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

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

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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.

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.

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

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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

Pleotropic effects of leptin to reverse insulin resistance and diabetic ketoacidosis

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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...

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

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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...

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

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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.

Relationship between peripheral leptin receptor and leptin in obese subjects

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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

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

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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

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

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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.

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.

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

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

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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.

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

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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.

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

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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.

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

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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.

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

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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.

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

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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

The clinical meanings of leptin RIA in patients with chronic renal failure

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Zhang Baoqing; Chen Yongsheng; Zhao Yuexia; Wang Yihai

2006-01-01

Objective: To explore the relationship between chronic renal failure and serum leptin levels in patients with chronic renal failure. Methods: Serum leptin levels (with RIA) were determined in 134 patients (male, 73, female 61) with chronic renal failure and 40 controls. Results: The serum levels of leptin in the chronic renal failure group were significantly higher than those in the controls (t=2.39, P<0.01). There were no significant differences among the leptin levels in patients with different stages of renal failure. Conclusion: There were hyper-leptinemia and leptin resistance in patients with chronic renal failure. The increase of leptin levels is thought to be harmful in patients with chronic renal failure, however, the precise mechanism remains to be studied further. (authors)

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

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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...

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

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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

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

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

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

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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.

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

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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.

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)

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

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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.

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

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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.

Whole-Body Vibration Mimics the Metabolic Effects of Exercise in Male Leptin Receptor-Deficient Mice.

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McGee-Lawrence, Meghan E; Wenger, Karl H; Misra, Sudipta; Davis, Catherine L; Pollock, Norman K; Elsalanty, Mohammed; Ding, Kehong; Isales, Carlos M; Hamrick, Mark W; Wosiski-Kuhn, Marlena; Arounleut, Phonepasong; Mattson, Mark P; Cutler, Roy G; Yu, Jack C; Stranahan, Alexis M

2017-05-01

Whole-body vibration (WBV) has gained attention as a potential exercise mimetic, but direct comparisons with the metabolic effects of exercise are scarce. To determine whether WBV recapitulates the metabolic and osteogenic effects of physical activity, we exposed male wild-type (WT) and leptin receptor-deficient (db/db) mice to daily treadmill exercise (TE) or WBV for 3 months. Body weights were analyzed and compared with WT and db/db mice that remained sedentary. Glucose and insulin tolerance testing revealed comparable attenuation of hyperglycemia and insulin resistance in db/db mice following TE or WBV. Both interventions reduced body weight in db/db mice and normalized muscle fiber diameter. TE or WBV also attenuated adipocyte hypertrophy in visceral adipose tissue and reduced hepatic lipid content in db/db mice. Although the effects of leptin receptor deficiency on cortical bone structure were not eliminated by either intervention, exercise and WBV increased circulating levels of osteocalcin in db/db mice. In the context of increased serum osteocalcin, the modest effects of TE and WBV on bone geometry, mineralization, and biomechanics may reflect subtle increases in osteoblast activity in multiple areas of the skeleton. Taken together, these observations indicate that WBV recapitulates the effects of exercise on metabolism in type 2 diabetes.

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

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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.

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)

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

Temporal changes in nutritional state affect hypothalamic POMC peptide levels independently of leptin in adult male mice.

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Mercer, Aaron J; Stuart, Ronald C; Attard, Courtney A; Otero-Corchon, Veronica; Nillni, Eduardo A; Low, Malcolm J

2014-04-15

Hypothalamic proopiomelanocortin (POMC) neurons constitute a critical anorexigenic node in the central nervous system (CNS) for maintaining energy balance. These neurons directly affect energy expenditure and feeding behavior by releasing bioactive neuropeptides but are also subject to signals directly related to nutritional state such as the adipokine leptin. To further investigate the interaction of diet and leptin on hypothalamic POMC peptide levels, we exposed 8- to 10-wk-old male POMC-Discosoma red fluorescent protein (DsRed) transgenic reporter mice to either 24-48 h (acute) or 2 wk (chronic) food restriction, high-fat diet (HFD), or leptin treatment. Using semiquantitative immunofluorescence and radioimmunoassays, we discovered that acute fasting and chronic food restriction decreased the levels of adrenocorticotropic hormone (ACTH), α-melanocyte-stimulating hormone (α-MSH), and β-endorphin in the hypothalamus, together with decreased DsRed fluorescence, compared with control ad libitum-fed mice. Furthermore, acute but not chronic HFD or leptin administration selectively increased α-MSH levels in POMC fibers and increased DsRed fluorescence in POMC cell bodies. HFD and leptin treatments comparably increased circulating leptin levels at both time points, suggesting that transcription of Pomc and synthesis of POMC peptide products are not modified in direct relation to the concentration of plasma leptin. Our findings indicate that negative energy balance persistently downregulated POMC peptide levels, and this phenomenon may be partially explained by decreased leptin levels, since these changes were blocked in fasted mice treated with leptin. In contrast, sustained elevation of plasma leptin by HFD or hormone supplementation did not significantly alter POMC peptide levels, indicating that enhanced leptin signaling does not chronically increase Pomc transcription and peptide synthesis.

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

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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.

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

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

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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 years of leptin: leptin and reproduction: past milestones, present undertakings, and future endeavors.

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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.

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...

Leptin and reproduction: a review.

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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.

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)

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

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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

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

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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.

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.

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.

Leptin in humans: lessons from translational research.

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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.

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

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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

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

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

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....

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

[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.

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

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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.

Variations in leptin, nesfatin-1 and irisin levels induced by aerobic exercise in young trained and untrained male subjects

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Sermin Algul

2017-12-01

Full Text Available The aims of this study were to investigate the impacts of acute aerobic exercise on circulating levels of hormones associated with energy metabolism, namely leptin, nesfatin-1 and irisin, in trained and untrained male subjects and to determine whether the timing of the exercise (i.e. morning or night amplified these impacts. Thirty trained (19.2±0.7 years and 30 untrained (19.5±0.6 years male subjects performed two aerobic running exercises (3 days between tests to 64-76% of the subjects’ maximal heart rate for about 30 min. Pre- and post-exercise venous blood samples were taken and analysed for leptin, nesfatin-1 and irisin using enzyme-linked immunosorbent assay (ELISA. Paired samples and independent samples t-tests were used to analyse data. Irisin levels increased in all the subjects (p<0.001. In both groups, nesfatin-1 levels increased significantly after the night-time exercise (p<0.05. Importantly, leptin and nesfatin-1 levels varied among the trained and untrained groups: Both leptin and nesfatin-1 levels increased in 4 (13% and 12 (40% subjects, respectively, after the morning exercises, and they increased in 9 (30% and 10 (33% subjects, respectively, after the night-time exercise. They decreased in 5 (16% and 7 (23% subjects, respectively, after the morning exercise and in 6 (20% and 3 (10% subjects, respectively, after the night-time exercise. Exercise may result in increased energy consumption by altering irisin levels. However, due to variations among individuals, increasing leptin and nesfatin-1 levels by reducing food intake may not be applicable.

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

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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

Leptin levels in children and adults with classic galactosaemia.

LENUS (Irish Health Repository)

Knerr, Ina

2012-11-07

Among the long-term complications of Classic Galactosaemia (Gal) is premature ovarian insufficiency (POI) in female patients with subtle abnormalities of reproductive function also reported in male patients. Leptin is a circulating hormone which reflects body energy stores and which affects the neuroendocrine reproductive axis and pubertal development.We measured serum leptin in 28 children (10 girls, 18 boys; mean age 7.6 years, range 0.5-17.9 years) and in 22 adults (10 females, 12 males; mean age 23.9 years, range 18-37 years) with Gal on a strict galactose-restricted diet in comparison with control data.Leptin levels (expressed as SDS for gender and pubertal stage) were lower in Gal children than controls (mean leptin-SDS = -0.71 for girls, p < 0.05, -0.97 for boys compared with SDS = 0 for controls, p < 0.05). In an age-related analysis, leptin levels did not correlate with age in children with Gal for both sexes as it did for matched controls.As expected, females had higher leptin levels than males in either group. In adults with Gal, leptin concentrations were within normal limits for both sexes when adjusted for gender and BMI. There was a linear relationship between log-leptin and BMI in children with Gal and in controls. For Gal women, log-leptin was also associated with BMI. However, for Gal men, and hence for the entire group of adult Gal patients, this association between log-leptin and BMI was not detectable. Our findings suggest that leptin dysregulation may play a role in fertility issues in individuals with Gal from an early age.

Congenital leptin deficiency and thyroid function

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Paz-Filho Gilberto

2009-11-01

Full Text Available Abstract Thyroid function is closely related to leptin's secretion by the adipose tissue. In states of leptin-deficiency, the circadian rhythm of TSH is altered, leading to central hypothyroidism in animal models. In humans, central hypothyroidism has also been described in rare cases of congenital leptin deficiency. However, the thyroid phenotype in these cases is heterogeneous, with the occurrence of central hypothyroidism in a minority of cases. Here we describe thyroid function in four leptin-deficient humans (2 males aged 5 and 27, and 2 females aged 35 and 40, before and during leptin replacement with recombinant human methionyl leptin (r-metHuLeptin. The child was evaluated for four years, and the adults, for eight years. In addition, the adults were submitted to a brief withdrawal of leptin during six weeks in the sixth year. Our results show that, regardless of leptin replacement, our leptin-deficient patients have normal thyroid function. In spite of having an important role in regulating the hypothalamic-pituitary-thyroidal axis, leptin is not required for normal thyroid function. Trial Registration ClinicalTrials.gov Identifiers: NCT00659828 and NCT00657605

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

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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.

Gender Specific Association of Serum Leptin and Insulinemic Indices with Nonalcoholic Fatty Liver Disease in Prediabetic Subjects.

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Israt Ara Hossain

Full Text Available Adipose tissue-derived hormone leptin plays a functional role in glucose tolerance through its effects on insulin secretion and insulin sensitivity which also represent the risk factors for nonalcoholic fatty liver disease (NAFLD. The present study explored the gender specific association of serum leptin and insulinemic indices with NAFLD in Bangladeshi prediabetic subjects. Under a cross-sectional analytical design a total of 110 ultrasound examined prediabetic subjects, aged 25-68 years consisting of 57.3% male (55.6% non NAFLD and 44.4% NAFLD and 42.7% female (57.4% non NAFLD and 42.6% NAFLD, were investigated. Insulin secretory function (HOMA%B and insulin sensitivity (HOMA%S were calculated from homeostasis model assessment (HOMA. Serum leptin showed significant positive correlation with fasting insulin (r = 0.530, P = 0.004, postprandial insulin (r = 0.384, P = 0.042 and HOMA-IR (r = 0.541, P = 0.003 as well as significant negative correlation with HOMA%S (r = -0.388, P = 0.046 and HOMA%B (r = -0.356, P = 0.039 in male prediabetic subjects with NAFLD. In multiple linear regression analysis, log transformed leptin showed significant positive association with HOMA-IR (β = 0.706, P <0.001 after adjusting the effects of body mass index (BMI, triglyceride (TG and HOMA%B in male subjects with NAFLD. In binary logistic regression analysis, only log leptin [OR 1.29 95% (C.I (1.11-1.51, P = 0.001] in male subjects as well as HOMA%B [OR 0.94 95% (C.I (0.89-0.98, P = 0.012], HOMA-IR [OR 3.30 95% (C.I (0.99-10.95, P = 0.049] and log leptin [OR 1.10 95% (C.I (1.01-1.20, P = 0.026] in female subjects were found to be independent determinants of NAFLD after adjusting the BMI and TG. Serum leptin seems to have an association with NAFLD both in male and female prediabetic subjects and this association in turn, is mediated by insulin secretory dysfunction and insulin resistance among these subjects.

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

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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.

The impact of leptin on perinatal development and psychopathology.

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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

Antidiabetic Effect of Hydroalcholic Urtica dioica Leaf Extract in Male Rats with Fructose-Induced Insulin Resistance

Science.gov (United States)

Ahangarpour, Akram; Mohammadian, Maryam; Dianat, Mahin

2012-01-01

Background: Urtica dioica has been used as antihypertensive, antihyperlipidemic and antidiabetic herbal medicine. The purpose of this study was to study the effect of hydroalcoholic extract of Urtica dioica on fructose-induced insulin resistance rats. Methods: Forty male Wistar rats were randomly divided into five groups including control, fructose, extract 50, extract 100 and extract 200. The control rat received vehicle, the fructose and extract groups received fructose 10% for eight weeks. The extract groups received single daily injection of vehicle, 50, 100 or 200 mg/kg/day for the two weeks. Blood glucose, insulin, last fasting insulin resistance index (FIRI), serum triglyceride (TG), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), high-density lipoprotein (HDL), alanin trasaminase (AST) and alkaline phosphatase (ALP), leptin and LDL/HDL ratio were determined. Results: Compared to control group, daily administration of fructose was associated with significant increase in FIRI, blood glucose and insulin, significant decrease in lepin, and no significant change in TG, HDL, LDL, LDL/HDL ratio, VLDL, ALT, and ALP. The extract significantly decreased serum glucose, insulin, LDL and leptin, and LDL/HDL ratio and FIRI. It also significantly increased serum TG, VLDL, and AST, but did not change serum ALP. Conclusion: We suggest that Urtica dioica extract, by decreasing serum glucose, and FIRI, may be useful to improve type 2 diabetes mellitus. Also, by positive effect on lipid profile and by decreasing effect on leptin, it may improve metabolic syndrome. PMID:23115450

Antidiabetic Effect of Hydroalcholic Urtica dioica Leaf Extract in Male Rats with Fructose-Induced Insulin Resistance

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Akram Ahangarpour

2012-09-01

Full Text Available Background: Urtica dioica has been used as antihypertensive, antihyperlipidemic and antidiabetic herbal medicine. The purpose of this study was to study the effect of hydroalcoholic extract of Urtica dioica on fructose-induced insulin resistance rats. Methods: Forty male Wistar rats were randomly divided into five groups including control, fructose, extract 50, extract 100 and extract 200. The control rat received vehicle, the fructose and extract groups received fructose 10% for eight weeks. The extract groups received single daily injection of vehicle, 50, 100 or 200 mg/kg/day for the two weeks. Blood glucose, insulin, last fasting insulin resistance index (FIRI, serum triglyceride (TG, low-density lipoprotein (LDL, very low-density lipoprotein (VLDL, high-density lipoprotein (HDL, alanin trasaminase (AST and alkaline phosphatase (ALP, leptin and LDL/HDL ratio were determined.Results: Compared to control group, daily administration of fructose was associated with significant increase in FIRI, blood glucose and insulin, significant decrease in lepin, and no significant change in TG, HDL, LDL, LDL/HDL ratio, VLDL, ALT, and ALP. The extract significantly decreased serum glucose, insulin, LDL and leptin, and LDL/HDL ratio and FIRI. It also significantly increased serum TG, VLDL, and AST, but did not change serum ALP.Conclusion: We suggest that Urtica dioica extract, by decreasing serum glucose, and FIRI, may be useful to improve type 2 diabetes mellitus. Also, by positive effect on lipid profile and by decreasing effect on leptin, it may improve metabolic syndrome.

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.

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.

Science.gov (United States)

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.

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.

Detection of leptin in serum from patients with polycystic ovary syndrome

International Nuclear Information System (INIS)

Chu Yongli; Sun Yongyu; Qiu Hongyu

2002-01-01

Objective: To investigate the relationship between leptin and insulin resistance in polycystic ovary syndrome (PCOS). Methods: Blood samples for leptin, LH/FSH, fasting insulin and glucose measurement from 17 patients with PCOS and 20 cases as control group were analyzed by radioimmunoassay or oxidase test. Results: It showed that leptin, LH/FSH levels of serum, insulin resistant index (IRI) and body mass index (BMI) in patients with PCOS were significantly higher than that in the control group (P<0.05). Leptin level was positively related with IRI and LH/FSH and BMI (P<0.01, P<0.05, P<0.01). Conclusion: It was suspected that leptin accelerate insulin resistance, the interaction of two factors aggravate the change of pathophysiology in PCOS

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.

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

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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.

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.

Gender Specific Association of Serum Leptin and Insulinemic Indices with Nonalcoholic Fatty Liver Disease in Prediabetic Subjects.

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Hossain, Israt Ara; Akter, Salima; Rahman, Mohammad Khalilur; Ali, Liaquat

2015-01-01

Adipose tissue-derived hormone leptin plays a functional role in glucose tolerance through its effects on insulin secretion and insulin sensitivity which also represent the risk factors for nonalcoholic fatty liver disease (NAFLD). The present study explored the gender specific association of serum leptin and insulinemic indices with NAFLD in Bangladeshi prediabetic subjects. Under a cross-sectional analytical design a total of 110 ultrasound examined prediabetic subjects, aged 25-68 years consisting of 57.3% male (55.6% non NAFLD and 44.4% NAFLD) and 42.7% female (57.4% non NAFLD and 42.6% NAFLD), were investigated. Insulin secretory function (HOMA%B) and insulin sensitivity (HOMA%S) were calculated from homeostasis model assessment (HOMA). Serum leptin showed significant positive correlation with fasting insulin (r = 0.530, P = 0.004), postprandial insulin (r = 0.384, P = 0.042) and HOMA-IR (r = 0.541, P = 0.003) as well as significant negative correlation with HOMA%S (r = -0.388, P = 0.046) and HOMA%B (r = -0.356, P = 0.039) in male prediabetic subjects with NAFLD. In multiple linear regression analysis, log transformed leptin showed significant positive association with HOMA-IR (β = 0.706, P binary logistic regression analysis, only log leptin [OR 1.29 95% (C.I) (1.11-1.51), P = 0.001] in male subjects as well as HOMA%B [OR 0.94 95% (C.I) (0.89-0.98), P = 0.012], HOMA-IR [OR 3.30 95% (C.I) (0.99-10.95), P = 0.049] and log leptin [OR 1.10 95% (C.I) (1.01-1.20), P = 0.026] in female subjects were found to be independent determinants of NAFLD after adjusting the BMI and TG. Serum leptin seems to have an association with NAFLD both in male and female prediabetic subjects and this association in turn, is mediated by insulin secretory dysfunction and insulin resistance among these subjects.

Leptin as a Potential Regulator of FGF21

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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.

Apelin-13 increased food intake with serum ghrelin and leptin levels in male rats.

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Saral, S; Alkanat, M; Sumer, A; Canpolat, S

2018-01-01

In this study, we aimed to explain the role of apelin-13 on body weight, food and water intake with serum leptin, ghrelin, neuropeptid Y (NPY) and peptid YY (PYY) levels in male rat. Thirty-two Sprague-Dawley male rats were used for the study. The rats were injected SP (0.9 %) intraperitoneally (i.p) in the control group and 30 (AP30), 100 (AP100) and 300 (AP300) µg/kg apelin-13 in the study groups, respectively, 10 min before the transition to dark period, for 10 days. During the experimental period, with light and dark periods of food and water intake, body weights were recorded in rats. Rats were euthanized and serum samples were obtained. In serum samples leptin, ghrelin, NPY and PYY levels were measured with specific ELISA kit. Apelin-13 was increased body weights in all three (AP30, AP100 and AP300) groups compared with the control group. AP100 and AP300 groups had increased food intake in the dark and the cumulative period, but in the light period food intake values were not significantly increased (p > 0.05). As for the value of water intake, compared with the control group, all dose of apelin-13 increased water intake during the dark and the cumulative period. There was no significant change in water intake in the light period. On the other hand, compared with the control group, serum leptin levels were found to increase in the groups administered 100 and 300 µg/kg of apelin-13 (p Ghrelin levels were found high in all groups treated with apelin-13. Serum levels of NPY decreased only in the 300 µg/kg apelin-13 treated group (p 0.05). Apelin-13 increases body weight in rats as well as food and water intake (dark and cumulative period). Additionally, ghrelin can mediate the orexigenic effect of apelin-13 in the regulation of food intake (Fig. 4, Ref. 37).

Puberty is delayed in male mice with dextran sodium sulfate colitis out of proportion to changes in food intake, body weight, and serum levels of leptin.

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Deboer, Mark D; Li, Yongli

2011-01-01

In boys, inflammatory bowel disease often results in delayed puberty associated with decreased bone mineral density and decreased linear growth. Our goal was to investigate whether pubertal timing and levels of leptin differed between prepubertal male mice with colitis and food-restricted (FR) mice maintained at a similar weight. We induced colitis in 32-d-old male mice using dextran sodium sulfate (DSS), resulting in 10 d of worsening colitis. We followed up these mice for separation of the prepuce from the glans penis as a marker of pubertal progression. Compared with free-feeding control mice, DSS and FR mice had significantly lower weight on d 7-10 of treatment. DSS mice had later puberty than control and FR mice. DSS mice also had smaller testes, lower FSH levels, increased systemic cytokines, and increased colonic inflammation by histology. Leptin levels were similar between DSS and FR mice, whereas both had decreases in leptin compared with controls. We conclude that DSS colitis causes delayed puberty in sexually immature male mice beyond what is seen among FR mice of similar weight, food intake, and leptin levels. These experiments provide support for the hypothesis that pubertal delay in colitis is influenced by factors beyond poor weight gain alone.

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

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)

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.

The Effects of Fetal Gender on Maternal and Fetal Insulin Resistance.

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Jennifer M Walsh

Full Text Available Gender plays a role in the development of a number of cardiovascular and metabolic diseases and it has been suggested that females may be more insulin resistant in utero. We sought to assess the relationship between infant gender and insulin resistance in a large pregnancy cohort.This is a secondary analysis of a cohort from the ROLO randomized control trial of low GI diet in pregnancy. Serum insulin, glucose and leptin were measured in early pregnancy and at 28 weeks. At delivery cord blood C-peptide and leptin were measured. A comparison of maternal factors, fetal biometry, insulin resistance and leptin was made between male and female offspring. A multivariate regression model was built to account for the possible effects of maternal BMI, birthweight and original study group assignment on findings.A total of 582 women were included in this secondary analysis, of whom 304 (52.2% gave birth to male and 278 (47.8% gave birth to female infants. Compared to male infants at birth, female infants were significantly lighter, (3945 ± 436 vs. 4081± 549g, p<0.001, shorter in length (52.36 ± 2.3 vs. 53.05 ± 2.4cm, p<0.001 and with smaller head circumferences (35.36 ± 1.5 vs. 36.10 ± 1.1cm, p<0.001 than males. On multiple regression analysis, women pregnant with female fetuses were less insulin resistant in early pregnancy, i.e. had lower HOMA indices (B = -0.19, p = 0.01. Additionally female fetuses had higher concentrations of both cord blood leptin and C-peptide at birth when compared to male offspring (B = 0.38, p<0.001 and B = 0.31, p = 0.03 respectively.These findings suggest gender is a risk factor for insulin resistance in-utero. Additionally, carrying a female fetus decreases the risk of insulin resistance in the mother, from as early as the first trimester.

The Effects of Fetal Gender on Maternal and Fetal Insulin Resistance.

Science.gov (United States)

Walsh, Jennifer M; Segurado, Ricardo; Mahony, Rhona M; Foley, Michael E; McAuliffe, Fionnuala M

2015-01-01

Gender plays a role in the development of a number of cardiovascular and metabolic diseases and it has been suggested that females may be more insulin resistant in utero. We sought to assess the relationship between infant gender and insulin resistance in a large pregnancy cohort. This is a secondary analysis of a cohort from the ROLO randomized control trial of low GI diet in pregnancy. Serum insulin, glucose and leptin were measured in early pregnancy and at 28 weeks. At delivery cord blood C-peptide and leptin were measured. A comparison of maternal factors, fetal biometry, insulin resistance and leptin was made between male and female offspring. A multivariate regression model was built to account for the possible effects of maternal BMI, birthweight and original study group assignment on findings. A total of 582 women were included in this secondary analysis, of whom 304 (52.2%) gave birth to male and 278 (47.8%) gave birth to female infants. Compared to male infants at birth, female infants were significantly lighter, (3945 ± 436 vs. 4081± 549g, p<0.001), shorter in length (52.36 ± 2.3 vs. 53.05 ± 2.4cm, p<0.001) and with smaller head circumferences (35.36 ± 1.5 vs. 36.10 ± 1.1cm, p<0.001) than males. On multiple regression analysis, women pregnant with female fetuses were less insulin resistant in early pregnancy, i.e. had lower HOMA indices (B = -0.19, p = 0.01). Additionally female fetuses had higher concentrations of both cord blood leptin and C-peptide at birth when compared to male offspring (B = 0.38, p<0.001 and B = 0.31, p = 0.03 respectively). These findings suggest gender is a risk factor for insulin resistance in-utero. Additionally, carrying a female fetus decreases the risk of insulin resistance in the mother, from as early as the first trimester.

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 ...

Hypothalamic Leptin Gene Therapy Reduces Bone Marrow Adiposity in ob/ob Mice Fed Regular and High Fat Diets

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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

Leptin regulates bone formation via the sympathetic nervous system

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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.

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...

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....

Changes in circulating leptin levels during the initial stage of cessation are associated with smoking relapse.

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Lemieux, Andrine; Nakajima, Motohiro; Hatsukami, Dorothy K; Allen, Sharon; al'Absi, Mustafa

2015-09-01

Leptin has been linked to tobacco craving and withdrawal-related symptoms. Very few studies have examined leptin prospectively in both male and female nonsmokers and smokers. We examine leptin concentrations prospectively in both male and female nonsmokers and smokers to assess the associations of leptin with psychological symptoms and smoking relapse during ad libitum smoking, the first 48 h post quit, and 4 weeks post-cessation. Self-report psychological, anthropomorphic, and biological measures (cotinine, carbon monoxide, and plasma leptin) were collected before and after 48 h of smoking abstinence. Smokers were stratified at 28 days post quit as abstinent or relapsed if they had smoked daily for seven consecutive days at any point in the 28 days. Leptin concentration (square root transformed ng/ml) increased over the 48-h abstinence, but only in female abstainers. In contrast, leptin was very stable across time for nonsmokers, relapsers, and males. Cox regression supported that increased leptin was associated with decreased risk of relapse. Leptin was correlated negatively with withdrawal symptoms for abstainers only. Females produce more leptin than males and this level increases from ad libitum smoking to 48-h post quit. The current analysis indicates that a leptin increase early in cessation predicts abstinence. The increase in women, but not men, in response to abstinence provides further evidence of important gender differences. The negative correlation between leptin and withdrawal symptoms indicates a possible protective effect of leptin. Further research is ongoing to elucidate the psychological and biological determinants of this effect.

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

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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.

[Leptin and the feedback regulation of body weight].

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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.

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

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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

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

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....

The leptin system and its expression at different nutritional and pregnant stages in lined seahorse (Hippocampus erectus

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Huixian Zhang

2016-10-01

Full Text Available Leptin is an essential hormone for the regulation of energy metabolism and food intake in vertebrate animals. To better understand the physiological roles of leptin in nutrient regulation in paternal ovoviviparous fish (family Syngnathidae, the present study cloned the full-length of leptin-a and leptin receptor (lepr genes in lined seahorse (Hippocampus erectus. Results showed that there was a 576-bp intron between two exons in leptin-a gene but no leptin-b gene in seahorse. Although the primary amino acid sequence conservation of seahorse leptin-a was very low, the 3-D structure modeling of seahorse leptin-a revealed strong conservation of tertiary structure with other vertebrates. Seahorse leptin-a mRNA was highly expressed in brain, whereas lepr mRNA was mainly expressed in ovary and gill. Interestingly, both leptin-a and lepr mRNA were expressed in the brood pouch of male seahorse, suggesting the leptin system plays a role during the male pregnancy. Physiological experiments showed that the expression of hepatic leptin-a and lepr mRNA in unfed seahorses was significantly higher than that in those fed 100%, as well as 60%, of their food during the fasting stage, showing that seahorse might initiate the leptin system to regulate its energy metabolism while starving. Moreover, the expression of leptin-a in the brood pouch of pregnant seahorse was significantly upregulated compared with non-pregnant seahorse, whereas the expression of lepr was downregulated, suggesting that the leptin system might be involved in the male pregnancy. In conclusion, the leptin system plays a role in the energy metabolism and food intake, and might provide new insights into molecular regulation of male pregnancy in seahorse.

The leptin system and its expression at different nutritional and pregnant stages in lined seahorse (Hippocampus erectus).

Science.gov (United States)

Zhang, Huixian; Qin, Geng; Zhang, Yanhong; Li, Shuisheng; Lin, Qiang

2016-10-15

Leptin is an essential hormone for the regulation of energy metabolism and food intake in vertebrate animals. To better understand the physiological roles of leptin in nutrient regulation in paternal ovoviviparous fish (family Syngnathidae), the present study cloned the full-length of leptin-a and leptin receptor (lepr) genes in lined seahorse (Hippocampus erectus). Results showed that there was a 576-bp intron between two exons in leptin-a gene but no leptin-b gene in seahorse. Although the primary amino acid sequence conservation of seahorse leptin-a was very low, the 3-D structure modeling of seahorse leptin-a revealed strong conservation of tertiary structure with other vertebrates. Seahorse leptin-a mRNA was highly expressed in brain, whereas lepr mRNA was mainly expressed in ovary and gill. Interestingly, both leptin-a and lepr mRNA were expressed in the brood pouch of male seahorse, suggesting the leptin system plays a role during the male pregnancy. Physiological experiments showed that the expression of hepatic leptin-a and lepr mRNA in unfed seahorses was significantly higher than that in those fed 100%, as well as 60%, of their food during the fasting stage, showing that seahorse might initiate the leptin system to regulate its energy metabolism while starving. Moreover, the expression of leptin-a in the brood pouch of pregnant seahorse was significantly upregulated compared with non-pregnant seahorse, whereas the expression of lepr was downregulated, suggesting that the leptin system might be involved in the male pregnancy. In conclusion, the leptin system plays a role in the energy metabolism and food intake, and might provide new insights into molecular regulation of male pregnancy in seahorse. © 2016. Published by The Company of Biologists Ltd.

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

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

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

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

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.

Sexual dimorphism in circulating leptin concentrations is not accounted for by differences in adipose tissue distribution.

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Rosenbaum, M; Pietrobelli, A; Vasselli, J R; Heymsfield, S B; Leibel, R L

2001-09-01

Circulating concentrations of leptin normalized to total adipose tissue mass are significantly greater in females than in males. Rates of leptin expression (per gram of adipose tissue) are significantly greater in subcutaneous (SAT) than visceral (VAT) adipose tissue and the relative amount of fat stored as SAT vs VAT is significantly greater in pre-menopausal females than in males. Gender-related differences in the relative amounts of SAT and VAT may account for the greater circulating leptin concentration relative to fat-mass in females than males. We examined body composition and anatomic fat distribution by dual energy X-ray-absorptiometry (DEXA) and magnetic resonance imaging (MRI), and post-absorptive circulating concentrations of leptin and insulin in 58 subjects (26 females, 32 males). Stepwise multiple linear regression analyses, treating gender as a dichotomous variable, were performed to determine inter-relationships among leptin concentrations and insulin concentrations, VAT and SAT. Body composition by DEXA and MRI were highly correlated (r(2)=0.97, P<0.0001). There were significant gender effects on leptin/total fat mass (males, 0.17+/-0.01 ng/ml/kg; females, 0.49+/-0.05 ng/ml/kg; P<0.0001) and relative amounts of fat in SAT and VAT depots (ratio of SAT/VAT; males, 12.3+/-1.5; females, 32.9+/-3.2; P<0.0001). Circulating leptin concentration was significantly correlated with insulin concentration (P=0.001), SAT (P<0.0001) and gender (P=0.033). Circulating concentrations of insulin were significantly correlated with VAT, but not SAT, in males and with SAT, but not VAT, in females. The sexual dimorphism in the relationship between leptin and adipose tissue mass cannot be explained by differences in the relative amounts of VAT and SAT. Thus, the sexual dimorphism in plasma leptin concentration appears to reflect, at least in part, effects of circulating concentrations of gonadal steroids (especially androgens) and/or primary genetic differences that are

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

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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.

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.

Impact of risperidone on leptin and insulin in children and adolescents with autistic spectrum disorders.

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Srisawasdi, Pornpen; Vanwong, Natchaya; Hongkaew, Yaowaluck; Puangpetch, Apichaya; Vanavanan, Somlak; Intachak, Boontarika; Ngamsamut, Nattawat; Limsila, Penkhae; Sukasem, Chonlaphat; Kroll, Martin H

2017-08-01

To evaluate the influence of dose and duration of risperidone treatment on cardiovascular and diabetes risk biomarkers in children and adolescents with autistic spectrum disorders (ASDs). In this cross-sectional analysis, a total of 168 ASDs patients (89% male) treated with a risperidone-based regimen for ≥12months were included. Blood samples were analyzed for glucose and lipid metabolic markers, adiponectin, leptin, prolactin, cortisol and high sensitive C-reactive protein. The mean concentrations of glucose, insulin, prolactin and leptin and HOMA-IR significantly rose with risperidone dosage (all P<0.025), but those of adiponectin and cortisol did not. Using regression analysis, insulin, leptin, prolactin and glucose concentrations and HOMA-IR show significant association with dosage. None of the markers except adiponectin showed dependence on duration of treatment. However, insulin and leptin concentrations and HOMA-IR clearly increased with increasing both dosage and duration. Dosage and duration of treatment had minimal effect on standard lipid profile and lipoprotein subclasses. Risperidone treatment disturbed glucose homeostasis and endocrine regulation (particularly leptin) in children and adolescents with ASDs, in a dose- and duration-dependent manner, being suggestive of leptin and insulin resistance mechanisms. Metabolic adverse effects, especially development of type 2 diabetes mellitus should be closely monitored, particularly in individuals receiving high doses and/or long-term risperidone treatment. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

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....

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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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.

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.

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

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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…

Leptin Induces an Inflammatory Phenotype in Lean Wistar Rats

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Monique Allman

2009-01-01

Full Text Available The present study addressed the hypothesis that leptin promotes leukocyte trafficking into adipose tissue. Accordingly, male Wistar rats were treated with saline or recombinant rat leptin (1 mg/kg via the tail vein. Leukocyte trafficking in mesenteric venules was quantified by intravital microscopy. Treatment with leptin resulted in a 3- and 5-fold increases in rolling and firm adhesion, respectively. Compared to vehicle controls, leptin enhanced mRNA levels of IL-6 (8-fold and MCP-1 (5-fold in mesenteric adipose tissue (MAT. Similar increases in these markers were observed in mesenteric venules and in liver. Finally, the direct effect of leptin was assessed in C3A hepatocytes treated with leptin for 24 hours (7.8 ng/mL–125 ng/mL. Consistent with observations in vivo, production of ICAM-1, MCP-1, and IL-6 by hepatocytes was increased significantly. These findings support the hypothesis that leptin directly initiates inflammation in the local environment of mesenteric adipose tissue as well as systemically.

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.

Resveratrol attenuates intermittent hypoxia-induced macrophage migration to visceral white adipose tissue and insulin resistance in male mice.

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Carreras, Alba; Zhang, Shelley X L; Almendros, Isaac; Wang, Yang; Peris, Eduard; Qiao, Zhuanhong; Gozal, David

2015-02-01

Chronic intermittent hypoxia during sleep (IH), as occurs in sleep apnea, promotes systemic insulin resistance. Resveratrol (Resv) has been reported to ameliorate high-fat diet-induced obesity, inflammation, and insulin resistance. To examine the effect of Resv on IH-induced metabolic dysfunction, male mice were subjected to IH or room air conditions for 8 weeks and treated with either Resv or vehicle (Veh). Fasting plasma levels of glucose, insulin, and leptin were obtained, homeostatic model assessment of insulin resistance index levels were calculated, and insulin sensitivity tests (phosphorylated AKT [also known as protein kinase B]/total AKT) were performed in 2 visceral white adipose tissue (VWAT) depots (epididymal [Epi] and mesenteric [Mes]) along with flow cytometry assessments for VWAT macrophages and phenotypes (M1 and M2). IH-Veh and IH-Resv mice showed initial reductions in food intake with later recovery, with resultant lower body weights after 8 weeks but with IH-Resv showing better increases in body weight vs IH-Veh. IH-Veh and IH-Resv mice exhibited lower fasting glucose levels, but only IH-Veh had increased homeostatic model assessment of insulin resistance index vs all 3 other groups. Leptin levels were preserved in IH-Veh but were significantly lower in IH-Resv. Reduced VWAT phosphorylated-AKT/AKT responses to insulin emerged in both Mes and Epi in IH-Veh but normalized in IH-Resv. Increases total macrophage counts and in M1 to M2 ratios occurred in IH-Veh Mes and Epi compared all other 3 groups. Thus, Resv ameliorates food intake and weight gain during IH exposures and markedly attenuates VWAT inflammation and insulin resistance, thereby providing a potentially useful adjunctive therapy for metabolic morbidity in the context of sleep apnea.

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

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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.

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

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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.

Assessment of leptin and some Antioxidants in Blood of Chronic Renal Failure Patients

International Nuclear Information System (INIS)

Ahmed, A.M.

2004-01-01

The aim of the present work is to study the effect of haemodialysis on the state of the antioxidants glutathione peroxidase (GPx) and vitamin C and the role of leptin hormone on the redox homeostasis in patients with chronic renal failure (CRF). This study was carried out on 25 patients (15 females and 10 males) with CRF,aged 19-55 years, in addition to 25 healthy control (10 females and 15 males). Patients were subjected to regular haemodialysis for 4 hours three times weekly and blood samples were collected before haemodialysis. In this study, plasma leptin was significantly increased in CRF group than normal control. Vitamin C and GPx were decreased significantly in CRF group in comparison with normal control. There was non-significant difference in serum leptin level between males and females in both control and patient groups. Patients showed significant lower body mass index (BMI) and albumin and higher cholesterol. In the control group, serum leptin levels showed significant positive correlation with BMI, while CRF group had significant negative correlation. In CRF group, serum leptin showed significant negative correlation with serum albumin and non-significant negative correlation with both creatinine and cholesterol. This is probably due to malnutrition status commonly occurs in renal failure. Serum leptin levels showed non-significant negative correlation between both GPx and Vitamin C in control group while in patient group, leptin showed significant positive correlation with GPx and vitamin C. In conclusion leptin acts on energy metabolism and plays a role in the modulation of cellular redox balance while the oxidative stress plays a role in many disease states. These diseases had increased incidence in uremia and particularly in haemodialysis

Transport across the blood-brain barrier of pluronic leptin.

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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.

Leptin and adiponectin in the female life course

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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.

[The leptin concentration in patients with primary arterial hypertension].

Science.gov (United States)

Jołda-Mydłowska, Beata; Przewłocka-Kosmala, Monika; Zyśko, Dorota; Gajek, Jacek; Mazurek, Walentyna

2006-01-01

moderate and severe hypertension the leptin serum concentration is significantly higher than mild hypertension, and in patients with severe hypertension the leptin serum concentration is significantly higher than in patients with moderate hypertension. 2. In patients suffering from arterial hypertension the leptin serum concentration is positively correlated with the body mass index. 3. The leptin serum concentration is statistically significantly higher in women with arterial hypertension as compared to the male patients with the same disease. 4. In both male and female groups of patients the leptin serum concentration is positively correlated with the arterial hypertension degree. 5. In female patients suffering from arterial hypertension the leptin serum concentration is positively correlated with the body mass and body mass index.

[The association of leptin with dislipidemia in group of ethnic Kirghiz].

Science.gov (United States)

Kerimkulova, A S; Lunegova, O S; Mirrakhimov, A E; Alibayeva, N T; Neronova, K V; Baiyramukova, A A; Mirrakhimov, E M

2014-01-01

The article deals with results of evaluation of relationship between leptin and lipid indicators in group of ethnic Kirghiz. The sampling included 322 ethnic Kirghiz (145 males and 177 females) aged from 30 to 75 years. To all patients was applied general clinical examination, anthropometric examination (height, body mass, waist circumference, thighs circumference). The body mass index was calculated. The level of glucose (on an empty stomach), lipids spectrum and leptin of blood serum were measured. The average age of patients consisted 57.7 +/- 9.6 years and average level of leptin was 7.8 ng/ml. The patients were allocated to three groups depending of tertile of leptin ( or = 5.52 ng/ml in males; 9.6; 9.6-16.6; > or = 16.7 ng/ml in females). In patients from upper tertile as compared with patients from lower tertiles are noted high values of triglycerides (p dislipidemia, obesity, including abdominal obesity.

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

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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

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

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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.

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

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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.

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

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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.

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

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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.

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

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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

Inhibiting Endogenous Cortisol Blunts the Meal-Entrained Rise in Serum Leptin

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Laferrère, Blandine; Abraham, Cynthia; Awad, Marianne; Jean-Baptiste, Stephanie; Hart, Allison B.; Garcia-Lorda, Pilar; Kokkoris, Peter; Russell, Colleen D.

2010-01-01

Context Administration of glucocorticoids increases serum leptin levels in lean and obese individuals. A morning meal produces an increase in insulin, a cortisol peak, and an increase in leptin; these changes do not occur during fasting. Objective The objective of this study was to investigate whether inhibiting endogenous cortisol secretion with metyrapone decreases 24-h serum leptin levels and to determine whether a meal-related midmorning surge in cortisol is a prerequisite for the meal-entrained nocturnal rise in leptin. Design This was a randomized, cross-over study. Setting The study was performed at the General Clinical Research Center. Participants Lean males were studied. Intervention In study 1, seven lean men were studied for 24 h while their endogenous cortisol secretions were manipulated as follows: 1) CONTROL; 2) cortisol suppression by metyrapone (MET); and 3) MET and oral hydrocortisone (at 0900 h) (MET + CORT). Subjects were all fed a eucaloric diet (two meals at 1100 and 1700 h). In study 2, six men were studied without pharmacological intervention for 24 h on two occasions: once under a complete fast (FAST) and once in a feeding condition (one meal at 1100 h; FED). Main Outcome Measure The main outcome measure was serum leptin. Results MET significantly suppressed serum cortisol at 0800 h, midmorning, and over the 24-h period. As a result of cortisol suppression, 24-h serum leptin levels were decreased vs. control values despite similar insulin responses to meals. Administering a single dose of hydrocortisone to MET subjects potently stimulated serum leptin compared with the effect of MET alone. Conclusions Our data demonstrate that endogenous cortisol secretion is necessary for the maintenance of serum leptin levels over 24 h in lean, normally fed males. PMID:16537679

Role of leptin in female reproduction.

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Pérez-Pérez, Antonio; Sánchez-Jiménez, Flora; Maymó, Julieta; Dueñas, José L; Varone, Cecilia; Sánchez-Margalet, Víctor

2015-01-01

Reproductive function is dependent on energy resources. The role of weight, body composition, fat distribution and the effect of diet have been largely investigated in experimental female animals as well as in women. Any alteration in diet and/or weight may induce abnormalities in timing of sexual maturation and fertility. However, the cellular mechanisms involved in the fine coordination of energy balance and reproduction are largely unknown. The brain and hypothalamic structures receive endocrine and/or metabolic signals providing information on the nutritional status and the degree of fat stores. Adipose tissue acts both as a store of energy and as an active endocrine organ, secreting a large number of biologically important molecules termed adipokines. Adipokines have been shown to be involved in regulation of the reproductive functions. The first adipokine described was leptin. Extensive research over the last 10 years has shown that leptin is not only an adipose tissue-derived messenger of the amount of energy stores to the brain, but also a crucial hormone/cytokine for a number of diverse physiological processes, such as inflammation, angiogenesis, hematopoiesis, immune function, and most importantly, reproduction. Leptin plays an integral role in the normal physiology of the reproductive system with complex interactions at all levels of the hypothalamic-pituitary gonadal (HPG) axis. In addition, leptin is also produced by placenta, where it plays an important autocrine function. Observational studies have demonstrated that states of leptin excess, deficiency, or resistance can be associated with abnormal reproductive function. This review focuses on the leptin action in female reproduction.

Child-Pugh classification dependent alterations in serum leptin levels among cirrhotic patients: a case controlled study

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Zeyrek Fadile

2004-09-01

Full Text Available Abstract Background As anorexia and hypermetabolism are common in cirrhosis, leptin levels may be increased in this disease. In this study, we investigated the relation between the severity of disease and serum leptin levels in post-hepatitis cirrhosis and the role of body composition, gender and viral aetiology of cirrhosis in this association. Methods Thirty-five cases with post-hepatitis cirrhosis and 15 healthy controls were enrolled in this study. Body composition including body mass index, body fat percentage and body fat mass were determined. Serum leptin levels were assayed. Results Leptin levels were significantly higher among cirrhotic patients independent of sex compared to controls (p = 0.001. Female patients in both groups have had higher leptin levels than males (in cirrhotics p = 0.029, in controls p = 0.02. Cirrhotic patients in each of A, B and C subgroups according to the Child- Pugh classification revealed significantly different levels compared to controls (p = 0.046, p = 0.004, p = 0.0001, respectively. Male cirrhotics in Child-Pugh Class B and C subgroups had significantly higher leptin levels compared to male controls (p = 0.006, p = 0.008. On the other hand, female patients only in Child Pugh class C subgroup have had higher levels of serum leptin compared to controls (p = 0.022. Child-Pugh classification has been found to be the sole discriminator in determination of leptin levels in cirrhotics by linear regression (beta: 0.435 p = 0.015. Conclusion Serum leptin levels increase in advanced liver disease independently of gender, body composition in posthepatitic cirrhosis. The increase is more abundant among patients that belong to C subgroup according to the Child- Pugh classification.

Gender differences of cannabis smoking on serum leptin levels: population-based study

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Fernanda P. Moreira

2018-02-01

Full Text Available Objective: To evaluate the serum leptin levels in cannabis smokers. Methods: This was a cross-sectional population-based study of participants between the ages of 18 and 35 years. The data were collected through a self-administered questionnaire covering sociodemographic data and the use of psychoactive substances. Leptin levels were measured using a commercial ELISA kit. Results: Of the 911 participants, 6.7% were identified as cannabis smokers and had significantly lower leptin levels (p = 0.008. When stratified by gender, there was a significant decrease in leptin levels among male smokers (p = 0.039. Conclusion: Cannabis smoking was linked to leptin levels in men, suggesting that the response to biological signals may be different between men and women.

Association of adiponectin/leptin ratio with carbohydrate and lipid metabolism parameters in HIV-infected patients during antiretroviral therapy.

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Tiliscan, Catalin; Arama, Victoria; Mihailescu, Raluca; Munteanu, Daniela; Iacob, Diana Gabriela; Popescu, Cristina; Catana, Remulus; Negru, Anca; Lobodan, Alina; Arama, Stefan Sorin

2018-02-16

Adiponectin and leptin are adipose tissue hormones that regulate important lipid and glucose metabolic pathways. Our objective was to evaluate the interplay of these hormones described by the adiponectin/leptin ratio (ALR) in correlation to lipid and carbohydrate metabolism parameters in nondiabetic HIV-infected patients during antiretroviral therapy (ART). We enrolled consecutive nondiabetic patients with confirmed HIV infection, undergoing stable ART regimens for at least six months. Blood samples were collected and tested for immunological and virological parameters, adiponectin and leptin, fasting insulin, fasting plasma glucose, fasting triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol. ALR was computed for each patient. Resistance to insulin was assessed by calculating the Quantitative Insulin Sensitivity Check Index (QUICKI). We enrolled 87 HIV-infected persons, with a mean age of 31.7 years (range: 18-65), including 47 men (mean age = 32.8 years) and 40 women (mean age = 30.5 years). The median value of ALR was 6.8 (interquartile range - IQR = 17.1). In male patients, ALR was inversely associated with the serum level of triglycerides (R = 0.285, p = 0.05), total cholesterol (R = 0.326, p = 0.02), and LDL cholesterol (R = 0.298, p = 0.04). Also for the male cohort, an increase in ALR seemed to improve insulin sensitivity (R = 0.323, p = 0.02) and serum HDL cholesterol (R = 0.597, p = 0.01). None of these correlations were observed in HIV-infected women. Adiponectin and leptin seem to play important but different gender-specific roles in the pathogenesis of lipid and glucose metabolism of HIV-infected patients undergoing antiretroviral therapy. ALR, adiponectin/leptin ratio; BMI, body mass index; LDL, low-density lipoprotein; HDL, high-density lipoprotein; QUICKI, Quantitative Insulin Sensitivity Check Index.

Maternal Fructose Intake Induces Insulin Resistance and Oxidative Stress in Male, but Not Female, Offspring

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Lourdes Rodríguez

2015-01-01

Full Text Available Objective. Fructose intake from added sugars correlates with the epidemic rise in metabolic syndrome and cardiovascular diseases. However, consumption of beverages containing fructose is allowed during gestation. Recently, we found that an intake of fructose (10% wt/vol throughout gestation produces an impaired fetal leptin signalling. Therefore, we have investigated whether maternal fructose intake produces subsequent changes in their progeny. Methods. Blood samples from fed and 24 h fasted female and male 90-day-old rats born from fructose-fed, glucose-fed, or control mothers were used. Results. After fasting, HOMA-IR and ISI (estimates of insulin sensitivity were worse in male descendents from fructose-fed mothers in comparison to the other two groups, and these findings were also accompanied by a higher leptinemia. Interestingly, plasma AOPP and uricemia (oxidative stress markers were augmented in male rats from fructose-fed mothers compared to the animals from control or glucose-fed mothers. In contrast, female rats did not show any differences in leptinemia between the three groups. Further, insulin sensitivity was significantly improved in fasted female rats from carbohydrate-fed mothers. In addition, plasma AOPP levels tended to be diminished in female rats from carbohydrate-fed mothers. Conclusion. Maternal fructose intake induces insulin resistance, hyperleptinemia, and plasma oxidative stress in male, but not female, progeny.

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

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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.

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

Fetal life malnutrition was not reflected in the relative abundances of adiponectin and leptin mRNAs in adipose tissue in male mink kits at 9.5 weeks of age

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Matthiesen, Connie Frank; Tauson, Anne-Helene

2016-01-01

Background: Malnutrition in fetal life and during suckling have in some animal studies resulted in adaptive changes related to the fat and glucose metabolism, which in the long term might predispose the offspring for metabolic disorders such as obesity later in life. The objective was to study...... the effect of fetal life malnutrition in male mink on the gene expression of leptin and adiponectin in different adipose tissue sites. Results: Thirty-two male mink, strict carnivore species, exposed to low (FL) or adequate (FA) protein provision the last 16.3 ± 1.8 days of fetal life and randomly assigned.......5 weeks of age. Relative abundances of leptin and adiponectin mRNAs were different between adipose tissue sites and were significantly higher in subcutaneous than in perirenal and mesenteric tissues. Conclusion:Fetal life protein malnutrition in male mink, did not result in adaptive changes in the gene...

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.

Leptin Intake at Physiological Doses Throughout Lactation in Male Wistar Rats Normalizes the Decreased Density of Tyrosine Hydroxylase-Immunoreactive Fibers in the Stomach Caused by Mild Gestational Calorie Restriction

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Nara Szostaczuk

2018-03-01

Full Text Available Introduction: Gestational under nutrition in rats has been shown to decrease expression of sympathetic innervation markers in peripheral tissues of offspring, including the stomach. This has been linked to lower gastric secretion and decreased circulating levels of ghrelin. Considering the critical role of leptin intake during lactation in preventing obesity and reversing adverse developmental programming effects, we aimed to find out whether leptin supplementation may reverse the above mentioned alterations caused by mild gestational calorie restriction.Methods: Three groups of male rats were studied at a juvenile age (25 days old and during adulthood (3 and 6 months old: the offspring of ad libitum fed dams (controls, the offspring of dams that were diet restricted (20% from days 1 to 12 of gestation (CR, and CR rats supplemented with a daily oral dose of leptin (equivalent to 5 times the average amount they could receive each day from maternal milk throughout lactation (CR-Leptin. The density of TyrOH-immunoreactive (TyrOH+ fibers and the levels of Tyrosine hydroxylase (TyrOH—used as potential markers of functional sympathetic innervation—were measured in stomach. Plasma leptin and ghrelin levels were also determined.Results: Twenty five-day-old CR rats, but not CR-Leptin rats, displayed lower density of TyrOH+ fibers (−46% and TyrOH levels (−47% in stomach compared to controls. Alterations in CR animals were mitigated at 6 months of age, and differences were not significant. Adult CR-Leptin animals showed higher plasma ghrelin levels than CR animals, particularly at 3 months (+16%, and a lower leptin/ghrelin ratio (−28 and −37% at 3 and 6 months, respectively.Conclusion: Leptin intake during lactation is able to reverse the alterations in the density of TyrOH+ fibers in the stomach and normalize the increased leptin/ghrelin ratio linked to a mild gestational calorie restriction in rats, supporting the relevance of leptin as an

The Relationship between Maternal Plasma Leptin and Adiponectin Concentrations and Newborn Adiposity

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Natália P. Castro

2017-02-01

Full Text Available Increased maternal blood concentrations of leptin and decreased adiponectin levels, which are common disturbances in obesity, may be involved in offspring adiposity by programming fetal adipose tissue development. The aim of this study was to assess the relationship between maternal leptin and adiponectin concentrations and newborn adiposity. This was a cross-sectional study involving 210 healthy mother-newborn pairs from a public maternity hospital in São Paulo, Brazil. Maternal blood samples were collected after delivery and leptin and adiponectin concentrations were measured by enzyme-linked immunosorbent assay. Newborn body composition was estimated by air displacement plethysmography. The association between maternal leptin and adiponectin concentrations and newborn adiposity (fat mass percentage, FM% was evaluated by multiple linear regression, controlling for maternal age, socioeconomic status, parity, pre-pregnancy body mass index (BMI, weight gain, gestational age, and newborn age at the time of measurement. No relationship was found between maternal leptin and FM% of male or female newborn infants. Maternal adiponectin (p = 0.001 and pre-pregnancy BMI (p < 0.001; adj. R2 = 0.19 were positively associated with FM% of newborn males, indicating that maternal adiponectin is involved in fetal fat deposition in a sex-specific manner. Large-scale epidemiological, longitudinal studies are necessary to confirm our results.

The Relationship between Maternal Plasma Leptin and Adiponectin Concentrations and Newborn Adiposity.

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Castro, Natália P; Euclydes, Verônica V; Simões, Fernanda A; Vaz-de-Lima, Lourdes R A; De Brito, Cyro A; Luzia, Liania A; Devakumar, Delan; Rondó, Patrícia H C

2017-02-23

Increased maternal blood concentrations of leptin and decreased adiponectin levels, which are common disturbances in obesity, may be involved in offspring adiposity by programming fetal adipose tissue development. The aim of this study was to assess the relationship between maternal leptin and adiponectin concentrations and newborn adiposity. This was a cross-sectional study involving 210 healthy mother-newborn pairs from a public maternity hospital in São Paulo, Brazil. Maternal blood samples were collected after delivery and leptin and adiponectin concentrations were measured by enzyme-linked immunosorbent assay. Newborn body composition was estimated by air displacement plethysmography. The association between maternal leptin and adiponectin concentrations and newborn adiposity (fat mass percentage, FM%) was evaluated by multiple linear regression, controlling for maternal age, socioeconomic status, parity, pre-pregnancy body mass index (BMI), weight gain, gestational age, and newborn age at the time of measurement. No relationship was found between maternal leptin and FM% of male or female newborn infants. Maternal adiponectin ( p = 0.001) and pre-pregnancy BMI ( p < 0.001; adj. R ² = 0.19) were positively associated with FM% of newborn males, indicating that maternal adiponectin is involved in fetal fat deposition in a sex-specific manner. Large-scale epidemiological, longitudinal studies are necessary to confirm our results.

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

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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.

Turmeric Supplementation Improves Serum Glucose Indices and Leptin Levels in Patients with Nonalcoholic Fatty Liver Diseases.

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Navekar, Roya; Rafraf, Maryam; Ghaffari, Aida; Asghari-Jafarabadi, Mohammad; Khoshbaten, Manouchehr

2017-01-01

Insulin and leptin resistance are important risk factors for non-alcoholic fatty liver disease (NAFLD). There is limited evidence regarding the effects of turmeric on NAFLD. The aim of this study was to investigate the effects of turmeric supplementation on glycemic status and serum leptin levels in patients with NAFLD. This double-blind randomized controlled clinical trial was conducted on 46 patients with NAFLD (21males and 25 females) aged 20-60 years old and body mass index (BMI) between 24.9 and 40 kg/m2. The turmeric group (n = 23) was given six turmeric capsules daily for 12 weeks. Each capsule contained 500 mg turmeric powder (6×500 mg). The placebo group (n = 23) was given six placebo capsules daily for the same period. Fasting blood samples, anthropometric measurements, and physical activity levels were collected at the baseline and at the end of the study. Daily dietary intakes also were obtained throughout the study. Data were analyzed by independent t test, paired t test and analysis of covariance. Turmeric consumption decreased serum levels of glucose, insulin, HOMA-IR and leptin (by 1.22, 17.69, 19.48 and 21.33% respectively, p Turmeric supplementation improved glucose indexes and serum leptin levels and may be useful in the control of NAFLD complications.

Adipocytokine Associations with Insulin Resistance in British South Asians

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D. R. Webb

2013-01-01

Full Text Available Aims. Adipocytokines are implicated in the pathogenesis of type 2 diabetes and may represent identifiable precursors of metabolic disease within high-risk groups. We investigated adiponectin, leptin, and TNF-α and assessed the contribution of these molecules to insulin resistance in south Asians. Hypothesis. South Asians have adverse adipocytokine profiles which associate with an HOMA-derived insulin resistance phenotype. Methods. We measured adipocytokine concentrations in south Asians with newly diagnosed impaired glucose tolerance or Type 2 Diabetes Mellitus in a case-control study. 158 (48.5% males volunteers aged 25–75 years with risk factors for diabetes but no known vascular or metabolic disease provided serum samples for ELISA and bioplex assays. Results. Total adiponectin concentration progressively decreased across the glucose spectrum in both sexes. A reciprocal trend in leptin concentration was observed only in south Asian men. Adiponectin but not leptin independently associated with HOMA-derived insulin resistance after logistic multivariate regression. Conclusion. Diasporic south Asian populations have an adverse adipocytokine profile which deteriorates further with glucose dysregulation. Insulin resistance is inversely associated with adiponectin independent of BMI and waist circumference in south Asians, implying that adipocytokine interplay contributes to the pathogenesis of metabolic disease in this group.

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

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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.

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

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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.

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

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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.

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

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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.

Association of plasma leptin with coronary artery calcium (CAC) in adults

International Nuclear Information System (INIS)

Imran, S.; Jafri, L.; Majid, H.; Sajjad, Z.; Khan, A.H.

2018-01-01

To determine the correlation between leptin and CAC in scores subjects without cardiovascular disease (CVD) risk. Study Design: Cross sectional study. Place and Duration of Study: Aga Khan University Hospital, from Mar 2014 to Jun 2015. Material and Methods: Total 128 subjects were included. The study was approved by ethical review committee. After informed consent a predesigned questionnaire was documented. Subjects without known cardiac disease history, coming for non-contrast CT scan for abdominal indications were included. Leptin levels were measured by Enzyme immunoassay. CAC scores were assessed on a 64 slice non-contrast CT scan. Data analyzed by SPSS version 20. Results: Total 128 subjects were included with mean age 42.82 +- 13.1 years and 78.1% (n=100) were males. Mean BMI and waist circumference was 27.1 +- 5.4 kg/m2 and 94.8 +- 9.0cm respectively. High median leptin levels were seen in 11.7% (n=15) of study subjects. Leptin levels were also significantly higher in female compared to male [12.5ng/ml (0.3-60.9) vs. 2.5ng/ml (0.1-50); p-value=0.001]. High CAC score was present in 15% (n=19) of study subjects. Statistically significant correlation of leptin was found with waist circumference, (r 0.50; p=0.001), positive correlation with BMI (r 0.51, p<0.05) with higher levels noted in obese subjects compared to overweight and normal BMI subjects [median 7.5ng/ml (0.3-60.9) vs. 3.3ng/ml (0.1-40) and 0.1 ng/ml (0.1-0.1)]; No correlation was found between CAC score and serum leptin levels (r 0.073; p=0.41). Conclusions: Leptin levels are not correlated with CAC scores in subjects with low CVD risk. However, leptin was significantly higher in females and subjects with increased waist circumference. (author)

Correlation Between Insulin, Leptin and Polycystic Ovary Syndrome

African Journals Online (AJOL)

Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of fertile age. .... Serum leptin level rises in both studied groups (control and ... resistant group) with high significant difference (P < 0.01).

Study on the relationship between serum leptin level and ischemic cerebrovascular disease (ICVD)

International Nuclear Information System (INIS)

Luo Nanping; Hu Chengjing; Wang Ruishan; Yin Qiuxia; Niu Aijun; Xue Lian; Xue Shenwu; Chen Qing

2004-01-01

Objective: To investigate the inter-relationship among serum leptin insulin resistance and blood lipids, and to explore the role of leptin in the pathogenesis of ischemic cerebrovascular diseases (ICVD). Methods: Levels of serum leptin, insulin and blood lipids were determined with RIA in 131 patients with different types of ICVD and 36 controls. Results: The levels of serum leptin in ICVD patients were significantly higher than those in the controls (P<0.01). Changes of blood lipids and insulin paralleled those of leptin (cxcept with HDL-C). The serum leptin were positively correlated to cholesterol, TG and insulin levels (r=0.45, P<0.05; r=0.31, P<0.05, r=0.55, P<0.01), but negatively correlated to HDL-C (r=-0.88, P<0.05). Conclusion: The high expression of leptin in ICVD patients is associated with high lipid and insulin levels. The close relationship among them indicates that high leptin levels play an important role in the pathogenesis of metabolic syndrome as well as atheromatous cerebrovascular diseases. (authors)

Goldfish Leptin-AI and Leptin-AII: Function and Central Mechanism in Feeding Control

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Ai-Fen Yan

2016-05-01

Full Text Available In mammals, leptin is a peripheral satiety factor that inhibits feeding by regulating a variety of appetite-related hormones in the brain. However, most of the previous studies examining leptin in fish feeding were performed with mammalian leptins, which share very low sequence homologies with fish leptins. To elucidate the function and mechanism of endogenous fish leptins in feeding regulation, recombinant goldfish leptin-AI and leptin-AII were expressed in methylotrophic yeast and purified by immobilized metal ion affinity chromatography (IMAC. By intraperitoneal (IP injection, both leptin-AI and leptin-AII were shown to inhibit the feeding behavior and to reduce the food consumption of goldfish in 2 h. In addition, co-treatment of leptin-AI or leptin-AII could block the feeding behavior and reduce the food consumption induced by neuropeptide Y (NPY injection. High levels of leptin receptor (lepR mRNA were detected in the hypothalamus, telencephalon, optic tectum and cerebellum of the goldfish brain. The appetite inhibitory effects of leptins were mediated by downregulating the mRNA levels of orexigenic NPY, agouti-related peptide (AgRP and orexin and upregulating the mRNA levels of anorexigenic cocaine-amphetamine-regulated transcript (CART, cholecystokinin (CCK, melanin-concentrating hormone (MCH and proopiomelanocortin (POMC in different areas of the goldfish brain. Our study, as a whole, provides new insights into the functions and mechanisms of leptins in appetite control in a fish model.

Effects of Metformin on Serum Levels of Secreted Klotho and Leptin in PCOS Women

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Savadali Saifi Novashnag

2016-07-01

Patients’ weights showed some decline. Fasting plasma glucose levels and insulin resistance decreased significantly (p<0.01. Hormonal assays indicated significant decrease in leptin and insulin levels and rise in Klotho levels. BMIs did not change meaningfully. Measurements of leptin and klotho levels showed a decrease in mean leptin levels from 34.74 to 28.41 ng/l and the level of klotho increased from 4.01 to 5.43 ng/l. Conclusion: This study showed that metformin treatment can cause a rise in klotho and a decrease in leptin levels without considerable effects on the weights of women with PCOS. Probably, leptin exerts its physiological effects in low concentrations while klotho in contrast acts physiologically in higher concentrations.

Leptin promotor mutations affect leptin levels and performance traits in dairy cows

NARCIS (Netherlands)

Liefers, S.C.; Pas, te M.F.W.; Veerkamp, R.F.; Platje, M.; Delavaud, C.; Chilliard, Y.; Lende, van der T.

2005-01-01

Leptin concentrations in body fluids and tissues undergo dynamic changes during the periparturient period. Polymorphisms in the leptin gene have been shown to be associated with differences in leptin concentration during late pregnancy but not during lactation. As the promoter of leptin regulates

Pleiotropic Effects of DDT Resistance on Male Size and Behaviour.

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Rostant, Wayne G; Bowyer, Jemima; Coupland, Jack; Facey, James; Hosken, David J; Wedell, Nina

2017-07-01

Understanding the evolution and spread of insecticide resistance requires knowing the relative fitness of resistant organisms. In the absence of insecticides, resistance is predicted to be costly. The Drosophila melanogaster DDT resistance allele (DDT-R) is associated with a male mating cost. This could be because resistant males are generally smaller, but DDT-R may also alter courtship behaviours. Here we tested for body size and courtship effects of DDT-R on mating success in competitive and non-competitive mating trials respectively. We also assessed relative aggression in resistant and susceptible males because aggression can also influence mating success. While the effect of DDT-R on male size partly contributed to reduced mating success, resistant males also had lower rates of courtship and were less aggressive than susceptible males. These differences contribute to the observed DDT-R mating costs. Additionally, these pleiotropic effects of DDT-R are consistent with the history and spread of resistance alleles in nature.

Puberty Is Delayed in Male Mice With Dextran Sodium Sulfate Colitis Out of Proportion to Changes in Food Intake, Body Weight, and Serum Levels of Leptin

OpenAIRE

DEBOER, MARK D.; LI, YONGLI

2011-01-01

In boys, inflammatory bowel disease often results in delayed puberty associated with decreased bone mineral density and decreased linear growth. Our goal was to investigate whether pubertal timing and levels of leptin differed between prepubertal male mice with colitis and food-restricted (FR) mice maintained at a similar weight. We induced colitis in 32-d-old male mice using dextran sodium sulfate (DSS), resulting in 10 d of worsening colitis. We followed up these mice for separation of the ...

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

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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.

Clinical significance of serum leptin levels in patients with graves' disease

International Nuclear Information System (INIS)

Hou Ying; Du Fuman; Teng Haikun; Yang Yuzhi

2008-01-01

Objective: To investigate the levels of serum leptin in patients with graves' disease. Methods: Serum leptin levels were measured with IRMA in 51 patients with hyperthyroidism as well as 46 hypothyroid and 50 euthyroid subjects as controls. Serum TSH, free T 3 and free T 4 (FT 3 and FT 4 ) were also measured. Body fat percentage (% Fat) and body mass index (BMI) were calculated. Results: Serum leptin levels were significantly lower in patients with graves' disease (male 2.05 ± 1.54μg/L, female 7.47±5. 08 μg/L), than those in hypothyroid and euthyroid subjects. Levels in hypothyroid patients were significantly higher than those in controls, however, excluding the body fat factor, there were no obvious difference. Serum leptin levels in all the 3 groups were significantly positively correlated with BMI. The levels were negatively correlated with FT 3 , FT 4 levels and positively correlated with TSH levels but both were not significant. Serum leptin levels were 2-3 times higher in women than in men among all 3 groups. Conclusion: Thyroid functional status affected serum leptin levels indirectly through the amount of body fat. (authors)

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

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Gloria Lena Vega

2013-01-01

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

Changes in serum leptin level in patients with diabetic retinopathy

International Nuclear Information System (INIS)

Yu Jing; Cao Huiling

2003-01-01

Objective: To explore the regulation of changes in serum leptin level in patients with diabetic retinopathy. Methods: The 120 participating subjects were of four groups: healthy controls, diabetic patients without retinopathy, patients with NPDR and patients with PDR, each group consisted of 18 males and 12 females with comparable BMI. The levels of serum leptin, IVC, insulin and blood glucose of these patients were measured and the correlation between serum leptin level and other parameters was analysed. Results: The level of serum leptin in controls, diabetic patients without retinopathy, patients with NPDR and patients with PDR were 6.91 ± 1.87 μg/L, 7,83 ±2.11 μg/L, 9.56 ± 2.43 μg/L and 11.69 ± 2.57 μg/L respectively. The patients with PDR had higher serum leptin levels than patients with NPDR (t=2.15, p < 0.05), diabetic patients without retinopathy (t = 2.71, p < 0.01), and controls (t = 3.50, p < 0.001), the patients with NPDR had higher serum leptin levels than diabetic patients without retinopathy (t = 2.23, p < 0.05) and controls (t = 2.75, p < 0.01), while the difference in serum leptin was not significant between diabetic patients without retinopathy and controls. The serum level was positively correlated to BMI (r = 0.22, p < 0.05) and FINS (r = 0.28, p < 0.01). Conclusion: Serum leptin level is elevated in patients with diabetic retinopathy and is positively correlated to the severity of the disease

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

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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

Leptin and adiponectin levels in girls with central precocious puberty before and during GnRH agonist treatment

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Jae Won Yoo

2016-12-01

Full Text Available PurposeThe effects of gonadotropin-releasing hormone agonist (GnRHa treatment on the energy metabolism in girls with central precocious puberty (CPP are controversial. We focused the changes and related factors of serum levels of leptin and adiponectin in girls with CPP before and during GnRHa treatment.MethodsThirty girls with idiopathic CPP were enrolled in the study. Their auxological data and fasting blood were collected at the baseline and after six months of GnRHa treatment.ResultsAfter treatment, height (P<0.001, weight (P<0.001, and serum leptin levels (P=0.033 were significantly increased, whereas body mass index (BMI, homeostasis model of assessment-insulin resistance, serum adiponectin levels, and adiponectin/leptin ratio exhibited no significant changes. A Pearson correlation analysis showed that height, weight, BMI, and their standard deviation scores (SDSs, but not basal LH, FSH, and estradiol, were significantly correlated with serum leptin levels before and after GnRHa treatment. After a multiple linear regression analysis, only BMI was associated with serum leptin levels. Moreover, leptin SDSs adjusted for BMI were not significantly different before and after GnRHa. The Δ leptin levels (r2=0.207, P=0.012, but not with Δ leptin SDS (r2=0.019, P=0.556, during GnRHa treatment were positively correlated with Δ BMI.ConclusionThese results suggest that GnRHa treatment in girls with CPP does not affect serum levels of leptin and adiponectin and insulin resistance. Serum leptin levels were depend on the changes in BMI during GnRHa treatment.

[Serum leptin levels and soluble leptin receptors in female patients with anorexia nervosa].

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Jiskra, J; Haluzík, M; Svobodová, J; Haluzíková, D; Nedvídková, J; Parízková, J; Kotrlíková, E

2000-10-25

Leptin action in peripheral tissues is enabled by an interaction with specific transmembrane receptors. Several of leptin receptor isoforms were identified, including soluble leptin receptor isoform structurally identical to extracellular domain of the the long leptin receptor isoform. The soluble receptor isoform is released to the circulation and acts probably as leptin-binding factor. The aim of our study was to measure serum concentrations of the soluble leptin receptor in patients with anorexia nervosa and in the control group of healthy women. Relationships of soluble leptin receptor levels to body mass index (BMI), body fat content, serum leptin, TNF-alpha and insulin levels were also studied. 16 patients with anorexia nervosa and 16 age-matched lean healthy women were included into the study. All of the subjects were measured and weighed, the body fat content was estimated from the skinfold thickness measurement. The blood for the determination of leptin, soluble leptin receptor and other hormonal parameters was obtained from all subjects after the overnight fasting. BMI, body fat content, serum leptin and insulin levels in patients with anorexia nervosa were significantly lower than in the control group (BMI: 14.98 +/- 2.32 vs. 22.21 +/- 2.48, p anorexia nervosa were significantly higher compared the to control group (24.67 +/- 8.3 U.ml-1 vs. 15.71 +/- 2.79 U.ml-1, p anorexia nervosa were significantly higher in comparison with the healthy subjects. Except of the negative correlation between serum soluble leptin receptor levels and BMI no statistically significant relationships between serum soluble leptin receptor and the rest of parameters studied were found.

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

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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.

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)

Serum Leptin Levels in Epileptic Patients Treated with Topiramate and Valproic Acid

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İrem Fatma Uludağ

2011-03-01

Full Text Available OBJECTIVE: Leptin is considered to be a signal factor that regulates body weight and energy expenditure, and there is a strong correlation between serum leptin concentrations, body mass index, and body fat mass in humans. Our aim in this study was to evaluate the role of leptin in valproic acid (VPA and topiramate (TPM related weight changes in epileptic patients. METHODS: Body mass index is calculated and serum leptin and insulin levels are measured in 56 patients with epilepsy (40 patients taking VPA and 16 patients taking VPA and TPM and in 40 healty control subjects. RESULTS: Obesity was seen in 21 patients (52.5% in VPA treated group, in 15 patients (37.5% in the control group and in only one male (6.3% in VPA and TPM treated group. Body mass index was lower in the group treated with VPA and TPM (p<0.001. Serum leptin concentrations were correlated with the body mass index (r=0.49, p<0.001 and were significantly higher in obese subjects (p<0.001 and in women (p<0.001. Serum leptin levels were significantly lower in patients treated with VPA and TPM (p<0.05. CONCLUSION: High levels of serum leptin in patients taking VPA and significantly low levels of serum leptin in patients taking VPA and TPM in our study are in agreement with the hypotheses that weight changes induced with VPA and TPM are related with the alterations in serum leptin levels

Serum Leptin Levels in Epileptic Patients Treated with Topiramate and Valproic Acid

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İrem Fatma Uludağ

2011-03-01

Full Text Available OBJECTIVE: Leptin is considered to be a signal factor that regulates body weight and energy expenditure, and there is a strong correlation between serum leptin concentrations, body mass index, and body fat mass in humans. Our aim in this study was to evaluate the role of leptin in valproic acid (VPA and topiramate (TPM related weight changes in epileptic patients. METHODS: Body mass index is calculated and serum leptin and insulin levels are measured in 56 patients with epilepsy (40 patients taking VPA and 16 patients taking VPA and TPM and in 40 healty control subjects. RESULTS: Obesity was seen in 21 patients (52.5% in VPA treated group, in 15 patients (37.5% in the control group and in only one male (6.3% in VPA and TPM treated group. Body mass index was lower in the group treated with VPA and TPM (p<0.001. Serum leptin concentrations were correlated with the body mass index (r=0.49, p<0.001 and were significantly higher in obese subjects (p<0.001 and in women (p<0.001. Serum leptin levels were significantly lower in patients treated with VPA and TPM (p<0.05. CONCLUSION: High levels of serum leptin in patients taking VPA and significantly low levels of serum leptin in patients taking VPA and TPM in our study are in agreement with the hypotheses that weight changes induced with VPA and TPM are related with the alterations in serum leptin levels.

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

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

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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.

Genetic variants of estrogen beta and leptin receptors may cause gynecomastia in adolescent.

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Eren, Erdal; Edgunlu, Tuba; Korkmaz, Huseyin Anil; Cakir, Esra Deniz Papatya; Demir, Korcan; Cetin, Esin Sakalli; Celik, Sevim Karakas

2014-05-15

Gynecomastia is a benign breast enlargement in males that affects approximately one-third of adolescents. The exact mechanism is not fully understood; however, it has been proposed that estrogen receptors and aromatase enzyme activity may play important roles in the pathogenesis of gynecomastia. While many studies have reported that aromatase enzyme (CYP19) gene polymorphism is associated with gynecomastia, only one study has shown a relationship between estrogen receptor (ER) alpha and beta gene polymorphism and gynecomastia. Thus, the aim of this study was to evaluate the relationships between CYP19 (rs2414096), ER alpha (rs2234693), ER beta (rs4986938), leptin (rs7799039), and leptin receptor (rs1137101) gene polymorphisms and gynecomastia. This study included 107 male adolescents with gynecomastia and 97 controls. Total serum testosterone (T) and estradiol (E2) levels were measured, and DNA was extracted from whole blood using the PCR-RFLP technique. The polymorphic distributions of CYP19, ER alpha, ER beta, leptin and leptin receptor genes were compared. The median E2 level was 12.41 (5.00-65.40) pg/ml in the control group and 16.86 (2.58-78.47) pg/ml in the study group (pgynecomastia and leptin receptor rs1137101 (p=0.002) and ER beta receptor rs4986938 gene polymorphisms (p=0.002). According to our results, increased E2 level and ER beta gene rs4986938 polymorphism might explain why some adolescents have gynecomastia. Leptin receptor gene rs1137101 polymorphism might affect susceptibility to gynecomastia. Copyright © 2014 Elsevier B.V. All rights reserved.

Leptin responsiveness to energy restriction: genetic variation in the leptin receptor gene.

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Mars, Monica; van Rossum, Caroline T M; de Graaf, Cees; Hoebee, Barbara; De Groot, Lisette C P G M; Kok, Frans J

2004-03-01

Serum leptin concentrations are an important afferent signal in energy balance homeostasis. It has been speculated that the leptin responsiveness to energy restriction is affected by the functionality of the leptin receptor. The purpose of this analysis was to explore the effect of polymorphisms in the LEPR gene on the acute decline in leptin after 4 days of 65% energy restriction. Leptin concentrations of the study group (n = 44; all men) declined by 2.3 +/- 1.5 micro g/L [-39.4% (95% confidence interval: -43.6 to -34.9)]. Leptin responses did not statistically differ between noncarriers and carriers of three mutant variants of the polymorphisms: Lys109/Lys109 (-41.4%) vs. Arg109/+ (-37.0%) (p = 0.33); Gln223/Gln223 (-41.5%) vs. Arg223/+ (-37.8%) (p = 0.40); Lys656/Lys656 (-39.5%) vs. Asn656/+ (-39.3%) (p = 0.96). No effect of the assessed polymorphisms in the LEPR gene on the acute decline in leptin after energy restriction was observed. Power calculations are provided for future studies on the leptin responsiveness to energy restriction.

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

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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.

Serum leptin concentration during puberty in healthy nonobese adolescents

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Brandão C.M.A.

2003-01-01

Full Text Available Data obtained during the past five years have indicated that there are important age- and gender-based differences in the regulation and action of leptin in humans. To study the physiological changes of leptin during puberty in both sexes, and its relationship with body composition and sexual maturation, we measured leptin concentrations in 175 healthy adolescents (80 girls, 95 boys, 10-18 years of age, representing all pubertal stages. We excluded individuals with a body mass index (BMI below the 5thor above the 95th percentile relative to age. Serum concentrations of leptin were determined by a monoclonal antibody-based immunofluorimetric assay, developed in our laboratory. Body composition was determined by dual-energy X-ray absorptiometry. Pubertal stage was assigned by physical examination, according to Tanner criteria for breast development in females and genital development in males. Leptin concentration in girls (N = 80 presented a positive linear correlation with age (r = 0.35, P = 0.0012, BMI (r = 0.65, P < 0.0001 and %fat mass (r = 0.76, P < 0.0001. In boys (N = 95 there was a positive correlation with BMI (r = 0.49, P < 0.0001 and %fat mass (r = 0.85, P < 0.0001, but a significant negative linear correlation with Tanner stage (r = -0.45, P < 0.0001 and age (r = -0.40, P < 0.0001. The regression equation revealed that %fat mass and BMI are the best parameters to be used to estimate leptin levels in both sexes. Thus, the normal reference ranges for circulating leptin during adolescence should be constructed according to BMI or %fat mass to assure a correct evaluation.

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

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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

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

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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.

Alterations in mouse hypothalamic adipokine gene expression and leptin signaling following chronic spinal cord injury and with advanced age.

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Gregory E Bigford

Full Text Available Chronic spinal cord injury (SCI results in an accelerated trajectory of several cardiovascular disease (CVD risk factors and related aging characteristics, however the molecular mechanisms that are activated have not been explored. Adipokines and leptin signaling are known to play a critical role in neuro-endocrine regulation of energy metabolism, and are now implicated in central inflammatory processes associated with CVD. Here, we examine hypothalamic adipokine gene expression and leptin signaling in response to chronic spinal cord injury and with advanced age. We demonstrate significant changes in fasting-induced adipose factor (FIAF, resistin (Rstn, long-form leptin receptor (LepRb and suppressor of cytokine-3 (SOCS3 gene expression following chronic SCI and with advanced age. LepRb and Jak2/stat3 signaling is significantly decreased and the leptin signaling inhibitor SOCS3 is significantly elevated with chronic SCI and advanced age. In addition, we investigate endoplasmic reticulum (ER stress and activation of the uncoupled protein response (UPR as a biological hallmark of leptin resistance. We observe the activation of the ER stress/UPR proteins IRE1, PERK, and eIF2alpha, demonstrating leptin resistance in chronic SCI and with advanced age. These findings provide evidence for adipokine-mediated inflammatory responses and leptin resistance as contributing to neuro-endocrine dysfunction and CVD risk following SCI and with advanced age. Understanding the underlying mechanisms contributing to SCI and age related CVD may provide insight that will help direct specific therapeutic interventions.

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

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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.

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

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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

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

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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.

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

Leptin in pediatrics: A hormone from adipocyte that wheels several functions in children

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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.

Leptin in pediatrics: A hormone from adipocyte that wheels several functions in children

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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

Effect of Raised Body Fat on Vitamin D, Leptin and Bone Mass

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Fatima, S. S.; Alam, F.

2015-01-01

Objectives: To estimate leptin, vitamin D and bone mineral density levels in individuals with high fat mass, and to assess any correlation. Methods: The cross-sectional study was conducted at the Basic Medical Sciences Institute, Jinnah Post Graduate Medical Centre, Karachi, and Aga Khan University, Karachi, from August 2012 to July 2014, and comprised healthy male volunteers between the ages of 18-60 years. Body fat percentage was determined using bioelectrical impedance analysis and the participants were classified as: Group A (15-21.9); Group B (22-27.9); and Group C (>28). Bone mineral density was calculated by ultrasound bone densitometer (T-score between +1 and -1 considered normal). Enzyme-linked immunosorbent assay kits were used to determine the levels of vitamin D and leptin. SPSS 19 was used for statistical analysis. Results: A total of 132 male subjects participated in this study, with each of the 3 groups having 44(33.3 percent). Despite all groups having low Vitamin D, a marked decrease was observed in group C compared to groups A and B (p <0.018). Bone mineral density T-score was <-1; total calcium was within normal range in all three groups. Serum leptin was raised in Group C compared to group A and B (p=0.03). Body fat percentage was negatively associated with vitamin D (p=0.004; r = -0.351), while it was positively correlated with leptin (p =0.038; r = 0.256). Conclusion: Excess of body fat percentage led to decreased vitamin D and raised leptin. However, bone mineral density and calcium levels were within normal range, suggesting that other factors might have played a role in maintaining bone mass in obese individuals, such as leptin. (author)

The effect of opium addiction on serum adiponectin and leptin levels in male subjects: a case control study from Kerman Coronary Artery Disease Risk Factors Study (KERCADRS).

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Shahouzehi, Beydolah; Shokoohi, Mostafa; Najafipour, Hamid

2013-01-01

Serum adiponectin and leptin levels have been shown to be related to obesity, insulin resistance and cardiovascular diseases (CVD). Opium addiction has a positive association with endocrine system disorders. The relationship between adipokines and opium addiction is unclear. In the present study, we aimed to determine serum adiponectin and leptin levels in opium addicted subjects. 176 men, 88 opium addicts and 88 non- addicts were randomly selected from subjects who participated in Kerman Coronary Artery Disease Risk factors Study (KERCADRS); a population-based study. Serum adiponectin and leptin levels were measured using ELISA and compared between two groups. We adjusted the effect of some confounding factors such as the patients' demographic, clinical and medical history in multivariate analysis model. The serum level of adiponectin in opium addicts was significantly lower than control group (6.5±3.6 vs. 9.8±8.1 µg/ml, Popium addicts, p = 0.80). In the multivariate analysis, after adjusting for age, cigarette smoking, body mass index, type 2 diabetes, hypertension, cholesterol, triglyceride and high and low density lipoproteins, the negative association between opium addiction and decreased adiponectin level was still present (β = -0.144, P value = 0.005). The results showed that opium addiction reduces serum adiponectin level. Since adiponectin has been shown to have anti-diabetic and anti-atherogenic effects, its reduction may account for increase in the risk of metabolic disorders such as insulin resistance and CVD amongst opium addicted patients.

The features of leptin and its receptor expression in metastatic cutaneous melanoma

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A. A. Lushnikova

2015-01-01

Full Text Available Leptin is a multifunctional hormone with the activity of cytokines, which regulates critical signaling pathways that can induce cell proliferation, invasion, angiogenesis and tumor growth. Leptin plays an important role in the regulation of metabolism, energy exchange, functions of the neuro-endocrine system, including the pituitary, hypothalamus, adrenals, and immune system functions. Recently, some evidences have been appeared concerning the role of leptin in induction of chronic inflammatory processes, autoimmune pathologies, type 2 diabetes and cancer. An elevated blood level of the hormone is considered as a risk factor for different neoplasm developmentObjective. Analysis of the hormone leptin (Lep, the long and short isoforms of its receptor (LepR1 and LepR2 expression in blood, tumor cells and normal skin fibroblasts in the patients with metastatic cutaneous melanoma (CM with various clinico-pathological characteristics for prognostic assessment.Materials and methods. 15 patients with metastatic CM (10 women and 5 men, aged 22 to 67 years with body mass from normal to obese have been studied. The expression of Lep / LepR in the patient and donor blood sera, tumor and normal skin fibroblasts were determined using enzyme-linked immunosorbent assay (ELISA and RT PCR using total RNAs isolated from pairs of tumor samples and normal tissue.Results. Average level of leptin in the blood of CM patients and in tumor cells exceeds the normal one. Concentration of lepin in female CM patients was higher than in male patients. The expression level of Lep and LepR1 genes (but not LepR2 in tumor cells was relatively higher than in normal skin fibroblasts of these patients, and above the level of GAPDH gene expression. In the female patients with overweight (body mass index = 25,00–29,99 kg/m2 there was a trend to higher concentrations of leptin in the blood in comparison of the patients with normal body mass and leptin level in the sera of male CM

Leptin responsiveness to energy restriction: genetic variation in the leptin receptor gene

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Mars, M.; Rossum, van C.T.M.; Graaf, de C.; Hoebee, B.; Groot, de C.P.G.M.; Kok, F.J.

2004-01-01

Serum leptin concentrations are an important afferent signal in energy balance homeostasis. It has been speculated that the leptin responsiveness to energy restriction is affected by the functionality of the leptin receptor. The purpose of this analysis was to explore the effect of polymorphisms in

Acute up-regulation of the rat brain somatostatin receptor-effector system by leptin is related to activation of insulin signaling and may counteract central leptin actions.

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Perianes-Cachero, A; Burgos-Ramos, E; Puebla-Jiménez, L; Canelles, S; Frago, L M; Hervás-Aguilar, A; de Frutos, S; Toledo-Lobo, M V; Mela, V; Viveros, M P; Argente, J; Chowen, J A; Arilla-Ferreiro, E; Barrios, V

2013-11-12

Leptin and somatostatin (SRIF) have opposite effects on food seeking and ingestive behaviors, functions partially regulated by the frontoparietal cortex and hippocampus. Although it is known that the acute suppression of food intake mediated by leptin decreases with time, the counter-regulatory mechanisms remain unclear. Our aims were to analyze the effect of acute central leptin infusion on the SRIF receptor-effector system in these areas and the implication of related intracellular signaling mechanisms in this response. We studied 20 adult male Wister rats including controls and those treated intracerebroventricularly with a single dose of 5 μg of leptin and sacrificed 1 or 6h later. Density of SRIF receptors was unchanged at 1h, whereas leptin increased the density of SRIF receptors at 6h, which was correlated with an elevated capacity of SRIF to inhibit forskolin-stimulated adenylyl cyclase activity in both areas. The functional capacity of SRIF receptors was unaltered as cell membrane levels of αi1 and αi2 subunits of G inhibitory proteins were unaffected in both brain areas. The increased density of SRIF receptors was due to enhanced SRIF receptor subtype 2 (sst2) protein levels that correlated with higher mRNA levels for this receptor. These changes in sst2 mRNA levels were concomitant with increased activation of the insulin signaling, c-Jun and cyclic AMP response element-binding protein (CREB); however, activation of signal transducer and activator of transcription 3 was reduced in the cortex and unchanged in the hippocampus and suppressor of cytokine signaling 3 remained unchanged in these areas. In addition, the leptin antagonist L39A/D40A/F41A blocked the leptin-induced changes in SRIF receptors, leptin signaling and CREB activation. In conclusion, increased activation of insulin signaling after leptin infusion is related to acute up-regulation of the SRIF receptor-effector system that may antagonize short-term leptin actions in the rat brain

Effects of leptin treatment and Western diet on wheel running in selectively bred high runner mice.

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Meek, Thomas H; Dlugosz, Elizabeth M; Vu, Kim T; Garland, Theodore

2012-05-15

The role of leptin in regulating physical activity is varied. The behavioral effects of leptin signaling depend on the type of activity and the animal's physiological state. We used mice from lines selectively bred for high voluntary wheel running to further study how leptin regulates volitional exercise. Mice from four replicate high runner (HR) lines typically run ~3-fold more revolutions per day than those from four non-selected control (C) lines. HR mice have altered dopamine function and differences from C in brain regions known to be important in leptin-mediated behavior. Furthermore, male HR mice have been found to dramatically increase running when administered Western diet, an effect possibly mediated through leptin signaling. Male mice from generation 61 (representing three HR lines and one C line) were allowed wheel access at 24 days of age and given either Western diet (high in fat and with added sucrose) or standard chow. After four weeks, Western diet significantly increased circulating leptin, insulin, C-peptide, gastric inhibitory polypeptide, and inflammatory hormone resistin concentrations in HR mice (C mice not measured). Western diet increased running in HR mice, but did not significantly affect running in C mice. During the fifth week, all mice received two days of intra-peritoneal sham injections (physiological saline) followed by three days of murine recombinant leptin injections, and then another six days of sham injections. Leptin treatment significantly decreased caloric intake (adjusted for body mass) and body mass in all groups. Wheel running significantly increased with leptin injections in HR mice (fed Western or standard diet), but was unaffected in C mice. Whether Western diet and leptin treatment stimulate wheel running in HR mice through the same physiological pathways awaits future study. These results have implications for understanding the neural and endocrine systems that control locomotor activity, food consumption, and body

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.

Gene Expression of Leptin and Long Leptin Receptor Isoform in Endometriosis: A Case-Control Study

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Andrea Prestes Nácul

2013-01-01

Full Text Available In this study, leptin/BMI ratio in serum and peritoneal fluid and gene expression of leptin and long form leptin receptor (OB-RL were assessed in eutopic and ectopic endometria of women with endometriosis and controls. Increased serum leptin/BMI ratio was found in endometriosis patients. Leptin and OB-RL gene expression was significantly higher in ectopic versus eutopic endometrium of patients and controls. A positive, significant correlation was observed between leptin and OB-RL transcripts in ectopic endometria and also in eutopic endometria in endometriosis and control groups. A negative and significant correlation was found between OB-RL mRNA expression and peritoneal fluid leptin/BMI ratio only in endometriosis. These data suggest that, through a modulatory interaction with its active receptor, leptin might play a role in the development of endometrial implants.

Neonatal Overnutrition Increases Testicular Size and Expression of Luteinizing Hormone β-Subunit in Peripubertal Male Rats

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Pilar Argente-Arizón

2018-04-01

Full Text Available Proper nutrition is important for growth and development. Maturation of the reproductive axis and the timing of pubertal onset can be delayed when insufficient nutrition is available, or possibly advanced with nutritional abundance. The childhood obesity epidemic has been linked to a secular trend in advanced puberty in some populations. The increase in circulating leptin that occurs in association with obesity has been suggested to act as a signal that an adequate nutritional status exists for puberty to occur, allowing activation of central mechanisms. However, obesity-associated hyperleptinemia is linked to decreased leptin sensitivity, at least in adults. Here, we analyzed whether neonatal overnutrition modifies the response to an increase in leptin in peripubertal male rats, as previously demonstrated in females. Wistar rats were raised in litters of 4 (neonatal overnutrition or 12 pups (controls per dam. Leptin was administered sc (3 µg/g body weight at postnatal day 35 and the rats killed 45 min or 2 h later. Postnatal overfeeding resulted in increased body weight and circulating leptin levels; however, we found no overweight-related changes in the mRNA levels of neuropeptides involved in metabolism or reproduction. In contrast, pituitary expression of luteinizing hormone (LH beta-subunit was increased in overweight rats, as was testicular weight. There were no basal differences between L4 and L12 males or in their response to leptin administration in pSTAT3 levels in the hypothalamus at either 45 min or 2 h. In contrast, pJAK2 was found to be higher at 45 min in L4 compared to L12 males regardless of leptin treatment, while at 2 h it was higher in L4 leptin-treated males compared to L12 leptin-treated males, as well as L4 vehicle-treated rats. There were no changes in response to leptin administration in the expression of the neuropeptides analyzed. However, serum LH levels rose only in L4 males in response to leptin, but

Neonatal Overnutrition Increases Testicular Size and Expression of Luteinizing Hormone β-Subunit in Peripubertal Male Rats

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Argente-Arizón, Pilar; Castro-González, David; Díaz, Francisca; Fernández-Gómez, María J.; Sánchez-Garrido, Miguel A.; Tena-Sempere, Manuel; Argente, Jesús; Chowen, Julie A.

2018-01-01

Proper nutrition is important for growth and development. Maturation of the reproductive axis and the timing of pubertal onset can be delayed when insufficient nutrition is available, or possibly advanced with nutritional abundance. The childhood obesity epidemic has been linked to a secular trend in advanced puberty in some populations. The increase in circulating leptin that occurs in association with obesity has been suggested to act as a signal that an adequate nutritional status exists for puberty to occur, allowing activation of central mechanisms. However, obesity-associated hyperleptinemia is linked to decreased leptin sensitivity, at least in adults. Here, we analyzed whether neonatal overnutrition modifies the response to an increase in leptin in peripubertal male rats, as previously demonstrated in females. Wistar rats were raised in litters of 4 (neonatal overnutrition) or 12 pups (controls) per dam. Leptin was administered sc (3 µg/g body weight) at postnatal day 35 and the rats killed 45 min or 2 h later. Postnatal overfeeding resulted in increased body weight and circulating leptin levels; however, we found no overweight-related changes in the mRNA levels of neuropeptides involved in metabolism or reproduction. In contrast, pituitary expression of luteinizing hormone (LH) beta-subunit was increased in overweight rats, as was testicular weight. There were no basal differences between L4 and L12 males or in their response to leptin administration in pSTAT3 levels in the hypothalamus at either 45 min or 2 h. In contrast, pJAK2 was found to be higher at 45 min in L4 compared to L12 males regardless of leptin treatment, while at 2 h it was higher in L4 leptin-treated males compared to L12 leptin-treated males, as well as L4 vehicle-treated rats. There were no changes in response to leptin administration in the expression of the neuropeptides analyzed. However, serum LH levels rose only in L4 males in response to leptin, but with no change

Increased leptin/leptin receptor pathway affects systemic and airway inflammation in COPD former smokers

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Bruno A

2011-05-01

Full Text Available Andreina Bruno1, Marinella Alessi2, Simona Soresi2, Anna Bonanno1, Loredana Riccobono1, Angela Marina Montalbano1, Giusy Daniela Albano1, Mark Gjomarkaj1, Mirella Profita11Institute of Biomedicine and Molecular Immunology, Italian National Research Council, Palermo, Italy; 2Dipartimento Biomedico di Biomedicina Interna e Specialistica, University Palermo, ItalyBackground: Leptin, a hormone produced mainly by adipose tissue, regulates food intake and energy expenditure. It is involved in inflammatory diseases such as chronic obstructive pulmonary disease (COPD and its deficiency is associated with increased susceptibility to the infection. The leptin receptor is expressed in the lung and in the neutrophils.Methods: We measured the levels of leptin, tumor necrosis factor alpha (TNF-a and soluble form of intercellular adhesion molecule-1 (sICAM-1 in sputum and plasma from 27 smoker and former smoker patients with stable COPD using ELISA methods. Further we analyzed leptin and its receptor expression in sputum cells from 16 COPD patients using immunocytochemistry.Results: In plasma of COPD patients, leptin was inversely correlated with TNF-a and positively correlated with the patient weight, whereas the levels of sICAM-1 were positively correlated with TNF-a. In sputum of COPD patients leptin levels were correlated with forced expiratory volume in 1 second/forced vitality capacity. Additionally, increased levels of sputum leptin and TNF-a were observed in COPD former smokers rather than smokers. Further the expression of leptin receptor in sputum neutrophils was significantly higher in COPD former smokers than in smokers, and the expression of leptin and its receptor was positively correlated in neutrophils of COPD former smokers.Conclusion: Our findings suggest a role of leptin in the local and systemic inflammation of COPD and, taking into account the involvement of neutrophils in this inflammatory disease, describe a novel aspect of the leptin/leptin

Effect of leptin gene methylation on glucose metabolism in pregnant rats

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Zhen LI

2011-11-01

Full Text Available Objective To examine the dynamic level of progesterone,insulin,and leptin,as well as the change in the features of leptin gene methylation in the promoter region of pregnant rats during different gestation stages and to analyze the correlation and effect of these conditions on glucose metabolism during gestation.Methods C57BL/6J pregnant rats are divided to four different groups,namely,early,mid-,and late gestation,as well as seven days postpartum(five rats for each group.Five C57BL/6J non-pregnant rats are taken as the control group.The change in glucose metabolism during gestation was determined by measuring the glucose tolerance of rats in different groups and by testing the level of progesterone,insulin,and leptin in the sera and the level of the methylation of leptin gene promoters during different stages of gestation.Results The levels of insulin [(13.70±0.70,14.78±0.91,and 16.07±0.55mU/L],progesterone [(10.10±0.37,11.41±0.50,and 15.34±0.65μg/L],and leptin [(1356.73±100.41,1628.02±53.03,and 1954.12±39.71ng/L] in pregnant rats in the three groups(early,mid-,and late gestation are apparently higher than that of the non-pregnant rats [(12.25±1.62mU/L,(7.14±0.38μg/L,and(934.38±62.29ng/L] and the postpartum group [(12.46±0.93mU/L,(9.74±0.82μg/L,and(1259.19±105.74ng/L].The difference among the different stages of gestation has statistical significance(P < 0.01,but the difference between the non-pregnant and postpartum groups is statistically insignificant.Fasting blood glucose during gestation is low.The level of blood glucose in mid-gestation and late-gestation rats after being injected with glucose is apparently higher than that of the non-pregnant group(P < 0.01.The level of methylation in the leptin gene promoter zone of the placenta drops along with gestation.Conclusions High levels of progesterone,insulin,and leptin contribute to physiological insulin resistance during gestation,resulting in reduced fasting blood glucose

Sheep oocyte expresses leptin and functional leptin receptor mRNA

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Seyyed Jalil Taheri

2016-09-01

Conclusions: The result of present study reveals that leptin and its functional receptor (Ob-Rb mRNA are expressed in sheep oocyte and further studies should investigate the role(s of leptin on sheep oocyte physiology and embryo development.

Characterization of Leptin Intracellular Trafficking

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E Walum

2009-12-01

Full Text Available Leptin is produced by adipose tissue, and its concentration in plasma is related to the amount of fat in the body. The leptin receptor (OBR is a member of the class I cytokine receptor family and several different isoforms, produced by alternative mRNA splicing are found in many tissues, including the hypothalamus. The two predominant isoforms includes a long form (OBRl with an intracellular domain of 303 amino acids and a shorter form (OBRs with an intracellular domain of 34 amino acids. Since OBRl is mainly expressed in the hypotalamus, it has been suggested to be the main signalling form. The peripheral production of leptin by adipocyte tissue and its effects as a signal of satiety in the central nervous system imply that leptin gains access to regions of the brain regulating in energy balance by crossing the blood-brain barrier. In an attempt to characterize the intracellular transport of leptin, we have followed binding internalization and degradation of leptin in HEK293 cells. We have also monitored the intracellular transport pathway of fluorescent conjugated leptin in HEK293 cells. Phenylarsine oxide, a general inhibitor of endocytosis, as well as incubation at mild hypertonic conditions, prevented the uptake of leptin, confirming a receptor-mediated internalization process. When internalized, 125I-leptin was rapidly accumulated inside the cells and reached a maximum after 10 min. After 70 minutes about 40-50% of total counts in each time point were found in the medium as TCA-soluble material. Leptin sorting, at the level of early endosomes, did not seem to involve recycling endosomes, since FITC-leptin was sorted from Cy3- transferrin containing compartments at 37°C. At 45 minutes of continuos internalization, FITC-leptin appeared mainly accumulated in late endocytic structures colocalizing with internalized rhodamine coupled epidermial growth factor (EGF and the lysosomal marker protein lamp-1. The transport of leptin was also shown

Elevated circulating leptin levels in arterial hypertension: relationship to arteriovenous overflow and extraction of leptin

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Henriksen, Jens Henrik Sahl; Holst, J J; Moller, S

2000-01-01

Leptin, a peptide hormone produced mainly in fat cells, appears to be important for the regulation of metabolism, insulin secretion/sensitivity and body weight. Recently, elevated plasma leptin levels have been reported in patients with arterial hypertension. Because a change in circulating leptin...... concentrations in such patients could be caused by altered rates of production or disposal, or both, the aim of the present study was to identify regions of leptin overflow into the bloodstream and of leptin extraction. Patients with arterial hypertension (n=12) and normotensive controls (n=20) were studied...... during catheterization with elective blood sampling from different vascular beds (artery, and renal, hepatic, iliac and cubital veins). Plasma leptin was determined by a radioimmunoassay. Patients with hypertension had significantly elevated levels of circulating leptin (12.8 ng/l, compared with 4.1 ng...

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

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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

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

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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.

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

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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)

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

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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.

Kinetics of leptin binding to the Q223R leptin receptor.

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Hans Verkerke

Full Text Available Studies in human populations and mouse models of disease have linked the common leptin receptor Q223R mutation to obesity, multiple forms of cancer, adverse drug reactions, and susceptibility to enteric and respiratory infections. Contradictory results cast doubt on the phenotypic consequences of this variant. We set out to determine whether the Q223R substitution affects leptin binding kinetics using surface plasmon resonance (SPR, a technique that allows sensitive real-time monitoring of protein-protein interactions. We measured the binding and dissociation rate constants for leptin to the extracellular domain of WT and Q223R murine leptin receptors expressed as Fc-fusion proteins and found that the mutant receptor does not significantly differ in kinetics of leptin binding from the WT leptin receptor. (WT: ka 1.76×106±0.193×106 M-1 s-1, kd 1.21×10-4±0.707×10-4 s-1, KD 6.47×10-11±3.30×10-11 M; Q223R: ka 1.75×106±0.0245×106 M-1 s-1, kd 1.47×10-4±0.0505×10-4 s-1, KD 8.43×10-11±0.407×10-11 M. Our results support earlier findings that differences in affinity and kinetics of leptin binding are unlikely to explain mechanistically the phenotypes that have been linked to this common genetic variant. Future studies will seek to elucidate the mechanism by which this mutation influences susceptibility to metabolic, infectious, and malignant pathologies.

Association between Follicular Fluid Leptin and Serum Insulin Levels in Nonoverweight Women with Polycystic Ovary Syndrome

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G. Garruti

2014-01-01

Full Text Available Aims. We evaluated the links between leptin and visfatin levels and fertilization rates in nonoverweight (NOW women with PCOS (NOW-PCOS from Apulia undergoing in vitro fertilization/embryo transfer (IVF. Materials and Methodology. We recruited 16 NOW women with PCOS (NOW-PCOS and 10 normally ovulating NOW women (control-NOW. All women underwent IVF. Androgens, 17-β-estradiol (17β-E2, and insulin levels were measured in plasma and/or serum and leptin and visfatin levels were assayed in both serum and follicular fluid (FF-leptin, FF-visfatin. Results. In NOW-PCOS, both serum and FF-leptin were significantly lower than in control-NOW. In NOW-PCOS, significant correlations were found between BMI and serum leptin and insulinemia and FF-leptin. By contrast, in control-NOW, FF-leptin levels were not correlated with insulinemia. Serum visfatin levels were not significantly different in NOW-PCOS and control-NOW, but FF-visfatin levels were 1.6-fold higher, although not significantly, in NOW-PCOS than in control-NOW. Conclusions. Both serum leptin levels and FF-leptin are BMI- and insulin-related in Southern Italian NOW-PCOS from Apulia. In line with other reports showing that FF-leptin levels are predictive of fertilization rates, lower than normal FF-leptin levels in NOW-PCOS may explain their lower fertilization rate and this may be related to the level of insulin and/or insulin resistance.

Studies on the relationship between leptin secretion and several pregnancy-related hormones during pregnancy in the golden hamster

International Nuclear Information System (INIS)

Wang Chen; Yang Liguo; Gen Watanabe; Kazuyoshi Taya

2003-01-01

Objective: To determine the relationships between leptin secretion and several pregnancy related hormones, the body weight as well as food intaken in the golden hamster during pregnancy and early lactation. Methods: 100 golden hamsters were mated and divided into 16 groups. Blood specimens were taken at 11:00 daily and were determined for plasma leptin, growth hormone (GH), follicular stimulating hormone (FSH), luteinizing hormone (LH), progesterone estradiol and inhibin with RIA. Relationships between leptin level and food intake as well as material body weight were also noted. Results: A plasma leptin peak level occurred on day 12 of the pregnancy. Leptin levels were significantly correlated with levels of gonadal hormones but not with pituitary hormones. Food intake and material total body weight (including the fetus) bore no significant correlationship with plasma leptin throughout the whole pregnancy stage. However, if the fetus weight was subtracted, the net maternal body weight would be significantly correlated with the leptin concentration. Conclusion: These results suggest that leptin-resistance may exits in the golden hamster during pregnancy. Some pregnancy-related hormones, especially gonadal hormones, have regulatory effect on the secretion of leptin. Positive correlation between leptin and net maternal body weight suggests that leptin is still a signal of the body weight to the central nerves system during pregnancy

Novel Insights into How Overnutrition Disrupts the Hypothalamic Actions of Leptin

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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.

Autosomal male determination in a spinosad-resistant housefly strain from Denmark

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Højland, Dorte H; Scott, Jeffrey G; Vagn Jensen, Karl-Martin

2014-01-01

males in this strain. The factor responsible for spinosad resistance in the strain is unknown, but previous studies suggest a role of cytochrome P450s for detoxification of spinosad. Sex determination in the housefly is controlled by a male-determining factor (M), either located on the Y chromosome......BACKGROUND The housefly, Musca domestica L., is a global pest and has developed resistance to most insecticides applied for its control. The insecticide spinosad plays an important role in housefly control. Females of the Danish housefly strain 791spin are threefold more resistant to spinosad than...... of resistance to spinosad. Sex determination in 791spin is due to a male factor on autosome 3. CONCLUSIONS The most likely explanation for the differentiation of spinosad resistance between males and females is a recessive spinosad resistance factor on autosome III. © 2013 Society of Chemical Industry...

Leptin concentration and risk of impaired physical function in older adults: the Seniors-ENRICA cohort.

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Lana, Alberto; Struijk, Ellen; Guallar-Castillón, Pilar; Martín-Moreno, Jose María; Rodríguez Artalejo, Fernando; Lopez-Garcia, Esther

2016-11-01

leptin resistance, which may develop during the ageing process, stimulates the production of pro-inflammatory cytokines and insulin resistance that could impair the muscle function. However, the role of leptin on physical functioning among older adults has not yet been elucidated. to examine the association between serum leptin levels and physical function impairment in older adults. prospective study of 1,556 individuals 60 years and older from the Seniors-ENRICA cohort, who were free of physical function limitation at baseline. serum leptin was measured in 2008-10, and incident functional limitation was assessed through 2012. Self-reported limitations in agility and mobility were assessed with the Rosow and Breslau scale, limitation in the lower extremity function was measured with the Short Physical Performance Battery, and impairment in the overall physical performance with the physical component summary of the SF-12. after adjustment for potential confounders and compared to individuals in the lowest quartile of leptin concentration, those in the highest quartile showed increased risk of impaired physical function; the odds ratio (95% confidence interval) and P-trend was: 1.95 (1.11-3.43), P = 0.006 for self-reported impaired mobility; 1.76 (1.08-2.87), P = 0.02 for self-reported impaired agility; 1.48 (1.02-2.15), P = 0.04 for limitation in the lower extremity function; and 1.97 (1.20-3.22), P = 0.01, for decreased overall physical performance. These associations were only modestly explained by C-reactive protein and insulin resistance. Moreover, the associations held across groups with varying health status and were independent of estimated total body fat. higher leptin concentration was associated with increased risk of impaired physical function. Preserving metabolic function during the old age could help delaying physical function decline. © The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All

Lung function testing according leptin levels in patients with chronic obstructive pulmonary disease

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O. Radchenko

2017-02-01

Full Text Available Chronic obstructive pulmonary disease (COPD belongs to urgent medical and social problems of our time. Prognosis of COPD is often determined by a comorbidity, in particular obesity. The key chain, which unites COPD and obesity, is systemic inflammation, in the development of which the hormone of fatty tissue leptin plays an important role. The presence of receptors to leptin in the alveolar and bronchial epithelial cells, in smooth muscle tissue and submucous bronchial membrane allowes to assume that leptin takes pathogenetic part in COPD progression. The aim of our research was to estimate the leptin level in COPD patient and analyze changes of the respiratory function depending on it. Methods. We have been examined 26 patients with exacerbation of COPD (13 male and 13 female, 58 y.o. and 20 healthy people representative by gender, age and body mass. The level of serum leptin has been defined by the solid phase enzyme linked immunosorbent analysis, lung function – by computed testing. Results and conclusion. With the leptin level increase all of the lung function parameters progressively decreased, most significant - forced vital capacity and peak expiratory flow. Patients with hyperleptinemia had significantly lower measurements of forced expiratory volume in 1 second and vital lungs capacity. Severe degree of both obstructive and restrictive changes has been found more often among patients with hyperleptinemia and leptin level has been associated with the bronchial obstruction severity.

Relationship of Neonatal Leptin and Insulin to Birth Weight and Gender Difference as well as Their Relationship to Maternal Levels

International Nuclear Information System (INIS)

Ashry, Kh.M.

2005-01-01

Normal intrauterine growth and development is dependent on many factors of which hormonal factors have been implicated. The aim of the present work was to study the relationship of neonatal leptin and insulin to birth weight and gender difference as well as their relationship to maternal levels. Serum leptin level was assessed by competitive enzyme immunoassay and insulin level by radioimmunoassay in the cord blood of sixty neonates and the venous blood of their mothers. The neonates were classified according to their birth weight into: 23 appropriate for gestational age (AGA) (12 females and 11 males); 20 large for gestational age (LGA) (11 females and 9 males) and 17 small for gestational age (SGA) (9 femals and 8 males). Our results revealed a highly significant increase in maternal serum levels of leptin and insulin (24.1±11.8 ng/ml and 22.3±5.8 μ U/ml, respectively) when compared to neonatal levels (10.0 ± 7.4ng/ml and 7.4±4.3 μ U/ml, p<0.001, respectively). Cord blood leptin and insulin levels showed statistically significant differences between all weight classes with the highest levels in LGA neonates

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

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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

Phocid seal leptin: tertiary structure and hydrophobic receptor binding site preservation during distinct leptin gene evolution.

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John A Hammond

Full Text Available The cytokine hormone leptin is a key signalling molecule in many pathways that control physiological functions. Although leptin demonstrates structural conservation in mammals, there is evidence of positive selection in primates, lagomorphs and chiropterans. We previously reported that the leptin genes of the grey and harbour seals (phocids have significantly diverged from other mammals. Therefore we further investigated the diversification of leptin in phocids, other marine mammals and terrestrial taxa by sequencing the leptin genes of representative species. Phylogenetic reconstruction revealed that leptin diversification was pronounced within the phocid seals with a high dN/dS ratio of 2.8, indicating positive selection. We found significant evidence of positive selection along the branch leading to the phocids, within the phocid clade, but not over the dataset as a whole. Structural predictions indicate that the individual residues under selection are away from the leptin receptor (LEPR binding site. Predictions of the surface electrostatic potential indicate that phocid seal leptin is notably different to other mammalian leptins, including the otariids. Cloning the grey seal leptin binding domain of LEPR confirmed that this was structurally conserved. These data, viewed in toto, support a hypothesis that phocid leptin divergence is unlikely to have arisen by random mutation. Based upon these phylogenetic and structural assessments, and considering the comparative physiology and varying life histories among species, we postulate that the unique phocid diving behaviour has produced this selection pressure. The Phocidae includes some of the deepest diving species, yet have the least modified lung structure to cope with pressure and volume changes experienced at depth. Therefore, greater surfactant production is required to facilitate rapid lung re-inflation upon surfacing, while maintaining patent airways. We suggest that this additional

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

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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.

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

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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.

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

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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

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

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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.

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

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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.

Leptin signaling in GABA neurons, but not glutamate neurons, is required for reproductive function.

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Zuure, Wieteke A; Roberts, Amy L; Quennell, Janette H; Anderson, Greg M

2013-11-06

The adipocyte-derived hormone leptin acts in the brain to modulate the central driver of fertility: the gonadotropin releasing hormone (GnRH) neuronal system. This effect is indirect, as GnRH neurons do not express leptin receptors (LEPRs). Here we test whether GABAergic or glutamatergic neurons provide the intermediate pathway between the site of leptin action and the GnRH neurons. Leptin receptors were deleted from GABA and glutamate neurons using Cre-Lox transgenics, and the downstream effects on puberty onset and reproduction were examined. Both mouse lines displayed the expected increase in body weight and region-specific loss of leptin signaling in the hypothalamus. The GABA neuron-specific LEPR knock-out females and males showed significantly delayed puberty onset. Adult fertility observations revealed that these knock-out animals have decreased fecundity. In contrast, glutamate neuron-specific LEPR knock-out mice displayed normal fertility. Assessment of the estrogenic hypothalamic-pituitary-gonadal axis regulation in females showed that leptin action on GABA neurons is not necessary for estradiol-mediated suppression of tonic luteinizing hormone secretion (an indirect measure of GnRH neuron activity) but is required for regulation of a full preovulatory-like luteinizing hormone surge. In conclusion, leptin signaling in GABAergic (but not glutamatergic neurons) plays a critical role in the timing of puberty onset and is involved in fertility regulation throughout adulthood in both sexes. These results form an important step in explaining the role of central leptin signaling in the reproductive system. Limiting the leptin-to-GnRH mediators to GABAergic cells will enable future research to focus on a few specific types of neurons.

Circulating leptin and thyroid dysfunction

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Zimmermann-Belsing, Tina; Brabant, Georg; Holst, Jens Juul

2003-01-01

and triiodothyronine are involved in the starvation-induced decrease in thermogenesis. Both rodent and human studies of leptin have failed to show any consistent relationship between thyroid function and serum leptin concentrations. However, leptin might have an important role in thyroid pathophysiology due to thyroid...

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

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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

Sweet taste of saccharin induces weight gain without increasing caloric intake, not related to insulin-resistance in Wistar rats.

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Foletto, Kelly Carraro; Melo Batista, Bruna Aparecida; Neves, Alice Magagnin; de Matos Feijó, Fernanda; Ballard, Cíntia Reis; Marques Ribeiro, Maria Flávia; Bertoluci, Marcello Casaccia

2016-01-01

In a previous study, we showed that saccharin can induce weight gain when compared with sucrose in Wistar rats despite similar total caloric intake. We now question whether it could be due to the sweet taste of saccharin per se. We also aimed to address if this weight gain is associated with insulin-resistance and to increases in gut peptides such as leptin and PYY in the fasting state. In a 14 week experiment, 16 male Wistar rats received either saccharin-sweetened yogurt or non-sweetened yogurt daily in addition to chow and water ad lib. We measured daily food intake and weight gain weekly. At the end of the experiment, we evaluated fasting leptin, glucose, insulin, PYY and determined insulin resistance through HOMA-IR. Cumulative weight gain and food intake were evaluated through linear mixed models. Results showed that saccharin induced greater weight gain when compared with non-sweetened control (p = 0.027) despite a similar total caloric intake. There were no differences in HOMA-IR, fasting leptin or PYY levels between groups. We conclude that saccharin sweet taste can induce mild weight gain in Wistar rats without increasing total caloric intake. This weight gain was not related with insulin-resistance nor changes in fasting leptin or PYY in Wistar rats. Copyright © 2015 Elsevier Ltd. All rights reserved.

Leptin Inhibits the Proliferation of Vascular Smooth Muscle Cells Induced by Angiotensin II through Nitric Oxide-Dependent Mechanisms

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Amaia Rodríguez

2010-01-01

Full Text Available Objective. This study was designed to investigate whether leptin modifies angiotensin (Ang II-induced proliferation of aortic vascular smooth muscle cells (VSMCs from 10-week-old male Wistar and spontaneously hypertensive rats (SHR, and the possible role of nitric oxide (NO. Methods. NO and NO synthase (NOS activity were assessed by the Griess and 3H-arginine/citrulline conversion assays, respectively. Inducible NOS (iNOS and NADPH oxidase subutnit Nox2 expression was determined by Western-blot. The proliferative responses to Ang II were evaluated through enzymatic methods. Results. Leptin inhibited the Ang II-induced proliferative response of VSMCs from control rats. This inhibitory effect of leptin was abolished by NOS inhibitor, NMMA, and iNOS selective inhibitor, L-NIL, and was not observed in leptin receptor-deficient fa/fa rats. SHR showed increased serum leptin concentrations and lipid peroxidation. Despite a similar leptin-induced iNOS up-regulation, VSMCs from SHR showed an impaired NOS activity and NO production induced by leptin, and an increased basal Nox2 expression. The inhibitory effect of leptin on Ang II-induced VSMC proliferation was attenuated. Conclusion. Leptin blocks the proliferative response to Ang II through NO-dependent mechanisms. The attenuation of this inhibitory effect of leptin in spontaneous hypertension appears to be due to a reduced NO bioavailability in VSMCs.

Endogenous leptin contributes to baroreflex suppression within the solitary tract nucleus of aged rats

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Arnold, Amy C.

2014-01-01

The decline in cardiovagal baroreflex function that occurs with aging is accompanied by an increase in circulating leptin levels. Our previous studies showed that exogenous leptin impairs the baroreflex sensitivity for control of heart rate in younger rats, but the contribution of this hormone to baroreflex dysfunction during aging is unknown. Thus we assessed the effect of bilateral leptin microinjection (500 fmol/60 nl) within the solitary tract nucleus (NTS) on the baroreflex sensitivity in older (66 ± 2 wk of age) urethane/chloralose anesthetized Sprague-Dawley rats with elevated circulating leptin levels. In contrast to the 63% reduction observed in younger rats, leptin did not alter the baroreflex sensitivity for bradycardia evoked by phenylephrine in older rats (0.76 ± 0.19 baseline vs. 0.71 ± 0.15 ms/mmHg after leptin; P = 0.806). We hypothesized that this loss of sensitivity reflected endogenous suppression of the baroreflex by elevated leptin, rather than cardiovascular resistance to the peptide. Indeed, NTS administration of a leptin receptor antagonist (75 pmol/120 nl) improved the baroreflex sensitivity for bradycardia in older rats (0.73 ± 0.13 baseline vs. 1.19 ± 0.26 at 10 min vs. 1.87 ± 0.32 at 60 min vs. 1.22 ± 0.54 ms/mmHg at 120 min; P = 0.002), with no effect in younger rats. There was no effect of the leptin antagonist on the baroreflex sensitivity for tachycardia, responses to cardiac vagal chemosensitive fiber activation, or resting hemodynamics in older rats. These findings suggest that the actions of endogenous leptin within the NTS, either produced locally or derived from the circulation, contribute to baroreflex suppression during aging. PMID:25260611

Genetic Variation in the Leptin Receptor Gene, Leptin, and Weight Gain in Young Dutch Adults

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Rossum, van C.T.M.; Hoebee, B.; Baak, van M.A.; Mars, M.; Saris, W.H.M.; Seidell, J.C.

2003-01-01

Objective: To investigate the association between leptin levels, polymorphisms in the leptin receptor (LEPR) gene, and weight gain. Research Methods and Procedures: From two large prospective cohorts in The Netherlands (n = 17, 500), we compared the baseline leptin of 259 subjects who had gained an

Association between A59V polymorphism in exon 3 of leptin gene ...

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ONOS

2010-09-06

Sep 6, 2010 ... pregnancy (P < 0.01). Animals with the AA genotype had higher length of pregnancy than other ... resistance (Dubuc, 1976). Treatments of the ob/ob ... species, as leptin dose-dependently attenuated insulin- induced steroid ...

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

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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.

Plasma leptin concentration in donkeys.

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Díez, E; López, I; Pérez, C; Pineda, C; Aguilera-Tejero, E

2012-01-01

Donkeys appear to be more predisposed than large breed horses to suffer from hyperlipemia. The reason for that predisposition is unknown but anorexia is a consistent feature of the disease. Leptin, a protein synthesized in fat tissue, is one of the major inhibitors of appetite in mammals. We hypothesized that donkeys could have elevated plasma leptin concentrations compared to horses. Blood samples were obtained from 50 donkeys for measurement of leptin, triglycerides (TGs), glucose, and insulin. Glucose/insulin ratio, modified insulin to glucose ratio, and reciprocal of the square root of insulin were calculated. Based on their body condition score (BCS), donkeys were classified as lean (n = 18), normal (n = 16), or overweight (n = 16). The results were compared with reference values from our laboratory and with a group of horses (n = 25) used as an internal control. Values of both leptin and TGs in donkeys were above the horse reference range and also significantly higher than those of the control horses: leptin (11.2 ± 1.7 versus 5.8 ± 0.5 µg/L, p donkeys had leptin (19.3 ± 2.9 µg/L) and TG (1.3 ± 0.2 mmol/L) concentrations that were significantly (p donkeys. A significant positive correlation (p Donkeys have higher plasma leptin concentrations than horses and leptin is correlated with BCS.

The correlation between serum leptin and blood pressure after exposure to noise at work

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Muayad S Rahma

2013-01-01

Full Text Available Several epidemiologic studies have reported that exposure to noise is associated with cardiovascular disease. The increased body weight is often associated with metabolic as well as increased blood pressure. The aim of this study is to investigate the correlation between the elevation of blood pressure and serum leptin hormones due to the effects of noise in the work place. A total of 80 volunteer males where included in this study with an age range between of 20 and 45 years, they were divided in two groups equally, the 1 st group were exposed to noise in the workplace while the 2 nd group were not. The individual noise exposure was determined by using a sound level meter. The range of noise was 80-100 dBA. Body Mass Index was also taken for each individual by a standard measure, blood pressure was measured by OMRON sphygmomanometer and serum leptin was measured through venous blood sample analysis enzyme linked immunosorbent assay. Spearman rank order correlation was used to examine the correlations between Blood pressure value (Systolic, Diastolic and Leptin. All the relationships between parameters showed a positive correlation. Systolic and diastolic blood pressure values had a significant correlation to leptin hormone level in comparison to the control. There was a significant relation between leptin and blood pressure. leptin effects on the sympathetic nervous system may provide a partial explanation. Therefore, Leptin might have diverse cardiovascular actions.

Discovery of the elusive leptin in birds: identification of several 'missing links' in the evolution of leptin and its receptor.

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Jeremy W Prokop

Full Text Available Leptin is a pleiotropic protein best known for regulation of appetite and fat storage in mammals. While many leptin orthologs have been identified among vertebrates, an authentic leptin in birds has remained elusive and controversial. Here we identify leptin sequence from the Peregrine falcon, Falco peregrinus (pfleptin, and identify sequences from two other birds (mallard and zebra finch, and 'missing' vertebrates (elephant shark, alligator, Indian python, Chinese soft-shelled turtle, and coelacanth. The pattern of genes surrounding leptin (snd1, rbm28 is syntenic between the falcon and mammalian genomes. Phylogenetic analysis of all known leptin protein sequences improves our understanding of leptin's evolution. Structural modeling of leptin orthologs highlights a highly conserved hydrophobic core in the four-helix cytokine packing domain. A docked model of leptin with the leptin receptor for Peregrine falcon reveals several conserved amino acids important for the interaction and possible coevolution of leptin with its receptor. We also show for the first time, an authentic avian leptin sequence that activates the JAK-STAT signaling pathway. These newly identified sequences, structures, and tools for avian leptin and its receptor will allow elucidation of the function of these proteins in feral and domestic birds.

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

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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.

Diurnal intermittent fasting during Ramadan: the effects on leptin and ghrelin levels.

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Mohammed A Alzoghaibi

Full Text Available We aimed to assess the effect of Islamic intermittent fasting, during and outside of Ramadan, on plasma levels of leptin and ghrelin while controlling for several potential confounding variables. Eight healthy male volunteers with a mean age of 26.6±4.9 years reported to the sleep disorders center (SDC at King Saud University on four occasions: 1 adaptation; 2 4 weeks before Ramadan while performing Islamic fasting for 1 week (baseline fasting (BLF; 3 1 week before Ramadan (non-fasting baseline (BL; and 4 during the second week of Ramadan while fasting. Plasma leptin and ghrelin levels were measured using enzyme-linked immunoassays at 22:00, 02:00, 04:00, 06:00, and 11:00. During BLF, there were significant reductions in plasma leptin concentrations at 22:00 and 02:00 compared with the baseline concentrations (at 22:00: 194.2±177.2 vs. 146.7±174.5; at 02:00: 203.8±189.5 vs. 168.1±178.1; p<0.05. During Ramadan, there was a significant reduction in plasma leptin levels at 22:00 (194.2±177.2 vs. 132.6±130.4, p<0.05. No significant difference in plasma ghrelin concentrations was detected during the BL, BLF, or Ramadan periods. Cosinor analyses of leptin and ghrelin plasma levels revealed no significant changes in the acrophases of the hormones during the three periods. The nocturnal reduction in plasma leptin levels during fasting may be the result of the changes in meal times during fasting.

Diurnal intermittent fasting during Ramadan: the effects on leptin and ghrelin levels.

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Alzoghaibi, Mohammed A; Pandi-Perumal, Seithikurippu R; Sharif, Munir M; BaHammam, Ahmed S

2014-01-01

We aimed to assess the effect of Islamic intermittent fasting, during and outside of Ramadan, on plasma levels of leptin and ghrelin while controlling for several potential confounding variables. Eight healthy male volunteers with a mean age of 26.6±4.9 years reported to the sleep disorders center (SDC) at King Saud University on four occasions: 1) adaptation; 2) 4 weeks before Ramadan while performing Islamic fasting for 1 week (baseline fasting) (BLF); 3) 1 week before Ramadan (non-fasting baseline) (BL); and 4) during the second week of Ramadan while fasting. Plasma leptin and ghrelin levels were measured using enzyme-linked immunoassays at 22:00, 02:00, 04:00, 06:00, and 11:00. During BLF, there were significant reductions in plasma leptin concentrations at 22:00 and 02:00 compared with the baseline concentrations (at 22:00: 194.2±177.2 vs. 146.7±174.5; at 02:00: 203.8±189.5 vs. 168.1±178.1; p<0.05). During Ramadan, there was a significant reduction in plasma leptin levels at 22:00 (194.2±177.2 vs. 132.6±130.4, p<0.05). No significant difference in plasma ghrelin concentrations was detected during the BL, BLF, or Ramadan periods. Cosinor analyses of leptin and ghrelin plasma levels revealed no significant changes in the acrophases of the hormones during the three periods. The nocturnal reduction in plasma leptin levels during fasting may be the result of the changes in meal times during fasting.

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

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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.

Photoperiod-Induced Increases in Bone Mineral Apposition Rate in Siberian Hamsters and the Involvement of Seasonal Leptin Changes.

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Kokolski, Marie; Ebling, Francis J; Henstock, James R; Anderson, Susan I

2017-01-01

sustained over 6 months, implying that leptin has a negative effect on bone growth in this model. The unexpected finding that MAR increased after peripheral leptin administration in LD suggests that leptin exerts different effects on bone growth dependent on initial leptin status. This adds further weight to the hypothesis that leptin-treated LD animals display central leptin resistance.

Behavioral changes induced by cocaine in mice are modified by a hyperlipidic diet or recombinant leptin

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E. Erhardt

2006-12-01

Full Text Available The objective of the present study was to determine if the acute behavioral effects of cocaine acutely administered intraperitoneally (ip at doses of 5, 10 and 20 mg/kg on white male CF1 mice, 90 days of age, would be influenced by leptin acutely administered ip (at doses of 5, 10 and 20 µg/kg or by endogenous leptin production enhanced by a high-fat diet. The acute behavioral effects of cocaine were evaluated in open-field, elevated plus-maze and forced swimming tests. Results were compared between a group of 80 mice consuming a balanced diet and a high-fat diet, and a group of 80 mice fed a commercially available rodent chow formula (Ralston Purina but receiving recombinant leptin (rLeptin or saline ip. Both the high-fat-fed and rLeptin-treated mice showed decreased locomotion in the open-field test, spent more time in the open arms of the elevated plus-maze and showed less immobility time in the forced swimming test (F(1,68 = 7.834, P = 0.007. There was an interaction between diets and cocaine/saline treatments in locomotion (F(3,34 = 3.751, P = 0.020 and exploration (F(3,34 = 3.581, P = 0.024. These results suggest that anxiolytic effects and increased general activity were induced by leptin in cocaine-treated mice and that low leptin levels are associated with behavioral depression. Chronic changes in diet composition producing high leptin levels or rLeptin treatment may result in an altered response to cocaine in ethologic tests that measure degrees of anxiety and depression, which could be attributed to an antagonistic effect of leptin.

Leptin promotes wound healing in the skin.

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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.

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

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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.

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

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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

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

Impact of diisobutyl phthalate and other PPAR agonists on steroidogenesis and plasma insulin and leptin levels in fetal rats

International Nuclear Information System (INIS)

Boberg, Julie; Metzdorff, Stine; Wortziger, Rasmus; Axelstad, Marta; Brokken, Leon; Vinggaard, Anne Marie; Dalgaard, Majken; Nellemann, Christine

2008-01-01

Endocrine disrupting chemicals can induce malformations and impairment of reproductive function in experimental animals and may have similar effects in humans. Recently, the environmental obesogen hypothesis was proposed, suggesting that environmental chemicals contribute to the development of obesity and insulin resistance. These effects could be related to chemical interaction with nuclear receptors such as the peroxisome proliferator activated receptors (PPARs). As several testosterone-reducing drugs are PPAR activators, we aimed to examine whether four PPAR agonists were able to affect fetal testosterone production and masculinization of rats. Additionally, we wished to examine whether these chemicals affected fetal plasma levels of insulin and leptin, which play important roles in the developmental programming of the metabolic system. Pregnant Wistar rats were exposed from gestation day (GD) 7-21 to diisobutyl phthalate (DiBP), butylparaben, perfluorooctanoate, or rosiglitazone (600, 100, 20, or 1 mg/kg bw/day, respectively). Endocrine endpoints were studied in offspring at GD 19 or 21. DiBP, butylparaben and rosiglitazone reduced plasma leptin levels in male and female offspring. DiBP and rosiglitazone additionally reduced fetal plasma insulin levels. In males, DiBP reduced anogenital distance, testosterone production and testicular expression of Insl-3 and genes related to steroidogenesis. PPARα mRNA levels were reduced by DiBP at GD 19 in testis and liver. In females, DiBP increased anogenital distance and increased ovarian aromatase mRNA levels. This study reveals new targets for phthalates and parabens in fetal male and female rats and contributes to the increasing concern about adverse effects of human exposure to these compounds

Photoperiod-Induced Increases in Bone Mineral Apposition Rate in Siberian Hamsters and the Involvement of Seasonal Leptin Changes

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Marie Kokolski

2017-12-01

life and sustained over 6 months, implying that leptin has a negative effect on bone growth in this model. The unexpected finding that MAR increased after peripheral leptin administration in LD suggests that leptin exerts different effects on bone growth dependent on initial leptin status. This adds further weight to the hypothesis that leptin-treated LD animals display central leptin resistance.

The effect of combined exercise training on plasma Leptin levels and hormonal factors in overweight men

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saeed Emamdost

2014-06-01

Full Text Available Background: The purpose of this study was to determine the effect of a period of combined exercise training on the plasma leptin level and hormonal factors in overweight men.   Materials and Methods: The subjects of this research consisted of thirty males (22-42 years old, BMI ≥29 who randomly were divided into experimental (n=15 and control groups(n=15. The experimental group performed for 8 weeks aerobic and resistance training, 3 sessions per week and each session included 10-12 station strength training at 75-70% of One Repetition Maximum (1RM for the first 4 weeks and at 75-80% of 1RM for the second 4 weeks. At the end, 10 minutes aerobic runing training at 70-75% of MHR in the first 4 weeks and 13 minute at 75-80% of MHR in the second 4 weeks were conducted.   Results: Leptin, body weight, Body Mass Index (BMI and insulin significantly decreased after the training ((P<0.05. However, There were no significant differences in the serum levels of cortisol and testosteron after 8 weeks concurrent training. The ratio of testosteron to cortisol (T/C in the experimental group showed a slight increase.   Conclusion: Generally, it appears that decrease of leptin due to a period of combined exercise training is more associated with reduce of body fat, weight and BMI than the change of testosteron or cortisol. In contrast to most researches, it seems that combined exercise training is more effective.

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

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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

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

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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.

Central insulin and leptin-mediated autonomic control of glucose homeostasis.

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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.

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

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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.

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...

Control of blood pressure, appetite, and glucose by leptin in mice lacking leptin receptors in proopiomelanocortin neurons.

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do Carmo, Jussara M; da Silva, Alexandre A; Cai, Zhengwei; Lin, Shuying; Dubinion, John H; Hall, John E

2011-05-01

Although the central nervous system melanocortin system is an important regulator of energy balance, the role of proopiomelanocortin (POMC) neurons in mediating the chronic effects of leptin on appetite, blood pressure, and glucose regulation is unknown. Using Cre/loxP technology we tested whether leptin receptor deletion in POMC neurons (LepR(flox/flox)/POMC-Cre mice) attenuates the chronic effects of leptin to increase mean arterial pressure (MAP), enhance glucose use and oxygen consumption, and reduce appetite. LepR(flox/flox)/POMC-Cre, wild-type, LepR(flox/flox), and POMC-Cre mice were instrumented for MAP and heart rate measurement by telemetry and venous catheters for infusions. LepR(flox/flox)/POMC-Cre mice were heavier, hyperglycemic, hyperinsulinemic, and hyperleptinemic compared with wild-type, LepR(flox/flox), and POMC-Cre mice. Despite exhibiting features of metabolic syndrome, LepR(flox/flox)/POMC-Cre mice had normal MAP and heart rate compared with LepR(flox/flox) but lower MAP and heart rate compared with wild-type mice. After a 5-day control period, leptin was infused (2 μg/kg per minute, IV) for 7 days. In control mice, leptin increased MAP by ≈5 mm Hg despite decreasing food intake by ≈35%. In contrast, leptin infusion in LepR(flox/flox)/POMC-Cre mice reduced MAP by ≈3 mm Hg and food intake by ≈28%. Leptin significantly decreased insulin and glucose levels in control mice but not in LepR(flox/flox)/POMC-Cre mice. Leptin increased oxygen consumption in LepR(flox/flox)/POMC-Cre and wild-type mice. Activation of POMC neurons is necessary for the chronic effects of leptin to raise MAP and reduce insulin and glucose levels, whereas leptin receptors in other areas of the brain other than POMC neurons appear to play a key role in mediating the chronic effects of leptin on appetite and oxygen consumption.

Role of leptin in farm animals: a review.

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Mácajová, M; Lamosová, D; Zeman, M

2004-05-01

The discovery of hormone leptin has led to better understanding of the energy balance control. In addition to its effects on food intake and energy expenditure, leptin has now been implicated as a mediator of diverse physiological functions. Recently, leptin has been cloned in several domestic species. The sequence similarity suggests a common function or mechanism of this peptide hormone across species. Leptin receptors are expressed in most of tissues, which is consistent with the multiplicity of leptin functions. The main goal of this review was to summarize knowledge about effect of leptin on physiology of farm animals. Experiments point to a stimulatory action of leptin on growth hormone (GH) secretion, normal growth and development of the brain. Surprisingly, leptin is synthesized at a high rate in placenta and may function as a growth factor for fetus, signalling the nutritional status from the mother to her offspring. Maturation of reproductive system can be stimulated by leptin administration. Morphological and hormonal changes, consistent with a major role of leptin in the reproductive system, have also been described, including the stimulation of the release of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin. Leptin has a substantial effect on food intake and feeding behaviour in animals. Administration of leptin reduces food intake. Its level decrease within hours after initiation of fasting. Leptin also serves as a mediator of the adaptation to fasting, and this role may be the primary function for which was the molecule evolved.

The administration of long-term high-fat diet in ovariectomized wistar rat (Study on Daily Food Intake, Lee Index, Abdominal Fat Mass and Leptin Serum Levels

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Dita Fitriani

2016-12-01

Conclusion: Serum leptin levels positively correlated with Lee index and abdominal fat mass, but negatively correlated with daily food intake. Administration of long-term high-fat diet in this study cannot induce leptin resistance.

Leptin deficiency: clinical implications and opportunities for therapeutic interventions.

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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.

Leptin promoter gene polymorphism on -2549 position decreases plasma leptin and increases appetite in normal weight volunteers

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Sandra Bragança Coelho

2014-05-01

Full Text Available Introduction: Investigate whether polymorphism in the promoter region encoding leptin and leptin receptor gene, in normal weight individuals, affects hormonal and appetite responses to peanuts.Materials and methods: Appetite, anthropometric indices, body composition, physical activity, dietary intake and leptin, ghrelin and insulin levels were monitored. Polymorphism analyses were also carried out.Results: None of the treatments led to statistical differences in the analyzed hormones. No polymorphism was found for leptin receptor gene, while for leptin gene, 50% of the volunteers presented one polymorphic allele and 13% presented both polymorphic alleles. These last ones presented lower body fat mass, leptin and ghrelin plasma concentrations, and fullness rates. They also presented higher hunger, desire to eat, and desire to eat sweet and salty foods.Conclusions: Peanut did not affect appetite and presented no different hormonal responses, compared to other foods studied. Polymorphic allele carriers in both alleles presented higher probability to develop obesity. However, the magnitude of this probability could not be measured.

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

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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.

Leptin levels are negatively correlated with 2-arachidonoylglycerol in the cerebrospinal fluid of patients with osteoarthritis.

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James Nicholson

Full Text Available There is compelling evidence in humans that peripheral endocannabinoid signaling is disrupted in obesity. However, little is known about the corresponding central signaling. Here, we have investigated the relationship between gender, leptin, body mass index (BMI and levels of the endocannabinoids anandamide (AEA and 2-arachidonoylglycerol (2-AG in the serum and cerebrospinal fluid (CSF of primarily overweight to obese patients with osteoarthritis.Patients (20 females, 15 males, age range 44-78 years, BMI range 24-42 undergoing total knee arthroplasty for end-stage osteoarthritis were recruited for the study. Endocannabinoids were quantified by liquid chromatography - mass spectrometry. AEA and 2-AG levels in the serum and CSF did not correlate with either age or BMI. However, 2-AG levels in the CSF, but not serum, correlated negatively with CSF leptin levels (Spearman's ρ -0.48, P=0.0076, n=30. No such correlations were observed for AEA and leptin.In the patient sample investigated, there is a negative association between 2-AG and leptin levels in the CSF. This is consistent with pre-clinical studies in animals, demonstrating that leptin controls the levels of hypothalamic endocannabinoids that regulate feeding behavior.

Leptin levels are negatively correlated with 2-arachidonoylglycerol in the cerebrospinal fluid of patients with osteoarthritis.

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Nicholson, James; Azim, Syed; Rebecchi, Mario J; Galbavy, William; Feng, Tian; Reinsel, Ruth; Rizwan, Sabeen; Fowler, Christopher J; Benveniste, Helene; Kaczocha, Martin

2015-01-01

There is compelling evidence in humans that peripheral endocannabinoid signaling is disrupted in obesity. However, little is known about the corresponding central signaling. Here, we have investigated the relationship between gender, leptin, body mass index (BMI) and levels of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in the serum and cerebrospinal fluid (CSF) of primarily overweight to obese patients with osteoarthritis. Patients (20 females, 15 males, age range 44-78 years, BMI range 24-42) undergoing total knee arthroplasty for end-stage osteoarthritis were recruited for the study. Endocannabinoids were quantified by liquid chromatography - mass spectrometry. AEA and 2-AG levels in the serum and CSF did not correlate with either age or BMI. However, 2-AG levels in the CSF, but not serum, correlated negatively with CSF leptin levels (Spearman's ρ -0.48, P=0.0076, n=30). No such correlations were observed for AEA and leptin. In the patient sample investigated, there is a negative association between 2-AG and leptin levels in the CSF. This is consistent with pre-clinical studies in animals, demonstrating that leptin controls the levels of hypothalamic endocannabinoids that regulate feeding behavior.

Human skeletal muscle releases leptin in vivo

DEFF Research Database (Denmark)

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

2012-01-01

Leptin is considered an adipokine, however, cultured myocytes have also been found to release leptin. Therefore, as proof-of-concept we investigated if human skeletal muscle synthesized leptin by measuring leptin in skeletal muscle biopsies. Following this, we quantified human skeletal muscle...... was unaltered. During saline infusion the adipose tissue release averaged 0.8 ± 0.3 ng min(-1) 100g tissue(-1) whereas skeletal muscle release was 0.5 ± 0.1 ng min(-1) 100g tissue(-1). In young healthy humans, skeletal muscle contribution to whole body leptin production could be substantial given the greater...

Presynaptic Regulation of Leptin in a Defined Lateral Hypothalamus-Ventral Tegmental Area Neurocircuitry Depends on Energy State.

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Liu, Jing-Jing; Bello, Nicholas T; Pang, Zhiping P

2017-12-06

Synaptic transmission controls brain activity and behaviors, including food intake. Leptin, an adipocyte-derived hormone, acts on neurons located in the lateral hypothalamic area (LHA) to maintain energy homeostasis and regulate food intake behavior. The specific synaptic mechanisms, cell types, and neural projections mediating this effect remain unclear. In male mice, using pathway-specific retrograde tracing, whole-cell patch-clamp recordings and post hoc cell type identification, we found that leptin reduces excitatory synaptic strength onto both melanin-concentrating hormone- and orexin-expressing neurons projecting from the LHA to the ventral tegmental area (VTA), which may affect dopamine signaling and motivation for feeding. A presynaptic mechanism mediated by distinct intracellular signaling mechanisms may account for this regulation by leptin. The regulatory effects of leptin depend on intact leptin receptor signaling. Interestingly, the synaptic regulatory function of leptin in the LHA-to-VTA neuronal pathway is highly sensitive to energy states: both energy deficiency (acute fasting) and excessive energy storage (high-fat diet-induced obesity) blunt the effect of leptin. These data revealed that leptin may regulate synaptic transmission in the LHA-to-VTA neurocircuitry in an inverted "U-shape" fashion dependent on plasma glucose levels and related to metabolic states. SIGNIFICANCE STATEMENT The lateral hypothalamic area (LHA) to ventral tegmental area (VTA) projection is an important neural pathway involved in balancing whole-body energy states and reward. We found that the excitatory synaptic inputs to both orexin- and melanin-concentrating hormone expressing LHA neurons projecting to the VTA were suppressed by leptin, a peptide hormone derived from adipocytes that signals peripheral energy status to the brain. Interestingly, energy states seem to affect how leptin regulates synaptic transmission since both the depletion of energy induced by acute food

Decreases in fasting leptin and insulin concentrations after acute energy restriction and subsequent compensation in food intake.

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Mars, Monica; de Graaf, Cees; de Groot, Lisette C P G M; Kok, Frans J

2005-03-01

The decrease in leptin after energy restriction is a starvation signal to the brain. Several studies have found an association between this decrease and subjective appetite; however, no solid data are available on the acute decrease in fasting leptin concentration and subsequent caloric compensation. The objective was to assess the effect of acute decreases in fasting leptin concentrations, induced by energy restriction, on subsequent energy intake compensation. We hypothesized that men with a large decrease in fasting leptin concentrations would have larger ad libitum energy intakes than would men with a small decrease in leptin. Thirty-four male unrestrained eaters [age: 23 +/- 3 y; body mass index (in kg/m(2)): 22.3 +/- 1.6] participated in a semicontrolled intervention study. Fasting serum leptin and insulin concentrations were measured before and 2 d after 62% energy restriction. Energy intake was measured on the 2 following days on which food was provided ad libitum. During energy restriction, fasting leptin and insulin concentrations decreased by 27.2% (95% CI: -34.4%, -19.9%) and 30.7% (95% CI: -41.0%, -20.4%), respectively. Subjects consumed 143 +/- 27% of their estimated energy requirements (18.3 +/- 2.9 MJ) on the first day and 124 +/- 20% (16.0 +/- 2.6 MJ) on the second day of ad libitum intake. No significant correlations were observed between decreases in fasting leptin or insulin concentrations and subsequent ad libitum energy intake; however, decreases in insulin were correlated with an increase in carbohydrate intake (r=-0.49, P < 0.01). Although fasting leptin concentrations decreased significantly during energy restriction and subjects showed compensatory behavior during subsequent ad libitum food intake, no association was observed between the decrease in fasting leptin concentrations and caloric compensation.

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

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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.

The neuroanatomical function of leptin in the hypothalamus.

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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.

Role of proopiomelanocortin neuron Stat3 in regulating arterial pressure and mediating the chronic effects of leptin.

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Dubinion, John H; do Carmo, Jussara M; Adi, Ahmad; Hamza, Shereen; da Silva, Alexandre A; Hall, John E

2013-05-01

Although signal transducer and activator of transcription 3 (Stat3) is a key second messenger by which leptin regulates appetite and body weight, its role in specific neuronal populations in metabolic regulation and in mediating the chronic effects of leptin on blood pressure is unknown. The current study tested the hypothesis that Stat3 signaling in proopiomelanocortin (POMC) neurons mediates the chronic effects of leptin on mean arterial pressure (MAP), as well as on glucose regulation, energy expenditure, and food intake. Stat3(flox/flox) mice were crossed with POMC-Cre mice to generate mice with Stat3 deletion specifically in POMC neurons (Stat3(flox/flox)/POMC-Cre). Oxygen consumption (Vo2), carbon dioxide respiration (Vco2), motor activity, heat production, food intake, and MAP were measured 24 hours/d. After baseline measurements, leptin was infused (4 μg/kg per min, IP) for 7 days. Stat3(flox/flox)/POMC-Cre mice were hyperphagic, heavier, and had increased respiratory quotients compared with control Stat3(flox/flox) mice. Baseline MAP was not different between the groups, and chronic leptin infusion reduced food intake similarly in both groups (27 versus 29%). Vo2, Vco2, and heat production responses to leptin were not significantly different in control and Stat3(flox/flox)/POMC-Cre mice. However, leptin-mediated increases in MAP were completely abolished, and blood pressure responses to acute air-jet stress were attenuated in male Stat3(flox/flox)/POMC-Cre mice. These results indicate that Stat3 signaling in POMC neurons is essential for leptin-mediated increases in MAP, but not for anorexic or thermogenic effects of leptin.

A link between hypothyroidism, obesity and male reproduction.

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Aiceles, Veronica; da Fonte Ramos, Cristiane

2016-01-01

Hypothyroidism is a condition in which the serum levels of thyroid hormones are below that necessary to carry out physiological functions in the body. Hypothyroidism is related to obesity as an increase in body weight gain is seen in hypothyroid patients. Moreover, an inverse correlation between free thyroxine values and body mass index has been reported. Leptin, a polypeptide hormone produced by adipocytes, was originally thought to be an antiobesity hormone due its anorexic effects on hypothalamic appetite regulation. However, nowadays it is known that leptin conveys information about the nutritional status to the brain being considered a crucial endocrine factor for regulating several physiological processes including reproduction. Since the identification of thyroid hormone and leptin receptors on the testes, these hormones are being recognized as having important roles in male reproductive functions. A clear link exists among thyroid hormones, leptin and reproduction. Both hormones can negatively affect spermatogenesis and consequently may cause male infertility. The World Health Organization (WHO) estimates the overall prevalence of primary infertility ranging from 8 to 15%. The fact that 30% of couples' inability to conceive is related to a male factor and that the longer hypothyroidism persisted, the greater the damage to the testes, strongly suggest that more studies attempting to clarify both hormones actions directly in the testes need to be conducted specially in cases of congenital hypothyroidism. Therefore, the goal of this review is to highlight the relationship of such hormones in the reproductive system.

Leptin promotes wound healing in the oral mucosa.

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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.

Serum leptin and insulin tests in obesity

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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)

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

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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.

Leptin-like immunoreactivity in the central nervous system, digestive organs, and gonads of the giant freshwater prawn, Macrobrachium rosenbergii.

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Poljaroen, Jaruwan; Tinikul, Yotsawan; Tinikul, Ruchanok; Anurucpreeda, Panat; Sobhon, Prasert

2017-06-01

Leptin, a highly conserved adipocyte-derived hormone, plays important roles in a variety of physiological processes, including the control of fat storage and metabolic status which are linked to food intake, energy homeostasis, and reproduction in all vertebrates. In the present study, we hypothesize that leptin is also present in various organs of the fresh water prawns, Macrobrachium rosenbergii. The existence and distribution of a leptin-like peptide in prawn tissues were verified by using Western blotting (WB) and immunohistochemical detection (ID) using primary antibody against human leptin. With WB, a leptin-like peptide, having a molecular weight of 15kDa, was detected in the brain, thoracic ganglia, abdominal ganglia, parts of the gastro-intestinal tract, hepatopancreas, adipocytes and gonads. By ID, leptin immunoreactivity (leptin-ir) was detected in the brain, thoracic ganglia and intersegmental commissural nerve fibers of abdominal ganglia. In the gastrointestinal tract, there was intense leptin-ir in the apical part of the epithelial cells of the cardiac and pyloric parts of the stomach. In the midgut and hindgut, the leptin-ir was detected in epithelial cells and basal cells located near the basal lamina of the epithelium. In addition, there was leptin-ir in the Restzellen cells in the hepatopancreas which produce digestive enzymes. In the ovary, the strong intensity of a leptin-ir was detected in the cytoplasm of middle to late stage oocytes, whereas no positive staining was detected in follicular cells. An intense leptin-ir was detected in spermatocytes and sustentacular cells in the seminiferous tubules in the testes of small and orange claw males. Taken together, the detection of the leptin-ir in several organs implicates the existence of a leptin-like peptide in various organs of the freshwater prawn; and like in vertebrates this peptide may be an important hormonal factor in controlling feeding and reproductive process. Copyright © 2017 Elsevier

Leptin receptor (Ob-R) mRNA expression and serum leptin concentration in patients with colorectal and metastatic colorectal cancer

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Erkasap, N.; Ozkurt, M. [Department of Physiology, Osmangazi University Medical Faculty, Meselik, Eskisehir (Turkey); Erkasap, S.; Yasar, F. [Department of General Surgery, Osmangazi University Medical Faculty, Meselik, Eskisehir (Turkey); Uzuner, K. [Department of Physiology, Osmangazi University Medical Faculty, Meselik, Eskisehir (Turkey); Ihtiyar, E. [Department of General Surgery, Osmangazi University Medical Faculty, Meselik, Eskisehir (Turkey); Uslu, S.; Kara, M. [Department of Biochemistry, Osmangazi University Medical Faculty, Meselik, Eskisehir (Turkey); Bolluk, O. [Department of Biostatistics, Osmangazi University Medical Faculty, Meselik, Eskisehir (Turkey)

2013-03-19

The objective of the present study was to investigate the effect of leptin on the progression of colorectal carcinoma to metastatic disease by analyzing the serum leptin concentration and Ob-R gene expression in colon cancer tissues. Tissue samples were obtained from 31 patients who underwent surgical resection for colon (18 cases) and metastatic colon (13 cases) cancer. Serum leptin concentration was determined by an enzyme-linked immunosorbent assay (ELISA) and Ob-R mRNA expression by real-time polymerase chain reaction (RT-PCR) for both groups. ELISA data were analyzed by the Student t-test and RT-PCR data were analyzed by the Mann-Whitney U-test. RT-PCR results demonstrated that mRNA expression of Ob-R in human metastatic colorectal cancer was higher than in local colorectal cancer tissues. On the other hand, mean serum leptin concentration was significantly higher in local colorectal cancer patients compared to patients with metastatic colorectal cancer. The results of the present study suggest a role for leptin in the progression of colon cancer to metastatic disease without weight loss. In other words, significantly increased Ob-R mRNA expression and decreased serum leptin concentration in patients with metastatic colon cancer indicate that sensitization to leptin activity may be a major indicator of metastasis to the colon tissue and the determination of leptin concentration and leptin gene expression may be used to aid the diagnosis.

Leptin receptor (Ob-R) mRNA expression and serum leptin concentration in patients with colorectal and metastatic colorectal cancer

International Nuclear Information System (INIS)

Erkasap, N.; Ozkurt, M.; Erkasap, S.; Yasar, F.; Uzuner, K.; Ihtiyar, E.; Uslu, S.; Kara, M.; Bolluk, O.

2013-01-01

The objective of the present study was to investigate the effect of leptin on the progression of colorectal carcinoma to metastatic disease by analyzing the serum leptin concentration and Ob-R gene expression in colon cancer tissues. Tissue samples were obtained from 31 patients who underwent surgical resection for colon (18 cases) and metastatic colon (13 cases) cancer. Serum leptin concentration was determined by an enzyme-linked immunosorbent assay (ELISA) and Ob-R mRNA expression by real-time polymerase chain reaction (RT-PCR) for both groups. ELISA data were analyzed by the Student t-test and RT-PCR data were analyzed by the Mann-Whitney U-test. RT-PCR results demonstrated that mRNA expression of Ob-R in human metastatic colorectal cancer was higher than in local colorectal cancer tissues. On the other hand, mean serum leptin concentration was significantly higher in local colorectal cancer patients compared to patients with metastatic colorectal cancer. The results of the present study suggest a role for leptin in the progression of colon cancer to metastatic disease without weight loss. In other words, significantly increased Ob-R mRNA expression and decreased serum leptin concentration in patients with metastatic colon cancer indicate that sensitization to leptin activity may be a major indicator of metastasis to the colon tissue and the determination of leptin concentration and leptin gene expression may be used to aid the diagnosis

Leptin receptor (Ob-R mRNA expression and serum leptin concentration in patients with colorectal and metastatic colorectal cancer

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N. Erkasap

Full Text Available The objective of the present study was to investigate the effect of leptin on the progression of colorectal carcinoma to metastatic disease by analyzing the serum leptin concentration and Ob-R gene expression in colon cancer tissues. Tissue samples were obtained from 31 patients who underwent surgical resection for colon (18 cases and metastatic colon (13 cases cancer. Serum leptin concentration was determined by an enzyme-linked immunosorbent assay (ELISA and Ob-R mRNA expression by real-time polymerase chain reaction (RT-PCR for both groups. ELISA data were analyzed by the Student t-test and RT-PCR data were analyzed by the Mann-Whitney U-test. RT-PCR results demonstrated that mRNA expression of Ob-R in human metastatic colorectal cancer was higher than in local colorectal cancer tissues. On the other hand, mean serum leptin concentration was significantly higher in local colorectal cancer patients compared to patients with metastatic colorectal cancer. The results of the present study suggest a role for leptin in the progression of colon cancer to metastatic disease without weight loss. In other words, significantly increased Ob-R mRNA expression and decreased serum leptin concentration in patients with metastatic colon cancer indicate that sensitization to leptin activity may be a major indicator of metastasis to the colon tissue and the determination of leptin concentration and leptin gene expression may be used to aid the diagnosis.

Leptin Deficiency: Clinical Implications and Opportunities for Therapeutic Interventions

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Bl?her, Susan; Shah, Sunali; Mantzoros, Christos S.

2009-01-01

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 e...

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

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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

Exposure to a high-fat diet alters leptin sensitivity and elevates renal sympathetic nerve activity and arterial pressure in rabbits.

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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.

Diurnal Intermittent Fasting during Ramadan: The Effects on Leptin and Ghrelin Levels

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Alzoghaibi, Mohammed A.; Pandi-Perumal, Seithikurippu R.; Sharif, Munir M.; BaHammam, Ahmed S.

2014-01-01

We aimed to assess the effect of Islamic intermittent fasting, during and outside of Ramadan, on plasma levels of leptin and ghrelin while controlling for several potential confounding variables. Eight healthy male volunteers with a mean age of 26.6±4.9 years reported to the sleep disorders center (SDC) at King Saud University on four occasions: 1) adaptation; 2) 4 weeks before Ramadan while performing Islamic fasting for 1 week (baseline fasting) (BLF); 3) 1 week before Ramadan (non-fasting baseline) (BL); and 4) during the second week of Ramadan while fasting. Plasma leptin and ghrelin levels were measured using enzyme-linked immunoassays at 22:00, 02:00, 04:00, 06:00, and 11:00. During BLF, there were significant reductions in plasma leptin concentrations at 22:00 and 02:00 compared with the baseline concentrations (at 22:00: 194.2±177.2 vs. 146.7±174.5; at 02:00: 203.8±189.5 vs. 168.1±178.1; pfasting may be the result of the changes in meal times during fasting. PMID:24637892

Effects of leptin on sperm count and morphology in Sprague-Dawley rats and their reversibility following a 6-week recovery period.

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Almabhouh, F A; Osman, K; Siti Fatimah, I; Sergey, G; Gnanou, J; Singh, H J

2015-09-01

Altered epididymal sperm count and morphology following leptin treatment has been reported recently. This study examined the effects of 42 days of leptin treatment on sperm count and morphology and their reversibility during a subsequent 56-day recovery period. Twelve-week-old male Sprague-Dawley rats were randomised into four leptin and four saline-treated control groups (n = 6). Intraperitoneal injections of leptin were given daily (60 μg Kg(-1) body weight) for 42 days. Controls received 0.1 ml of 0.9% saline. Leptin-treated animals and their respective age-matched controls were euthanised on either day 1, 21, 42 or 56 of recovery for collection of epididymal spermatozoa. Sperm concentration was determined using a Makler counting chamber. Spermatozoa were analysed for 8-hydroxy-2-deoxyguanosine and DNA fragmentation (Comet assay). Data were analysed using anova. Sperm concentration was significantly lower but fraction of abnormal spermatozoa, and levels of 8-hydroxy-2-deoxyguanosine were significantly higher in leptin-treated rats on day 1 of recovery. Comet assays revealed significant DNA fragmentation in leptin-treated rats. These differences were reduced by day 56 of recovery. It appears that 42 days of leptin treatment to Sprague-Dawley rats has significant adverse effects on sperm count and morphology that reverse following discontinuation of leptin treatment. © 2014 Blackwell Verlag GmbH.

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.

Identifikasi Leptin pada Kesembuhan Luka Tikus yang Diberi Pakan Lemak Tinggi dan Aplikasi Zinc Topikal (LEPTIN IDENTIFICATION ON WOUND HEALING OF RAT GIVEN HIGH FAT DIET AND TOPICAL ZINC APPLICATION

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Devita Anggraeni

2013-07-01

Full Text Available Leptin is a hormone produced by adipocytes and play an important role in wound healing. The objectiveof this research was to study the role of leptin in wound healing in mice experimentally given high fat dietsand its correlation to zinc. Thirty two male Sprague Dawley rats at three months of age were used in thisstudy. Rats were randomly allotted into four groups (A,B,C and D of 8. Rats in group A and B were fednormal diet, while rats in group C and D were fed high fat diet. After two months of treatment, skin incisionsurgery was performed at the back side of the rat. Incision wound was closed with single interruptedsuture. The wound of rats in group A and C were treated with vaseline, while in the group B and D weretreated with zinc 10%. One day after surgery, blood sample were collected frpm four rats from each groupand analysed for leptin (Rat leptin ELISA Int, Genway Biotech Inc. Wounded skin from all animals werealso taken for histopathological examination (Haematoxylin and Eosin. Three days after the surgery, thesame analysis were done for the remaining rats. Leptin level was analyzed statistically using ANOVA forfactorial experiment, while histopathologic analysis was done descriptively. The results showed that theleptin level was significantly affected by time (P<0.05, as leptin level in blood at three days after surgerywas significantly lower than the level at one day after surgery. Meanwhile, histopathological examinationshowed that the percentage of epidermal closure in animals in group A,B,C,and D were 75%, 100%, 25%and 75%, respectivelly. Therefore, it was concluded that topical application of zinc might have significanteffect on the wound healing of the rats fed normal diets as well as these that given a high fat diet.

Leptin: A proliferative factor for breast cancer?

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Caldefie-Chezet, F.; Damez, M.; Latour, M. de; Konska, G.; Mishellani, F.; Fusillier, C.; Guerry, M.; Penault-Llorca, F.; Guillot, J.; Vasson, M.-P.

2005-01-01

Mammary adipose tissue is an important source of paracrine mitogens and anti-mitogens, including insulin-like growth factor, transforming growth factors, and cytokines (especially, TNFα and IL-1β). Nevertheless, it is also an important source of the adipocytokine, leptin. Recently, leptin was reported to stimulate the proliferation of various cell types (pancreatic β cells, prostate, colorectal, lung, etc.) as a new growth factor. It was also shown to stimulate the proliferation of breast cancer cell lines. In this study, we conducted an immunohistochemical analysis of leptin expression in normal tissue and benign and malignant ductal breast cell, representing the different states of the invasion process. We determined for the first time that leptin is expressed both by ductal breast tumors and by benign lesions as atypical hyperplasia. This suggests that leptin may be taken up or synthesized by all modified ductal breast cells, and may prove a proliferative factor. Moreover, leptin is unexpressed by normal tissue in the healthy breast but is exhibited by the normal tissue in near vicinity of the malignant ductal breast lesions. We also postulated that leptin may be a prognostic or diagnostic factor for ductal breast cancer. These putative hypotheses require further study

Circulating ghrelin, leptin, and soluble leptin receptor concentrations and cardiometabolic risk factors in a community-based sample.

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

2008-08-01

The conjoint effects and relative importance of ghrelin, leptin, and soluble leptin receptor (sOB-R), adipokines involved in appetite control and energy expenditure in mediating cardiometabolic risk, is unknown. The objective of the study was to study the cross-sectional relations of these adipokines to cardiometabolic risk factors in a community-based sample. We measured circulating ghrelin, leptin, and sOB-R in 362 participants (mean age 45 yr; 54% women) of the Framingham Third Generation Cohort. Body mass index, waist circumference (WC), blood pressure, lipid measures, fasting glucose, smoking, and metabolic syndrome (MetS) were measured. Ghrelin and leptin concentrations were significantly higher in women (P risk.

The Effects of High-fat-diet Combined with Chronic Unpredictable Mild Stress on Depression-like Behavior and Leptin/LepRb in Male Rats.

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Yang, Jin Ling; Liu, De Xiang; Jiang, Hong; Pan, Fang; Ho, Cyrus Sh; Ho, Roger Cm

2016-10-14

Leptin plays a key role in the pathogenesis of obesity and depression via the long form of leptin receptor (LepRb). An animal model of comorbid obesity and depression induced by high-fat diet (HFD) combined with chronic unpredictable mild stress (CUMS) was developed to study the relationship between depression/anxiety-like behavior, levels of plasma leptin and LepRb in the brains between four groups of rats, the combined obesity and CUMS (Co) group, the obese (Ob) group, the CUMS group and controls. Our results revealed that the Co group exhibited most severe depression-like behavior in the open field test (OFT), anxiety-like behavior in elevated plus maze test (EMT) and cognitive impairment in the Morris water maze (MWM). The Ob group had the highest weight and plasma leptin levels while the Co group had the lowest levels of protein of LepRb in the hypothalamus and hippocampus. Furthermore, depressive and anxiety-like behaviors as well as cognitive impairment were positively correlated with levels of LepRb protein and mRNA in the hippocampus and hypothalamus. The down-regulation of leptin/LepRb signaling might be associated with depressive-like behavior and cognitive impairment in obese rats facing chronic mild stress.

Endothelial function and its relationship to leptin, homocysteine, and insulin resistance in lean and overweight eumenorrheic women and PCOS patients: a pilot study.

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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.

Correlation between visceral fat accumulation, leptin and eating disorder in peritoneal dialysis patients

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Mochizuki, Takahiro; Kojima, Chiari; Oishi, Tetsuya; Takahashi, Motohiro

2003-01-01

Eating disorder may be a major factor for protein-energy malnutrition occurs in patients with chronic renal failure (CRF). Some peritoneal dialysis (PD) patients demonstrate eating disorder in association with massive visceral fat accumulation. Markedly elevated leptin levels have been documented in CRF patients, especially in those who are treated with PD. Leptin is secreted by adipocytes, regulates both body composition and appetite behavior. This study evaluated the correlation between visceral fat accumulation, leptin and eating disorder in PD patients. Plasma leptin, albumin, insulin-like growth factor-1 (IGF-1), normalized protein catabolic rate (nPCR), C-reactive protein (CRP) and body composition were measured in 46 PD patients (27 males and 19 females; median age 62.7 years). Computed tomography was used for determination of visceral fat area (VFA) and subcutaneous fat area (SFA), at the initial state and during PD. The VFA and the SFA increased during PD treatment, and the ratio of increase in each fat area was significantly higher in VFA than in SFA (1.47±0.63 vs. 1.23±0.41 p<0.01, respectively). Serum leptin elevated (19.5±21.9 ng/mL), and correlated significantly with the percentage of body fat (r=0.584), body mass index (BMI: r=0.574), VFA (r=0.476) and SFA (r=0.684). Dietary intake correlated inversely with the visceral fat mass, and the low nPCR group had a higher VFA/BMI ratio (p<0.05). A negative correlation was found between nPCR and either serum leptin (r=-0.52), leptin/BMI (r=-0.44), or CRP (r=-0.55). Our data suggest that visceral fat accumulation and hyperleptinemia in PD patients are closely associated with eating disorder. Therefore, a new peritoneal solution containing an alternative osmotic agent instead of glucose may be useful to prevent accumulation of visceral fat in PD patients. (author)

Maternal Aerobic Exercise during Pregnancy Can Increase Spatial Learning by Affecting Leptin Expression on Offspring's Early and Late Period in Life Depending on Gender

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Ayfer Dayi

2012-01-01

Full Text Available Maternal exercise during pregnancy has been suggested to exert beneficial effects on brain functions of the offspring. Leptin is an adipocytokine which is secreted from adipose tissues and has positive effects on learning, memory, and synaptic plasticity. In this study, pregnant rats were moderately exercised and we observed the effects of this aerobic exercise on their prepubertal and adult offsprings' spatial learning, hippocampal neurogenesis, and expression of leptin. All the pups whose mothers exercised during pregnancy learned the platform earlier and spent longer time in the target quadrant. Their thigmotaxis times were shorter than those measured in the control group. It is shown that hippocampal CA1, CA3 neuron numbers increased in both prepubertal and adult pups, in addition that GD neuron numbers increased in adult pups. Leptin receptor expression significantly increased in the prepubertal male, adult male, and adult female pups. In our study, maternal running during pregnancy resulted in significant increase in the expression of leptin receptor but not in prepubertal female pups, enhanced hippocampal cell survival, and improved learning memory capability in prepubertal and adult rat pups, as compared to the control group. In conclusion, maternal exercise during pregnancy may regulate spatial plasticity in the hippocampus of the offspring by increasing the expression of leptin.

Leptin stimulates aromatase in the growth plate: limiting catch-up growth efficiency.

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Masarwi, Majdi; Shamir, Raanan; Phillip, Moshe; Gat-Yablonski, Galia

2018-06-01

Catch-up growth (CUG) in childhood is defined as periods of growth acceleration, after the resolution of growth attenuation causes, bringing the children back to their original growth trajectory. Sometimes, however, CUG is incomplete, leading to permanent growth deficit and short stature. The aim of this study was to investigate the mechanisms that limit nutritional-CUG. Specifically, we focused on the crosstalk between leptin, increased by re-feeding, and sex hormones, which increase with age. In vivo studies were performed in young male Sprague Dawley rats fed ad libitum or subjected to 10/36 days of 40% food restriction followed by 90-120 days of re-feeding. In vitro studies were performed on ATDC5 cells. Analyses of mRNA and protein levels were done using qPCR and Western blot, respectively. CUG was complete in body weight and humerus length in animals that were food-restricted for 10 days but not for those food-restricted for 36 days. In vitro studies showed that leptin significantly increased aromatase gene expression and protein level as well as the expression of estrogen and leptin receptors in a dose- and time-dependent manner. The effect of leptin on aromatase was direct and was mediated through the MAPK/Erk, STAT3 and PI3K pathways. The crosstalk between leptin and aromatase in the growth plate suggests that re-feeding during puberty may lead to increased estrogen level and activity, and consequently, irreversible premature epiphyseal growth plate closure. These results may have important implications for the development of novel treatment strategies for short stature in children. © 2018 Society for Endocrinology.

Plasma leptin values in postmenopausal women with osteoporosis.

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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.

Chronic leptin infusion advances, and immunoneutralization of leptin postpones puberty onset in normally fed and feed restricted female rats

NARCIS (Netherlands)

Zeinoaldini, S.; Swarts, J.J.M.; Heijning, van de B.J.M.

2006-01-01

Does leptin play a vital role in initiating puberty in female rats and can it overrule a nutrionally imposed (i.e. a 30% feed restriction, FR) delay in puberty onset? Prepubertal female rats were chronically infused for 14 days with leptin (icv or sc) or leptin-antiserum (icv) while puberty onset

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

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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

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

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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.

The importance of leptin in animal science

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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.

Resistant starch lowers postprandial glucose and leptin in overweight adults consuming a moderate-to-high-fat diet: a randomized-controlled trial.

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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�

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

OpenAIRE

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

2008-01-01

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

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

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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.

Bone mass regulation of leptin and postmenopausal osteoporosis with obesity.

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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.

Ghrelin, leptin and adiponectin as possible predictors of the hedonic value of odors.

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Trellakis, Sokratis; Tagay, Sefik; Fischer, Cornelia; Rydleuskaya, Alena; Scherag, André; Bruderek, Kirsten; Schlegl, Sandra; Greve, Jens; Canbay, Ali E; Lang, Stephan; Brandau, Sven

2011-02-25

Several lines of evidence point to a close relationship between the hormones of energy homeostasis and the olfactory system. Examples are the localization of leptin and adiponectin receptors in the olfactory system or increased activation of brain regions related to the palatability and the hedonic value of food in response to food pictures after application of ghrelin. In this preliminary study, we tested in 31 subjects (17 male and 14 female) if and to what extent the peripheral blood concentrations of "satiety" hormones, such as leptin, adiponectin, and ghrelin (acyl and total), are correlated with the self-ratings of odor pleasantness and with the objective olfactory and gustatory ability. The hedonic values of some odors were found to be differently rated between donors depending on gender and body weight. The concentrations of leptin, adiponectin and total ghrelin were significantly associated with the hedonic value of pepper black oil, but failed to show significant correlations for 5 other odors tested. Except for a significant association between leptin and odor identification, hormone concentrations were not linked to the abilities of smell and taste. Peripheral adipokines and gut hormones may alter the perception and pleasantness of specific odors, presumably either directly through their receptors in the olfactory system or indirectly through central interfaces between the regulation systems of olfaction, appetite control, memory and motivation. Copyright © 2010 Elsevier B.V. All rights reserved.

Leptin reverses hyperglycemia and hyperphagia in insulin deficient diabetic rats by pituitary-independent central nervous system actions.

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Alexandre A da Silva

Full Text Available The hypothalamic-pituitary-adrenal (HPA axis has been postulated to play a major role in mediating the antidiabetic effects of leptin. We tested if the pituitary is essential for the chronic central nervous system mediated actions of leptin on metabolic and cardiovascular function in insulin-dependent diabetic and non-diabetic rats. Male 12-week-old hypophysectomized Sprague-Dawley rats (Hypo, n = 5 were instrumented with telemetry probes for determination of mean arterial pressure (MAP and heart rate (HR 24-hrs/day and an intracerebroventricular (ICV cannula was placed into the brain lateral ventricle for continuous leptin infusion. In additional groups of Hypo and control rats (n = 5/group, diabetes was induced by single injection of streptozotocin (50 mg/kg, IP. Hypo rats were lighter, had lower MAP and HR (83±4 and 317±2 vs 105±4 mmHg and 339±4 bpm, with similar caloric intake per kilogram of body weight and fasting plasma glucose levels (84±4 vs 80±4 mg/dl compared to controls. Chronic ICV leptin infusion (7 days, 0.62 μg/hr in non-diabetic rats reduced caloric intake and body weight (-10% in Hypo and control rats and markedly increased HR in control rats (~25 bpm while causing only modest HR increases in Hypo rats (8 bpm. In diabetic Hypo and control rats, leptin infusion reduced caloric intake, body weight and glucose levels (323±74 to 99±20 and 374±27 to 108±10 mg/dl, respectively; however, the effects of leptin on HR were abolished in Hypo rats. These results indicate that hypophysectomy attenuates leptin's effect on HR regulation without altering leptin's ability to suppress appetite or normalize glucose levels in diabetes.

Leptin's effect on taste bud calcium responses and transmitter secretion.

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Meredith, Tricia L; Corcoran, Alan; Roper, Stephen D

2015-05-01

Leptin, a peptide hormone released by adipose tissue, acts on the hypothalamus to control cravings and appetite. Leptin also acts to decrease taste responses to sweet substances, though there is little detailed information regarding where leptin acts in the taste transduction cascade. The present study examined the effects of leptin on sweet-evoked responses and neuro transmitter release from isolated taste buds. Our results indicate that leptin moderately decreased sweet-evoked calcium mobilization in isolated mouse taste buds. We also employed Chinese hamster ovary biosensor cells to examine taste transmitter release from isolated taste buds. Leptin reduced ATP and increased serotonin release in response to sweet stimulation. However, leptin has no effect on bitter-evoked transmitter release, further showing that the action of leptin is sweet specific. Our results support those of previous studies, which state that leptin acts on taste tissue via the leptin receptor, most likely on Type II (Receptor) cells, but also possibly on Type III (Presynaptic) cells. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Duplicated leptin receptors in two species of eel bring new insights into the evolution of the leptin system in vertebrates

DEFF Research Database (Denmark)

Morini, M.; Pasquier, J.; van den Thillart, G.

2015-01-01

Since its discovery in mammals as a key-hormone in reproduction and metabolism, leptin has been identified in an increasing number of tetrapods and teleosts. Tetrapods possess only one leptin gene, while most teleosts possess two leptin genes, as a result of the teleost third whole genome duplica...

Relationship Between the Serum Leptin and Children with Malnutrition

International Nuclear Information System (INIS)

Xu Jixun

2010-01-01

To investigate the relationship between the serum leptin and the children with malnutrition, the serum leptin levels in 50 malnourished children and 50 normal children were determined by RIA. The results showed that the serum leptin levels in children with malnutrition were significantly lower than that in control group (P<0.05). The serum leptin levels in children with malnutrition were positively correlated with body mass index values (r= 0.650, P<0.05), and positively correlated with serum albumin values (r= 0.740,P<0.05). The serum leptin levels in female children were higher than that in men children. The leptin may involve in the regulation of the body nutritional status of children. The serum leptin level may be correlated with the degree of child malnutrition and may be used as a laboratory indicator for the diagnosis of child malnutrition. (authors)

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

Long-term leptin fluctuations in female donkeys.

Science.gov (United States)

Čebulj-Kadunc, N; Škibin, A; Kosec, M

2015-11-01

The interest in donkeys is growing due to their integration in the systems of ecological farming, among other reasons. Due to limited reports on leptin concentrations in donkeys, the aim of the present study was to examine age-dependent and seasonal changes in the circulating leptin concentration in female donkeys (jennies) and thus contribute to knowledge about the physiological characteristics of this species. Prospective longitudinal study. The study was performed over a year (September 2008 to September 2009) on 20 yearling and young adult (pregnant, lactating or barren) jennies aged 1-5 years at the onset of the study; the animals were kept on pasture from May to September and stabled for the rest of the year. Blood samples were taken monthly and analysed for serum leptin concentrations by a commercial radioimmunoassay kit. Circulating leptin concentrations in studied jennies were lower than those reported for donkeys and horses. Despite the tendency for lower values in yearling vs. young adult jennies, the age range of the examined animals was insufficient to confirm any age-related leptin variations. Significant seasonal leptin fluctuations with peak levels in late spring and the lowest levels in autumn months, correlated with photoperiod, were detected in yearling, barren as well as pregnant jennies. Therefore, it was impossible to identify any effects of gestation or lactation on leptin concentrations of jennies. The results of this study cannot be used as evidence of a causal relationship between the photoperiod and seasonal circulating leptin fluctuations in donkeys, but could reflect changes induced by various external or internal factors enabling adaptations of grazing animals in variable submediterranean environments. © 2014 EVJ Ltd.

Leptin does not mediate short-term fasting-induced changes in growth hormone pulsatility but increases IGF-I in leptin deficiency states.

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Chan, Jean L; Williams, Catherine J; Raciti, Patricia; Blakeman, Jennifer; Kelesidis, Theodore; Kelesidis, Iosif; Johnson, Michael L; Thorner, Michael O; Mantzoros, Christos S

2008-07-01

States of acute and chronic energy deficit are characterized by increased GH secretion and decreased IGF-I levels. The objective of the study was to determine whether changes in levels of leptin, a key mediator of the adaptation to starvation, regulate the GH-IGF system during energy deficit. We studied 14 healthy normal-weight men and women during three conditions: baseline fed and 72-h fasting (to induce hypoleptinemia) with administration of placebo or recombinant methionyl human leptin (r-metHuLeptin) (to reverse the fasting associated hypoleptinemia). We also studied eight normal-weight women with exercise-induced chronic energy deficit and hypothalamic amenorrhea at baseline and during 2-3 months of r-metHuLeptin treatment. GH pulsatility, IGF levels, IGF and GH binding protein (GHBP) levels were measured. During short-term energy deficit, measures of GH pulsatility and disorderliness and levels of IGF binding protein (IGFBP)-1 increased, whereas leptin, insulin, IGF-I (total and free), IGFBP-4, IGFBP-6, and GHBP decreased; r-metHuLeptin administration blunted the starvation-associated decrease of IGF-I. In chronic energy deficit, total and free IGF-I, IGFBP-6, and GHBP levels were lower, compared with euleptinemic controls; r-metHuLeptin administration had no major effect on GH pulsatility after 2 wk but increased total IGF-I levels and tended to increase free IGF-I and IGFBP-3 after 1 month. The GH/IGF system changes associated with energy deficit are largely independent of leptin deficiency. During acute energy deficit, r-metHuLeptin administration in replacement doses blunts the starvation-induced decrease of IGF-I, but during chronic energy deficit, r-metHuLeptin administration increases IGF-I and tends to increase free IGF-I and IGFBP-3.

Leptin Suppresses Mouse Taste Cell Responses to Sweet Compounds.

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Yoshida, Ryusuke; Noguchi, Kenshi; Shigemura, Noriatsu; Jyotaki, Masafumi; Takahashi, Ichiro; Margolskee, Robert F; Ninomiya, Yuzo

2015-11-01

Leptin is known to selectively suppress neural and behavioral responses to sweet-tasting compounds. However, the molecular basis for the effect of leptin on sweet taste is not known. Here, we report that leptin suppresses sweet taste via leptin receptors (Ob-Rb) and KATP channels expressed selectively in sweet-sensitive taste cells. Ob-Rb was more often expressed in taste cells that expressed T1R3 (a sweet receptor component) than in those that expressed glutamate-aspartate transporter (a marker for Type I taste cells) or GAD67 (a marker for Type III taste cells). Systemically administered leptin suppressed taste cell responses to sweet but not to bitter or sour compounds. This effect was blocked by a leptin antagonist and was absent in leptin receptor-deficient db/db mice and mice with diet-induced obesity. Blocking the KATP channel subunit sulfonylurea receptor 1, which was frequently coexpressed with Ob-Rb in T1R3-expressing taste cells, eliminated the effect of leptin on sweet taste. In contrast, activating the KATP channel with diazoxide mimicked the sweet-suppressing effect of leptin. These results indicate that leptin acts via Ob-Rb and KATP channels that are present in T1R3-expressing taste cells to selectively suppress their responses to sweet compounds. © 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.

Leptin and cancer: Pathogenesis and modulation

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Deep Dutta

2012-01-01

Full Text Available Leptin, a product of Ob gene from adipocytes regulates appetite, energy expenditure and body mass composition by decreasing orexigenic and increasing anorexigenic neuropeptide release from hypothalamus. Research over the past few years have suggested leptin/leptin receptor dysregulation to have a role in the development of a large variety of malignancies like breast ca, thyroid ca, endometrial ca and gastrointestinal malignancies, predominantly through JAK/STAT pathway which modulates PI3K/AKT3 signaling, ERK1/2 signaling, expression of antiapoptotic proteins (like XIAP, systemic inflammation (TNF-α, IL6, angiogenic factors (VEGF and hypoxia inducible factor-1a (HIF-1a expression. In this review, the current understanding of leptin′s role in carcinogenesis has been elaborated. Also a few agents modulating leptin signaling to inhibit cancer cell growth has been described.

Elevated serum leptin levels in patients with acute myocardial infarction; correlation with coronary angiographic and echocardiographic findings

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Khafaji Hadi AR

2012-05-01

Full Text Available Abstract Background To assess the relationship between serial serum leptin levels in patients with acute myocardial infarction (AMI who received thrombolysis and the degree of coronary atherosclerosis, coronary reperfusion, echocardiographic findings, and clinical outcome. 51 consecutive patients presenting with AMI were studied. Clinical characteristics including age, sex, body mass index (BMI and cardiovascular risk factors were recorded. Serial serum leptin levels at the time of admission and subsequently at 0, 6, 12, 24, 36, 60 hours afterwards were obtained. Coronary angiography was performed in 34 patients; the relation between serum leptin levels and evidence of coronary reperfusion as well as the extent of coronary atherosclerosis according to the coronary artery surgery study classification (CASS were evaluated. Echocardiographic evaluation was performed in all patients. 36 matched patients were enrolled as control group who had serum leptin level 9.4 ± 6.5 ng/ml. Results The patients mean age was 50.5 ± 10.6 years. There were 47 males and 3 females. 37.1% were diabetics, 23.5% were hypertensive, 21.6% were dyslipidemic and 22.7% were obese (BMI ≥ 30. Leptin concentrations (ng/ml increased and peaked at the 4th sample (36 hrs after admission (mean ± SD sample (1 =9.55 ± 7.4, sample (2 =12.9 ± 8.4, sample (3 =13.8 ± 10.4, sample (4 =18.9 ± 18.1, sample (5 =11.4 ± 6.5, sample (6 =10.8 ± 8.9 ng/ml. There was a significant correlation between serum leptin and BMI (r = 0.342; p = 0.03. Leptin levels correlated significantly to creatine kinase level on the second day (r = 0.43, p ≤ 0.01. Significant correlation of mean serum leptin with the ejection fraction (P p = 0.8. There was a trend for an increase in the mean serum leptin levels with increasing number of diseased vessels. There was no correlation between serum leptin levels and outcome neither during the

Leptin in first trimester pregnancy serum

DEFF Research Database (Denmark)

Hedley, Paula; Pihl, Kasper; Krebs, Lone

2009-01-01

and its relation to fetal growth disturbances were examined in this study. The study is a case-control study with 36 small-for-gestational-age (SGA) (pregnancies and 108 appropriate-for-gestational-age (AGA) (> or =5th percentile) pregnancies. The groups were matched by maternal age...... maternal BMI. There was no significant difference in maternal serum leptin concentrations between SGA and AGA pregnancies. In conclusion, SGA pregnancies are not associated with a lower maternal serum leptin concentration in first trimester. The maternal serum leptin concentration is largely determined...

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.

Association of Leptin with Body Pain in Women.

Science.gov (United States)

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

2016-07-01

Leptin, an appetite-regulatory hormone, is also known to act as a proinflammatory adipokine. One of the effects of increased systemic leptin concentrations may be greater sensitivity to pain. We report the results of two studies examining the association between leptin and pain: a small pilot longitudinal study, followed by a large cross-sectional study. In Study 1, three women with physician-diagnosed fibromyalgia provided blood draws daily for 25 consecutive days, as well as daily self-reported musculoskeletal pain. Daily fluctuations in serum leptin were positively associated with pain across all three participants (F (1,63) = 12.8, p BMI) was also included as a predictor of pain. Both leptin and BMI were found to be independently associated with self-reported pain (p = 0.001 and p BMI each being associated with greater pain. Leptin appears to be a predictor of body pain both within- and between-individuals and may be a driver of generalized pain states such as fibromyalgia.

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)

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.

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.

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.

Leptin and Pathological Indexes in Women with Breast Cancer

Directory of Open Access Journals (Sweden)

B Noori Alavicheh

2015-06-01

Full Text Available Background & aim: Breast cancer is the most common cancer among women and one of the factors threatening the health of women worldwide. Leptin is a 16 kD glycoprotein hormone produced predominantly by white adipose tissue. Leptin binds to receptors in the hypothalamus and plays a key role in regulation of metabolism. Both leptin and leptin receptor have recently been implicated in processes and progress leading to breast cancer initiation. The aim of this study was to identify if there is association between leptin and pathological indexes in patients with breast cancer Methods: 45women with breast cancer were enrolled. Serum leptin levels of patients were measured by the ELISA method. Pathological information such as stage of the breast cancer, Hormonal receptor (ER, PR and Her2 status in these patients were determined. Result: Results revealed that the patients who were in stage one and two, the mean serum leptin level was (34.18±21.22 ng/ml And patients who were in stage three and four, the mean serum leptin level was (32.21±21/93 ng/ml. Also the mean serum leptin levels in patients whose receptor status of ER, PR and HER2 positive were (35.90±23.55, 35.74±23.91and 37.02±24.25ng/ml, respectively. The Patients whose receptor status of ER, PR and HER2 negative were 26.64±13.13, 28.17±14.26and31.32±19.9ng/ml respectively. No significant association was found between leptin leveland stage of the breast cancer, hormonal receptor (ER, PR and Her2 status in Patients with Breast cancer(p>0.05. Conclusions: In this study, no association was found between serum leptin level and pathological indices in women with Breast cancer in Yasuj, Iran.

Preferential effects of leptin on CD4 T cells in central and peripheral immune system are critically linked to the expression of leptin receptor

Energy Technology Data Exchange (ETDEWEB)

Kim, So Yong; Lim, Ju Hyun [Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of); Choi, Sung Won [Department of Molecular Biology, School of Arts and Sciences (S.W.C), Cornell University, Ithaca, NY 18450 (United States); Kim, Miyoung; Kim, Seong-Tae [Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of); Kim, Min-Seon; Cho, You Sook [Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-600 (Korea, Republic of); Chun, Eunyoung, E-mail: chun.eunyoung@gmail.com [Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of); Lee, Ki-Young, E-mail: thylee@med.skku.ac.kr [Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of)

2010-04-09

Leptin can enhance thymopoiesis and modulate the T-cell immune response. However, it remains controversial whether these effects correlate with the expression of leptin receptor, ObR. We herein addressed this issue by using in vivo animal models and in vitro culture systems. Leptin treatment in both ob/ob mice and normal young mice induced increases of CD4 SP thymocytes in thymus and CD4 T cells in the periphery. Interestingly, expression of the long form ObR was significantly restricted to DN, DP and CD4 SP, but not CD8 SP thymocytes. Moreover, in the reaggregated DP thymocyte cultures with leptin plus TSCs, leptin profoundly induced differentiation of CD4 SP but not CD8 SP thymocytes, suggesting that the effects of leptin on thymocyte differentiation might be closely related to the expression of leptin receptor in developing thymocytes. Surprisingly, ObR expression was markedly higher in peripheral CD4 T cells than that in CD8 T cells. Furthermore, leptin treatment with or without IL-2 and PHA had preferential effects on cell proliferation of CD4 T cells compared to that of CD8 T cells. Collectively, these data provide evidence that the effects of leptin on differentiation and proliferation of CD4 T cells might be closely related to the expression of leptin receptor.

Preferential effects of leptin on CD4 T cells in central and peripheral immune system are critically linked to the expression of leptin receptor

International Nuclear Information System (INIS)

Kim, So Yong; Lim, Ju Hyun; Choi, Sung Won; Kim, Miyoung; Kim, Seong-Tae; Kim, Min-Seon; Cho, You Sook; Chun, Eunyoung; Lee, Ki-Young

2010-01-01

Leptin can enhance thymopoiesis and modulate the T-cell immune response. However, it remains controversial whether these effects correlate with the expression of leptin receptor, ObR. We herein addressed this issue by using in vivo animal models and in vitro culture systems. Leptin treatment in both ob/ob mice and normal young mice induced increases of CD4 SP thymocytes in thymus and CD4 T cells in the periphery. Interestingly, expression of the long form ObR was significantly restricted to DN, DP and CD4 SP, but not CD8 SP thymocytes. Moreover, in the reaggregated DP thymocyte cultures with leptin plus TSCs, leptin profoundly induced differentiation of CD4 SP but not CD8 SP thymocytes, suggesting that the effects of leptin on thymocyte differentiation might be closely related to the expression of leptin receptor in developing thymocytes. Surprisingly, ObR expression was markedly higher in peripheral CD4 T cells than that in CD8 T cells. Furthermore, leptin treatment with or without IL-2 and PHA had preferential effects on cell proliferation of CD4 T cells compared to that of CD8 T cells. Collectively, these data provide evidence that the effects of leptin on differentiation and proliferation of CD4 T cells might be closely related to the expression of leptin receptor.

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)

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

Leptin regulates the pro-inflammatory response in human epidermal keratinocytes.

Science.gov (United States)

Lee, Moonyoung; Lee, Eunyoung; Jin, Sun Hee; Ahn, Sungjin; Kim, Sae On; Kim, Jungmin; Choi, Dalwoong; Lim, Kyung-Min; Lee, Seung-Taek; Noh, Minsoo

2018-05-01

The role of leptin in cutaneous wound healing process has been suggested in genetically obese mouse studies. However, the molecular and cellular effects of leptin on human epidermal keratinocytes are still unclear. In this study, the whole-genome-scale microarray analysis was performed to elucidate the effect of leptin on epidermal keratinocyte functions. In the leptin-treated normal human keratinocytes (NHKs), we identified the 151 upregulated and 53 downregulated differentially expressed genes (DEGs). The gene ontology (GO) enrichment analysis with the leptin-induced DEGs suggests that leptin regulates NHKs to promote pro-inflammatory responses, extracellular matrix organization, and angiogenesis. Among the DEGs, the protein expression of IL-8, MMP-1, fibronectin, and S100A7, which play roles in which is important in the regulation of cutaneous inflammation, was confirmed in the leptin-treated NHKs. The upregulation of the leptin-induced proteins is mainly regulated by the STAT3 signaling pathway in NHKs. Among the downregulated DEGs, the protein expression of nucleosome assembly-associated centromere protein A (CENPA) and CENPM was confirmed in the leptin-treated NHKs. However, the expression of CENPA and CENPM was not coupled with those of other chromosome passenger complex like Aurora A kinase, INCENP, and survivin. In cell growth kinetics analysis, leptin had no significant effect on the cell growth curves of NHKs in the normal growth factor-enriched condition. Therefore, leptin-dependent downregulation of CENPA and CENPM in NHKs may not be directly associated with mitotic regulation during inflammation.

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

Plumbagin Inhibits Leptin-Induced Proliferation of Hepatic Stellate ...

African Journals Online (AJOL)

Purpose: To investigate the protective effects of plumbagin against liver fibrosis and explore the influence of plumbagin on the proliferation of hepatic stellate cells (HSCs). Methods: HSC-LX2 cells were divided into blank/control group, 100 ng/ml leptin group, 100 ng/ml leptin + 2 μmol/L plumbagin group, 100 ng/ml leptin + ...

Serum bile acids and leptin interact with glucose metabolism in patients with liver cirrhosis

NARCIS (Netherlands)

Valentini, Luzia; Glaeser, Silja; Schuetz, Tatjana; Omar, Ajmal; Kasim, Esmatollah; Kroencke, Thomas; Tietge, Uwe J. F.; Lochs, Herbert; Schulzke, Joerg-Dieter; Brabant, Georg; Ockenga, Johann

Background & aims: We investigated possible involvements of bile acids (BA) and leptin in hepatogenous insulin resistance being present in up to 90% of cirrhotic patients. Methods: Blood was analysed in 10 cirrhotic patients (8m/2f, 48 +/- 10.4 yrs) and 10 controls (8m/2f, 43 +/- 9.3 yrs) after oral

Allelic polymorphism of Makoei sheep leptin gene identified by ...

African Journals Online (AJOL)

use

2011-12-05

Dec 5, 2011 ... Lord et al., 1998) have shed light on the influence of leptin on both the .... A weak correlation between leptin serum levels and cow body condition ... Detection of polymorphisms in the ovine leptin (LEP) gene: .... Signals that.

Plasma leptin levels in healthy children and adolescents

DEFF Research Database (Denmark)

Blum, W F; Englaro, P; Hanitsch, S

1997-01-01

children. With this assay, leptin proved to be a comparatively stable protein under common conditions of blood sampling and storage. Leptin levels increased in girls with age (r = 0.47, P stage showed a steady...... increase in girls between 2.51 micrograms/L (median) at Tanner stage 1 to 6.24 micrograms/L at Tanner stage 5. In boys, leptin levels were highest at Tanner stage 2 (2.19 micrograms/L) and declined thereafter to 0.71 microgram/L at Tanner stage 5. A strong exponential relationship was observed for leptin...... levels with body mass index (BMI) and percentage body fat as determined by bioelectric impedance measurements in a subgroup of subjects. This relationship was similar between boys and girls at Tanner stages 1 and 2. In boys, there was a significant decline of leptin at a given BMI with further...

Influence of serum leptin levels and Q223R leptin receptor polymorphism on clinical characteristic of patients with rheumatoid arthritis from Western Mexico.

Science.gov (United States)

Angel-Chávez, Luis I; Ruelas-Cinco, Elizabeth; Hernández-Bello, Jorge; Castro, Elena; Vázquez-Villamar, Mirna; Parra-Rojas, Isela; Brennan-Bourdon, L Michele; Muñoz-Barrios, Salvador; Guerrero-Velázquez, Celia; Muñoz-Valle, José Francisco

2018-04-01

The aim of the present study was to evaluate the possible association between the Q223R Leptin receptor (LEPR) polymorphism (A>G; rs1137101) and leptin levels in patients with rheumatoid arthritis (RA) from Western Mexico. A cross-sectional study was performed with 70 RA patients and 74 controls subject (CS). Disease activity was evaluated using DAS28 score, the Q223R LEPR polymorphism was determined by the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and serum leptin levels, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and rheumatoid factor (RF) were quantified. RA patients had significant high serum leptin levels compared with CS; leptin levels correlated strongly with body composition measures, but not with inflammatory markers, disease evolution, and activity. The genotype and allele frequencies of the Q223R LEPR polymorphism were not associated with RA. Similarly, leptin levels did not differ between Q223R LEPR genotypes. The LEPR Q223R polymorphism was not associated with RA risk in patients from Mexican population, even though high levels of serum leptin were present and these could explain the low weight observed in RA patients when they were compared to control subjects. However, the serum leptin levels did not correlate with inflammatory markers, severity and disease evolution.

Modulation of the mesolimbic dopamine system by leptin.

Science.gov (United States)

Opland, Darren M; Leinninger, Gina M; Myers, Martin G

2010-09-02

Nutritional status modulates many forms of reward-seeking behavior, with caloric restriction increasing the drive for drugs of abuse as well as for food. Understanding the interactions between the mesolimbic dopamine (DA) system (which mediates the incentive salience of natural and artificial rewards) and the neural and hormonal systems that sense and regulate energy balance is thus of significant importance. Leptin, which is produced by adipocytes in proportion to fat content as a hormonal signal of long-term energy stores, acts via its receptor (LepRb) on multiple populations of central nervous system neurons to modulate neural circuits in response to body energy stores. Leptin suppresses feeding and plays a central role in the control of energy balance. In addition to demonstrating that leptin modulates hypothalamic and brainstem circuits to promote satiety, recent work has begun to explore the mechanisms by which leptin influences the mesolimbic DA system and related behaviors. Indeed, leptin diminishes several measures of drug and food reward, and promotes a complex set of changes in the mesolimbic DA system. While many of the details remain to be worked out, several lines of evidence suggest that leptin regulates the mesolimbic DA system via multiple neural pathways and processes, and that distinct sets of LepRb neurons each modulate unique aspects of the mesolimbic DA system and behavior in response to leptin. 2010 Elsevier B.V. All rights reserved.

Leptin and its potential interest in assisted reproduction cycles.

Science.gov (United States)

Catteau, A; Caillon, H; Barrière, P; Denis, M G; Masson, D; Fréour, T

2016-04-01

Leptin, an adipose hormone, has been shown to control energy homeostasis and food intake, and exert many actions on female reproductive function. Consequently, this adipokine is a pivotal factor in studies conducted on animal models and humans to decipher the mechanisms behind the infertility often observed in obese women. A systematic PubMed search was conducted on all articles, published up to January 2015 and related to leptin and its actions on energy balance and reproduction, using the following key words: leptin, reproduction, infertility, IVF and controlled ovarian stimulation. The available literature was reviewed in order to provide an overview of the current knowledge on the physiological roles of leptin, its involvement in female reproductive function and its potential interest as a prognostic marker in IVF cycles. Animal and human studies show that leptin communicates nutritional status to the central nervous system and emerging evidence has demonstrated that leptin is involved in the control of reproductive functions by acting both directly on the ovaries and indirectly on the central nervous system. With respect to the clinical use of leptin as a biomarker in IVF cycles, a systematic review of the literature suggested its potential interest as a predictor of IVF outcome, as high serum and/or follicular fluid leptin concentrations have correlated negatively with cycle outcome. However, these preliminary results remain to be confirmed. Leptin regulates energy balance and female reproductive function, mainly through its action on hypothalamic-pituitary-ovarian function, whose molecular and cellular aspects are progressively being deciphered. Preliminary studies evaluating leptin as a biomarker in human IVF seem promising but need further confirmation. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Association between Salivary Leptin Levels and Taste Perception in Children

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Lénia Rodrigues

2017-01-01

Full Text Available The satiety inducing hormone leptin acts not only at central nervous system but also at peripheral level. Leptin receptors are found in several sense related organs, including the mouth. A role of leptin in sweet taste response has been suggested but, until now, studies have been based on in vitro experiments, or in assessing the levels of the hormone in circulation. The present study investigated whether the levels of leptin in saliva are related to taste perception in children and whether Body Mass Index (BMI affects such relationship. Sweet and bitter taste sensitivity was assessed for 121 children aged 9-10 years and unstimulated whole saliva was collected for leptin quantification, using ELISA technique. Children females with lower sweet taste sensitivity presented higher salivary leptin levels, but this is only in the normal weight ones. For bitter taste, association between salivary leptin and caffeine threshold detection was observed only in preobese boys, with higher levels of salivary hormone in low sensitive individuals. This study is the first presenting evidences of a relationship between salivary leptin levels and taste perception, which is sex and BMI dependent. The mode of action of salivary leptin at taste receptor level should be elucidated in future studies.

Relationship between Plasma Leptin Level and Chronic Kidney Disease

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Anoop Shankar

2012-01-01

Full Text Available Background. Leptin is an adipose tissue-derived hormone shown to be related to several metabolic, inflammatory, and hemostatic factors related to chronic kidney disease. Recent animal studies have reported that infusion of recombinant leptin into normal rats for 3 weeks fosters the development of glomerulosclerosis. However, few studies have examined the association between leptin and CKD in humans. Therefore, we examined the association between plasma leptin levels and CKD in a representative sample of US adults. Methods. We examined the third National Health and Nutrition Examination Survey participants >20 years of age (n=5820, 53.6% women. Plasma leptin levels were categorized into quartiles (≤4.3 Fg/L, 4.4–8.7 Fg/L, 8.8–16.9 Fg/L, >16.9 Fg/L. CKD was defined as a glomerular filtration rate of <60 mL/min/1.73 m2 estimated from serum creatinine. Results. Higher plasma leptin levels were associated with CKD after adjusting for age, sex, race/ethnicity, education, smoking, alcohol intake, body mass index (BMI, diabetes, hypertension, and serum cholesterol. Compared to quartile 1 of leptin (referent, the odds ratio (95% confidence interval of CKD associated with quartile 4 was 3.31 (1.41 to 7.78; P-trend = 0.0135. Subgroup analyses examining the relation between leptin and CKD by gender, BMI categories, diabetes, and hypertension status also showed a consistent positive association. Conclusion. Higher plasma leptin levels are associated with CKD in a representative sample of US adults.

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.

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.

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.

Pest control and resistance management through release of insects carrying a male-selecting transgene.

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Harvey-Samuel, Tim; Morrison, Neil I; Walker, Adam S; Marubbi, Thea; Yao, Ju; Collins, Hilda L; Gorman, Kevin; Davies, T G Emyr; Alphey, Nina; Warner, Simon; Shelton, Anthony M; Alphey, Luke

2015-07-16

Development and evaluation of new insect pest management tools is critical for overcoming over-reliance upon, and growing resistance to, synthetic, biological and plant-expressed insecticides. For transgenic crops expressing insecticidal proteins from the bacterium Bacillus thuringiensis ('Bt crops') emergence of resistance is slowed by maintaining a proportion of the crop as non-Bt varieties, which produce pest insects unselected for resistance. While this strategy has been largely successful, multiple cases of Bt resistance have now been reported. One new approach to pest management is the use of genetically engineered insects to suppress populations of their own species. Models suggest that released insects carrying male-selecting (MS) transgenes would be effective agents of direct, species-specific pest management by preventing survival of female progeny, and simultaneously provide an alternative insecticide resistance management strategy by introgression of susceptibility alleles into target populations. We developed a MS strain of the diamondback moth, Plutella xylostella, a serious global pest of crucifers. MS-strain larvae are reared as normal with dietary tetracycline, but, when reared without tetracycline or on host plants, only males will survive to adulthood. We used this strain in glasshouse-cages to study the effect of MS male P. xylostella releases on target pest population size and spread of Bt resistance in these populations. Introductions of MS-engineered P. xylostella males into wild-type populations led to rapid pest population decline, and then elimination. In separate experiments on broccoli plants, relatively low-level releases of MS males in combination with broccoli expressing Cry1Ac (Bt broccoli) suppressed population growth and delayed the spread of Bt resistance. Higher rates of MS male releases in the absence of Bt broccoli were also able to suppress P. xylostella populations, whereas either low-level MS male releases or Bt broccoli

Relationship of leptin administration with production of reactive oxygen species, sperm DNA fragmentation, sperm parameters and hormone profile in the adult rat.

Science.gov (United States)

Abbasihormozi, Shima; Shahverdi, Abdolhossein; Kouhkan, Azam; Cheraghi, Javad; Akhlaghi, Ali Asghar; Kheimeh, Abolfazl

2013-06-01

Leptin, an adipose tissue-derived hormone, plays an important role in energy homeostasis and metabolism, and in the neuroendocrine and reproductive systems. The function of leptin in male reproduction is unclear; however, it is known to affect sex hormones, sperm motility and its parameters. Leptin induces mitochondrial superoxide production in aortic endothelia and may increase oxidative stress and abnormal sperm production in leptin-treated rats. This study aims to evaluate whether exogenous leptin affects sperm parameters, hormone profiles, and the production of reactive oxygen species (ROS) in adult rats. A total of 65 Sprague-Dawley rats were divided into three treated groups and a control group. Treated rats received daily intraperitoneal injections of 5, 10 and 30 μg/kg of leptin administered for a duration of 7, 15, and 42 days. Control rats were given 0.1 mL of 0.9 % normal saline for the same period. One day after final drug administration, we evaluated serum specimens for follicle-stimulating hormone (FSH), leutinizing hormone (LH), free testosterone (FT), and total testosterone (TT) levels. Samples from the rat epididymis were also evaluated for sperm parameters and motility characteristics by a Computer-Aided Semen Analysis (CASA) system. Samples were treated with 2',7'-dichlorofluorescein-diacetate (DCFH-DA) and analyzed using flow cytometry and TUNEL to determine the impact of leptin administration on sperm DNA fragmentation. According to CASA, significant differences in all sperm parameters in leptin-treated rats and their age-matched controls were detected, except for TM, ALH and BCF. Serum FSH and LH levels were significantly higher in rats that received 10 and 30 μg/kg of leptin compared to those treated with 5 μg/kg of leptin in the same group and control rats (P control group (P hormone profile modulation.

Longitudinal study of leptin levels in chronic hemodialysis patients

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Averbukh Zhan

2011-06-01

Full Text Available Abstract Background The influence of serum leptin levels on nutritional status and survival in chronic hemodialysis patients remained to be elucidated. We conducted a prospective longitudinal study of leptin levels and nutritional parameters to determine whether changes of serum leptin levels modify nutritional status and survival in a cohort of prevalent hemodialysis patients. Methods Leptin, dietary energy and protein intake, biochemical markers of nutrition and body composition (anthropometry and bioimpedance analysis were measured at baseline and at 6, 12, 18 and 24 months following enrollment, in 101 prevalent hemodialysis patients (37% women with a mean age of 64.6 ± 11.5 years. Observation of this cohort was continued over 2 additional years. Changes in repeated measures were evaluated, with adjustment for baseline differences in demographic and clinical parameters. Results Significant reduction of leptin levels with time were observed (linear estimate: -2.5010 ± 0.57 ng/ml/2y; p Conclusions Thus leptin levels reflect fat mass depots, rather than independently contributing to uremic anorexia or modifying nutritional status and/or survival in chronic hemodialysis patients. The importance of such information is high if leptin is contemplated as a potential therapeutic target in hemodialysis patients.

[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.

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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

Role of leptin in energy expenditure : The hypothalamic perspective

NARCIS (Netherlands)

Pandit, R.; Beerens, S.; Adan, R. A.H.

2017-01-01

The adipocyte-derived hormone leptin is a peripheral signal that informs the brain about the metabolic status of an organism. Although traditionally viewed as an appetite-suppressing hormone, studies in the past decade have highlighted the role of leptin in energy expenditure. Leptin has been shown

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

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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.

Serum leptin levels in pregnant women with type 1 diabetes mellitus

DEFF Research Database (Denmark)

Lauszus, Finn; Schmitz, Ole; Vestergaard, H

2001-01-01

Leptin is an important weight regulator and during pregnancy leptin is not only synthesized in adipose tissue but also in the placenta.......Leptin is an important weight regulator and during pregnancy leptin is not only synthesized in adipose tissue but also in the placenta....

Children's psychosocial stress and emotional eating: A role for leptin?

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Michels, Nathalie; Sioen, Isabelle; Ruige, Johannes; De Henauw, Stefaan

2017-05-01

Psychosocial stress can be a health threat by stimulating unhealthier eating behaviors. We aim to test the role of the hormone leptin in the association between stress and diet/emotional eating as detected in primary school children. In a two-wave longitudinal study with 308 Belgian children (5-12y) in 2010-2012, the association of fasting serum leptin with reported stress (negative events and emotional problems), measured stress by salivary cortisol (overall cortisol output and awakening response), emotional eating and food consumption frequency was examined. Analyses were split by sex. Mediation and moderation by leptin change were tested. One stress marker (overall cortisol output) was significantly correlated with high leptin levels, but only in girls and cross-sectionally. Only in boys, leptin was associated with low emotional eating. Leptin was not a significant predictor of unhealthy food consumption. Leptin change was not a mediator but an enhancing moderator in the link between stress (high cortisol output and emotional problems) and emotional eating in girls: high reports of emotional eating in 2012 were present in the case of combined high 2-year leptin increase and high stress at baseline. Stress (represented by emotional problems and high daily cortisol) seems to lead to hyperleptinemia in girls; and the combination of high stress and hyperleptinemia might make girls more vulnerable to stress-induced eating. No functional data on leptin sensitivity were present, but results might suggest that stress induces lower sensitivity to the anorexigenic leptin activity. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:471-480). © 2016 Wiley Periodicals, Inc.

Leptina, acercamiento hacia una hormona: an approach to a hormone Leptine:

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Alvin Mena Cantero

2009-09-01

Full Text Available INTRODUCCIÓN: la leptina tiene un importante papel en la patogenia de la obesidad, al informar al hipotálamo del contenido de grasa corporal y regular la ingesta alimentaria, no obstante, esta hormona constituye un elemental mediador de varias funciones fisiológicas en nuestro organismo. MÉTODOS: se realizó una revisión bibliográfica que incluyó un total de 32 documentos de la especialidad de Endocrinología, a fin de describir el mecanismo fisiológico de la leptina y su relación con diversos trastornos neuroendocrinos. RESULTADOS: las concentraciones de leptina son inferiores en el sexo masculino, lo que está en relación con el incremento de testosterona, que ejerce un efecto inhibitorio en su producción. Entre otros de sus efectos fisiológicos, interviene también en la regulación del inicio de la pubertad y participa en la respuesta inflamatoria. CONCLUSIONES: actualmente las posibilidades de tratamiento de la obesidad y otros trastornos de fertilidad con el uso de leptina recombinante están abiertas.INTRODUCTION: leptine has a significant role in obesity pathogeny, which informs to hypothalamus of the body fat content and regulates the food consumption; however, this hormone is a elementary mediator of some physiologic functions in our organism. METHODS: a bibliographic review was carried out including a total of 32 data from Endocrinology specialty, to describe the physiologic mechanism of Leptine, and its relation with diverse neuroendocrine disorders. RESULTS: concentrations of Leptine are lower in male sex a feature related to the testosterone increase exerting an inhibitory effect on its production. Among other physiologic effects is the regulation of puberty onset and it is involved in inflammatory response. CONCLUSIONS: nowadays, obesity treatment possibilities and other fertility disorders related to use of Leptine are open.

Maternal leptin and body composition in the first trimester of pregnancy.

LENUS (Irish Health Repository)

Fattah, Chro

2012-02-01

BACKGROUND: Leptin is produced mainly by adipocytes. Levels are increased in women with obesity and during pregnancy. Increased levels are also associated with pregnancy complications such as, pre-eclampsia and gestational diabetes mellitus. OBJECTIVE: We studied what component of body composition correlated best with maternal leptin in the first trimester of pregnancy and, whether maternal leptin correlated better with visceral fat rather than fat distributed elsewhere. SUBJECTS AND METHODS: Women were recruited in the first trimester. Maternal adiposity was measured using body mass index and advanced bioelectrical impedance analysis. Maternal leptin was measured using an enzyme-linked immunosorbent assay technique. RESULTS: Of the 100 subjects studied, the mean leptin concentration was 37.7 ng\\/ml (range: 2.1-132.8). Leptin levels did not correlate with gestational age in the first trimester, maternal age, parity or birth weight. Serum leptin correlated positively with maternal weight and body mass index, and with the different parameters of body composition. On multiple regression analysis, serum leptin correlated with visceral fat but not fat distributed elsewhere. CONCLUSIONS: Visceral fat is the main determinant of circulating maternal leptin in the first trimester of pregnancy. This raises the possibility that maternal leptin in early pregnancy may be a marker for the development of metabolic syndrome, including diabetes mellitus.

Leptin signaling molecular actions and drug target in hepatocellular carcinoma

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Jiang N

2014-11-01

Full Text Available Nan Jiang,1,* Rongtong Sun,2,* Qing Sun3 1Shandong University School of Medicine, Jinan, Shandong Province, People’s Republic of China; 2Weihai Municipal Hospital, Weihai, Shandong Province, People’s Republic of China; 3Department of Pathology, QianFoShan Hospital Affiliated to Shandong University, Jinan, Shandong Province, People’s Republic of China *These authors contributed equally to this work Abstract: Previous reports indicate that over 13 different tumors, including hepatocellular carcinoma (HCC, are related to obesity. Obesity-associated inflammatory, metabolic, and endocrine mediators, as well as the functioning of the gut microbiota, are suspected to contribute to tumorigenesis. In obese people, proinflammatory cytokines/chemokines including tumor necrosis factor-alpha, interleukin (IL-1 and IL-6, insulin and insulin-like growth factors, adipokines, plasminogen activator inhibitor-1, adiponectin, and leptin are found to play crucial roles in the initiation and development of cancer. The cytokines induced by leptin in adipose tissue or tumor cells have been intensely studied. Leptin-induced signaling pathways are critical for biological functions such as adiposity, energy balance, endocrine function, immune reaction, and angiogenesis as well as oncogenesis. Leptin is an activator of cell proliferation and anti-apoptosis in several cell types, and an inducer of cancer stem cells; its critical roles in tumorigenesis are based on its oncogenic, mitogenic, proinflammatory, and pro-angiogenic actions. This review provides an update of the pathological effects of leptin signaling with special emphasis on potential molecular mechanisms and therapeutic targeting, which could potentially be used in future clinical settings. In addition, leptin-induced angiogenic ability and molecular mechanisms in HCC are discussed. The stringent binding affinity of leptin and its receptor Ob-R, as well as the highly upregulated expression of both

Central leptin gene therapy ameliorates diabetes type 1 and 2 through two independent hypothalamic relays; a benefit beyond weight and appetite regulation.

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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.

Leptina como marcadora do dimorfismo sexual em recém-nascidos Leptin as a marker of sexual dimorphism in newborn infants

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Inês M. C. G. Pardo

2004-08-01

Full Text Available OBJETIVO: Avaliar os níveis de leptina do cordão umbilical em recém-nascidos adequados para a idade gestacional conforme sexo, peso, comprimento e índice ponderal de nascimento. MÉTODO: Estudo tipo transversal, envolvendo 132 recém-nascidos adequados para idade gestacional (68 do sexo feminino, 64 do sexo masculino, com idade gestacional de 35-42 semanas. Os dados foram obtidos mediante entrevista com as mães na maternidade, pelo estudo antropométrico dos recém-nascidos e pela dosagem de leptina, estradiol e testosterona no cordão umbilical por meio da coleta imediata após o parto. RESULTADOS: Os recém-nascidos do sexo feminino apresentaram níveis de leptina significativamente maiores que os do sexo masculino (8,34±0,65 ng/ml versus 6,06±0,71 ng/ml; p = 0,000. Os níveis de estradiol e testosterona não variaram conforme o sexo. A leptina se correlacionou positivamente com idade gestacional (r = 0,394, p OBJECTIVE: To determine cord blood leptin levels in newborns appropriate for gestational age, according to gender, birth weight, birth height and ponderal index. METHODS: A cross-sectional study was carried out with 132 term newborns appropriate for gestational age (68 females, 64 males, gestational age between 35-42 weeks. Data were collected through interviews with the mothers at the maternity, anthropometrycal study of the newborns, and cord blood estradiol, testosterone and leptin assays obtained immediately after birth. RESULTS: The levels of leptin were significantly higher in females than in males (8.34±0.65 ng/ml versus 6.06±0.71 ng/ml; p = 0.000. The concentrations of estradiol and testosterone did not differ between males and females. Leptin levels were positively correlated with gestational age (r = 0.394, p < 0.01, birth weight (r = 0.466, p < 0.01, birth length (r = 0.335, p < 0.01 and ponderal index (r = 0.326, p < 0.01. CONCLUSIONS: Leptin concentration in the umbilical cord is positively correlated with

Serum leptin concentration in patients with type 2 diabetes

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Malecha-Jedraszek Arleta

2015-12-01

Full Text Available With the increasing importance of early type 2 diabetes (DM2 and obesity detection, it is useful to reevaluate leptin role in these conditions. Our study aimed at investigating circulating leptin concentrations in a group of patients with DM2, and at assessing in detail whether leptin concentrations correlate with selected biochemical, clinical parameters and markers of systemic inflammation in patients with DM2 and in healthy volunteers. In our work, we analysed samples and data drawn from 71 patients aged 61.4 ± 11.7 years, who have been diagnosed with type 2 diabetes, as well as from a healthy control group (HC consisting of 51 healthy subjects with a mean age of 57.8 ± 13.7 years. Therein, the concentration of leptin in the DM2 patients was significantly higher than in the HC (p < 0.01, with median value of 16.59 (IQR 8.58-33.39 ng/ml in the DM2, vs median value of 6.66 (IQR 4.52-21.40 ng/ml in the HC. In the analysis of variance, higher leptin concentrations were revealed in the DM2 group as compared to the HC, and this figure remained significant after adjusting for gender and age (p < 0.001. Moreover, it was independent of HOMA-IR (p = 0.003. However, the differences in leptin levels between the groups disappeared when additional adjustments for anthropometric parameters (BMI, waist circumference were applied (p = 0.088. Beyond the aforementioned, significant positive correlations were found in the DM 2 group between leptin level and CRP (r=0.256; p < 0.05 and IL-6 (r = 0.345; p < 0.01. Among the selected variables, only gender and BMI were included in the predictive model explaining the variability of leptin, and, in total, were responsible for 72.6% of the original variation of the studied adipocytokine. The results of this study have led to conclusion that leptin may participate in the complex pathogenesis of DM2 and be a predictor of the development of this disease. As higher concentrations of leptin coexist with obesity, and this

[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.

Leptin and insulin pathways in POMC and AgRP neurons that modulate energy balance and glucose homeostasis

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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

Uroguanylin levels in intestine and plasma are regulated by nutritional status in a leptin-dependent manner.

Science.gov (United States)

Folgueira, C; Sanchez-Rebordelo, E; Barja-Fernandez, S; Leis, R; Tovar, S; Casanueva, F F; Dieguez, C; Nogueiras, R; Seoane, L M

2016-03-01

Uroguanylin (UGN) is a 16 amino acid peptide produced mainly by intestinal epithelial cells. Nutrients intake increases circulating levels of prouroguanylin that is processed and converted to UGN to activate the guanylyl cyclase 2C receptor (GUCY2C). Given that the UGN-GUCY2C system has been proposed as a novel gut-brain endocrine axis regulating energy balance, the aim of the present study was to investigate the regulation of UGN protein levels in duodenum and circulating levels in lean and obese mice under different nutritional conditions and its potential interaction with leptin. Swiss, C57BL/6 wild-type and ob/ob male adult mice under different nutritional conditions were used: fed ad libitum standard diet (control); 48 h fasting (fasted); 48 h fasting followed by 24 h of feeding (refed); and fed high-fat diet (45 %) during 10 weeks. In addition, peripheral leptin administration was performed. Intestinal uroguanylin expression was studied by Western blot analysis; plasma levels were measured by ELISA. Food deprivation significantly reduced plasma UGN levels, which were correlated with the lower protein levels of UGN in duodenum. These effects were reverted after refeeding and leptin challenge. Consistently, in ob/ob mice UGN expression was decreased, whereas leptin treatment up-regulated UGN levels in duodenum in these genetically modified mice compared to WT. Diet-induced obese mice displayed increased UGN levels in intestine and plasma in comparison with lean mice. Our findings suggest that UGN levels are correlated with energy balance status and that the regulation of UGN by nutritional status is leptin-dependent.

Pivotal role of leptin in insulin effects

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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.

Plasma leptin determination in ruminants: effect of nutritional status and body fatness on plasma leptin concentration assessed by a specific RIA in sheep.

Science.gov (United States)

Delavaud, C; Bocquier, F; Chilliard, Y; Keisler, D H; Gertler, A; Kann, G

2000-05-01

A specific leptin RIA was developed to assess concentrations of leptin in ovine plasma, and was shown to be efficient with bovine and caprine plasma. A specific, high-affinity antibody was generated against recombinant ovine leptin which, when used in a competitive leptin RIA, provided valid estimates of linearity (r=+0.989-0.998), recovery (102%), repeatability (13%) and limit of sensitivity (0.83 ng/ml for 100 microl sample size). Serial dilutions of five ovine, bovine or caprine plasma samples showed good linearity and parallelism with the recombinant ovine leptin standard curve. A comparison of this RIA was made with a commercial 'multi-species' RIA kit using 56 ovine plasma samples. Major differences were found in assay sensitivity. Non-lactating, non-pregnant, ovariectomized ewes were fed a ration for 65 days which provided 90+/-9% (control; n=12) or 39+/-2% of maintenance energy requirements (underfed; n=16) in order to analyse the respective effects of body fatness (estimated by either an in vivo dilution technique or body condition scoring) and of nutritional status on plasma leptin concentration. There was a significant positive correlation between body fatness or body condition score and plasma leptin levels (r=+0.68, Pnutritional status (17%).

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.

Enhancement of Bovine oocyte maturation by leptin is accompanied by an upregulation in mRNA expression of leptin receptor isoforms in cumulus cells

NARCIS (Netherlands)

van Tol, Helena T A; van Eerdenburg, Frank J C M; Colenbrander, Ben; Roelen, Bernard A J

In this study, the mechanisms of supposed leptin action on oocyte maturation were examined. Expression of leptin mRNA, as determined with RT-PCR, was present in oocytes but not in cumulus cells. The long isoform of the leptin receptor (ObR-L) was expressed exclusively in cumulus cells after 7 and 23

Serum leptin levels in patients with coronary artery disease

International Nuclear Information System (INIS)

Akram, S.; Ahmed, Z.; Fayyaz, I.; Mehmood, S.; Chani, M.

2011-01-01

Cardiovascular diseases (CVD) are the leading cause of morbidity, mortality and disability worldwide. Leptin, a 16kDa product of ob gene, is an endocrine hormone produced by white adipose tissue. It is primarily involved in the regulation of food intake and energy expenditure. Hyperleptinemia is one of the novel risk factors contributing in many ways to CVD. Objective: The objective of the study was to find the level of leptin in patients with coronary artery disease (CAD) and compare it with healthy people in our population. Methods: Our study was an analytical and cross-sectional study. Our study included 60 patients with a history of CAD and 60 healthy controls (aged 40-60 years, both sexes). Leptin levels were measured by ELISA. Results: Mean serum leptin level in patients was 11.48+-11.25 g/ml, while control group had a mean leptin level of 8.22+-8.01 g/ml (p=0.071). Conclusion: Leptin levels were higher in patients but the difference was non-significant. More studies are needed with larger sample size in our population. (author)

Mammary gland leptin in relation to lactogenesis in the periparturient dairy goat

DEFF Research Database (Denmark)

Rasmussen, Alice Neess; Nielsen, Mette Olaf; Tauson, Anne-Helene

2008-01-01

The role of leptin in development of mammary gland secretory function was studied during the periparturient period in dairy goats. Changes in mammary leptin and leptin receptor (short cytoplasmic form) expression were evaluated by real-time RT-PCR and related to changes in milk and plasma leptin...... peak in milk leptin 2 days post-partum needs to be understood. We did not find evidence that milk leptin can be absorbed, and thus play a role in systemic regulation, of the neonatal goat....

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

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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

High circulatory leptin mediated NOX-2-peroxynitrite-miR21 axis activate mesangial cells and promotes renal inflammatory pathology in nonalcoholic fatty liver disease

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Firas Alhasson

2018-07-01

Full Text Available High circulatory insulin and leptin followed by underlying inflammation are often ascribed to the ectopic manifestations in non-alcoholic fatty liver disease (NAFLD but the exact molecular pathways remain unclear. We have shown previously that CYP2E1-mediated oxidative stress and circulating leptin in NAFLD is associated with renal disease severity. Extending the studies, we hypothesized that high circulatory leptin in NAFLD causes renal mesangial cell activation and tubular inflammation via a NOX2 dependent pathway that upregulates proinflammatory miR21. High-fat diet (60% kcal was used to induce fatty liver phenotype with parallel insulin and leptin resistance. The kidneys were probed for mesangial cell activation and tubular inflammation that showed accelerated NASH phenotype and oxidative stress in the liver. Results showed that NAFLD kidneys had significant increases in α-SMA, a marker of mesangial cell activation, miR21 levels, tyrosine nitration and renal inflammation while they were significantly decreased in leptin and p47 phox knockout mice. Micro RNA21 knockout mice showed decreased tubular immunotoxicity and proinflammatory mediator release. Mechanistically, use of NOX2 siRNA or apocynin,phenyl boronic acid (FBA, DMPO or miR21 antagomir inhibited leptin primed-miR21-mediated mesangial cell activation in vitro suggesting a direct role of leptin-mediated NOX-2 in miR21-mediated mesangial cell activation. Finally, JAK-STAT inhibitor completely abrogated the mesangial cell activation in leptin-primed cells suggesting that leptin signaling in the mesangial cells depended on the JAK-STAT pathway. Taken together the study reports a novel mechanistic pathway of leptin-mediated renal inflammation that is dependent on NOX-2-miR21 axis in ectopic manifestations underlying NAFLD-induced co-morbidities. Keywords: Leptin, NOX-2, NADPH, Mesangial cells, miR21, Oxidative stress, NAFLD, JAK/STAT, siRNA

Relationship of leptin and insulin-like growth factor I to nutritional status in hemodialyzed children.

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Besbas, Nesrin; Ozaltin, Fatih; Coşkun, Turgay; Ozalp, Sila; Saatçi, Umit; Bakkaloğlu, Aysin; El Nahas, A Meguid

2003-12-01

Malnutrition is prevalent in patients with end-stage renal disease (ESRD). Elevated serum leptin levels were thought to contribute to the anorexia and poor nutrition in renal failure. However, studies of the relationship between nutritional status and leptin concentration in chronic renal failure have yielded conflicting results. Plasma insulin-like growth factor I (IGF-I) level has been used as an indicator of nutritional status in patients with renal failure. The relationship between leptin and IGF-I is controversial. The present study was conducted with the aim of assessing the relationship between nutritional status, hyperleptinemia, and serum IGF-I. Seventeen ESRD patients (8 male, 9 female), aged 8-18 years (mean 15.3+/-3.3 years) and undergoing standard hemodialysis for 58.8+/-23.1 months were enrolled. Nine age-matched healthy children served as controls. In all patients, energy and protein intakes were 40-70 kcal/kg per day and 1-1.54 g/kg per day, respectively. Predialysis serum leptin and IGF-I levels were measured by radioimmunoassay. Body mass index was decreased in 13 (76%) patients. Triceps skinfold thickness (TST) was reduced (below the 5th percentile) in 7 (41%), whereas mid arm circumference and mid arm muscle circumference were reduced in 14 (82.5%) and 13 (76.5%), respectively. The median serum leptin level was significantly higher in patients than in controls [13.7 interquartile range (IQR) 30.50 pg/ml vs. 6.50 IQR 8.65 pg/ml, P=0.01]. The median serum IGF-I level was lower in the patients (205.1 ng/ml IQR 194.4 ng/l) than controls (418.0 ng/l IQR 310.5 ng/ml) ( P=0.01). IGF-I levels were more decreased in patients with severe malnutrition, defined according to TST (145.0 ng/ml IQR 125.5 ng/l) than patients without malnutrition (301.2 ng/l IQR 218.8 ng/ml) ( P=0.03) and healthy children ( P=0.002). Although statistically not significant, IGF-I levels tended to be decreased, while leptin levels were increased. The median plasma insulin

Role of leptin as a link between metabolism and the immune system.

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Pérez-Pérez, Antonio; Vilariño-García, Teresa; Fernández-Riejos, Patricia; Martín-González, Jenifer; Segura-Egea, Juan José; Sánchez-Margalet, Víctor

2017-06-01

Leptin is an adipocyte-derived hormone not only with an important role in the central control of energy metabolism, but also with many pleiotropic effects in different physiological systems. One of these peripheral functions of leptin is a regulatory role in the interplay between energy metabolism and the immune system, being a cornerstone of the new field of immunometabolism. Leptin receptor is expressed throughout the immune system and the regulatory effects of leptin include cells from both the innate and adaptive immune system. Leptin is one of the adipokines responsible for the inflammatory state found in obesity that predisposes not only to type 2 diabetes, metabolic syndrome and cardiovascular disease, but also to autoimmune and allergic diseases. Leptin is an important mediator of the immunosuppressive state in undernutrition status. Placenta is the second source of leptin and it may play a role in the immunomodulation during pregnancy. Finally, recent work has pointed to the participation of leptin and leptin receptor in the pathophysiology of inflammation in oral biology. Therefore, leptin and leptin receptor should be considered for investigation as a marker of inflammation and immune activation in the frontier of innate-adaptive system, and as possible targets for intervention in the immunometabolic mediated pathophysiology. Copyright © 2017 Elsevier Ltd. All rights reserved.

Leptin and its cardiovascular effects: Focus on angiogenesis

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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.

Leptin in humans: lessons from translational research1234

OpenAIRE

Blüher, Susann; Mantzoros, Christos S

2009-01-01

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 wi...

Growth restriction, leptin, and the programming of adult behavior in mice.

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Meyer, Lauritz R; Zhu, Vivian; Miller, Alise; Roghair, Robert D

2014-12-15

Prematurity and neonatal growth restriction (GR) are risk factors for autism and attention deficit hyperactivity disorder (ADHD). Leptin production is suppressed during periods of undernutrition, and we have shown that isolated neonatal leptin deficiency leads to adult hyperactivity while neonatal leptin supplementation normalizes the brain morphology of GR mice. We hypothesized that neonatal leptin would prevent the development of GR-associated behavioral abnormalities. From postnatal day 4-14, C57BL/6 mice were randomized to daily injections of saline or leptin (80ng/g), and GR was identified by a weanling weight below the tenth percentile. The behavioral phenotypes of GR and control mice were assessed beginning at 4 months. Within the tripartite chamber, GR mice had significantly impaired social interaction. Baseline escape times from the Barnes maze were faster for GR mice (65+/-6s vs 87+/-7s for controls, phormone leptin mitigates these effects. We speculate neonatal leptin deficiency may contribute to the adverse neurodevelopmental outcomes associated with postnatal growth restriction, and postnatal leptin therapy may be protective. Copyright © 2014 Elsevier B.V. All rights reserved.

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

Leptin differentially regulates chondrogenesis in mouse vertebral and tibial growth plates.

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Yu, Bo; Jiang, Kaibiao; Chen, Bin; Wang, Hantao; Li, Xinfeng; Liu, Zude

2017-05-31

Leptin plays an important role in mediating chondrogenesis of limb growth plate. Previous studies suggest that bone structures and development of spine and limb are different. The expression of Ob-Rb, the gene that encodes leptin receptors, is vertebral and appendicular region-specific, suggesting the regulation of leptin on VGP and TGP chondrogenesis may be very different. The aim of the present study was to investigate the differential regulation of leptin on the chondrogenesis of vertebral growth plate (VGP) and tibial growth plate (TGP). We compared the VGP and TGP from wild type (C57BL/6) and leptin-deficient (ob/ob) mice. We then generated primary cultures of TGP and VGP chondrocytes. By treating the primary cells with different concentrations of leptin in vitro, we analyzed proliferation and apoptosis of the primary chondrocytes from TGP and VGP. We further measured expression of chondrogenic-related genes in these cells that had been incubated with different doses of leptin. Leptin-deficient mice of 8-week-old had shorter tibial and longer vertebral lengths than the wide type mice. Disturbed columnar structure was observed for TGP but not for VGP. In primary chondrocyte cultures, leptin inhibited VGP chondrocyte proliferation but promoted their apoptosis. Collagen IIA and aggrecan mRNA, and the protein levels of proliferation- and chondrogenesis-related markers, including PCNA, Sox9, and Smad4, were downregulated by leptin in a dose-dependent manner. In contrast, leptin stimulated the proliferation and chondrogenic differentiation of TGP chondrocytes at physiological levels (i.e., 10 and 50 ng/mL) but not at high levels (i.e., 100 and 1000 ng/mL). Leptin exerts a stimulatory effect on the proliferation and chondrogenic differentiation of the long bone growth plate but an inhibitory effect on the spine growth plate. The ongoing study will shed light on the regulatory mechanisms of leptin in bone development and metabolism.

Prevalence of the metabolic syndrome, insulin resistance index, leptin and thyroid hormone levels in the general population of Merida (Venezuela).

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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.

Serum Leptin Concentrations during the Menstrual Cycle in Iranian Healthy Women

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Nahid Einollahi

2010-09-01

Full Text Available "nLeptin, a circulating 16-kd polypeptide consisting of 167 amino acids, appears to be involved in the body weight homeostasis. Moreover leptin plays an important role for the reproductive system, early embryogenesis, and fat metabolism during pregnancy and puberty. Significant correlations have been found between leptin and sexual hormones, which is a cytokine and has hormonal properties. The aim of this study was to determine serum leptin levels during the menstrual cycle, and the association between serum leptin and reproductive hormones in young, healthy Iranian women. 42 healthy women volunteered for the study. They all had regular menstrual cycles, with cycle length varying between 26 and 32 days. None of them used oral contraceptives. All were of normal weight, with body mass index ( BMI < 25 Kg/m2. Fasting blood samples were collected during the follicular phase, mid cycle and luteal phase of the menstrual cycle. FSH and LH were measured with coated tube immunoradiometric assay. Estrogen and progesterone were measured using antibody -coated tubes. Serum Leptin concentration were measured by Leptin (sandwich ELISA. In menstruating women, serum leptin increased from 13.15+/-1.60 ng/ml in the early follicular phase to 16.57+/-1.68 ng/ml (P<0.01 at the luteal phase. Serum leptin concentration negatively correlated with LH and progesterone (P<0.05. Mean serum leptin levels correlated with body mass index (BMI (r =0.78, P<0.001.

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.

Clinical characteristics of high plasma adiponectin and high plasma leptin as risk factors for arterial stiffness and related end-organ damage.

Science.gov (United States)

Kohara, Katsuhiko; Ochi, Masayuki; Okada, Yoko; Yamashita, Taiji; Ohara, Maya; Kato, Takeaki; Nagai, Tokihisa; Tabara, Yasuharu; Igase, Michiya; Miki, Tetsuro

2014-08-01

The relationship between plasma levels of adiponectin and cardiovascular events is inconclusive. We evaluated the clinical characteristics of people with high plasma adiponectin and high plasma leptin levels. Thousand seven hundred participants recruited from visitors to the Anti-Aging Doc were divided into four groups by combining the bipartiles of plasma adiponectin and leptin levels in men and women separately: AL, high adiponectin and high leptin; Al, high adiponectin and low leptin; al, low adiponectin and low leptin; aL, low adiponectin and high leptin. Body composition, including visceral fat area and thigh muscle cross-sectional area (CSA), brachial-ankle pulse wave velocity (baPWV), periventricular hyperintensity, and urinary albumin excretion, were determined. Twenty percent of the studied population fell within the AL group. This group had a significantly higher visceral fat area than the Al group. Thigh muscle CSA was lowest in the AL group among groups. baPWV, brain white matter lesions, and albuminuria findings in the AL group were significantly higher than those of the Al group. Multiple and logistic regression analyses with confounding parameters further confirmed that plasma adiponectin was not an independent determinant for brain and renal small vessel-related disease. These findings suggest that the plasma level of adiponectin alone is not enough for the risk stratification of cardiovascular disease. Leptin resistance associated with skeletal muscle loss in addition to obesity may need to be addressed to identify high risk people with high plasma adiponectin levels. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Leptin in milk and plasma of dairy asses

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F. Fantuz

2010-04-01

Full Text Available Milk and plasma leptin levels have been studied in dairy asses machine milked according to two different routines: 20 pregnant, pluriparous asses, were divided into two groups subjected, every 28 d for 150 d, to two consecutive milkings carried out at different intervals, i.e. 20 vs. 4 hours interval, respectively for group A and group B. During the study, the declining total milk obtained by machine milking was unaffected by the different milking strategies; body condition score of asses as well did not vary between the groups. Different milking intervals did not significantly influence skimmed milk leptin content neither plasma leptin level. Moreover, we did not find significant variation in plasma leptin neither correlation with BCS, indicating that in donkey pregnancy inhibits the cross talk between hypothalamus and adipose tissue.

MOLECULAR CLONING OF OVINE cDNA LEPTIN GENE

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CLAUDIA TEREZIA SOCOL

2008-05-01

Full Text Available An efficient bacterial transformation system suitable for cloning the coding sequence of the ovine leptin gene in E. coli DH5α host cells using the pGEMT easy vector it is described in this paper. The necessity of producing leptin is based on the fact that the role of this molecule in the animal and human organism is still unknown, leptin not existing as commercial product on the Romanian market. The results obtained in the bacterial transformation, cloning, recombinant clones selection, control of the insertion experiments and DNA computational analysis represent the first steps in further genetic engineering experiments such as production of DNA libraries, DNA sequencing, protein expression, etc., for a further contribution in elucidating the role of leptin in the animal and human organism.

Study on the relationship between serum levels of leptin thyroid hormones

International Nuclear Information System (INIS)

Lin Pingan; Zhai Chuntao; Yuan Sufen

2005-01-01

Objective: To evaluate the relationship between serum levels of leptin and thyroid functional status. Methods: Serum leptin (with RIA) and pituitary-thyroid axis hormones (with CLIA) were measured in 75 euthyroid controls, 44 hyperthyroid subjects and 27 hypothyroid subjects. Results: The levels of leptin in euthyroid controls, hyperthyroid subjects and hypothyroid subjects were (5.40 ± 3.78) ng/ml, (5.99 ± 5.24) ng/ml and (5.59 ± 4.23) ng/ml respectively with no significant differences among them. The serum leptin levels were positively correlated with serum TSH levels (r=0.27, P<0.01). Conclusion: Thyroid function has no effect on serum leptin levels and TSH levels correlates closely with those of serum leptin. (authors)

Leptin regulates dopamine responses to sustained stress in humans.

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Burghardt, Paul R; Love, Tiffany M; Stohler, Christian S; Hodgkinson, Colin; Shen, Pei-Hong; Enoch, Mary-Anne; Goldman, David; Zubieta, Jon-Kar

2012-10-31

Neural systems that identify and respond to salient stimuli are critical for survival in a complex and changing environment. In addition, interindividual differences, including genetic variation and hormonal and metabolic status likely influence the behavioral strategies and neuronal responses to environmental challenges. Here, we examined the relationship between leptin allelic variation and plasma leptin levels with DAD2/3R availability in vivo as measured with [(11)C]raclopride PET at baseline and during a standardized pain stress challenge. Allelic variation in the leptin gene was associated with varying levels of dopamine release in response to the pain stressor, but not with baseline D2/3 receptor availability. Circulating leptin was also positively associated with stress-induced dopamine release. These results show that leptin serves as a regulator of neuronal function in humans and provides an etiological mechanism for differences in dopamine neurotransmission in response to salient stimuli as related to metabolic function. The capacity for leptin to influence stress-induced dopaminergic function is of importance for pathological states where dopamine is thought to play an integral role, such as mood, substance-use disorders, eating disorders, and obesity.

Cross-talk between estrogen and leptin signaling in the hypothalamus.

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Gao, Qian; Horvath, Tamas L