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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: 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]

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]

Temporary cessation or restriction of breastfeeding can lead to metabolic disorders in adulthood. However, data on the effect of fasting in the early postnatal period on the functions of the endocrine system in adulthood are rare and contradictory. Approaches for the correction of metabolic and hormonal disorders caused by premature cessation of breastfeeding have not been developed yet. The aim of the work was to study the metabolic and hormonal parameters and changes in the hormonal status of the gonadal and thyroid systems in 10-month-old male rats with interruption of breastfeeding on days P19-P21, as well as to evaluate the restorative effect on them of four weeks of treatment with intranasal insulin (II) administered in the postnatal period (P28-P55) or in adulthood (P183-P210). Lactation interruption has been induced by treatment of lactating females with bromocriptine (10 mg/day/rat, P19-P21). Male rats with temporary cessation of breastfeeding developed characteristic signs of the metabolic syndrome (obesity, dyslipidemia, impaired glucose tolerance, hyperleptinemia), decreased levels of testosterone and thyroid hormones (fT4, tT3) and weakened the synthesis of testosterone and thyroxine, stimulated respectively by GnRH and thyroliberin. This was due to a decrease in the sensitivity of the testes to luteinizing hormone (LH) and the thyroid gland to thyroid-stimulating hormone (TSH). Treatment with II in early ontogenesis reduced body weight and fat, improved lipid profile, sensitivity to insulin, leptin, LH and TSH, restored the levels of testosterone and thyroid hormones and their stimulation by releasing factors. Treatment with II in adulthood normalized the levels of testosterone, thyroid hormones, their stimulation by releasing factors, but had a little effect on metabolic and hormonal parameters. The obtained data point to a wide range of metabolic and hormonal disorders in adult male rats with the "neonatal" model of metabolic syndrome and to the effectiveness of various strategies for their correction using long-term II treatment.

Obesity is strongly related to leptin resistance that refers to the state in which leptin fails to inhibit appetite, enhance energy expenditure and regulate glycolipid metabolism, whereas decreasing leptin resistance is important for obesity treatment. Leptin resistance that develops in brain and also directly in peripheral tissues is considered as central and peripheral leptin resistance, respectively. The mechanism of central leptin resistance is the focus of intensive studies but still not totally clarified. A challenged notion about the effect of impaired leptin BBB transport emerges and a concept of "selective leptin resistance" is discussed. Peripheral leptin resistance, especially leptin resistance in muscle, has drawn more attention recently, while its mechanism remains unclear. Exercise is an effective way to reduce obesity, which is at least in part due to the alleviation of leptin resistance. Here, we summarized newly discovered data about the associated factors of central leptin resistance and peripheral leptin resistance, and the actions of exercise on leptin resistance, which is important to understand the mechanisms of leptin resistance and exercise-induced alleviation of leptin resistance, and to facilitate clinical application of leptin in obesity treatment. • Reduced muscle mass and FAO contribute to leptin resistance (LR) in muscle. • Hyperleptinemia and impaired trafficking of LepR contribute to central LR. • Exercise lowers central LR by regulating neuron activity, leptin signaling or IL-6. • Exercise reduces peripheral LR by decreasing fat mass or muscular SOCS3 and PTP1B. [ABSTRACT FROM AUTHOR]

Increasing adipose tissue mass in obesity directly correlates with elevated circulating leptin levels. Leptin is an adipokine known to play a role in numerous biological processes including regulation of energy homeostasis, inflammation, vascular function and angiogenesis. While physiological concentrations of leptin may exhibit multiple beneficial effects, chronically elevated pathophysiological levels or hyperleptinemia, characteristic of obesity and diabetes, is a major risk factor for development of atherosclerosis. Hyperleptinemia results in a state of selective leptin resistance such that while beneficial metabolic effects of leptin are dampened, deleterious vascular effects of leptin are conserved attributing to vascular dysfunction. Leptin exerts potent proatherogenic effects on multiple vascular cell types including macrophages, endothelial cells and smooth muscle cells; these effects are mediated via an interaction of leptin with the long form of leptin receptor, abundantly expressed in atherosclerotic plaques. This review provides a summary of recent in vivo and in vitro studies that highlight a role of leptin in the pathogenesis of atherosclerotic complications associated with obesity and diabetes. [ABSTRACT FROM AUTHOR]

Although novel pharmacological options for the treatment of type 2 diabetes mellitus (DM2) have been observed to modulate the functionality of several key organs in glucose homeostasis, successful regulation of insulin resistance (IR), body weight management, and pharmacological treatment of obesity remain notable problems in endocrinology. Leptin may be a pivotal player in this scenario, as an adipokine which centrally regulates appetite and energy balance. In obesity, excessive caloric intake promotes a low-grade inflammatory response, which leads to dysregulations in lipid storage and adipokine secretion. In turn, these entail alterations in leptin sensitivity, leptin transport across the blood-brain barrier and defects in post-receptor signaling. Furthermore, hypothalamic inflammation and endoplasmic reticulum stress may increase the expression of molecules which may disrupt leptin signaling. Abundant evidence has linked obesity and leptin resistance, which may precede or occur simultaneously to IR and DM2. Thus, leptin sensitivity may be a potential early therapeutic target that demands further preclinical and clinical research. Modulators of insulin sensitivity have been tested in animal models and small clinical trials with promising results, especially in combination with agents such as amylin and GLP-1 analogs, in particular, due to their central activity in the hypothalamus., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

We treated the case of a 22-year-old male patient with liver dysfunction. At 1 year of age, hepatic fibrosis was suspected. In addition, due to the presence of retinitis pigmentosa, renal failure, obesity, mental retardation, and hypogonadism, he was diagnosed with Bardet-Biedl syndrome (BBS). Skipping of exons 14 and 17 in the sodium channel and clathrin linker 1 (SCLT1) gene was observed. At 22 years of age, the liver enzyme levels were further elevated and a diagnosis of microvesicular steatohepatitis was made. Insulin resistance, a reduction of muscle mass, an impairment of the fatty acid metabolism, and hyperleptinemia in this syndrome may cause steatohepatitis.

Scope: To identify the age-dependent effect of diets containing elevated amounts of either saturated or unsaturated fatty acids on cardiac steatosis in mice., Methods and Results: Five- and eight-week-old C57BL/6J mice cohorts are given free access to either a saturated or an unsaturated fatty-acid-enriched diet during 8 weeks. Body weight (BW) and food intake are monitored during this period. Cardiac lipid content, carnitine palmitoyltransferase-I (CPT-I) activity, and the amount of uncoupling proteins 2 and 3 (UCP2 and UCP3) are analyzed and correlated with blood leptin concentration. Leptin and PPARγ gene expression is quantified in white adipose tissue (WAT). Both diets have a similar effect on food intake, BW, and adiposity, independently of the age. Nevertheless, cardiac steatosis is specifically identified in adolescent mice consuming the saturated diet. These animals also display lower activity of cardiac CPT-I, a down-regulation of cardiac UCP2, together with lower concentration of plasma leptin. Accordingly, leptin gene expression is reduced in the visceral WAT., Conclusion: Consumption of diets containing elevated amounts of saturated fat during adolescence and early adult life promotes cardiac steatosis in mice. An insufficient endocrine activity of WAT, in terms of leptin production, may account for such an effect., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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.

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) promotes hepatic insulin clearance. Consistently, mice with null mutation of Ceacam1 (Cc1(-/-)) exhibit impaired insulin clearance with increased lipid production in liver and redistribution to white adipose tissue, leading to visceral obesity at 2 months of age. When the mutation is propagated on the C57/BL6J genetic background, total fat mass rises significantly with age, and glucose intolerance and systemic insulin resistance develop at 6 months of age. This study was carried out to determine the mechanisms underlying the marked increase in total fat mass in 6-month-old mutants. Indirect calorimetry analysis showed that Cc1(-/-) mice develop hyperphagia and a significant reduction in physical activity, in particular in the early hours of the dark cycle, during which energy expenditure is only slightly lower than in wild-type mice. They also exhibit increased triglyceride accumulation in skeletal muscle, due in part to incomplete fatty acid β-oxidation. Mechanistically, hypothalamic leptin signaling is reduced, as demonstrated by blunted STAT3 phosphorylation in coronal sections in response to an intracerebral ventricular injection of leptin. Hypothalamic fatty-acid synthase activity is also elevated in the mutants. Together, the data show that the increase in total fat mass in Cc1(-/-) mice is mainly attributed to hyperphagia and reduced spontaneous physical activity. Although the contribution of the loss of CEACAM1 from anorexigenic proopiomelanocortin neurons in the arcuate nucleus is unclear, leptin resistance and elevated hypothalamic fatty-acid synthase activity could underlie altered energy balance in these mice., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)