Search

The association between hypertension and obesity-induced cardiac damage is usually accepted. However, no studies have been focused on cardiac alterations in obesity, independently of blood pressure increase. It is well known that Cardiac TRH induces Left Ventricular Hypertrophy (LVH) and fibrosis, and its inhibition prevents the development of hypertrophy. Also, it has been described that the adiponectin leptin induces TRH expression. Thus, we hypothesized that in obesity, the increase in TRH induced by hyperleptinemia is responsible for LVH, until now mostly attributed to pressure load. We studied obese Agouti mice suffering from hypertension with hyperleptinemia and found a significant LVH development with increased TRH gene expression. Consequently, we found higher fibrotic (collagens and TGF-β) and hypertrophic markers (BNP and β-MHC) expression vs lean black controls. As pressure could explain these results, we treated obese mice with diuretic (hydrochlorothiazide 20 mg/kg/day) since weaning. Diuretic treatment was successful as the diuretic group was normotensive in contrast to control obese mice. Nevertheless, both groups showed LVH development, higher cardiac precursor TRH gene and peptide expressions and elevated fibrotic and hypertrophic markers expression, pointing out that obesity-induced LVH is not due to hypertension. In addition, we performed Cardiac TRH inhibition by specific siRNA injection compared to control siRNA treatment and evaluated cardiac damage. As expected, expressions and protein increase in hypertrophic and fibrotic markers observed in the AG mouse with the native cTRH system were not seen in the AG mouse with the cTRH silencing. Indeed, the AG + TRH-siRNA group showed hypertrophic markers expression and fibrosis measurements similar to the lean BL mice. On the whole, these results point out that the novel Leptin-Cardiac TRH pathway is responsible for the cardiac alterations present in hyperleptinemic obesity, independent of blood pressure, and cTRH long-term silencing since early stages totally prevent LVH development and cardiac fibrosis. [ABSTRACT FROM AUTHOR]

At the time of breast cancer diagnosis, most patients meet the diagnostic criteria to be classified as obese or overweight. This can significantly impact patient outcome: breast cancer patients with obesity (body mass index > 30) have a poorer prognosis compared to patients with a lean BMI. Obesity is associated with hyperleptinemia, and leptin is a well-established driver of metastasis in breast cancer. However, the effect of hyperleptinemia on angiogenesis in breast cancer is less well-known. Angiogenesis is an important process in breast cancer because it is essential for tumor growth beyond 1mm³ in size as well as cancer cell circulation and metastasis. This review investigates the role of leptin in regulating angiogenesis, specifically within the context of breast cancer and the associated tumor microenvironment in obese patients. [ABSTRACT FROM AUTHOR]

Glucose‐dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone secreted by K cells in the small intestine and is considered an obesity‐promoting factor. In this study, we systematically investigated the anti‐obesity effects of intragastric safflower yellow (SY)/hydroxysafflor yellow A (HSYA) and the underlying mechanism for the first time. Our results showed that intragastric SY/HSYA, rather than an intraperitoneal injection, notably decreased serum GIP levels and GIP staining in the small intestine in diet‐induced obese (DIO) mice. Moreover, intragastric SY/HSYA was also first found to significantly suppress GIP receptor (GIPR) signaling in both the hypothalamus and subcutaneous White adipose tissue. Our study is the first to show that intragastric SY/HSYA obviously reduced food intake and body weight gain in leptin sensitivity experiments and decreased serum leptin levels in DIO mice. Further experiments demonstrated that SY treatment also significantly reduced leptin levels, whereas the inhibitory effect of SY on leptin levels was reversed by activating GIPR in 3 T3‐L1 adipocytes. In addition, intragastric SY/HSYA had already significantly reduced serum GIP levels and GIPR expression before the serum leptin levels were notably changed in high‐fat‐diet‐fed mice. These findings suggested that intragastric SY/HSYA may alleviate diet‐induced obesity in mice by ameliorating hyperleptinemia via dual inhibition of the GIP‐GIPR axis. [ABSTRACT FROM AUTHOR]

The objective of the study was to identify different phenotypes of overweight in women with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) based on body mass index (BMI) and serum leptin levels, as well as to determine the frequencies of various metabolic disorders, hypertension, and cardiovascular complications (CVCs) in individual phenotypes. The study included 50 women with RA and 46 with SLE aged 18 to 65 years without a history of diabetes and fasting hyperglycemia. In all patients, the concentration of leptin was determined by ELISA, the concentration of insulin was determined by electrochemiluminescence analysis, and the HOMA-IR index was calculated. Hyperleptinemia was diagnosed at leptin concentrations > 11.1 ng/mL; insulin resistance (IR), at HOMA-IR values ≥ 2.77. Three main phenotypes of overweight were distinguished: "classic" (BMI ≥ 25 kg/m2 + hyperleptinemia), "healthy" (BMI ≥ 25 kg/m2, without hyperleptinemia), "hidden" or "latent" (BMI < 25 kg/m2 + hyperleptinemia), as well as "normal weight" (BMI < 25 kg/m2, without hyperleptinemia). Patients with RA and SLE were similar in age (p = 0.4), disease duration (p = 0.2) and BMI (p = 0.5). Hyperleptinemia was found in 46% of women with RA and in 74% of women with SLE (p = 0.005), and IR was found in 10 and 22% of patients, respectively (p = 0.2). The "classic" phenotype of overweight was diagnosed in 30%, "healthy" in 8%, and "hidden" in 16% of cases with RA and in 44%, 0%, and 30% of cases with SLE, respectively. IR was found in 3% and hypertension in 6% of patients with "normal weight." With the "classic" phenotype, IR (29%) and hypertension (66%) were more common than with "normal weight" (p < 0.01 in all cases); with the "hidden" phenotype, significant differences were obtained only in hypertension frequency (45%; p = 0.0012), but not IR (18%). Three out of four women with a history of cardiovascular complications suffered from "classic" overweight, and one patient had a "normal weight." In women with SLE up to 65 years of age, the frequency of hyperleptinemia, but not IR, is higher than in patients with RA. In both diseases, the "classic" overweight phenotype is most common. In RA, a "hidden" phenotype was detected less often than in SLE, at the same time, a "healthy" phenotype is not characteristic of SLE. The frequency of metabolic disorders and hypertension is low with the "normal weight" and "healthy" phenotype, high with the "classic" phenotype, and intermediate with the "hidden" phenotype. [ABSTRACT FROM AUTHOR]

At the time of breast cancer diagnosis, most patients meet the diagnostic criteria to be classified as obese or overweight. This can significantly impact patient outcome: breast cancer patients with obesity (body mass index > 30) have a poorer prognosis compared to patients with a lean BMI. Obesity is associated with hyperleptinemia, and leptin is a well-established driver of metastasis in breast cancer. However, the effect of hyperleptinemia on angiogenesis in breast cancer is less well-known. Angiogenesis is an important process in breast cancer because it is essential for tumor growth beyond 1mm3 in size as well as cancer cell circulation and metastasis. This review investigates the role of leptin in regulating angiogenesis, specifically within the context of breast cancer and the associated tumor microenvironment in obese patients.

The so-called cafeteria diet (CD), rich in saturated fats and light fast-digesting carbohydrates, leads to obesity and is a risk factor for type 2 diabetes. Metformin (MF) is often used to correct diet-induced obesity, but in some patients, it elicits serious side effects, which requires dose reduction, including through its co-application with drugs potentiating MF effects. Intranasally administered insulin (INI), which per se has a restorative potential in the treatment of metabolic disorders, is a candidate for the role of such a drug. This work was aimed to study the efficacy of a 3-week combined course of MF (100 mg/kg/day, perorally) and INI (1.5 or 6.0 IU/kg/day) to correct metabolic and hormonal disorders in male rats with CD-induced obesity (CDIO). It was shown that in CDIO rats, the MF + INI combination normalized body weight and abdominal fat, as well as restored glucose homeostasis, lipid metabolism, basal and glucose-stimulated insulin and leptin levels. Compared to MF monotherapy, a combined course of MF + INI application more effectively restored insulin sensitivity, as assessed by a decrease in the insulin resistance index, and normalized glucose tolerance, as assessed by a decrease in AUC0–120, the integrated area under glucose concentration curves in the glucose tolerance test. The combination of MF with INI at a dose of 1.5 IU/kg/day normalized thyroidal status, disturbed in CDIO, while the combination of MF with INI at a dose of 6 IU/kg/day exacerbated the hypothyroid state, mainly due to hyperactivation of thyroid-stimulating hormone secretion and the development of thyroid resistance to this hormone. Thus, a combined course of MF with relatively low-dose INI, which has no negative effects on the thyroid axis, appears promising for correcting metabolic and hormonal indices in CDIO, including functional restoration of the thyroid system. [ABSTRACT FROM AUTHOR]

Background: Endoplasmic reticulum (ER) stress implicated in leptin resistance in the diet-induced obesity, which can accelerate the development of atherosclerosis forms the background of this study. Objective: This study aimed to investigate the effect of capsaicin on hyperleptinema by inhibiting ER stress in apolipoprotein E-deficient (ApoE-/-) mice fed a western diet (WD). Design: ApoE -/- mice were assigned one of three experimental diets: WD (60% kcal from fat, n = 10), WD + 0.015% capsaicin (n = 10, w/w), and WD + 1% PBA (n = 10, w/w) for 12 weeks. Results: In metabolic parameters, supplementation of dietary capsaicin displayed marked reduction of body weight gain and adipose tissue weight, plasma leptin, total cholesterol, and hepatic triglyceride levels without change in the plasma insulin level compared with WD fed ApoE-/- mice after 12 weeks. Capsaicin supplementation also attenuated the protein expression of ER stress markers such as eukaryotic translational initiation factor 2α and C/EBP homology protein in the liver, as well as glucose-related protein 78 localization in the aorta, indicating that capsaicin inhibits diet-induced hyperleptinemia in part by regulating the protein expression involved in ER stress. Conclusion: Capsaicin, therefore, may have potential as a therapeutic agent for individuals with diet-induced hyperleptinemia.

Purpose: Gestational diabetes mellitus (GDM) is a state of leptin resistance which develops a vicious cycle of hyperinsulinemia and hyperleptinemia leading to aggravation of an inflammatory situation. This study was done to find out the association between IL-6, leptin and insulin in gestational diabetes among North Indian women. Method: This cross-sectional study included 100 GDM, 100 non-GDM and 50 non-pregnant women. DIPSI (Diabetes in Pregnancy Study Group India) criteria was used for screening GDM among pregnant women. GDM and non-GDM pregnant women were further categorized into three groups according to the trimester of pregnancy. Serum IL-6, leptin and insulin were measured in all the enrolled women. Results: Serum IL-6 levels were significantly higher among GDM women as compared to non-GDM and non-pregnant women. Although the mean serum leptin and insulin levels were higher in GDM, but the difference was not statistically significant. When GDM and non-GDM women were categorized into three trimester, serum leptin levels were found to be significantly higher in 3rd trimester (p < 0.002) and IL-6 in 1st trimester (p < 0.017) among GDM women. No correlation was found between serum IL-6, leptin and insulin in GDM. Conclusion: Absence of any significant association between leptin and IL-6 signifies that leptin may not be associated with inflammation in gestational diabetes. However, IL-6 may serve as an early marker for screening glucose intolerance during pregnancy. [ABSTRACT FROM AUTHOR]

Objective – to identify different phenotypes of overweight in women with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) based on body mass index (BMI) and serum leptin levels, as well as to determine the frequencies of various metabolic disorders, hypertension and cardiovascular complications in individual phenotypes. Material and methods. The study included 50 women with RA and 46 with SLE aged 18 to 65 years without a history of diabetes and fasting hyperglycemia. The concentration of leptin (ELISA), insulin (electrochemiluminescence analysis) was determined in all patients, and the HOMA-IR index was calculated. Hyperleptinemia was diagnosed at leptin concentrations >11,1 ng/ml, insulin resistance (IR) – at HOMA-IR values ≥2,77. Three main phenotypes of overweight were distinguished: “classic” (BMI≥25 kg/m2 + hyperleptinemia), “healthy” (BMI≥25 kg/m2 , without hyperleptinemia), “hidden” or “latent” (BMI

Objective – to identify obesity/overweight phenotypes in patients with systemic lupus erythematosus (SLE) based on the body mass index (BMI) and serum leptin levels assessment, and to clarify the relationship of these phenotypes with different metabolic disorders.Material and methods. The study included 51 patients with SLE (48 women, 3 men) without diabetes mellitus. The median age of patients was 40 [31; 48] years, disease duration was 3.0 [0.6; 9.0] years. Glucocorticoids were received by 84% of patients, hydroxychloroquine – by 76%, immunosuppressants – by 20%, biological agents – by 10%. BMI was calculated and the fasting leptin level in serum was determined (ELISA) in all patients. Leptin concentrations >11.1 ng/ml in women and >5.6 ng/ml in men corresponded to hyperleptinaemia. There were three main obesity/overweight phenotypes: “classic” (BMI≥25 kg/m2 + hyperleptinemia), “healthy” (BMI≥25 kg/m2 , without hyperleptinemia), “hidden” or “latent” (BMI˂ 25 kg/m2 + hyperleptinemia), as well as “normal weight” (BMI˂ 25 kg/m2 , without hyperleptinemia).Results. The “classic” phenotype of obesity/overweight was diagnosed in 22 (43%) patients, the “healthy” – in 1 (2%), the “hidden” – in 14 (27.5%) patients with SLE. Insulin concentrations were: 10.0 [7.5; 17.9] μU/mL in the “classic” phenotype, 8.3 [6.0; 11.9] μU/mL in the “hidden” phenotype, and 5.3 [4.2; 6.3] μU/ml at “normal weight” (p=0.001). HOMA-IR index were: 2.18 [1.70; 4.23], 1.78 [1.23; 2.41] and 1.18 [0.95; 1.52], respectively (p=0.002). The levels of glucose, total cholesterol, ApoB did not differ in the groups. The uric acid concentrations were the highest in the “classic” phenotype group (334 [365; 388] μmol/l), the lowest in the group of “hidden” obesity/overweight (257 [214; 296] μmol/l), and intermediate in “normal weight” group (286 [236; 377] μmol/l) (p=0.04).Conclusion. The majority of SLE patients hade the “classic” obesity/overweight phenotype, while the “healthy” phenotype was extremely rare. In 27.5% of patients, the presence of a “latent” phenotype was confirmed, which, in terms of metabolic disorders, is an intermediate stage between “normal weight” and “classic” obesity. For rational and timely prevention of insulin resistance, metabolic syndrome and related complications, it is necessary to actively identify the “hidden” phenotype.

Elevated plasma leptin levels, or hyperleptinemia, have been demonstrated to correlate with metabolic syndrome markers, including obesity, and may be an independent risk factor for the development of cardiovascular disease. In this paper, we use cardiac models to study possible effects of hyperleptinemia on the electrophysiological properties of cardiomyocytes and cardiac arrhythmias. We modified the parameters of an improved Gattoni 2016 model of rat ventricular cardiomyocytes to simulate experimental data for the leptin effects on ionic currents. We used four model variants to investigate the effects of leptin-induced parameter modification at the cellular level and in 2D tissue. In all models, leptin was found to increase the duration of the action potential. In some cases, we observed a dramatic change in the shape of the action potential from triangular, characteristic of rat cardiomyocytes, to a spike-and-dome, indicating predisposition to arrhythmias. In all 2D tissue models, leptin increased the period of cardiac arrhythmia caused by a spiral wave and enhanced dynamic instability, manifesting as increased meandering, onset of hypermeandering, and even spiral wave breakup. The leptin-modified cellular models developed can be used in subsequent research in rat heart anatomy models. [ABSTRACT FROM AUTHOR]

Background: Early pregnancy loss occurs in both natural and in-vitro fertilization mediated pregnancies. Clinical miscarriages occur in 8% of pregnancies. Most clinically apparent miscarriages occur during the first trimester and aetiology is often unknown. Aim: To determine and compare the level of serum leptin in cases of unexplained early pregnancy loss and previous normal pregnancies and to observe the association between level of serum leptin and pregnancy outcome. Methodology: This case control study was carried out on total of 77 pregnant women in first trimester attending outpatient department and indoor cases in Swaroop Rani Nehru hospital and Kamla Nehru Memorial hospital, Prayagraj over a period of twelve months from September 2018 to August 2019. Patients were divided in two groups: Group I (n=52) included women with history of previous abortion and group II (n=25) included women with history of no previous abortions. Serum level of leptin hormone was measured using enzyme linked immunosorbent assay (ELISA) technique. Result: In this study the mean serum leptin level was 19.554±7.50 ng/ml in 1st sample at 5-8 week and 27.33± 9.705 ng/ml in 2nd sample at 9-12 week in cases with history of previous early pregnancy loss which was higher as compared to control (12.75±2.147 ng/ml and 17.62±6.53 ng/ml respectively) which was statically significant (p

Early weaning (EW) leads to metabolic disorders in adulthood, being one of the causes of metabolic syndrome (MS). However, the range of hormonal disorders in EW has not been studied well enough, and approaches to its correction have not been developed. The aim of this work was to study metabolic and hormonal changes, including in the hormonal status of the gonadal and thyroid axes, in adult (10-month-old) male rats that were weaned in the early postnatal period, as well as to explore the restorative effect of 4-week treatment with different doses of metformin (MF), moderate (120 mg/kg/day) and relatively high (250 mg/kg/day), on these changes. Lactation in nursing female rats was interrupted with bromocriptine (10 mg/kg/day) on days 19–21 of lactation. After forced starvation during this period, rat pups were transitioned to a standard diet. At the age of 10 months, early weaned male rats showed characteristic signs of MS, such as obesity, impaired glucose tolerance, insulin resistance, hyperleptinemia and dyslipidemia. They also had reduced levels of testosterone, luteinizing hormone (LH), and thyroid hormones, and elevated levels of the thyroid-stimulating hormone (TSH). A 4-week treatment of adult rats with MF at a moderate dose reduced body and fat weight, partially restored metabolic parameters, and completely normalized testosterone, LH, thyroxine, triiodothyronine and TSH levels. The treatment with MF at a relatively high dose restored metabolic parameters more effectively, normalized leptin and insulin levels, but had a little effect on hormonal levels of the gonadal and thyroid axes. Thus, long-term treatment of early weaned male rats with a moderate dose of MF improves metabolic parameters and completely restores the hormonal status of the gonadal and thyroid axes, which indicates the promise of using such doses for the correction of MS and endocrine dysfunctions caused by interrupted or ineffective breastfeeding. [ABSTRACT FROM AUTHOR]

Introduction: Leptin resistance is believed to cause insulin resistance though the exact mechanism is not fully understood. The present study aims to investigate the temporal profile of postprandial triglyceride (PPTG) and leptin levels, and their association with each other as well as with markers of metabolic syndrome. Materials and Methods: Serum leptin and PPTG levels were measured longitudinally till 26 weeks in Wistar rats fed on controlled diet (group 1) and high sucrose diet (HSD) (group 2). Two additional groups fed on HSD were taken and treated with pioglitazone (group 3) and atorvastatin (group 4). Body weight, homeostasis model assessment of insulin resistance (HOMA-IR), and glucose intolerance were also measured during this period. Comparison of the groups were done and Pearson's correlation coefficient was used to ascertain the association. Results: Leptin levels were significantly higher in all three groups receiving HSD compared to controlled diet group from week 2 to week 26 (P < 0.01). The postprandial triglyceride area under the curve (PPTG AUCs) were significantly higher in group 2 than controls during this period (P < 0.001). Body weight, HOMA-IR and glucose AUC were found to be significantly higher in group 2 rats than controls only from week 6, 8, and 12 respectively. In HSD-fed rats, but not in control, mean serum leptin levels from 2-26 weeks as well as peak (10th week) and 26th week were strongly associated with corresponding as well as preceding PPTG levels. Leptin levels significantly predicted HOMA-IR and prediabetes in group 2. Conclusion: This study found significant hyperleptinemia associated with postprandial hypertriglyceridemia that predicted insulin resistance and prediabetes in high sucrose diet–fed rats. [ABSTRACT FROM AUTHOR]

Leptin is the satiety hormone, synthesized in the adipose tissue that reduces food intake, being involved in glucose and lipid metabolism. Hyperleptinemia correlates with obesity and represents a risk factor in the pathology of the cardiovascular system. Increased concentrations of leptin have been observed in patients with hypertension or atherosclerosis. In vitro studies suggest the angiogenic role of leptin. The purpose of this review is to present the metabolic effects of hyperleptinemia in the cardiovascular system.

Obese patients, often accompanied by hyperleptinemia, are prone to develop liver fibrosis. A large body of data including the results from human studies suggested the promotion role of leptin, an adipocyte‐derived hormone, in liver fibrosis. Hepatic stellate cell (HSC) activation, a crucial step in liver fibrogenesis, requires global reprogramming of gene expression which is regulated by multiple mechanisms including epigenetic regulation such as methylation of DNA. S‐Adenosylmethionine is a principal biological methyl donor and its biosynthesis is catalyzed by a methionine adenosyltransferase (MAT) such as MATII. MATII consists of the catalytic subunit MAT2A and regulatory subunit MAT2B which are essential for HSC activation. The present research investigated the effect of leptin on the expression of Mat2b in HSCs in vitro and in a leptin‐deficient mouse model. Results demonstrated that leptin significantly increased Mat2b expression. Leptin‐induced Mat2b expression required the PI3K/AKT signaling pathway. c‐Jun, a component of activator protein (AP1), was phosphorylated by leptin‐induced PI3K/AKT signaling and thus potentiated its binding to the element around −964 bp in the Mat2b promoter. MAT2B was involved in leptin‐induced HSC activation and liver fibrosis in a leptin‐deficient mouse model. These results might broaden understanding of the mechanisms underlying the liver fibrogenesis in obese patients with hyperleptinemia. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Most obese patients develop hyperleptinaemia. Leptin, mainly produced by adipocytes, demonstrates a promotional role in liver fibrosis. Hepatic stellate cell (HSC) activation, a key step in liver fibrogenesis, requires global reprogramming of gene expression. The remodeling of DNA methylation is a mechanism of the epigenetic regulation of gene expression. The biosynthesis of S‐adenosylmethionine, a principle biological methyl donor, is catalyzed by methionine adenosyltransferase (MAT) such as MATⅡ which has been shown to promote HSC activation in vitro. This study was mainly aimed to determine the effect of leptin on MAT2A expression (the catalytic subunit of MATⅡ) in HSCs. Results showed that MAT2A knockdown reduced leptin‐induced HSC activation and liver fibrosis in the leptin‐deficient mouse model. Leptin promoted MAT2A expression in HSCs and increased MAT2A promoter activity. The axis of the β‐catenin pathway/E2F‐4 mediated the effect of leptin on MAT2A expression. Leptin‐induced β‐catenin signaling reduced E2F‐4 expression and thus abated E2F‐4 binding to MAT2A promoter at a site around −2779 bp, leading to an increase in the MAT2A promoter activity. These data might shed more light on the mechanisms responsible for liver fibrogenesis in obese patients with hyperleptinaemia. [ABSTRACT FROM AUTHOR]

Francis Agyemang Yeboah,1 Robert Amadu Ngala,1 Ahmed Tijani Bawah,2 Henry Asare-Anane,3 Huseini Alidu,2 Abdul-Wahab Mawuko Hamid,2 Joshua Dokurugu Kwame Wumbee4 1Department of Molecular Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, 2Department of Medical Laboratory Science, University of Health and Allied Sciences, Ho, 3Department of Chemical Pathology, School of Biomedical and Allied Health Sciences, University of Ghana, Accra, 4Internal Quality Control Unit, Quality Control Directorate, Kumasi Technical University, Kumasi, Ghana Background: Leptin levels start increasing from the early stages of pregnancy, irrespective of the maternal body mass index. Leptin levels are increased in pregnant women with preeclampsia (PE) and may precede the clinical onset of the disease, with peaks occurring around 28 weeks of gestation. This study was aimed at determining whether serum leptin concentration and body fat percentage are significantly altered during the first trimester in pregnancies that subsequently develop PE and whether such changes are useful in predicting the disease.Materials and methods: This was a prospective longitudinal study conducted among pregnant women in Ho municipality. A cohort of 314 pregnant women was monitored from the first antenatal visit to delivery period at the Volta Regional Hospital, Ho, Ghana. Maternal serum leptin and lipid profile were analyzed and body fat percentage determined during first trimester. Body mass index was also calculated.Results: First trimester serum leptin level (P

Obesity is a public health burden disturbing all body functions and reproductive hormones. As obesity increases among females, there will be a rising challenge to physicians in care from fertility problems. Evening primrose oil (EPR oil) contains essential fatty acids including omega-6 linoleic acid with strong anti-inflammatory activity. Since EPR oil has utility in alleviating dysmenorrhea, this study aimed to ascertain its modulatory effect on systemic inflammation, reproductive hormones and estrus cycle irregularity in female obese rats. Thirty-two female rats were distributed to 4 groups: (i) normal, (ii) dietary obese-control female rats, and (iii and iv) dietary obese female rats treated with EPR oil (5 or 10 g/kg). Rats were examined for estrus regularity by taking vaginal smears daily during the last 2 weeks of the experiment. Serum level of insulin, leptin, adiponectin, and inflammatory cytokines was measured. In addition, serum lipid profile, and liver enzyme activities were estimated. Adipose tissues were taken for histopathologic examination as well as determination of gene expression for leptin, leptin receptors, adiponectin, and visfatin. Obese rats exhibited significant weight gain (90.69 ± 8.9), irregular prolonged estrus cycles (83.33%), increased serum levels of insulin, leptin, prolactin and testosterone and decreased gonadotropin levels. EPR oil exhibited a curative effect on obesity-related irregularity in estrus cycle and ovarian pathology. The underlying molecular mechanism may be related to reduction of systemic inflammation, alleviating insulin resistance and modulation of adipokine expression. EPR oil may be considered as a promising therapeutic intervention against obesity-related female hormonal disturbances and estrus irregularity.

Obesity is a public health burden disturbing all body functions and reproductive hormones. As obesity increases among females, there will be a rising challenge to physicians in care from fertility problems. Evening primrose oil (EPR oil) contains essential fatty acids including omega-6 linoleic acid with strong anti-inflammatory activity. Since EPR oil has utility in alleviating dysmenorrhea, this study aimed to ascertain its modulatory effect on systemic inflammation, reproductive hormones and estrus cycle irregularity in female obese rats. Thirty-two female rats were distributed to 4 groups: (i) normal, (ii) dietary obese-control female rats, and (iii and iv) dietary obese female rats treated with EPR oil (5 or 10 g/kg). Rats were examined for estrus regularity by taking vaginal smears daily during the last 2 weeks of the experiment. Serum level of insulin, leptin, adiponectin, and inflammatory cytokines was measured. In addition, serum lipid profile, and liver enzyme activities were estimated. Adipose tissues were taken for histopathologic examination as well as determination of gene expression for leptin, leptin receptors, adiponectin, and visfatin. Obese rats exhibited significant weight gain (90.69 ± 8.9), irregular prolonged estrus cycles (83.33%), increased serum levels of insulin, leptin, prolactin and testosterone and decreased gonadotropin levels. EPR oil exhibited a curative effect on obesity-related irregularity in estrus cycle and ovarian pathology. The underlying molecular mechanism may be related to reduction of systemic inflammation, alleviating insulin resistance and modulation of adipokine expression. EPR oil may be considered as a promising therapeutic intervention against obesity-related female hormonal disturbances and estrus irregularity. [ABSTRACT FROM AUTHOR]

The C57BL/6J-Daruma mouse is an animal model of obesity derived from the original genetically obese ICR-Daruma mouse by transfer of the phenotype into the C57BL/6J background by backcrossing into the C57BL/6J strain. Although, like the original ICR-Daruma mouse model, both male and female C57BL/6J-Daruma mice develop obesity, the latter strain shows sex differences in several phenotypes. A sex difference in plasma insulin levels was especially notable in C57BL/6J-Daruma mice; only males showed hyperinsulinemia. Orchiectomy suppressed this hyperinsulinemia completely, whereas testosterone supplementation restored it. Glucose administration increased the plasma glucose level in both male and female Daruma mice to a greater extent than in wild-type control mice. Orchiectomy, but not ovariectomy, decreased the plasma glucose level to that seen in wild-type controls. On the other hand, this effect of orchiectomy was abrogated by testosterone supplementation. The expression of mRNAs for several genes related to insulin resistance was significantly changed in white adipose tissue and liver of C57BL/6J-Daruma mice, especially males, as early as 4 weeks of age. The present results suggest that testosterone may be involved in the hyperinsulinemia shown by male C57BL/6J-Daruma mice and that this strain may be an appropriate animal model for examining the relationship between obesity and sex hormones. [ABSTRACT FROM AUTHOR]

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.

Background: Major risk factors of hypertension (HTN) including obesity, insulin resistance, renal pathology, increased sympathetic nerve activity (SNA) and vascular inflammation are associated with hyperleptinemia. Therefore hyperleptinemia may act as a mediator of blood pressure, linking body fat mass with changes in insulin action, sympathetic neuronal outflow and renal pathology. Objective: The objective of our study was to explore the relationship between hyperleptinemia and HTN in Pakistani population. Materials and Methods: It was a case control study of 6 months duration, carried out at Shifa College of Medicine and Shifa International Hospital, Islamabad. One hundred and four male subjects, 52 with HTN and 52 without HTN were included in this study. Leptin levels were measured by enzyme-linked immunosorbent assay (ELISA) technique. The relationship of leptin (LEP), body mass index (BMI), fasting blood sugar (FBS) and cholesterol levels with blood pressure were assessed. Results: Patients with HTN versus patients without HTN had a higher body mass index (28.0 ± 0.12 to 24.11 ± 0.27 kg/m 2 ), FBS (169.20 ± 7.34 to 127.50 ± 2.30 mg/dl), total cholesterol (160 ± 3.72 to 158 ± 2.71 mg/dl) and LEP (53.40 ± 5.32 to 21.65±3.50 ng/ml) levels. In univariate analysis, obesity, hyperglycemia and hyperleptinemia (with P values of 0.000, 0.001, 0.000, respectively), whereas in multivariate analysis, hyperglycemia and hyperleptinemia (with P values of 0.006 and 0.001, respectively) were risk factors for HTN. Our study also showed that hyperleptinemia is an independent risk factor for HTN. Conclusions: We observed a strong positive relationship between hyperleptinemia and hypertension, thereby indicating that increased leptin levels could be considered as a risk factor for HTN and cardiovascular disease. Further studies are needed to probe the underlying pathophysiological mechanisms responsible for hyperleptinemia in HTN.

In the present study, we examined whether metallothionein-3 (Mt3), a zinc-binding protein that is specifically enriched in a brain, plays a role in obesity and hypothalamic leptin signaling in mice. Upon aging, male Mt3-null mice gained more body weight than male wild-type mice; however, the daily amount of food intake was little different. Rather, the obesity in male Mt3-null mice was likely the result of decreased metabolic rates, as indicated by lower oxygen consumption and carbon dioxide production. Consistent with this, mRNA levels for the mitochondrial proton carrier UCP1 were reduced in brown adipose tissue of Mt3-null mice. Although Mt3-null mice showed increases in serum leptin levels, probably due to increased fat mass, the level of the leptin receptor (Lepr) in the hypothalamus of these mice was significantly reduced. In addition, levels of phosphorylated extracellular signal-regulated kinase (p-Erk-1/2) were also reduced in the hypothalamus of Mt3-null mice. Because zinc released from Mt3 may activate Erk-1/2, we examined whether zinc is involved in the upregulation of Lepr levels through the activation of Erk-1/2. Consistent with this possibility, exposure of hypothalamic cells to zinc activated Erk-1/2 and induced Lepr expression in an Erk-dependent manner. The present results demonstrate that Mt3 in the brain of male mice, particularly in the hypothalamus, may be involved in central leptin signaling and the consequent increase in peripheral energy expenditure. In addition to providing insight into the role of zinc and metallothioneins in the development of obesity, this new information may help design ways to overcome the pervasive problem of obesity.

Background: The multiligand receptor megalin controls the brain uptake of a number of ligands, including insulin and leptin. Despite the role of megalin in the transport of these metabolically relevant hormones, the role of megalin at the blood-brain-barrier (BBB) has not yet been explored in the context of metabolic regulation.Methods: Here we investigate the role of brain endothelial megalin in energy metabolism and leptin signaling using an endothelial cell-specific megalin deficient (EMD) mouse model.Results: We found megalin is important to protect mice from developing obesity and metabolic syndrome when mice are fed a normal chow diet. EMD mice developed neuroinflammation, by triggering several pro-inflammatory cytokines, displayed reduced neurogenesis and mitochondrial deregulation.Conclusions: These results implicate brain endothelial megalin expression in obesity-related metabolic changes through the leptin signaling pathway proposing a potential link between obesity and neurodegeneration. [ABSTRACT FROM AUTHOR]

Adipokines contribute to the inflammatory process which can lead to obesity-associated cardiometabolic complications. Metabolically healthy obese individuals seem to be protected or more resistant to develop these complications and it is intriguing why some individuals develop comorbidities and others do not. Thus, we questioned whether the differences between metabolically healthy and unhealthy obese relied on the alterations in metabolic profile, characterized by serum leptin and adiponectin. A total of 142 obese adults were divided into 2 groups - metabolically healthy obese (MHO) or unhealthy obese (MUO) - and they were evaluated for anthropometric measures, body composition, blood pressure, dietary intakes and plasma levels of leptin and adiponectin. Leptin/adiponectin ratio (L/A) was calculated. Age, BMI and blood pressure were higher in the MUO. No differences in anthropometric measurements, body composition, dietary intake and dietary quality were observed between groups. Leptin were significantly higher in the MUO (53.07 ± 34.56 versus 36.27 ± 24.02 ng/ml in the MHO, r < 0.04). The logistic regression analysis demonstrated that leptin was an important factor associated with not being healthy, independent of age, body weight and BMI. There were no differences between groups for adiponectin and L/A. Leptin correlated positively with body weight (r = 0.25, r < 0.05), BMI (r = 0.38, r < 0.05) and BF (r = 0.74, r < 0.05), and negatively with FFM (r = -0.74, r < 0.05). Our findings suggest that leptin is an important cardiovascular disease marker to obese population and can contribute to evaluate metabolic risks in these individuals. [ABSTRACT FROM AUTHOR]

La leptina, insulina y hormona de crecimiento influyen en la masa grasa, composición corporal y distribución grasa. El propósito de este estudio fue determinar la relación entre los niveles de insulina, leptina y hormona de crecimiento con parámetros antropométricos y lipídicos en adolescentes. Se estudiaron 95 adolescentes entre 13 y 18 años. Se realizó una historia clínico-nutricional donde se midió el índice de masa corporal (IMC) y los pliegues subcutáneos. Se determinaron los niveles basales de glicemia, triglicéridos, colesterol total, HDL-C, LDL-C y VLDL-C, insulina, leptina y hormona de crecimiento. Los niveles de leptina e insulina se relacionaron positivamente con el IMC y el Índice de Obesidad (IOB). La insulina, leptina e indicadores de obesidad se relacionaron en forma negativa con la hormona de crecimiento. El 52% de los adolescentes con IMC≥21,09 Kg/m² e IOB >42,02 mm se consideraron metabólicamente obesos, debido a que comparados con los adolescentes normales, presentaron niveles elevados de insulina (18,68± 1,52 vs 10,08± 0,38 m U/ml), HOMA IR (3,34± 0,24 vs 1,76± 0,07), leptina (16,30± 1,24 vs 8,11± 1,32 ng/dl) y triglicéridos (78,56± 4,38 vs 64,39± 5,48 mg/dl) y disminución de HDL-C (39,09± 1,27 vs 43,30± 2,38 mg/dl). Estas mismas alteraciones se observaron en adolescentes obesos en quienes se produjo además una disminución significativa de la hormona de crecimiento. Se concluye que en los adolescentes estudiados existió una serie de factores de riesgo como hiperinsulinemia, hiperleptinemia y hormona de crecimiento disminuida relacionada con marcadores de obesidad, alteraciones lipídicas e insulino resistencia, lo cual puede conducir a la aparición temprana de diabetes tipo 2 y enfermedad cardiovascular.Leptin, insulin and growth hormone levels seem to regulate body composition, fat distribution and fat mass. The purpose of this study was to determine the relationship among insulin, leptin and growth hormone levels in a group of adolescents. Ninety five adolescents (31 boys and 64 girls) between 13 and 18 y. of age were studied. A medical and nutritional history was made which included body mass index (BMI) and subcutaneous skinfolds measurements. Basal levels of glucose, triglycerides, total cholesterol, HDL-C, LDL-C, VLDL-C, leptin, insulin and growth hormone were determined. The leptin and insulin levels were positively associated with body mass index (BMI) and obesity index (OBI). Insulin, leptin and obesity markers were negatively associated with growth hormone level. Fifty two percent of the adolescents with BMI ≥21.09 kg/m² were considered metabolically obese because they had elevated levels of insulin (18.68 ± 1.52 vs. 10.08 ± 0.38 m U/ml), HOMA IR (3.34± 0.24 vs. 1.76± 0.07), leptin (16.30± 1.24 vs. 8.11± 1.32 ng./dl) and triglycerides (78.56± 4.38 vs 64.39± 5.48 mg/dl) and lower levels of HDL-C (39.09± 1.27 vs 43.30± 2.38 mg/dl), compared with normal group. The same alterations were observed in the obese group, in which significative decrease in growth hormone level was added. We conclude that hyperinsulinemia, hyperleptinemia and low growth hormone levels, may be established as risk factors related to obesity markers, lipid alterations and insulin resistance that can lead to an early development of Type II diabetes and cardiovascular disease.

Background: Skin tags (ST) are benign lesions composed of loose fibrous tissue, associated with obesity and atherogenic profile. Thus help in the follow up by considering ST as a useful cutaneous sign for the risk factor of atherosclerosis. Aim: To evaluate the association of skin tags with BMI, serum leptin and lipid profile. Materials and Methods: The study was carried out in 40 cases with ST and 40 age and gender matched controls. Subjects on oral contraceptives and systemic drugs especially lipid lowering agents, pregnant women, cases with medical history of endocrine disease, acute infection, erythroderma and psoriasis, cases with a drug history of isotretinoin use in last six months were excluded from the study. Blood samples were collected. Serum lipids and serum leptin were estimated. Result: The acrochordons group showed significantly higher values of BMI, total cholesterol (TC) and TC/HDL ratio. 60% of the patients with ST were overweight and 10% were obese. There was no statistical significant difference in leptin levels between the groups. Leptin showed a positive significant correlation with BMI in the acrochordons group. Conclusion: All the above derangements confirm that ST is cutaneous findings frequently associated with obesity and dyslipidemia. Thus follow-up of these patients with regard to the development of diseases associated with atherosclerosis may be beneficial.

Leptin synthesized by adipose tissue has significant association with birth weight, body mass index and insulin-glucose ratio. Fetuses with growth restriction (FGR) have substantial reduction in adipose tissue; hence lower levels of leptin in cord blood. Hyperleptinemia has been observed in pregnancy induced hypertension (PIH). Objectives: To estimate leptin levels in cord blood of growth restricted and normal neonates and study the factors influencing the same. Methods: In this prospective study, a sample size of 40 each of growth restricted and appropriate for gestational age neonates were included. Data included maternal illnesses, anthropometry, maturity and ponderal index (PI). Cord leptin assay was done using commercial solid phase competitive ELISA and was expressed in ng/ml. Statistical analysis was done using t test and Pearson correlation co-efficient using recommended software. Results: Maternal PIH was the major etiological factor contributing to FGR (12, 30%, P =0.000). Mean cord leptin in ng/ml was 2.80±0.4 in growth restricted group and 3.53±0.5 in normal neonates with P value of 0.074. There was no correlation between cord leptin and birth weight (r=0.08; p=0.61) and PI (r=0.03; p=0.89). In female neonates and those born to mothers with PIH, mean leptin levels were 3.16±0.6 and 3.13±0.7 ng/ml respectively, higher in comparison with males and those born to mothers without hypertension. Conclusion: Mean cord leptin levels were lower in the growth restricted and higher in female gender and those born to maternal PIH. Cord leptin may be influenced by various maternal and fetal factors. [ABSTRACT FROM AUTHOR]

Breastfeeding is associated with obesity prevention. We showed previously that prolactin inhibition at the end of lactation causes hyperleptinemia at weaning (PN21) and programs for obesity, insulin resistance, dyslipidemia, and leptin resistance (PN180). Here, we evaluate the source of neonatal hyperleptinemia and how it develops during the nutritional transition from milk through solid food. Lactating rats were treated with bromocriptine (BRO), a prolactin inhibitor, 0.5 mg twice a day, or saline (CON) for the last 3 days of lactation. All parameters were studied at PN22 and PN30. At PN22, BRO-treated rats showed lower food intake, body mass, and body length. At PN30, only body length and mesenteric fat mass were lower. Despite normal plasma leptin levels at PN22, the adipose tissue leptin mRNA expression was lower, while plasma leptin was higher in PN30, possibly due to a higher adipose mesenteric tissue production. At PN22, the hypothalamus seems to be more sensitive to leptin, since OBR and STAT3 are higher. Conversely, at PN30 leptin signaling pathway is suggestive of leptin resistance with lower STAT3 and higher SOCS3 in hypothalamus and consequently higher NPY. Glycemia was lower at PN22 and higher at PN30, without changes in plasma insulin levels. At PN30, BRO-treated rats had other metabolic changes such as higher plasma cholesterol, lower HDL-c, higher hepatic cholesterol and AST, suggesting a liver dysfunction. Our data show that milk supply can exert a crucial role in the imprinting of a second leptin peak, which is important for survival adaptation to adverse nutritional conditions. [ABSTRACT FROM AUTHOR]

Background: The low-grade inflammatory state in obesity leads to insulin resistance and endothelial dysfunction, which promote cardiovascular diseases in individuals with obesity. The purpose of this study was to evaluate the early effects of weight loss achieved through bariatric surgery on the inflammatory and prothrombotic states. This study also aimed to identify the role of hyperleptinemia on the prothrombotic state. Methods: The sample was composed of 41 extremely obese who underwent Roux-en-Y gastric bypass (RYGB). Anthropometric and clinical data, and biochemical markers of inflammation were collected prior to surgery and 6 months post-RYGB. Results: It was found that plasminogen activator inhibitor-1 (PAI-1) concentrations were higher among extremely obese individuals with hyperleptinemia than in those without hyperleptinemia ( p < 0.01).In relation to the baseline, post-surgery body mass index (BMI) was reduced by 12.9 kg/m, corresponding to 63.50 % of excess weight loss. Additionally, waist circumference was found to decrease significantly from 126.2 to 101.4 cm. Plasma total cholesterol ( p < 0.01), LDL cholesterol ( p = 0.02), triglycerides ( p < 0.01), and glucose ( p = 0.01) were also found to decrease. Pro-inflammatory biomarkers were observed to decrease: PAI-1 by 55.9 ± 6.0 % ( p < 0.01), C-reactive protein (CRP) by 18.8 ± 3.4 % ( p < 0.01), intercellular adhesion molecule-1 (ICAM-1) by 89.9 ± 5.7 % ( p < 0.01), leptin by 27.9 ± 3.2 % ( p < 0.01), and resistin by 69.3 ± 5.8 % ( p < 0.01). Additionally, significant decreases of tumor necrosis factor alpha (TNF-α) and leptin/adiponectin ratio were observed. Anti-inflammatory cytokines adiponectin and interleukin-10 (IL-10) were significantly increased (170.7 ± 82.5 %, p < 0.01; 122.7 ± 55.1 %, p = 0.02). CRP levels were predictive of ICAM-1 ( p = 0.04), and changes in leptin concentrations were associated with decreased PAI-1 levels ( p = 0.03). Conclusions: We observed that individuals with obesity that have hyperleptinemia have higher circulating PAI-1 levels, which could indicate increased risk for cardiovascular disease. The biomarkers of inflammation and thrombosis measured in this study decreased after RYGB, suggesting that the surgery may be effective in reducing pro-inflammatory and thrombotic risk in individuals with extreme obesity. [ABSTRACT FROM AUTHOR]

Despite the fact that obesity is a major risk factor for preeclampsia (PE), the pathophysiological mechanisms whereby obesity and metabolic factors such as leptin increase this risk are unclear. While human data have shown that hyperleptinemia is associated with PE, the long-term effect of hyperleptinemia on blood pressure during pregnancy is unknown. Thus we tested the hypothesis whether chronic circulating leptin elevations in pregnant rats increase blood pressure and placental factors known to play a role in PE. On gestational day (GD)14, rats were assigned to the normal pregnant group with food intake ad libitum (control), leptin-treated (0.5 μg.kg-1min.-1 ip) pregnant group with food intake ad libitum (pregnant+LEP), and normal pregnant group with food intake adjusted to the food intake of pregnant+LEP rats (pregnant-FR). On GD19, mean arterial pressure (MAP) was assessed and tissues were collected. Serum leptin concentration was elevated in pregnant+ LEP compared with control and pregnant-FR (18.0 ± 2.8 vs. 0.8 ± 0.1 vs. 0.3 ± 0.1 ng/ml; P < 0.05), which was associated with increased MAP (121.3 ± 8.1 vs. 102.4 ± 2.4 vs. 101.3 ± 1.8 mmHg; P < 0.05). Food intake and body weight were reduced in pregnant+ LEP and pregnant-FR by the end of gestation. Additionally, placentas and fetuses of these groups were lighter than those of control. However, placental expression of tumor necrosis factor-a was significantly greater in pregnant+LEP compared with controls (1.6 ± 0.1 vs. 1.1 ± 0.1 pg/mg; P < 0.05). In conclusion, leptin increases blood pressure and placental tumor necrosis factor-a during pregnancy despite its effect of reducing food intake and body weight, and represents a mechanism whereby obesity can promote the development of hypertension in PE. [ABSTRACT FROM AUTHOR]

Leptin is an adipose tissue-derived hormone that has been involved in hypothalamic and systemic inflammation, altered food-intake patterns, and metabolic dysfunction in obese mice. However, it remains unclear whether leptin has a relationship with parameters of systemic inflammation and metabolic dysfunction in humans. We thus evaluated in a cross-sectional study the circulating levels of leptin in 40 non-obese and 41 obese Mexican individuals, examining their relationship with tumor necrosis factor alpha (TNF-a), interleukin (IL) 12, IL-10, central obesity, serum glucose and insulin levels, and serum triglyceride and cholesterol concentrations. Circulating levels of leptin, TNF-a, IL-12, IL-10, and insulin were measured by ELISA, while concentrations of glucose, triglyceride, and cholesterol were determined by enzymatic assays. As expected, serum levels of leptin exhibited a significant elevation in obese individuals as compared to non-obese subjects, showing a clear association with increased body mass index (r=0.4173), central obesity (r=0.4678), and body fat percentage (r=0.3583). Furthermore, leptin also showed a strong relationship with serum TNF-a (r=0.6989), IL-12 (r=0.3093), and IL-10 (r=-0.5691). Interestingly, leptin was also significantly related with high concentrations of fasting glucose (r=0.5227) and insulin (r=0.2229), as well as elevated levels of insulin resistance (r=0.3611) and circulating triglyceride (r=0.4135). These results suggest that hyperleptinemia is strongly associated with the occurrence of low-grade systemic inflammation and metabolic alteration in obese subjects. Further clinical research is still needed to determine whether hyperleptinemia may be a potential marker for recognizing the advent of obesity-related metabolic disorders in human beings.

Neuroendocrine axes adapt to nutrient availability. During fasting, the function of the hypothalamus-pituitary-thyroid axis (HPT) is reduced, whereas that of the hypothalamus- pituitary-adrenal axis (HPA) is increased. Overfeeding-induced hyperleptinemia during lactation may alter the regulatory set point of neuroendocrine axes and their adaptability to fasting in adulthood. Hyperleptinemia is developed in rodents by litter size reduction during lactation; adult rats from small litters become overweight, but their paraventricular nucleus (PVN) TRH synthesis is unchanged. It is unclear whether peptide expression still responds to nutrient availability. PVN corticotropin-releasing factor (CRF) expression has not been evaluated in this model. We analyzed adaptability of HPT and HPA axes to fasting-induced low leptin levels of reduced-litter adult rats. Offspring litters were reduced to 2-3/dam (earlyoverfed) or maintained at 8/dam (controls, C). At 10 weeks old, a subset of animals from each group was fasted for 48 h and leptin, corticosterone, and thyroid hormones serum levels were analyzed. In brain, expressions of leptin receptor, NPY and SOCS3, were evaluated in arcuate nucleus, and those of proTRH and proCRF in PVN by real-time PCR. ProTRH expression in anterior and medial PVN subcompartments was assayed by in situ hybridization. Earlyoverfed adults developed hyperphagia and excessive weight, together with decreased proTRH expression in anterior PVN, supporting the anorexigenic effects of TRH. Early-overfed rats presented low PVN proTRH synthesis, whereas fasting did not induce a further reduction. Fasting-induced stress was unable to increase corticosterone levels, contributing to reduced body weight loss in early-overfed rats. We concluded that early overfeeding impaired the adaptability of HPT and HPA axes to excess weight and fasting in adults. [ABSTRACT FROM AUTHOR]

The low-grade systemic inflammation seen in obesity may affect the actions of some adipose tissue-derived adipokines that are involved in the regulation of vascular function. We sought to verify whether hyperleptinemia may influence the inflammatory and atherogenic responses in obese adolescents undergoing interdisciplinary therapy. Thirty-four obese adolescents underwent interdisciplinary therapy for 1 year. Subjects were considered hyperleptinemic if they had baseline values of leptin above 20 ng/mL for boys and 24 ng/mL for girls. Both groups showed an improvement in body composition and a reduction in carotid intima-media thickness. However, only subjects in the non-hyperleptinemic group showed an increase in adiponectin concentration after therapy. Moreover, leptin concentration was positively correlated with adiponectin and inversely correlated with PAI-1 in this group. Hyperleptinemic state may impair the attenuation of inflammation in obese adolescents undergoing interdisciplinary therapy, particularly by impeding the increase in adiponectin concentration, which is directly involved in vascular protection. [ABSTRACT FROM AUTHOR]

Hyperleptinemia has emerged as a marker of proinflammatory status, while the adiponectin/ leptin ratio has been used to identify antiinflammatory state. In this context, the aims of the present study were to investigate the role of leptinemia, adjusted by tertiles, on infl ammatory state in obese adults according to obesity degree. This is a cross-sectional study comprised of 43 obese adults. The anthropometric variables and body composition were analyzed, as well as markers of infl ammation such as leptin, adiponectin, and plasminogen activator inhibitor. Subjects were grouped using adjusted tertiles of the leptin levels. The major finding was the negative correlation between leptin concentration with adiponectin/leptin ratio (r = - 0.622, p = 0.000) and the positive correlation with leptin/adiponectin ratio (r = 0.622, p = 0.000). Indeed, both ratios were decreased and increased, respectively, according to the obesity degree. Furthermore, in the stepwise multiple linear regression analysis, the high degree of obesity was an independent predictor of leptinemia when adjusted for age and BMI (β = 0.588, p = 0.000 and β = 0.778, p = 0.005). Finally, the strong negatively correlation between the leptinemia with adiponectin/leptin ratio and the positive correlation with leptin/adiponectin ratio reinforce the role of this adipokine as a biomarker of infl ammation in obese adults, according to obesity degree. Our findings can elucidate that hyperleptinemic status was a major factor in the proinflammatory status related to higher obesity degree. All together, these data reinforce the role of leptinemia state as a mediator of infl ammation in obese adults. [ABSTRACT FROM AUTHOR]

Leptin is an adipose tissue-derived hormone that has been involved in hypothalamic and systemic inflammation, altered food-intake patterns, and metabolic dysfunction in obese mice. However, it remains unclear whether leptin has a relationship with parameters of systemic inflammation and metabolic dysfunction in humans. We thus evaluated in a cross-sectional study the circulating levels of leptin in 40 non-obese and 41 obese Mexican individuals, examining their relationship with tumor necrosis factor alpha (TNF-α), interleukin (IL) 12, IL-10, central obesity, serum glucose and insulin levels, and serum triglyceride and cholesterol concentrations. Circulating levels of leptin, TNF-α, IL - 12 , IL -10 , and insulin were measured by ELISA, while concentrations of glucose, triglyceride, and cholesterol were determined by enzymatic assays. As expected, serum levels of leptin exhibited a significant elevation in obese individuals as compared to non-obese subjects, showing a clear association with increased body mass index (r = 0.4173), central obesity (r = 0.4678), and body fat percentage (r = 0.3583). Furthermore, leptin also showed a strong relationship with serum TNF-α (r = 0.6989), IL-12 (r = 0.3093), and IL-10 (r = -0.5691). Interestingly, leptin was also significantly related with high concentrations of fasting glucose (r = 0.5227) and insulin (r = 0.2229), as well as elevated levels of insulin resistance (r = 0.3611) and circulating triglyceride (r = 0.4135). These results suggest that hyperleptinemia is strongly associated with the occurrence of low-grade systemic inflammation and metabolic alteration in obese subjects. Further clinical research is still needed to determine whether hyperleptinemia may be a potential marker for recognizing the advent of obesity-related metabolic disorders in human beings. [ABSTRACT FROM AUTHOR]

Summary: The adipocyte product leptin is a pleiotropic adipokine and hormone, with a role extending beyond appetite suppression and increased energy expenditure. This review summarizes the biology of the leptin system and the roles of its different receptors in a multitude of cellular functions in different organs, with special emphasis on the kidney. Leptin''s physiological functions as well as deleterious effects in states of leptin deficiency or hyperleptinemia are emphasized. Chronic hyperleptinemia can increase blood pressure through the sympathetic nervous system and renal salt retention. The concept of selective leptin resistance in obesity is emerging, whereby leptin''s effect on appetite and energy expenditure is blunted, with a concomitant increase in leptin''s other effects as a result of the accompanying hyperleptinemia. The divergence in response likely is explained by different receptors and post-receptor activating mechanisms. Chronic kidney disease is a known cause of hyperleptinemia. There is an emerging view that the effect of hyperleptinemia on the kidney can contribute to the development and/or progression of chronic kidney disease in selective resistance states such as in obesity or type 2 diabetes mellitus. The mechanisms of renal injury are likely the result of exaggerated and undesirable hemodynamic influences as well as profibrotic effects. [Copyright &y& Elsevier]

Background: The prevalence of obesity is increasing exponentially world over. Leptin resistance/hyperleptinemia is attributed to its cause in majority of the obese humans where mutation in genetic component or ob gene has not been found operative. The generation of oxidative stress was suggested as its cause. In our previous study, we have reported that the inclusion of antioxidant enriched modified poultry egg (ME) in diet reversed the ionic imbalance and ameliorated the oxidative stress caused by excessive Zn in diet. In the present study, the efficacy of ME verses conventional egg (CE) was tested on Zn-induced leptin resistance in rat model to ascertain if the supplementation of antioxidants in the form of egg can reverse Zn-induced leptin resistance to leptin sensitive state. Methods: Hyperleptinemia was induced in rats by feeding them Zn-supplemented hyperleptinemic diets-I and II (Zn-HL-Diet) for 2 months. Thereafter, half of them were fed either on CE or ME mixed Zn-HL-diets I and II for another two months. The data was analyzed applying one way Anova and Tukey's HSD post hoc test. Results: The results revealed that food intake, gain in body weight, height and number/unit surface area of intestinal microvillus and serum leptin, glucose, insulin and cortisol were higher in CE and Zn-HL-Diet treated groups; serum Zn, Cu, Mg were higher and Cu and Mg in tissues were lower in them than the control group. In ME treated groups, these parameters were lower and were close to the control group. These changes resulted from the restoration of ionic balance of Zn, Cu and Mg in the blood serum and tissues including liver and hair in ME treated rats. Conclusion: The data suggest that Zn-induced leptin resistance can be attenuated through restoring the ionic balance of Zn, Cu and Mg through inclusion of antioxidants in diet such as these modified eggs. But further clinical studies are required before they are put to use for human consumption. [ABSTRACT FROM AUTHOR]

In men, as testosterone levels decrease, fat mass increases and muscle mass decreases. Increased fat mass in men, in particular central obesity, is a major risk factor for type 2 diabetes, cardiovascular disease, and all-cause mortality. Testosterone treatment has been shown to decrease fat mass and increase fat-free mass. We hypothesize that androgens act directly via the DNA binding-dependent actions of the androgen receptor (AR) to regulate genes controlling fat mass and metabolism. The aim of this study was to determine the effect of a global DNA binding-dependent (DBD) AR knockout (DBD-ARKO) on the metabolic phenotype in male mice by measuring body mass, fat mass, food intake, voluntary physical activity, resting energy expenditure, substrate oxidation rates, serum glucose, insulin, lipid, and hormone levels, and metabolic gene expression levels and second messenger protein levels. DBD-ARKO males have increased adiposity despite a decreased total body mass compared with wild-type (WT) males. DBD-ARKO males showed reduced voluntary activity, decreased food intake, increased serum leptin and adiponectin levels, an altered lipid metabolism gene profile, and increased phosphorylated CREB levels compared with WT males. This study demonstrates that androgens acting via the DNA binding-dependent actions of the AR regulate fat mass and metabolism in males and that the increased adiposity in DBD-ARKO male mice is associated with decreased voluntary activity, hyperleptinemia and hyperadiponectinemia and not with insulin resistance, increased food intake, or decreased resting energy expenditure. [ABSTRACT FROM AUTHOR]

Hyperleptinemia during lactation programs for higher serum leptin in 30-day-old and adult rats, associated with metabolic changes. Here we evaluated the inhibition of serum leptin at 29 and 30 days on the metabolic phenotype of rats programmed with leptin during lactation. Pups from Wistar rats were saline-injected or leptininjected from postnatal day 1 to day 10. At 29 and 30 days old, animals were injected with anti-leptin antibody (LA and CA) or saline (LS and CS). In adult animals, higher visceral ( + 53 % ) and total fat mass ( + 33 % ), hyperleptinemia ( + 67 % ), hypertriglyceridemia ( + 47 % ), and hypoadiponectinemia ( − 44 % ) observed in LS group compared to CS were prevented by immunoneutralization of leptin, since LA group had those parameters values similar to CS group. However, immunoblockade of leptin in normal animals led to the same metabolic changes seen in leptin-treated animals, in addition to lower serum adiponectin ( − 77 % vs. CS) and higher insulin resistance index ( + 37 % ). Liver sirtuin1 (SIRT1) was higher ( + 41 % ) only in LA group, suggesting a role for SIRT1 in the prevention of leptin programming. Hypothalamic OBR was lower and SOCS3 higher in LS group and these changes were normalized in LA group. In conclusion, blocking leptin action one week after weaning seems to revert most of the alterations observed in rats programmed by neonatal hyperleptinemia. Higher liver SIRT1 expression may be one of the mechanisms involved, leading to a better glucose and lipid metabolism. Our data suggest that the lack or the excess of leptin programs an adverse metabolic phenotype in adulthood. [ABSTRACT FROM AUTHOR]

Organotin compounds such as tributyltin (TBT) have been used worldwide in agriculture and industry as biocides, heat stabilizers, and chemical catalysts. However, few studies addressing the effects of TBT on growth and metabolism have been reported. This study was conducted to investigate the effects of TBT at low doses (0.5, 5, and 50 μg/kg) on body weight gain in male mice exposed as from puberty and to determine the alterations in related hormones. The results showed that exposure to TBT for 45 days resulted in an increase in body weight gain and hepatic steatosis accompanied with hyperinsulinemia and hyperleptinemia. Reduction of hepatic adiponectin levels in a dose-dependent manner was related to the lipid increase in the liver. These results suggest that chronic and repeat exposure to low doses of TBT can result in obesity and hepatic steatosis and induce the occurrence of insulin and leptin resistance. © 2009 Wiley Periodicals, Inc. Environ Toxicol 26: 79-85, 2011. [ABSTRACT FROM AUTHOR]