulin resistance in the obese state. Furthermore, crossover diet studies revealed that reduction in dietary fat composition improves glucose tolerance in obesity. In the context of the current obesity and diabetes epidemic, it is particularly important to fully understand the role of dietary macronutrients in the potentiation and amelioration of disease. Copyright © 2016 the American Physiological Society.

  2. [The role of uric acid in the insulin resistance in children and adolescents with obesity].

    Science.gov (United States)

    de Miranda, Josiane Aparecida; Almeida, Guilherme Gomide; Martins, Raissa Isabelle Leão; Cunha, Mariana Botrel; Belo, Vanessa Almeida; dos Santos, José Eduardo Tanus; Mourão-Júnior, Carlos Alberto; Lanna, Carla Márcia Moreira

    2015-12-01

    To investigate the association between serum uric acid levels and insulin resistance in children and adolescents with obesity. Cross-sectional study with 245 children and adolescents (134 obese and 111 controls), aged 8 to 18 years. The anthropometric variables (weight, height and waist circumference), blood pressure and biochemical parameters were collected. The clinical characteristics of the groups were analyzed by t-test or chi-square test. To evaluate the association between uric acid levels and insulin resistance the Pearson's test and logistic regression were applied. The prevalence of insulin resistance was 26.9%. The anthropometric variables, systolic and diastolic blood pressure and biochemical variables were significantly higher in the obese group (p<0.001), except for the high-density-lipoprotein cholesterol. There was a positive and significant correlation between anthropometric variables and uric acid with HOMA-IR in the obese and in the control groups, which was higher in the obese group and in the total sample. The logistic regression model that included age, gender and obesity, showed an odds ratio of uric acid as a variable associated with insulin resistance of 1.91 (95%CI 1.40 to 2.62; p<-0.001). The increase in serum uric acid showed a positive statistical correlation with insulin resistance and it is associated with and increased risk of insulin resistance in obese children and adolescents. Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  3. Dietary alleviation of maternal obesity and diabetes: increased resistance to diet-induced obesity transcriptional and epigenetic signatures.

    Science.gov (United States)

    Attig, Linda; Vigé, Alexandre; Gabory, Anne; Karimi, Moshen; Beauger, Aurore; Gross, Marie-Sylvie; Athias, Anne; Gallou-Kabani, Catherine; Gambert, Philippe; Ekstrom, Tomas J; Jais, Jean-Philippe; Junien, Claudine

    2013-01-01

    According to the developmental origins of health and diseases (DOHaD), and in line with the findings of many studies, obesity during pregnancy is clearly a threat to the health and well-being of the offspring, later in adulthood. We previously showed that 20% of male and female inbred mice can cope with the obesogenic effects of a high-fat diet (HFD) for 20 weeks after weaning, remaining lean. However the feeding of a control diet (CD) to DIO mice during the periconceptional/gestation/lactation period led to a pronounced sex-specific shift (17% to 43%) from susceptibility to resistance to HFD, in the female offspring only. Our aim in this study was to determine how, in the context of maternal obesity and T2D, a CD could increase resistance on female fetuses. Transcriptional analyses were carried out with a custom-built mouse liver microarray and by quantitative RT-PCR for muscle and adipose tissue. Both global DNA methylation and levels of pertinent histone marks were assessed by LUMA and western blotting, and the expression of 15 relevant genes encoding chromatin-modifying enzymes was analyzed in tissues presenting global epigenetic changes. Resistance was associated with an enhancement of hepatic pathways protecting against steatosis, the unexpected upregulation of neurotransmission-related genes and the modulation of a vast imprinted gene network. Adipose tissue displayed a pronounced dysregulation of gene expression, with an upregulation of genes involved in lipid storage and adipocyte hypertrophy or hyperplasia in obese mice born to lean and obese mothers, respectively. Global DNA methylation, several histone marks and key epigenetic regulators were also altered. Whether they were themselves lean (resistant) or obese (sensitive), the offspring of lean and obese mice clearly differed in terms of several metabolic features and epigenetic marks suggesting that the effects of a HFD depend on the leanness or obesity of the mother.

  4. Osteocalcin as a negative regulator of serum leptin concentration in humans: insight from triathlon competitions.

    Science.gov (United States)

    Guadalupe-Grau, Amelia; Ara, Ignacio; Dorado, Cecilia; Vicente-Rodríguez, German; Perez-Gomez, Jorge; Cabrero, Javier Chavarren; Serrano-Sanchez, José A; Santana, Alfredo; Calbet, Jose A L

    2010-10-01

    Osteocalcin is a hormone produced by osteoblasts which acts as a negative regulator of fat mass, protecting against diet induced obesity and insulin resistance in rodents. To determine if an acute increase in osteocalcin concentration is associated with opposed changes in circulating leptin levels and insulin resistance we studied 15 middle and long distance male triathletes, (age 32.1 ± 6.9 years), before and 48 h after an Olympic (OT) or an Ironman (IT) triathlon competition. Muscle power, anaerobic capacity, body composition (dual-energy X-ray absorptiometry), and serum concentrations of testosterone, dihydrotestosterone, osteocalcin, leptin, glucose, insulin and insulin resistance (HOMA) were determined pre- and post-race. Pre- and 48 h post-race total and regional lean body mass was not altered, but fat mass was similarly increased (~250 g) 48 h after the competitions. This elicited an increase in plasma leptin of 33% after the IT while it remained unchanged after the OT, likely due to a 25% increase in plasma osteocalcin which occurred only after the OT (all p < 0.05). Post-race HOMA remained unchanged in OT and IT. Performance was normalized 48 h after the competitions, with the exception of a slightly lower jumping capacity after the IT. Serum testosterone concentration tended to decrease by 10% after the IT whilst dihydrotestosterone was reduced by 24% after the IT. In conclusion, an acute increase in serum osteocalcin concentration blunts the expected increase of serum leptin concentration that should occur with fat mass gain. This study provides evidence for osteocalcin as a negative regulator of serum leptin in humans.

  5. High serum fasting peptide YY (3-36) is associated with obesity-associated insulin resistance and type 2 diabetes.

    Science.gov (United States)

    Ukkola, Olavi H; Puurunen, Veli-Pekka; Piira, Olli-Pekka; Niva, Jarkko T; Lepojärvi, E Samuli; Tulppo, Mikko P; Huikuri, Heikki V

    2011-10-10

    We studied whether serum fasting levels of active form of peptide YY (PYY), PYY(3-36), are associated with obesity and related phenotypes. The study population consisted of 428 patients with coronary artery disease and diagnosed type 2 diabetes and 440 patients with coronary artery disease but without evidence of diabetes from the ARTEMIS study. The patients were recruited from the consecutive series of patients undergoing coronary angiography in the Oulu University Hospital. The patients without diabetes underwent a 2-hour oral glucose tolerance test. PYY(3-36) levels were analyzed by human PYY(3-36) specific radioimmunoassay. Result suggested that when PYY(3-36) tertiles were considered, high serum fasting PYY(3-36) concentration was associated with high body mass index, waist circumference, hemoglobin A1c, fasting blood glucose, leptin, triglyceride (p for all p ≤ 0.001), serum insulin (p=0.013) and with a low high-density lipoprotein cholesterol (p=0.004) concentrations in the analyses adjusted for age, sex and study group. The link high PYY(3-36)-high insulin level was evident in subjects with normal glucose tolerance (pfasting glucose, impaired glucose tolerance and normal glucose tolerance (pfasting PYY(3-36) concentrations in type 2 diabetic subjects are high. Although high PYY(3-36) is strongly linked to obesity and associated insulin resistance, the relation between PYY(3-36) and type 2 diabetes is independent of body fatness. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Maternal obesity induced by diet in rats permanently influences central processes regulating food intake in offspring.

    Directory of Open Access Journals (Sweden)

    Shona L Kirk

    2009-06-01

    Full Text Available Hypothalamic systems which regulate appetite may be permanently modified during early development. We have previously reported hyperphagia and increased adiposity in the adult offspring of rodents fed an obesogenic diet prior to and throughout pregnancy and lactation. We now report that offspring of obese (OffOb rats display an amplified and prolonged neonatal leptin surge, which is accompanied by elevated leptin mRNA expression in their abdominal white adipose tissue. At postnatal Day 30, before the onset of hyperphagia in these animals, serum leptin is normal, but leptin-induced appetite suppression and phosphorylation of STAT3 in the arcuate nucleus (ARC are attenuated; the level of AgRP-immunoreactivity in the hypothalamic paraventricular nucleus (PVH, which derives from neurones in the ARC and is developmentally dependent on leptin, is also diminished. We hypothesise that prolonged release of abnormally high levels of leptin by neonatal OffOb rats leads to leptin resistance and permanently affects hypothalamic functions involving the ARC and PVH. Such effects may underlie the developmental programming of hyperphagia and obesity in these rats.

  7. Long-term characterization of the diet-induced obese and diet-resistant rat model

    DEFF Research Database (Denmark)

    Madsen, Andreas Nygaard; Hansen, Gitte; Paulsen, Sarah Juel

    2010-01-01

    , namely the selectively bred diet-induced obese (DIO) and diet-resistant (DR) rat strains. We show that they constitute useful models of the human obesity syndrome. DIO and DR rats were fed either a high-energy (HE) or a standard chow (Chow) diet from weaning to 9 months of age. Metabolic characterization......, the results underscore the effectiveness of GLP-1 mimetics both as anti-diabetes and anti-obesity agents....

  8. The peculiarities of sexual development of children with clinical manifestations of insulin and leptin resistance born from the persons exposed in the childhood to radiation due to Chornobyl accident

    International Nuclear Information System (INIS)

    Kopilova, O.V.; Stepanenko, O.A.; Tsvjet, L.O.; Matsyuk, Yi.V.

    2010-01-01

    The purpose of the study was to reveal the peculiarities of sexual development of the children with clinical manifestations of insulin and leptin resistance born from the persons who were exposed to radiation after Chornobyl accident in their childhood. The study involved 108 persons aged 12-14. The findings of the investigation demonstrated changes in the central and peripheral links of neurohumoral regulation disorders of thyroid metabolism, changes in menstrual cycle development.

  9. (HbA1c) levels with Iinsulin resistance in obese children.

    African Journals Online (AJOL)

    Objectives: We investigated the relationship between insulin resistance reflected by homeostasis model assessment (HOMA-IR) index and serum HbA1c levels of obese children. Material and Methods: This study included 70 obese and 60 normal weight healthy children between the ages of 3 and 15. Anthropometric ...

  10. Postmenopausal hypertension, abdominal obesity, apolipoprotein and insulin resistance.

    Science.gov (United States)

    Ben Ali, Samir; Belfki-Benali, Hanen; Ahmed, Decy Ben; Haddad, Najet; Jmal, Awatef; Abdennebi, Monia; Romdhane, Habiba Ben

    This study aimed to evaluate the association of abdominal obesity, apolipoprotein and insulin resistance (IR) with the risk of hypertension in postmenopausal women. We analyzed a total of 242 women aged between 35 and 70 years. Blood pressure (BP), anthropometric indices, lipid profile, fasting glucose, insulin, C-reactive protein (CRP) and apolipoprotein concentrations were measured. Homeostasis model assessment (HOMA) was used to assess IR. Hypertension was defined as a systolic BP (SBP) ≥140 mmHg and/or diastolic BP (DBP) ≥90 mmHg or current treatment with antihypertensive drugs. Women with hypertension showed significantly higher mean values of age, SBP and DBP, waist circumference (WC), fasting plasma glucose (FPG), insulin, HOMAIR and the apolipoprotein B (apoB). When analyses were done according to the menopausal status, higher prevalence of hypertension was observed in postmenopausal women (72.8% vs. 26.0%, p menopause (p = 0.008) were significantly associated with higher risk for hypertension. These results suggest that changes in WC, apoB and IR accompanying menopause lead to a greater prevalence of hypertension in postmenopausal women.

  11. Obesity, insulin resistance and comorbidities – Mechanisms of association

    Science.gov (United States)

    Castro, Ana Valeria B.; Kolka, Cathryn M.; Kim, Stella P.; Bergman, Richard N.

    2015-01-01

    Overall excess of fat, usually defined by the body mass index, is associated with metabolic (e.g. glucose intolerance, type 2 diabetes mellitus (T2DM), dyslipidemia) and non-metabolic disorders (e.g. neoplasias, polycystic ovary syndrome, non-alcoholic fat liver disease, glomerulopathy, bone fragility etc.). However, more than its total amount, the distribution of adipose tissue throughout the body is a better predictor of the risk to the development of those disorders. Fat accumulation in the abdominal area and in non-adipose tissue (ectopic fat), for example, is associated with increased risk to develop metabolic and non-metabolic derangements. On the other hand, observations suggest that individuals who present peripheral adiposity, characterized by large hip and thigh circumferences, have better glucose tolerance, reduced incidence of T2DM and of metabolic syndrome. Insulin resistance (IR) is one of the main culprits in the association between obesity, particularly visceral, and metabolic as well as non-metabolic diseases. In this review we will highlight the current pathophysiological and molecular mechanisms possibly involved in the link between increased VAT, ectopic fat, IR and comorbidities. We will also provide some insights in the identification of these abnormalities. PMID:25211442

  12. Leptin promotes wound healing in the oral mucosa.

    Science.gov (United States)

    Umeki, Hirochika; Tokuyama, Reiko; Ide, Shinji; Okubo, Mitsuru; Tadokoro, Susumu; Tezuka, Mitsuki; Tatehara, Seiko; Satomura, Kazuhito

    2014-01-01

    Leptin, a 16 kDa circulating anti-obesity hormone, exhibits many physiological properties. Recently, leptin was isolated from saliva; however, its function in the oral cavity is still unclear. In this study, we investigated the physiological role of leptin in the oral cavity by focusing on its effect on wound healing in the oral mucosa. Immunohistochemical analysis was used to examine the expression of the leptin receptor (Ob-R) in human/rabbit oral mucosa. To investigate the effect of leptin on wound healing in the oral mucosa, chemical wounds were created in rabbit oral mucosa, and leptin was topically administered to the wound. The process of wound repair was histologically observed and quantitatively analyzed by measuring the area of ulceration and the duration required for complete healing. The effect of leptin on the proliferation, differentiation and migration of human oral mucosal epithelial cells (RT7 cells) was investigated using crystal violet staining, reverse transcription polymerase chain reaction (RT-PCR) and a wound healing assay, respectively. Ob-R was expressed in spinous/granular cells in the epithelial tissue and vascular endothelial cells in the subepithelial connective tissue of the oral mucosa. Topical administration of leptin significantly promoted wound healing and shortened the duration required for complete healing. Histological analysis of gingival tissue beneath the ulceration showed a denser distribution of blood vessels in the leptin-treated group. Although the proliferation and differentiation of RT7 cells were not affected by leptin, the migration of these cells was accelerated in the presence of leptin. Topically administered leptin was shown to promote wound healing in the oral mucosa by accelerating epithelial cell migration and enhancing angiogenesis around the wounded area. These results strongly suggest that topical administration of leptin may be useful as a treatment to promote wound healing in the oral mucosa.

  13. The effect of exercise on insulin resistance in obese women with polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Heba S Kareem

    2014-01-01

    Conclusion Regular aerobic exercises improve insulin resistance, abdominal fat distribution, and body weight in obese diabetic and nondiabetic women with polycystic ovary, and they are advised to perform regular aerobic exercises.

  14. Leptin is essential for the hepatic fibrogenic response to chronic liver injury

    NARCIS (Netherlands)

    Leclercq, IA; Farrell, GC; Schriemer, R; Robertson, GR

    Background/Aims: Obesity is associated with hyperleptinemia and is also a risk factor for fibrosis and severity of fibrosis in several chronic liver diseases. The correlation between increased leptin, obesity and hepatic fibrosis prompted us to hypothesise that leptin has profibrogenic effects on

  15. The importance of leptin in animal science

    Directory of Open Access Journals (Sweden)

    Mirela Ahmadi

    2016-05-01

    Full Text Available There are two different neurons that control the energetic homeostasis in animals: appetite-stimulating and appetite-suppressing neurons. Leptin is a peptide hormone (also known as “satiety hormone”, released by adipose cells, being an anorexigenic compound which inhibit the hunger. Leptin function in animal organism is opposite by the action of ghrelin – a peptide hormone acting as an orexigenic compound that activate the hunger sensation. The quantity of leptin produced in organism is correlated by the size and the number of adipocytes, and of course by the lipid tissue mass. The action of leptin is in accordance with the neuropeptide Y that signaling the brain to increase the appetite and make the animal to eat. When the animals lose weight, the mass of adipose tissue is diminished, that has as consequence a decrease the leptin concentration in the blood. Blood leptin is correlated also with other characteristics, such as: fasting for a short term, stress, physical activity, sleep duration (prehibernation and hibernation, insulin concentration, obesity and diabetes.

  16. No association of defined variability in leptin, leptin receptor, adiponectin, proopiomelanocortin and ghrelin gene with food preferences in the Czech population.

    Science.gov (United States)

    Bienertova-Vasku, Julie; Bienert, Petr; Tomandl, Josef; Forejt, Martin; Vavrina, Martin; Kudelkova, Jana; Vasku, Anna

    2008-02-01

    Previously, it has been reported that mutations in the genes encoding for adipokines may be associated with impaired food intake and may serve as potential obesity biomarkers. The aim of this study was to investigate the possible associations of defined variability in leptin, leptin receptor, adiponectin, proopiomelanocortin and ghrelin genes with food preferences in the obese and non-obese Czech population and evaluate their potential as the obesity susceptibility genes. Using PCR followed by restriction analysis, we studied 185 volunteers. Basic anthropometrical characteristics associated to obesity were measured and the food intake was monitored using a 7-day record method. In the group of obese individuals, a subset of 34 morbidly obese patients was studied for plasma leptin and soluble leptin receptor levels. None of the examined polymorphisms was associated to anthropometrical or demographic characteristics of the study subjects. The Gln223Arg polymorphism within the leptin receptor gene was significantly associated with lower plasma leptin levels (the RR genotype being more frequent in patients with lower plasma leptin levels; P = 0.001). No associations of the examined polymorphisms with food preferences was observed. Based on our results, the examined polymorphisms in the adipokine genes do not seem to be the major risk factor for obesity development in the Czech population nor significantly affect food preferences.

  17. Resistência insulínica pode prejudicar a redução da espessura mediointimal em adolescentes obesos Insulin resistance can impair reduction on carotid intima-media thickness in obese adolescents

    Directory of Open Access Journals (Sweden)

    Priscila de Lima Sanches

    2012-10-01

    (IR n=39 and without insulin resistance (NIR n=27, and submitted to an interdisciplinary intervention over the course of 1 year. Common carotid artery intima-media thickness (cIMT, visceral and subcutaneous adipose tissue was determined by ultrasound. Body composition, blood pressure, HOMA-IR, lipid profile and adipokines concentrations [leptin, adiponectin, and plasminogen activator inhibitor type (PAI-1] were analyzed before and after the therapy. RESULTS: Both groups presented significant improvements in body composition, inflammatory state (reduction of leptin and PAI-1 concentration; increasing of plasma adiponectin and reduction of cIMT. Only NIR group showed positive correlation between changes in visceral fat (∆Visceral and changes in cIMT (∆ cIMT (r = 0.42; p < 0.05. Simple linear regression analyze revealed ∆Visceral to be an independent predictor to reduction of cIMT in this group (R2 adjusted = 0.14, p = 0.04. The final values of cIMT remained significantly higher in IR group when compared to NIR group. CONCLUSION: The presence of insulin resistance can impair changes in cIMT leading to early development of atherosclerosis in obese adolescents submitted to an interdisciplinary intervention..

  18. Adipose Expression of Tumor Necrosis Factor-α: Direct Role in Obesity-Linked Insulin Resistance

    Science.gov (United States)

    Hotamisligil, Gokhan S.; Shargill, Narinder S.; Spiegelman, Bruce M.

    1993-01-01

    Tumor necrosis factor-α (TNF-α) has been shown to have certain catabolic effects on fat cells and whole animals. An induction of TNF-α messenger RNA expression was observed in adipose tissue from four different rodent models of obesity and diabetes. TNF-α protein was also elevated locally and systemically. Neutralization of TNF-α in obese fa/fa rats caused a significant increase in the peripheral uptake of glucose in response to insulin. These results indicate a role for TNF-α in obesity and particularly in the insulin resistance and diabetes that often accompany obesity.

  19. Macrophage Migration Inhibitory Factor: Critical Role in Obesity, Insulin Resistance, and Associated Comorbidities

    Directory of Open Access Journals (Sweden)

    Robert Kleemann

    2010-01-01

    Full Text Available Obesity is associated with insulin resistance, disturbed glucose homeostasis, low grade inflammation, and comorbidities such as type 2 diabetes and cardiovascular disease. The cytokine macrophage migration inhibitory factor (MIF is an ubiquitously expressed protein that plays a crucial role in many inflammatory and autoimmune disorders. Increasing evidence suggests that MIF also controls metabolic and inflammatory processes underlying the development of metabolic pathologies associated with obesity. This is a comprehensive summary of our current knowledge on the role of MIF in obesity and obesity-associated comorbidities, based on human clinical data as well as animal models of disease.

  20. Plasma leptin values in postmenopausal women with osteoporosis.

    Science.gov (United States)

    Kocyigit, Hikmet; Bal, Serpil; Atay, Ayşenur; Koseoglu, Mehmet; Gurgan, Alev

    2013-08-01

    Obesity has a protective effect against osteoporosis and this effect has been attributed to a high body fat content. It has been shown that the leptin concentration is higher in obese patients. Leptin, the protein product of obesity gene, is a hormone produced in adipose tissue. Some studies suggest that endogenous leptin might influence bone metabolism in postmenopausal women. In this study, we investigated plasma leptin concentrations in postmenopausal women with osteoporosis and also analyzed the relationship between plasma leptin levels and bone mineral density (BMD) in order to understand the potential role of leptin in maintaining bone mass. Forty-two postmenopausal women with osteoporosis and thirty seven age and BMI-matched healthy postmenopausal women were included in the study. The mean femoral neck BMD value in the patient group was significantly lower than that in the control group (0.691±0.1 g/cm2 and 0.863±0.1 g/cm2, respectively; p0.05). Plasma leptin levels were correlated with BMI in both groups (p<0.001 in the patient group and p=0.001 in controls). There was also a strong positive correlation between plasma leptin levels and %fat in both groups (p<0.001 in the patient group and p<0.001 in controls). But there was no correlation between plasma leptin levels and femoral neck BMD values in both groups. Our results do not support the hypothesis that leptin itself plays an important role in maintaining bone mass in postmenopausal women.

  1. Central insulin and leptin-mediated autonomic control of glucose homeostasis.

    Science.gov (United States)

    Marino, Joseph S; Xu, Yong; Hill, Jennifer W

    2011-07-01

    Largely as a result of rising obesity rates, the incidence of type 2 diabetes is escalating rapidly. Type 2 diabetes results from multi-organ dysfunctional glucose metabolism. Recent publications have highlighted hypothalamic insulin- and adipokine-sensing as a major determinant of peripheral glucose and insulin responsiveness. The preponderance of evidence indicates that the brain is the master regulator of glucose homeostasis, and that hypothalamic insulin and leptin signaling in particular play a crucial role in the development of insulin resistance. This review discusses the neuronal crosstalk between the hypothalamus, autonomic nervous system, and tissues associated with the pathogenesis of type 2 diabetes, and how hypothalamic insulin and leptin signaling are integral to maintaining normal glucose homeostasis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Racial difference in Acylation Stimulating Protein (ASP correlates to triglyceride in non-obese and obese African American and Caucasian women

    Directory of Open Access Journals (Sweden)

    Cianflone Katherine

    2009-04-01

    Full Text Available Abstract Background Acylation Stimulating Protein (ASP has been shown to influence adipose tissue triglyceride (TG storage. The aim was to examine ethnic differences in ASP and leptin levels in relation to lipid profiles and postprandial changes amongst African American (AA and Caucasian American (CA women matched for BMI. Methods 129 women were recruited in total (age 21 – 73 y: 24 non-obese (BMI 2 CA, 27 obese (BMI ≥ 30 kg/m2 CA, 13 obese diabetic CA, 25 non-obese AA, 25 obese AA, and 15 obese diabetic AA. Cholesterol, HDL-C, LDL-C, apoB, glucose and insulin were measured at baseline. TG, non-esterified fatty acids, leptin, and ASP were measured at baseline and postprandially following a fat meal. Results ASP, leptin, insulin and TG were significantly increased in obese subjects within each race. However, AA women had significantly lower ASP and TG than CA women at all BMI. Obese and diabetic AA women had significantly lower apoB levels than CA women when compared to their respective counterparts. For AA women, fasting ASP was positively correlated with BMI, cholesterol, apoB, LDL-C and glucose. For CA women, fasting ASP was positively correlated with BMI, leptin, glucose and insulin. However, for any given BMI, ASP was significantly reduced in AA vs CA (p = 0.0004. Similarly, for any given leptin level or TG levels, ASP was significantly lower in AA women (p = 0.041 and p = 0.003, respectively. Conclusion CA women have higher baseline TG levels and an earlier TG peak that is accompanied with higher ASP levels suggesting increased ASP resistance, while AA women have lower baseline TG levels and a later TG peak at lower ASP levels suggesting increased ASP sensitivity. This may explain why AA women may have fewer metabolic complications, such as diabetes and CVD, when compared to their Caucasian counterparts at the same level of obesity.

  3. Arginase inhibition prevents the development of hypertension and improves insulin resistance in obese rats.

    Science.gov (United States)

    Peyton, Kelly J; Liu, Xiao-Ming; Shebib, Ahmad R; Johnson, Fruzsina K; Johnson, Robert A; Durante, William

    2018-04-27

    This study investigated the temporal activation of arginase in obese Zucker rats (ZR) and determined if arginase inhibition prevents the development of hypertension and improves insulin resistance in these animals. Arginase activity, plasma arginine and nitric oxide (NO) concentration, blood pressure, and insulin resistance were measured in lean and obese animals. There was a chronological increase in vascular and plasma arginase activity in obese ZR beginning at 8 weeks of age. The increase in arginase activity in obese animals was associated with a decrease in insulin sensitivity and circulating levels of arginine and NO. The rise in arginase activity also preceded the increase in blood pressure in obese ZR detected at 12 weeks of age. Chronic treatment of 8-week-old obese animals with an arginase inhibitor or L-arginine for 4 weeks prevented the development of hypertension and improved plasma concentrations of arginine and NO. Arginase inhibition also improved insulin sensitivity in obese ZR while L-arginine supplementation had no effect. In conclusion, arginase inhibition prevents the development of hypertension and improves insulin sensitivity while L-arginine administration only mitigates hypertension in obese animals. Arginase represents a promising therapeutic target in ameliorating obesity-associated vascular and metabolic dysfunction.

  4. Increased leptin expression in common carp (Cyprinus carpio) after food intake but not after fasting or feeding to satiation

    NARCIS (Netherlands)

    Huising, M.O.; Geven, E.J.; Kruiswijk, C.P.; Nabuurs, S.B.; Stolte, H.H.; Spanings, F.A.; Verburg-van Kemenade, B.M.L.; Flik, G.

    2006-01-01

    Leptin is a key factor in the regulation of food intake and is an important factor in the pathophysiology of obesity. However, more than a decade after the discovery of leptin in mouse, information regarding leptin in any nonmammalian species is still scant. We report the identification of duplicate

  5. Fasting Ghrelin Levels Are Decreased in Obese Subjects and Are Significantly Related With Insulin Resistance and Body Mass Index

    Directory of Open Access Journals (Sweden)

    Dimitrios Papandreou

    2017-10-01

    CONCLUSION: Obese subjects have low fasting ghrelin levels that they are significantly related to insulin resistance and body mass index. More prospective studies are needed to establish the role of ghrelin in the pathogenesis of human obesity.

  6. Obesity, insulin resistance and diabetes--a worldwide epidemic

    NARCIS (Netherlands)

    Seidell, J C

    Obesity is now commonly defined in adults as a BMI > 30 kg/m2. The prevalence of obesity in established market economies (Europe, USA, Canada, Australia, etc.) varies greatly, but a weighed estimate suggests an average prevalence in the order of 15-20%. The prevalence in these countries generally

  7. Roles of the Chemokine System in Development of Obesity, Insulin Resistance, and Cardiovascular Disease

    Science.gov (United States)

    Yao, Longbiao; Herlea-Pana, Oana; Heuser-Baker, Janet; Chen, Yitong; Barlic-Dicen, Jana

    2014-01-01

    The escalating epidemic of obesity has increased the incidence of obesity-induced complications to historically high levels. Adipose tissue is a dynamic energy depot, which stores energy and mobilizes it during nutrient deficiency. Excess nutrient intake resulting in adipose tissue expansion triggers lipid release and aberrant adipokine, cytokine and chemokine production, and signaling that ultimately lead to adipose tissue inflammation, a hallmark of obesity. This low-grade chronic inflammation is thought to link obesity to insulin resistance and the associated comorbidities of metabolic syndrome such as dyslipidemia and hypertension, which increase risk of type 2 diabetes and cardiovascular disease. In this review, we focus on and discuss members of the chemokine system for which there is clear evidence of participation in the development of obesity and obesity-induced pathologies. PMID:24741577

  8. Roles of the Chemokine System in Development of Obesity, Insulin Resistance, and Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Longbiao Yao

    2014-01-01

    Full Text Available The escalating epidemic of obesity has increased the incidence of obesity-induced complications to historically high levels. Adipose tissue is a dynamic energy depot, which stores energy and mobilizes it during nutrient deficiency. Excess nutrient intake resulting in adipose tissue expansion triggers lipid release and aberrant adipokine, cytokine and chemokine production, and signaling that ultimately lead to adipose tissue inflammation, a hallmark of obesity. This low-grade chronic inflammation is thought to link obesity to insulin resistance and the associated comorbidities of metabolic syndrome such as dyslipidemia and hypertension, which increase risk of type 2 diabetes and cardiovascular disease. In this review, we focus on and discuss members of the chemokine system for which there is clear evidence of participation in the development of obesity and obesity-induced pathologies.

  9. Insulin resistance, body composition, and fat distribution in obese children with nonalcoholic fatty liver disease.

    Science.gov (United States)

    Yang, Hye Ran; Chang, Eun Jae

    2016-01-01

    The aim of this study was to evaluate the influence of body composition, especially distribution of body fat, and insulin resistance on nonalcoholic fatty liver disease (NAFLD) in obese children. One hundred obese children (66 boys, 34 girls) with (n=60) and without NAFLD (n=40) were assessed. Anthropometry, laboratory tests, abdominal ultrasonography, and dual energy x-ray absorption metry (DXA) were evaluated in all subjects. Subject age and measurements of liver enzymes, γ- glutamyl transpeptidase (γGT), uric acid, high-density lipoprotein cholesterol, and insulin resistance were significantly different between the non-NAFLD group and NAFLD group. Body fat and trunk fat percentage were significantly different between the two groups (pfat percentage was not (p=0.683). Insulin resistance correlated significantly with body fat and trunk fat percentages, age, liver enzymes, γGT, and uric acid in obese children. Multiple logistic regression analysis indicated that insulin resistance and trunk fat percentage significantly affected the development of NAFLD in obese children. Body fat, especially abdominal fat, influences the development of insulin resistance and subsequent NAFLD in obese children. Therefore, body composition measurement using DXA, in conjunction with biochemical tests, may be beneficial in evaluating obese children with NAFLD.

  10. Intestine-targeted DGAT1 inhibition improves obesity and insulin resistance without skin aberrations in mice.

    Directory of Open Access Journals (Sweden)

    Naoto Tsuda

    Full Text Available OBJECTIVE: Diacylglycerol O-acyltransferase 1 (DGAT1 catalyzes the final committed step in triglyceride biosynthesis. DGAT1 null mice are known to be resistant to diet-induced obesity, and more insulin sensitive relative to the wild-type; however, the mice exhibit abnormalities in the skin. This work determined whether the intestine-targeted DGAT1 inhibitor could improve obesity and insulin resistance without skin aberrations in mice. DESIGN AND METHODS: We synthesized 2 DGAT1 inhibitors: Compound A, described in the patent application from the Japan Tobacco, and Compound B (A-922500, reported by Abbott Laboratories. Both compounds were evaluated for inhibitory activities against DGAT1 enzymes and effects on the skin in mice in vivo. Compound B was further investigated for effects on obesity and insulin resistance in diet-induced-obese (DIO mice. RESULTS: The 2 compounds comparably inhibited the DGAT1 enzyme activity and the cellular triglyceride synthesis in vitro, while they showed different distribution patterns in mice in vivo. Compound A, which distributed systemically, caused skin aberrations, while Compound B, which preferentially distributed to the intestine, improved obesity and insulin resistance without skin aberrations in DIO mice. CONCLUSIONS: Our results suggest that the intestine is the key tissue in which DGAT1 plays a role in promoting obesity and insulin resistance.

  11. The neuroanatomical function of leptin in the hypothalamus.

    Science.gov (United States)

    van Swieten, M M H; Pandit, R; Adan, R A H; van der Plasse, G

    2014-11-01

    The anorexigenic hormone leptin plays an important role in the control of food intake and feeding-related behavior, for an important part through its action in the hypothalamus. The adipose-derived hormone modulates a complex network of several intercommunicating orexigenic and anorexigenic neuropeptides in the hypothalamus to reduce food intake and increase energy expenditure. In this review we present an updated overview of the functional role of leptin in respect to feeding and feeding-related behavior per distinct hypothalamic nuclei. In addition to the arcuate nucleus, which is a major leptin sensitive hub, leptin-responsive neurons in other hypothalamic nuclei, including the, dorsomedial-, ventromedial- and paraventricular nucleus and the lateral hypothalamic area, are direct targets of leptin. However, leptin also modulates hypothalamic neurons in an indirect manner, such as via the melanocortin system. The dissection of the complexity of leptin's action on the networks involved in energy balance is subject of recent and future studies. A full understanding of the role of hypothalamic leptin in the regulation of energy balance requires cell-specific manipulation using of conditional deletion and expression of leptin receptors. In addition, optogenetic and pharmacogenetic tools in combination with other pharmacological (such as the recent discovery of a leptin receptor antagonist) and neuronal tracing techniques to map the circuit, will be helpful to understand the role of leptin receptor expressing neurons. Better understanding of these circuits and the involvement of leptin could provide potential sites for therapeutic interventions in obesity and metabolic diseases characterized by dysregulation of energy balance. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Convergence in insulin resistance between very severely obese and lean women at the end of pregnancy.

    Science.gov (United States)

    Forbes, Shareen; Barr, Sarah M; Reynolds, Rebecca M; Semple, Scott; Gray, Calum; Andrew, Ruth; Denison, Fiona C; Walker, Brian R; Norman, Jane E

    2015-11-01

    Disrupted intermediary metabolism may contribute to the adverse pregnancy outcomes in women with very severe obesity. Our aim was to study metabolism in such pregnancies. We recruited a longitudinal cohort of very severely obese (n = 190) and lean (n = 118) glucose-tolerant women for anthropometric and metabolic measurements at early, mid and late gestation and postpartum. In case-control studies of very severely obese and lean women we measured glucose and glycerol turnover during low- and high-dose hyperinsulinaemic-euglycaemic clamps (HEC) at early and late pregnancy and in non-pregnant women (each n = 6-9) and body fat distribution by MRI in late pregnancy (n = 10/group). Although greater glucose, insulin, NEFA and insulin resistance (HOMA-IR), and greater weight and % fat mass (FM) was observed in very severely obese vs lean participants, the degree of worsening was attenuated in the very severely obese individuals with advancing gestation, with no difference in triacylglycerol (TG) concentrations between very severely obese and lean women at term. Enhanced glycerol production was observed in early pregnancy only in very severely obese individuals, with similar intrahepatic FM in very severely obese vs lean women by late gestation. Offspring from obese mothers were heavier (p = 0.04). Pregnancies complicated by obesity demonstrate attenuation in weight gain and insulin resistance compared with pregnancies in lean women. Increased glycerol production is confined to obese women in early pregnancy and obese and lean individuals have similar intrahepatic FM by term. When targeting maternal metabolism to treat adverse pregnancy outcomes, therapeutic intervention may be most effective applied early in pregnancy.

  13. Impact of exercise training without caloric restriction on inflammation, insulin resistance and visceral fat mass in obese adolescents.

    Science.gov (United States)

    Mendelson, M; Michallet, A-S; Monneret, D; Perrin, C; Estève, F; Lombard, P R; Faure, P; Lévy, P; Favre-Juvin, A; Pépin, J-L; Wuyam, B; Flore, P

    2015-08-01

    Exercise training has been shown to improve cardiometabolic health in obese adolescents. Evaluate the impact of a 12-week exercise-training programme (without caloric restriction) on obese adolescents' cardiometabolic and vascular risk profiles. We measured systemic markers of oxidation, inflammation, metabolic variables and endothelial function in 20 obese adolescents (OB) (age: 14.5 ± 1.5 years; body mass index: 34.0 ± 4.7 kg m(-2) ) and 20 age- and gender-matched normal-weight adolescents (NW). Body composition was assessed by magnetic resonance imagery. Peak aerobic capacity and maximal fat oxidation were evaluated during specific incremental exercise tests. OB participated in a 12-week exercise-training programme. OB presented lower peak aerobic capacity (24.2 ± 5.9 vs. 39.8 ± 8.3 mL kg(-1)  min(-1) , P < 0.05) and maximal fat oxidation compared with NW (P < 0.05). OB displayed greater F2t-Isoprostanes (20.5 ± 6.7 vs. 13.4 ± 4.2 ng mmol(-1) creatinine), Interleukin-1 receptor antagonist (IL-1Ra) (1794.8 ± 532.2 vs. 835.1 ± 1027.4 pg mL(-1) ), Tumor Necrosis Factor-α (TNF-α) (2.1 ± 1.2 vs. 1.5 ± 1.0 pg mL(-1) ), Soluble Tumor Necrosis Factor-α Type II Receptor (sTNFαRII), leptin, insulin, homeostasis model assessment of insulin resistance, version 2 (HOMA2-IR), high-sensitive C-reactive protein, triglycerides and lower adiponectin and high-density lipoprotein cholesterol (all P < 0.05). After exercise training, despite lack of weight loss, VO2peak (mL.kg(-1) .min(-1) ) and maximal fat oxidation increased (P < 0.05). IL-1Ra and IFN-gamma-inducible protein 10 (IP-10) decreased (P < 0.05). Insulin and HOMA2-IR decreased (14.8 ± 1.5 vs. 10.2 ± 4.2 μUI mL(-1) and 1.9 ± 0.8 vs. 1.3 ± 0.6, respectively, P < 0.05). Change in visceral fat mass was inversely associated with change in maximal fat oxidation (r = -0.54; P = 0.024). The

  14. Insights into the role of macrophage migration inhibitory factor in obesity and insulin resistance.

    LENUS (Irish Health Repository)

    Finucane, Orla M

    2012-11-01

    High-fat diet (HFD)-induced obesity has emerged as a state of chronic low-grade inflammation characterised by a progressive infiltration of immune cells, particularly macrophages, into obese adipose tissue. Adipose tissue macrophages (ATM) present immense plasticity. In early obesity, M2 anti-inflammatory macrophages acquire an M1 pro-inflammatory phenotype. Pro-inflammatory cytokines including TNF-α, IL-6 and IL-1β produced by M1 ATM exacerbate local inflammation promoting insulin resistance (IR), which consequently, can lead to type-2 diabetes mellitus (T2DM). However, the triggers responsible for ATM recruitment and activation are not fully understood. Adipose tissue-derived chemokines are significant players in driving ATM recruitment during obesity. Macrophage migration inhibitory factor (MIF), a chemokine-like inflammatory regulator, is enhanced during obesity and is directly associated with the degree of peripheral IR. This review focuses on the functional role of macrophages in obesity-induced IR and highlights the importance of the unique inflammatory cytokine MIF in propagating obesity-induced inflammation and IR. Given MIF chemotactic properties, MIF may be a primary candidate promoting ATM recruitment during obesity. Manipulating MIF inflammatory activities in obesity, using pharmacological agents or functional foods, may be therapeutically beneficial for the treatment and prevention of obesity-related metabolic diseases.

  15. Herbal Formula HT048 Attenuates Diet-Induced Obesity by Improving Hepatic Lipid Metabolism and Insulin Resistance in Obese Rats

    Directory of Open Access Journals (Sweden)

    Yoon Hee Lee

    2016-10-01

    Full Text Available It is well established that obesity causes a variety of chronic diseases such as cardiovascular diseases and diabetes. Despite the diligent scientific efforts to find effective ways to lower the level of obesity, the size of obese population grows continuously around the world. Here we present the results that show feeding diet containing HT048, a mixture of the extracts of Crataegus pinnatifida leaves and Citrus unshiu peel, two of the well-known traditional herbal medicines in Eastern Asia, decreases obesity in rats. We fed rats with five different diets for 10 weeks: chow diet (STD, high-fat diet (HFD, high-fat diet with 0.04% orlistat, a drug to treat obesity (HFD + Orlistat, high-fat diet with 0.2% HT048 (w/w; HFD + 0.2% HT048, and high-fat diet with 0.6% HT048 (w/w; HFD + 0.6% HT048. It was found that both body and total white adipose tissue weight of HT048 groups significantly decreased compared to those of the HFD group. Moreover, HT048 decreased serum insulin levels in HFD-fed obese rats. At the molecular level, HT048 supplementation downregulated genes involved in lipogenesis, gluconeogenesis, and adipogenesis, while the expression level of β-oxidation genes was increased. Supplementation-drug interactions are not likely as HFD and HT048-containing diet did not significantly induce genes encoding CYPs. Collectively, this study suggests that HT048 taken as dietary supplement helps to decrease obesity and insulin resistance in HFD-fed obese rats.

  16. Obesity, ectopic lipids, and insulin resistance : Tissue-specific defects in nutrient handling

    NARCIS (Netherlands)

    ter Horst, K.W.

    2017-01-01

    This thesis described studies on the clinical, nutritional, and molecular aspects of insulin resistance in human obesity. We investigated methods for the identification of insulin resistance in high-risk patients and studied the nutritional and molecular mechanisms that may contribute to insulin

  17. Intestinal Microbiota Contributes to Energy Balance, Metabolic Inflammation, and Insulin Resistance in Obesity

    Directory of Open Access Journals (Sweden)

    Joseph F. Cavallari

    2017-09-01

    Full Text Available Obesity is associated with increased risk of developing metabolic diseases such as type 2 diabetes. The origins of obesity are multi-factorial, but ultimately rooted in increased host energy accumulation or retention. The gut microbiota has been implicated in control of host energy balance and nutrient extraction from dietary sources. The microbiota also impacts host immune status and dysbiosis-related inflammation can augment insulin resistance, independently of obesity. Advances in microbial metagenomic analyses and directly manipulating bacterial-host models of obesity have contributed to our understanding of the relationship between gut bacteria and metabolic disease. Foodborne, or drug-mediated perturbations to the gut microbiota can increase metabolic inflammation, insulin resistance, and dysglycemia. There is now some evidence that specific bacterial species can influence obesity and related metabolic defects such as insulin sensitivity. Components of bacteria are sufficient to impact obesity-related changes in metabolism. In fact, different microbial components derived from the bacterial cell wall can increase or decrease insulin resistance. Improving our understanding of the how components of the microbiota alter host metabolism is positioned to aid in the development of dietary interventions, avoiding triggers of dysbiosis, and generating novel therapeutic strategies to combat increasing rates of obesity and diabetes.

  18. Insulin Resistance, Dyslipidemia and Cardiovascular Changes in a Group of Obese Children

    Energy Technology Data Exchange (ETDEWEB)

    Pires, António, E-mail: pires1961@gmail.com; Martins, Paula [Centro Hospitalar e Universitário de Coimbra, Coimbra (Portugal); Pereira, Ana Margarida [Laboratório de Fisiologia - Instituto Biomédico de Investigação da Luz e Imagem da Faculdade de Medicina da Universidade de Coimbra, Coimbra (Portugal); Silva, Patricia Vaz; Marinho, Joana [Centro Hospitalar e Universitário de Coimbra, Coimbra (Portugal); Marques, Margarida [Laboratório de Estatística da Faculdade de Medicina da Universidade de Coimbra - Instituto Biomédico de Investigação da Luz e Imagem, Coimbra (Portugal); Castela, Eduardo [Centro Hospitalar e Universitário de Coimbra, Coimbra (Portugal); Sena, Cristina; Seiça, Raquel [Laboratório de Fisiologia - Instituto Biomédico de Investigação da Luz e Imagem da Faculdade de Medicina da Universidade de Coimbra, Coimbra (Portugal)

    2015-04-15

    Obesity-related comorbidities are present in young obese children, providing a platform for early adult cardiovascular disorders. To compare and correlate markers of adiposity to metabolic disturbances, vascular and cardiac morphology in a European pediatric obese cohort. We carried out an observational and transversal analysis in a cohort consisting of 121 obese children of both sexes, between the ages of 6 and 17 years. The control group consisted of 40 children with normal body mass index within the same age range. Markers of adiposity, plasma lipids and lipoproteins, homeostasis model assessment-insulin resistance, common carotid artery intima-media thickness and left ventricular diameters were analyzed. There were statistically significant differences between the control and obese groups for the variables analyzed, all higher in the obese group, except for age, high-density lipoprotein cholesterol and adiponectin, higher in the control group. In the obese group, body mass index was directly correlated to left ventricular mass (r=0.542; p=0.001), the homeostasis model assessment-insulin resistance (r=0.378; p=<0.001) and mean common carotid artery intima-media thickness (r=0.378; p=<0.001). In that same group, insulin resistance was present in 38.1%, 12.5% had a combined dyslipidemic pattern, and eccentric hypertrophy was the most common left ventricular geometric pattern. These results suggest that these markers may be used in clinical practice to stratify cardiovascular risk, as well as to assess the impact of weight control programs.

  19. Association between Myeloperoxidase Levels and Risk of Insulin Resistance in Egyptian Obese Women

    Science.gov (United States)

    Zaki, Moushira; Basha, Walaa; Reyad, Hanaa; Mohamed, Ramy; Hassan, Naglaa; Kholousi, Shams

    2018-01-01

    BACKGROUND: Myeloperoxidase (MPO) is an enzyme involved in the pathogenesis of several diseases. AIM: The current study aimed to investigate serum MPO levels in obese Egyptian women and assess its relation with insulin resistance (IR) and other biochemical risk parameters. METHODS: The study included 80 obese women and 50 age-and-sex-matched healthy controls. Insulin resistance (IR) was evaluated by the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR). Serum MPO, fasting glucose, insulin and blood lipids and anthropometry were measured. Obese cases were divided into three groups based on MPO tertiles. ROC analysis was performed to obtain the optimal cut-off values of MPO to predicate IR in obese women. RESULTS: The mean serum MPO was significantly higher in obese cases than controls. Cases in the highest MPO tertile had higher HOMA-IR, blood lipids and pressure levels compared with those in the lower tertile. The cutoff point of MPO was > 87.8 (ng/mL) and area under curves was 0.82 (p < 0.01) for diagnosis of IR. MPO levels were higher in obese Egyptian women than healthy controls. CONCLUSION: Elevation of MPO was associated with abnormal metabolic parameters. MPO might be used as an earlier biomarker for IR and metabolic disturbance in obese women. PMID:29731928

  20. Insulin Resistance, Dyslipidemia and Cardiovascular Changes in a Group of Obese Children

    International Nuclear Information System (INIS)

    Pires, António; Martins, Paula; Pereira, Ana Margarida; Silva, Patricia Vaz; Marinho, Joana; Marques, Margarida; Castela, Eduardo; Sena, Cristina; Seiça, Raquel

    2015-01-01

    Obesity-related comorbidities are present in young obese children, providing a platform for early adult cardiovascular disorders. To compare and correlate markers of adiposity to metabolic disturbances, vascular and cardiac morphology in a European pediatric obese cohort. We carried out an observational and transversal analysis in a cohort consisting of 121 obese children of both sexes, between the ages of 6 and 17 years. The control group consisted of 40 children with normal body mass index within the same age range. Markers of adiposity, plasma lipids and lipoproteins, homeostasis model assessment-insulin resistance, common carotid artery intima-media thickness and left ventricular diameters were analyzed. There were statistically significant differences between the control and obese groups for the variables analyzed, all higher in the obese group, except for age, high-density lipoprotein cholesterol and adiponectin, higher in the control group. In the obese group, body mass index was directly correlated to left ventricular mass (r=0.542; p=0.001), the homeostasis model assessment-insulin resistance (r=0.378; p=<0.001) and mean common carotid artery intima-media thickness (r=0.378; p=<0.001). In that same group, insulin resistance was present in 38.1%, 12.5% had a combined dyslipidemic pattern, and eccentric hypertrophy was the most common left ventricular geometric pattern. These results suggest that these markers may be used in clinical practice to stratify cardiovascular risk, as well as to assess the impact of weight control programs

  1. Obesity and Prader-Willi Syndrome Affect Heart Rate Recovery from Dynamic Resistance Exercise in Youth

    Directory of Open Access Journals (Sweden)

    Diobel M. Castner

    2016-01-01

    Full Text Available Following exercise, heart rate decline is initially driven by parasympathetic reactivation and later by sympathetic withdrawal. Obesity delays endurance exercise heart rate recovery (HRR in both children and adults. Young people with Prader-Willi Syndrome (PWS, a congenital cause for obesity, have shown a slower 60-s endurance exercise HRR compared to lean and obese children, suggesting compromised regulation. This study further evaluated effects of obesity and PWS on resistance exercise HRR at 30 and 60 s in children. PWS (8–18 years and lean and obese controls (8–11 years completed a weighted step-up protocol (six sets x 10 reps per leg, separated by one-minute rest, standardized using participant stature and lean body mass. HRR was evaluated by calculated HRR value (HRRV = difference between HR at test termination and 30 (HRRV30 and 60 (HRRV60 s post-exercise. PWS and obese had a smaller HRRV30 than lean (p < 0.01 for both. Additionally, PWS had a smaller HRRV60 than lean and obese (p = 0.01 for both. Obesity appears to delay early parasympathetic reactivation, which occurs within 30 s following resistance exercise. However, the continued HRR delay at 60 s in PWS may be explained by either blunted parasympathetic nervous system reactivation, delayed sympathetic withdrawal and/or poor cardiovascular fitness.

  2. Corticosteroids and obesity in steroid-sensitive and steroid-resistant nephrotic syndrome

    Directory of Open Access Journals (Sweden)

    Nina Lestari

    2015-07-01

    Full Text Available Background Children with nephrotic syndrome need high-dose corticosteroids to achieve remission. Studies have estimated a 35-43% risk of obesity in these patients after corticosteroid treatment. Objective To determine the prevalence of obesity in children who received corticosteroids for nephrotic syndrome, and to compare the risk of obesity in children with steroid-sensitive nephrotic syndrome (SSNS and steroid-resistant nephrotic syndrome (SRNS. Methods We performed a retrospective cohort study in 50 children with SSNS or SRNS who received corticosteroid treatment. Obesity was defined to be a BMI-for-age Z-score above +2.0 SD, according to the WHO Growth Reference 2007. Central obesity was defined to be a waist-to-height ratio > 0.50. Results The overall prevalence of obesity was 22%, with 29% and 14% in the SSNS and SRNS groups, respectively. The overall prevalence of central obesity was 50%, with 54% and 46% in the SSNS and SRNS groups, respectively. The cumulative steroid doses in this study were not significantly different between the SSNS and SRNS groups. There were also no significant differences between groups for risk of obesity (RR 2.53; 95%CI 0.58 to 10.99 or central obesity (RR 1.39; 95%CI 0.45 to 4.25. Conclusion In children with nephrotic syndrome who received corticosteroids, the prevalence of obesity is 22% and of central obesity is 50%. In a comparison of SSNS and SRNS groups, cumulative steroid dose as well as risks of obesity and central obesity do not significantly differ between groups.

  3. Leptin and Reproduction: Past Milestones, Present Undertakings and Future Endeavors

    Science.gov (United States)

    Chehab, Farid F.

    2014-01-01

    The association between leptin and reproduction originated with the leptin-mediated correction of sterility in ob/ob mice and initiation of reproductive function in normal female mice. The uncovering of a central leptin pathway regulating food intake prompted the dissection of neuroendocrine mechanisms involving leptin in the metabolic control of reproduction. The absence of leptin receptors on GnRH neurons incited a search for intermediary neurons situated between leptin responsive and GnRH neurons. This review addresses the most significant findings that have furthered our understanding of recent progress in this new field. The role of leptin in puberty was impacted by the discovery of neurons that co-express kisspeptin, neurokinin B and dynorphin and that could act as leptin intermediates. Furthermore, the identification of first-order leptin-responsive neurons in the premammilary ventral nucleus and other brain regions opens new avenues to explore their relationship to GnRH neurons. Central to these advances is the unveiling that AgRP/NPY neurons project onto GnRH and kisspeptin neurons, allowing a crosstalk between food intake and reproduction. Finally, whereas puberty is a state of leptin sensitivity, mid-gestation represents a state of leptin resistance aimed at building energy stores to sustain pregnancy and lactation. Mechanisms underlying leptin resistance in pregnancy have lagged, however the establishment of this natural state is significant. Reproduction and energy balance are tightly controlled and backed up by redundant mechanisms that are critical for the survival of our species. It will be the goal of the next decade to shed new light on these complex and essential pathways. PMID:25118207

  4. Insulin Resistance, Metabolic Syndrome, and Polycystic Ovary Syndrome in Obese Youth.

    Science.gov (United States)

    Platt, Adrienne M

    2015-07-01

    School nurses are well aware of the childhood obesity epidemic in the United States, as one in three youth are overweight or obese. Co-morbidities found in overweight or obese adults were not commonly found in youth three decades ago but are now increasingly "normal" as the obesity epidemic continues to evolve. This article is the second of six related articles discussing the co-morbidities of childhood obesity and discusses the complex association between obesity and insulin resistance, metabolic syndrome, and polycystic ovary syndrome. Insulin resistance increases up to 50% during puberty, which may help to explain why youth are more likely to develop co-morbidities as teens. Treatment of these disorders is focused on changing lifestyle habits, as a child cannot change his or her pubertal progression, ethnicity, or family history. School nurses and other personnel can assist youth with insulin resistance, metabolic syndrome, and polycystic ovary syndrome by supporting their efforts to make changes, reinforcing that insulin resistance is not necessarily type 2 diabetes even if the child is taking medication, and intervening with negative peer pressure. © 2015 The Author(s).

  5. The correlation of plasma omentin-1 with insulin resistance in non-obese polycystic ovary syndrome.

    Science.gov (United States)

    Yang, Hai-Yan; Ma, Yan; Lu, Xin-Hong; Liang, Xing-Huan; Suo, Ying-Jun; Huang, Zhen-Xing; Lu, De-Cheng; Qin, Ying-Fen; Luo, Zuo-Jie

    2015-10-01

    Aberrant circulating adipokines are considered to be related to the pathological mechanism of polycystic ovary syndrome (PCOS). This study aims to evaluate the relationship between plasma omentin-1 levels, metabolic and hormonal parameters in the setting of non-obese Chinese women with PCOS. This was a case-controlled, cross-sectional study of 153 non-obese (BMIovary volume were analyzed in all subjects. Plasma omentin-1 levels of non-obese PCOS individuals were significantly lower than in healthy non-obese controls. Body Mass Index (BMI), homeostasis model of assessment for insulin resistance index (HOMA-IR), levels of testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), LH/FSH ratio and ovary volume (OV) were significantly higher in subjects with PCOS than controls. In the HOMA-IR stratified subgroups, PCOS individuals with insulin resistance had lower omentin-1 than those without insulin resistance after BMI adjustment. Omentin-1 was negatively correlated with BMI, HOMA-IR and fasting insulin. Multiple linear regressions revealed that BMI contributed to omentin-1 levels. Ovary volume was negatively correlated to HOMA-IR but had no correlation with omentin-1. Plasma omentin-1 concentrations were decreased in the non-obese PCOS group. Insulin resistance could further decrease plasma omentin-1 in non-obese individuals with PCOS independent of BMI status. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  6. The Relationship between Serum Zonulin Level and Clinical and Laboratory Parameters of Childhood Obesity.

    Science.gov (United States)

    Küme, Tuncay; Acar, Sezer; Tuhan, Hale; Çatlı, Gönül; Anık, Ahmet; Gürsoy Çalan, Özlem; Böber, Ece; Abacı, Ayhan

    2017-03-01

    To investigate the relationship between zonulin levels and clinical and laboratory parameters of childhood obesity. The study included obese children with a body mass index (BMI) >95 th percentile and healthy children who were of similar age and gender distribution. Clinical (BMI, waist circumferences, mid-arm circumference, triceps skinfold, percentage of body fat, systolic blood pressure, diastolic blood pressure) and biochemical (glucose, insulin, lipid levels, thyroid function tests, cortisol, zonulin and leptin levels) parameters were measured. A total of 43 obese subjects (23 males, mean age: 11.1±3.1 years) and 37 healthy subjects (18 males, mean age: 11.5±3.5 years) were included in this study. Obese children had significantly higher insulin, homeostasis model assessment of insulin resistance, triglyceride, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), zonulin and leptin levels than healthy children (p0.05). Comparison of the obese children with and without insulin resistance showed no statistically significant differences for zonulin levels (p>0.05). Zonulin levels were found to negatively correlate with HDL-C and positively correlate with leptin levels, after adjusting for age and BMI. To the best of our knowledge, this is the first study investigating the relationship between circulating zonulin level (as a marker of intestinal permeability) and insulin resistance and leptin (as markers of metabolic disturbances associated with obesity) in childhood obesity. The results showed that zonulin was significantly higher in obese children when compared to healthy children, a finding indicating a potential role of zonulin in the etiopathogenesis of obesity and related disturbances.

  7. Leptin promoter variant G2548A is associated with serum leptin

    Indian Academy of Sciences (India)

    The aim of the current study was to investigate the relationship of such a promoter variant of the leptin gene, G-2548A polymorphism, with obesity and its effect on various anthropometric and metabolic parameters in a ... Department of Microbiology and Molecular Genetics, University of the Punjab, Lahore, Pakistan, 54590.

  8. Adipokines and Hepatic Insulin Resistance

    Science.gov (United States)

    Hassan, Waseem

    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, clarification of the regulatory processes about hepatic insulin resistance by adipokines in rodents and human would seem essential in order to understand the mechanism of type 2 diabetes and for developing novel therapeutic strategies to treat it. PMID:23762871

  9. Insulin resistance and neurodegeneration: Roles of obesity, type 2 diabetes mellitus and non-alcoholic steatohepatitis

    OpenAIRE

    de la Monte, Suzanne M; Longato, Lisa; Tong, Ming; Wands, Jack R

    2009-01-01

    Recent studies have linked obesity, type 2 diabetes mellitus (T2DM) or non-alcoholic steatohepatitis (NASH) to insulin resistance in the brain, cognitive impairment and neurodegeneration. Insulin resistance compromises cell survival, metabolism and neuronal plasticity, and increases oxidative stress, cytokine activation and apoptosis. T2DM/NASH has been demonstrated to be associated with increased ceramide generation, suggesting a mechanistic link between peripheral insulin resistance and neu...

  10. Prevalence of impaired glucose tolerance and insulin resistance among obese children and adolescents

    Directory of Open Access Journals (Sweden)

    Robabeh Ghergherechi

    2010-07-01

    Full Text Available Robabeh Ghergherechi1, Ali Tabrizi21Department of Pediatrics Endocrinology, Tabriz University of Medical Sciences, Tabriz, Iran; 2Students’ Research Committee, Tabriz University of Medical Sciences, Tabriz, IranPurpose: Obesity is one of the most important nutritional disorders in the world which has an obvious relationship with the incidence of metabolic diseases. Obesity prevalence has increased among children and adolescents during recent decades, leading to a rise in Type 2 diabetes mellitus (DM II prevalence in these two age brackets. Hence, the aim of this study was to assess impaired glucose tolerance and insulin resistance, and gather metabolic findings in obese children and adolescents.Methods and materials: We studied 110 obese children and adolescents (body mass index > 95th percentile for age and gender 4–18 years of age referred to the endocrine clinic of the Children’s Hospital at Tabriz University in a descriptive cross-sectional study. ­Fasting glucose, insulin, and lipid profile in all subjects were determined. Oral glucose tolerance test after eating 75 g/kg glucose was performed. Homeostatic model assessment was used to ­estimate insulin resistance.Results: Impaired glucose tolerance and insulin resistance prevalence in 68 obese adolescents was 14.7% and 31.8%, respectively. Impaired glucose tolerance and insulin resistance was not seen in 23.8% of 42 obese children. No case of DM II was seen. There was a significant statistical difference in glucose (P = 0.003 and insulin (P < 0.001 level at minute 120 in individuals with impaired glucose tolerance compared to obese children and adolescents without impaired glucose tolerance. Rate of insulin resistance in patients with impaired glucose tolerance was greater and had a significant statistical difference (P = 0.03.Conclusion: Obesity has a close relationship with increased risk of impaired glucose tolerance and insulin resistance in children and adolescents. Oral glucose

  11. Role of GABA Release From Leptin Receptor-Expressing Neurons in Body Weight Regulation

    Science.gov (United States)

    Xu, Yuanzhong; O'Brien, William G.; Lee, Cheng-Chi; Myers, Martin G.

    2012-01-01

    It is well established that leptin regulates energy balance largely through isoform B leptin receptor-expressing neurons (LepR neurons) in the brain and that leptin activates one subset of LepR neurons (leptin-excited neurons) while inhibiting the other (leptin-inhibited neurons). However, the neurotransmitters released from LepR neurons that mediate leptin action in the brain are not well understood. Previous results demonstrate that leptin mainly acts on γ-aminobutyric acid (GABA)ergic neurons to reduce body weight, and that leptin activates proopiomelanocortin neuron activity by reducing GABA release onto these neurons, suggesting a body weight-promoting role for GABA released from leptin-inhibited neurons. To directly examine the role of GABA release from LepR neurons in body weight regulation, mice with disruption of GABA release specifically from LepR neurons were generated by deletion of vesicular GABA transporter in LepR neurons. Interestingly, these mice developed mild obesity on chow diet and were sensitive to diet-induced obesity, which were associated with higher food intake and lower energy expenditure. Moreover, these mice showed blunted responses in both food intake and body weight to acute leptin administration. These results demonstrate that GABA plays an important role in mediating leptin action. In combination with the previous studies that leptin reduces GABA release onto proopiomelanocortin neurons through leptin-inhibited neurons and that disruption of GABA release from agouti gene-related protein neurons, one subset of LepR-inhibited neurons, leads to a lean phenotype, our results suggest that, under our experimental conditions, GABA release from leptin-excited neuron dominates over leptin-inhibited ones. PMID:22334723

  12. Modification of the β-Adrenoceptor Stimulation Pathway in Zucker Obese and Obese Diabetic Rat Myocardium.

    Science.gov (United States)

    Jiang, Cheng; Carillion, Aude; Na, Na; De Jong, Audrey; Feldman, Sarah; Lacorte, Jean-Marc; Bonnefont-Rousselot, Dominique; Riou, Bruno; Amour, Julien

    2015-07-01

    Although metabolic syndrome is associated with increased sympathetic activity that chronically stimulates β-adrenoceptors, the β-adrenoceptor signaling pathway has been poorly studied in this situation. We studied the β-adrenoceptor signaling pathway in Zucker lean, obese, and obese diabetic rats. Experimental, prospective study. University medical research lab