Leptin Secretion Research Articles

Bisphenol A disturbs metabolism of primary rat adipocytes without affecting adipokine secretion

Bisphenol A (BPA) is an ubiquitous synthetic chemical exerting numerous adverse effects. Results of rodent studies show that BPA negatively affects adipose tissue. However, the short-term influence of this compound addressing adipocyte metabolism and adipokine secretion is unknown. In the present study, isolated rat adipocytes were exposed for 2 h to 1 and 10 nM BPA. Insulin-induced glucose conversion to lipids along with glucose transport was significantly increased in the presence of BPA. However, basal glucose conversion to lipids, glucose oxidation, and formation of lipids from acetate were unchanged in adipocytes incubated with BPA. It was also shown that BPA significantly increases lipolytic response of adipocytes to epinephrine. However, lipolysis stimulated by dibutyryl-cAMP (a direct activator of protein kinase A) and the antilipolytic action of insulin were not affected by BPA. Moreover, BPA did not influence leptin and adiponectin secretion from adipocytes. Our new results show that BPA is capable of disturbing processes related to lipid accumulation in isolated rat adipocytes. This is associated with the potentiation of insulin and epinephrine action. The effects of BPA appear already after short-term exposure to low doses of this compound. However, BPA fails to change adipokine secretion.

Leptin and obesity.

An imbalance between calorie intake and energy expenditure produces obesity. It has been a major problem in societies of the developing and developed world. In obesity an excessive amount of fat accumulates in adipose tissue cells as well as in other vital organs like liver, muscles, and pancreas. The adipocytes contain ob genes and express leptin, a 16 kDa protein. In the present communication, we reviewed the molecular basis of the etiopathophysiology of leptin in obesity. Special emphasis has been given to the use of leptin as a drug target for obesity treatment, the role of diet in the modulation of leptin secretion, and reduction of obesity at diminished level of blood leptin induced by physical exercise.

The Effect of Energy Metabolism up to the Peak of Lactation on the Main Fractions of Fatty Acids in the Milk of Selected Dairy Cow Breeds.

Simple SummaryThe metabolism of cows up to the peak of lactation significantly influences production parameters and the quality of the production cycle. The aim of this study was to analyze the energy metabolism of selected breed groups of cows and its variability in different stages of early lactation. The analysis was performed using data on the following parameters: body condition score (BCS), fatty acid (FA) fractions, basic milk constituents, and serum parameters (BHBA, glucose, and leptin). Holstein-Friesian (HF) cows and HF crossbreds with Black-and-White Lowland (BW) bulls generally had higher daily yields and reached the peak of lactation earlier. These cows, however, suffered the greatest loss in BCS, which led to higher levels of non-esterified fatty acid (NEFA) in the blood than in the other groups. Cows entering the peak of lactation with less intensive production were shown to have lower levels of leptin and higher glucose concentrations in the blood. The smaller loss of BCS in these cows did not lead to rapid lipolysis, and therefore the release of large amounts of non-esterified fatty acids and β-hydroxybutyrate into the blood was limited. The milk of breed groups that had somewhat lower yield and reached the peak of lactation about 11 days later (Simmental and Black-and-White Lowland) had a more beneficial fatty acid profile and casein content. The results indicate that one of the important factors influencing the intensity of lipolysis is leptin, which regulates appetite. The Simmental and Black-and-White Lowland groups had lower concentrations of leptin. This suggests the need for further research on how appetite and the prolongation of feed intake is linked to longer availability of nutrients, including glucose.During early lactation in dairy cows, metabolic processes are adopted to provide energy and nutrients for the synthesis of milk compounds. High milk production potential includes sudden changes in energy metabolism (negative energy balance (NEB)) that can induce uncontrolled lipomobilization and high blood free fatty acid (FFA) levels. Destabilization of cows’ energy may interfere with endocrine homeostasis, such as the secretion of leptin, a co-regulator of the appetite center. Therefore, it is important to analyze the physiological aspects of the maintenance of energy homeostasis in various dairy breeds. Usually it is crucial for the health of cows, influences the production cycle and lifetime yield, and determines the profitability of production and milk quality. The aim of this study was to analyze the energy metabolism of selected breed groups of cows and its variability in different stages of early lactation. The analysis was performed using data on the following parameters: body condition score (BCS), fatty acid (FA) fractions, basic milk constituents, and serum parameters (BHBA, glucose, and leptin). These results were analyzed in relation to parameters of energy metabolism during the stage up to the peak of lactation. An earlier peak of lactation was shown to be conducive to an increase in the content of non-esterified fatty acids (NEFAs) and of casein and κ-casein. During the study period, parameters characterizing the maintenance of energy homeostasis were usually lower in the Simmental and Black-and-White Lowland cows. Compared to the group with the highest production, their yield was from 2.8 to 4.7 kg lower, but the milk had a more beneficial fatty acid profile and nutrient content, determining suitability for cheese making. At the same time, they had lower levels of NEFAs and β-hydroxybutyrate in the blood, which indicates less spontaneous lipolysis of fat reserves. Concentrations of the appetite regulator leptin in the blood were correlated negatively (p ≤ 0.05) with the glucose concentration (–0.259) and positively with NEFA (0.416). The level of NEFAs was at the same time positively correlated with the content of saturated fatty acids in the milk (0.282–0.652; p ≤ 0.05). These results contribute to our knowledge of the effect of production intensity on the maintenance of homeostasis up to the peak of lactation in dairy breeds with differing production potential. In practice, this may increase the possibilities of improving milk quality and the profitability of production.

STUDY OF ASSOCIATION OF RESISTIN AND LEPTIN WITH THYROID HORMONES IN HYPOTHYROID PATIENTS

Objective:The present study was aimed to evaluate the levels of resistin and leptin in hypothyroid patients and to find a possible association of thyroid hormones with resistin and leptin. Material and Methods:The present study was conducted on 100 previously diagnosed hypothyroid (PDH) patients (38 Males & 62 Females) and 100 newly diagnosed hypothyroid (NDH) patients (44 Males & 56 Females) attending the outpatient clinics or admitted in wards of J.L.N. Hospitals, Ajmer. 100 healthy control subjects of same age group of either gender were selected for the study. Blood samples were drawn from patients and controls, after overnight fast of at least 8 hours. Estimation of Serum Leptin, Resistin, free T3, free T4, and TSH was done by using Enzyme- Linked Immunosorbant Assay (ELISA) technique. Differences in the parameters among the groups were analyzed by ANOVA test followed by its Tukey HSD post hoc analysis. Correlations between variables were tested using the Pearson rho (r: Correlation coefficient) correlation test. Results:Findings of the present study shows that the levels of serum fT3 (1.79 ± 0.29 pg/mL) and serum fT4 (0.34 ± 0.11 ng/dL) were significantly lower in NDH group compared to PDH group (fT3 = 3.00 ± 0.32 pg/mL & fT4 = 0.81 ± 0.15 ng/dL) and control group (fT3 = 3.12 ± 0.31 pg/mL & fT4 = 0.85 ± 0.11ng/dL) whereas serum TSH levels were significantly higher in NDH group (40.59 ± 13.55 μIU/mL) compared to PDH group (5.34 ± 1.47 μIU/mL) and control group (3.23 ± 1.04 μIU/mL) [Table 1 Figure 1]. Serum leptin levels were significantly higher in NDH group (21.37 ± 6.44 ng/mL) compared to PDH group (16.51 ± 4.47 ng/mL) and control group (11.15 ± 5.29 ng/mL) [Table 2]. A highly significant variation (p<0.0001) in the levels of serum leptin was found between the groups. Serum resistin levels were significantly higher in NDH group (14.50 ± 2.72 ng/mL) compared to PDH group (11.33 ± 1.59 ng/mL) and control group (7.78 ± 1.19 ng/mL) [Table 2]. Highly Significant difference (p<0.0001) in resistin levels was found between the groups. Conclusion: It was suggested that thyroid dysfunction does not affect the leptin levels and also thyroid hormones were not involved in the synthesis and secretion of leptin. Further studies are required to gain more insight into the relationship between leptin and thyroid dysfunction. Resistin shows a significant correlation with thyroid hormones which indicate that serum resistin might be considered as a confirmation extra test for the early detection of atherosclerosis and atherosclerosis induced conditions in hypothyroid patients.

뽕잎 추출물 기원 Flavonoid Rich Fraction의 항비만효과

Background: This study investigated the anti-obesity effect of the flavonoid rich fraction (FRF) and its constituent, rutin obtained from the leaf of Morus alba L., on the lipid accumulation mechanism in 3T3-L1 adipocyte and C57BL/6 mouse models.BRMethods and Results: In Oil Red O staining, FRF (1,000 ㎍/㎖) treatments showed inhibition rate of 35.39% in lipid accumulation compared to that in the control. AdipoRedTM assay indicated that the triglyceride content in 3T3-L1 adipocytes treated with FRF (1,000 ㎍/㎖) was reduced to 23.22%, and free glycerol content was increased to 106.04% that of the control. FRF and its major constituent, rutin affected mRNA gene expression. Rutin contributed to the inhibition of Sterol regulatory element binding protein-1c (SREBP-1c) gene expression, and inhibited the transcription factors SREBP-1c, peroxisome proliferator-activated receptor gamma (PPAR-γ), CCAAT/enhancer binding protein α (C/EBPα), fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC). In addition, the effect of FRF administration on obesity development in C57BL/6 mice fed high-fat diet (HFD) was investigated. FRF suppressed weight gain, and reduced liver triglyceride and leptin secretion. FRF exerted potential anti-inflammatory effects by improving insulin resistance and adiponectin levels, and could thus be used to help counteract obesity. The mRNA expressions of PPAR-γ, FAS, ACC, and CPT-1 were determined in liver tissue. Quantitative real-time PCR analysis was also performed to evaluate the expression of IL-1β, IL-6, and TNF-α in epididymal adipose tissue. Compared to the control group, mice fed the HFD showed the up-regulation in PPAR-γ, FAS, IL-6, and TNF-α genes, and down-regulation in CPT1 gene expression. FRF treatement markedly reduced the expression of PPAR-γ, FAS, IL-6, and TNF-α compared to those in HFD control, whereas increased the expression level of CPT1.BRConclusions: These results suggest that the FRF and its major active constituent, rutin, can be used as effective anti-obesity agents.

RETRACTED: Protective effect of naringin on small intestine injury in NSAIDs related enteropathy by regulating ghrelin/GHS-R signaling pathway

To investigate the mechanism of Ghrelin/GHS-R signaling pathway in small intestine injury induced by NSAIDs related enteropathy. To clarify the mechanism network of intestinal mucosal repair with naringin as a new therapeutic method. Naringin was used as the intervention method, observed the damage of small intestinal mucosa and detected the expression of ghrelin, GHS-R, leptin and TNF-α by electron microscopy, HE staining and immunohistochemistry. Compared with the control group, the weight of rats in the model group decreased, the thickness of intestinal mucosa became thinner, the structure of intestinal mucosa changed, the expression of ghrelin, GHS-R and leptin decreased, the expression of TNF-α increased. Compared with the model group, the intestinal mucosa of the treatment group was repaired, the expression of ghrelin, GHS-R and leptin was increased, and the expression TNF-α was decreased. The mechanism of intestinal mucosal damage in patients with NSAIDs related enteropathy may be related to the decreased expression of ghrelin, GHS-R and leptin, and promotion of TNF-α secretion. Naringin can effectively promote the secretion of ghrelin and leptin, the expression of GSH-R, and inhibit the release of TNF-α, so as to repair intestinal mucosa naringin will become a new method to treat and prevent NSAIDs related intestinal diseases.

Examining the obesity paradox: A moderating effect of fitness on adipose endocrine function in older adults

Despite evidence linking obesity with increased mortality, older adults with excessive adiposity seem protected, resulting in a so-called obesity paradox. Obesity is characterized by leptin resistance, which contributes to increased risk of all-cause mortality. Therefore, lifestyle factors, such as physical fitness, that lower leptin independent of adiposity may be confounding the obesity paradox. To investigate this, we evaluated whether physical fitness moderated the relationship between leptin and adiposity. We found older adults with higher fitness had lower body mass (r(39) = -0.43, p < 0.01), leptin (r(39) = -0.29, p = 0.03) and inflammation (IL-1β: (r(39) = -0.69, p < 0.01); TNF-α: (r(39) = -0.30, p = 0.03)). Fitness moderated the relationship between leptin and adiposity (F(5, 37) = 3.73, p < 0.01, R2 = 0.33) to reveal the obesity paradox in moderately and high fit individuals (b = 216.24, t(37) = 1.46, p = 0.15; b= -88.10, t(37) = -0.49, p = 0.63) but not in low fit individuals. These results show the link between obesity and mortality may not be dependent on total adiposity, but rather on endocrine function and adipocyte leptin secretion. These results have important implications for older adults struggling to maintain healthy body composition and suggest that fitness may promote overall wellbeing.

Electroacupuncture improves obesity by lowering gastrointestinal motility, blood lipids and expression of intestinal leptin and cholecystokinin in obese rats

To investigate the effect of electroacupuncture (EA) on gastrointestinal motility and expression of leptin(LEP) and cholecystokinin(CCK) in the small intestine in obese rats，so as to explore the mechanism of EA underlying improvement of obesity. Male Wistar rats were randomized into 5 groups: normal control, obesity model, abdominal acupoints ［"Guanyuan" (CV4), "Zhongwan" (CV12) and bilateral "Tianshu" (ST25)］, lower-leg acupoints ［bilateral "Zusanli" (ST36) and bilateral "Fenglong" (ST40)］, and abdominal+ lower-leg acupoints (n=10 rats in each group). The obesity model was established by feeding the animals with high-fat diet for 8 weeks. EA was applied to the abovementioned acupoints for 20 min every time, 3 times a week for 8 weeks. The food intake and body mass were recorded. The white adipose tissue around the testicles and in the abdominal region was weighed. The serum total cholesterol (TC), triglyceride (TG) and non-esterified fatty acid(NEFA) were detected by using automatic biochemical analyzer. The gastric empty rate and intestinal propulsive rate were calculated. The contents of serum CCK and LEP were detected by using ELISA, and the expression levels of CCK and LEP proteins in the small intestine were detected by using Western blot. Following modeling, the food intake, body mass, weight of white adipose around the testicles and abdomen, the gastric empty rate, and serum TC, TG, NEFA and LEP contents as well as intestinal LEP expression were significantly increased (P<0.05, P<0.01), while the intestinal propulsive rate, serum CCK content and intestinal CCK expression were evidently decreased (P<0.01) in the model group relevant to the normal control group. After EA interventions and compared with the model group, the increased levels of food intake, body mass, white adipose weight, gastric empty rate, TC, TG, and LEP in serum and small intestine, and the decreased levels of intestinal propulsive rate, CCK in the serum and intestine were reversed in the abdominal acupoints, lower-leg acupoints and abdominal+lower-leg acupoints groups (P<0.05, P<0.01). No significant differences were found in the effects of the three EA groups in down-regulating food intake, body mass, white adipose weight, gastric empty rate, serum TC, TG and LEP levels (except NEFA) and in up-regulating intestinal propulsive rate and CCK level (P>0.05). EA stimulation of the abdominal and lower-leg acupoints or both can reduce body weight on obesity rats, which is associated with its functions in regulating intestinal motility, food intake, and secretion of LEP and CCK.

Epinephrine and glucose regulation of leptin synthesis and secretion in a teleost fish, the tilapia (Oreochromis mossambicus)

Acute stress is regulated through the sympathetic adrenergic axis where catecholamines mobilize energy stores including carbohydrates as a principal element of the endocrine stress response. Leptin is a cytokine critical for regulating energy expenditure in vertebrates and is stimulated by various stressors in fish such as fasting, hyperosmotic challenge, and hypoxia. However, little is known about the regulatory interactions between leptin and the endocrine stress axis in fishes and other ectothermic vertebrates. We evaluated the actions of epinephrine and glucose in regulating leptin A (LepA) in vivo and in vitro in tilapia. Using hepatocyte incubations and a homologous LepA ELISA, we show that LepA synthesis and secretion decline as ambient glucose levels increase (10–25 mM). By contrast, bolus glucose administration in tilapia increases lepa mRNA levels 14-fold at 6 h, suggesting systemic factors regulated by glucose may counteract the direct inhibitory effects of glucose on hepatic lepa mRNA observed in vitro. Epinephrine stimulated glucose and LepA secretion from hepatocytes in a dose-dependent fashion within 15 min but had little effect on lepa mRNA levels. An in vivo injection of epinephrine into tilapia stimulated a rapid rise in blood glucose which was followed by a 4-fold increase in hepatic lepa mRNA levels at 2.5 and 6 h. Plasma LepA was also elevated by 6 h relative to controls. Recombinant tilapia LepA administration in vivo did not have any significant effect on plasma epinephrine levels. The results of this study demonstrate LepA is negatively regulated by rises in extracellular glucose at the level of the hepatocyte but stimulated by hyperglycemia in vivo. Further, epinephrine increases LepA. This, along with previous work demonstrating a hyperglycemic and glycogenolytic effect of LepA in tilapia, suggests that epinephrine may stimulate leptin secretion to augment and fine tune glucose mobilization and homeostasis as part of the integrated, adaptive stress response.

The Importance of Leptin to Reproduction.

A healthy nutritional state is required for all aspects of reproduction and is signaled by the adipokine leptin. Leptin acts in a relatively narrow concentration range: too much or too little will compromise fertility. The leptin signal timing is important to prepubertal development in both sexes. In the brain, leptin acts on ventral premammillary neurons which signal kisspeptin (Kiss1) neurons to stimulate gonadotropin releasing hormone (GnRH) neurons. Suppression of Kiss1 neurons occurs when agouti-related peptide neurons are activated by reduced leptin, because leptin normally suppresses these orexigenic neurons. In the pituitary, leptin stimulates production of GnRH receptors (GnRHRs) and follicle-stimulating hormone at midcycle, by activating pathways that derepress actions of the messenger ribonucleic acid translational regulatory protein Musashi. In females, rising estrogen stimulates a rise in serum leptin, which peaks at midcycle, synchronizing with nocturnal luteinizing hormone pulses. The normal range of serum leptin levels (10-20 ng/mL) along with gonadotropins and growth factors promote ovarian granulosa and theca cell functions and oocyte maturation. In males, the prepubertal rise in leptin promotes testicular development. However, a decline in leptin levels in prepubertal boys reflects inhibition of leptin secretion by rising androgens. In adult males, leptin levels are 10% to 50% of those in females, and high leptin inhibits testicular function. The obesity epidemic has elucidated leptin resistance pathways, with too much leptin in either sex leading to infertility. Under conditions of balanced nutrition, however, the secretion of leptin is timed and regulated within a narrow level range that optimizes its trophic effects.

HM-chromanone inhibits adipogenesis by regulating adipogenic transcription factors and AMPK in 3T3-L1 adipocytes

Portulaca oleracea L. is used as a folk medicine in many countries because of its wide range of pharmacological effects. HM-chromanone, isolated from P. oleracea using bioassay-guided fractionation and HPLC, belongs to the homoisoflavonoid group and has been shown to exert several biological effects. In this study, we evaluated whether HM-chromanone inhibits adipogenesis by regulating adipogenic transcription factors in 3T3-L1 adipocytes. The results showed that HM-chromanone suppresses adipocyte differentiation and adipogenesis in a dose-dependent manner in 3T3-L1 adipocytes. The HM-chromanone-treated adipocytes exhibited lower triglyceride accumulation and leptin secretion, and higher glycerol and adiponectin secretion than the control adipocytes. Microscopic observation using oil red O staining revealed a dose-dependent reduction in the number of lipid droplets in the HM-chromanone-treated adipocytes compared to the control group. HM-chromanone significantly down-regulated the protein expression of major adipogenic transcription factors sterol regulatory element binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor γ (PPARγ), and CCAAT/enhancer binding protein α (C/EBPα) and markedly inhibited several key adipogenic enzymes including fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC). In addition, adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) were both more activated in the HM-chromanone-treated adipocytes than in the control adipocytes. HM-chromanone also promoted the phosphorylation of 5′ Adenosine monophosphate-activated protein kinase (AMPK), which inhibits adipogenesis through the regulation of adipogenic transcription factors. These results suggest that HM-chromanone may be an effective anti-adipogenesis agent that functions via the suppression of adipogenic transcription factors and the activation of AMPK.

Leptin Downregulates Angulin-1 in Active Crohn's Disease via STAT3.

Crohn’s disease (CD) has an altered intestinal barrier function, yet the underlying mechanisms remain to be disclosed. The tricellular tight junction protein tricellulin is involved in the maintenance of the paracellular macromolecule barrier and features an unchanged expression level in CD but a shifted localization. As angulins are known to regulate the localization of tricellulin, we hypothesized the involvement of angulins in CD. Using human biopsies, we found angulin-1 was downregulated in active CD compared with both controls and CD in remission. In T84 and Caco-2 monolayers, leptin, a cytokine secreted by fat tissue and affected in CD, decreased angulin-1 expression. This effect was completely blocked by STAT3 inhibitors, Stattic and WP1066, but only partially by JAK2 inhibitor AG490. The effect of leptin was also seen at a functional level as we observed in Caco-2 cells an increased permeability for FITC-dextran 4 kDa indicating an impaired barrier against macromolecule uptake. In conclusion, we were able to show that in active CD angulin-1 expression is downregulated, which leads to increased macromolecule permeability and is inducible by leptin via STAT3. This suggests that angulin-1 and leptin secretion are potential targets for intervention in CD to restore the impaired intestinal barrier.

Modulation of IR as a therapeutic target to prevent NASH using NRF from Diceratella elliptica (DC.) jonsell. Strong Nrf2 and leptin inducer as well as NF-kB inhibitor

BackgroundInsulin resistance (IR) and lipotoxicity were evidenced as the major nonalcoholic steatohepatitis (NASH) initiators. However, absence of the effective treatment against NASH progression raised our aim to discover a new promising insulin modulator and NSH preventer. PurposeOur study aimed to extract and prepare a nitriles rich fraction (NRF) from Diceratella elliptica (DC.) Jonsell, investigate its insulin-sensitizing & anti-NASH potentialities and address its molecular targets in IR-NASH pathogenesis. Study designNRF was prepared using natural autolysis method and compounds were identified. Then, seventy male Wistar rats were feed high fat diet (HFD) or normal pellets for 35 days. In day 14th, HFD rats were injected by Streptozotocin (STZ) once and treatment was started in day 21st with either NRF (30, 60 and 120 mg/kg; orally) or pioglitazone (PioG) (10 mg/kg; i.p) beside HFD. While, NRF-alone rats were treated with NRF (120 mg/kg; orally) beside the normal pellets. Body weight, glucose homeostasis, hepatopathological examinations were performed. MethodsGas liquid chromatography-mass spectrophotometry (GLC/MS) was used for compounds’ identification while spectrophotometer was used for total glucosinolates (GLS) quantification. Also, the biochemical and molecular investigations concerned with liver lipotoxicity, oxidative stress, inflammation and insulin signaling pathway were investigated and confirmed with the computational prediction of the major compounds’ targets. ResultsButenyl and benzyl GLS were the major along with other volatile compounds. NRF had significantly increased the insulin sensitivity and improved NASH-hisptopathology showing hepatoprotective effect. While, the fraction's anti-NASH potentiality was evidenced in the normalized hepatic steatosis markers, inflammation and oxidative stress key transcriptional factors resulting in induction of insulin receptor substrates (IRSs) phosphorylation and its downstream effectors. ConclusionNRF has reversed IR, stimulated leptin secretion and prevented NASH initiation showing promising anti-NASH and anti-fibrotic effects.

Nutritional regulators of the hypothalamic–pituitary axis in pigs

Nutritional signals are detected by the central nervous system (CNS) and translated by the neuroendocrine system into signals that alter secretion of LH and growth hormone (GH). Furthermore, these signals directly affect the activity of the pituitary gland independently of CNS input. Insulin-like growth factor I (IGF-I), insulin, leptin and specific metabolites, such as glucose and free fatty acids (FFA)', are potential signals of the metabolic status to the brain-pituitary axis. Intravenous injection of a lipid emulsion or glucose suppressed the GH and LH response to GH releasing hormone (GHRH) and GnRH, respectively. Insulin and IGF-I regulation of LH and GH secretion occur at the pituitary gland. Feed deprivation for 24 h suppressed leptin secretion without affecting LH or GH secretion, whereas central administration of leptin resulted in a decrease in feed intake and an increase in GH secretion. Oestrogen-induced leptin gene expression in adipose tissue increased with age and adiposity in pigs. Leptin stimulated GnRH release from hypothalamic tissue in vitro. These results identify putative signals that link metabolic status and neuroendocrine control of growth and reproduction by altering endocrine function during periods of fasting, feed restriction and lactation.

HIV Protease Inhibitor Ritonavir Impairs Endothelial Function Via Reduction in Adipose Mass and Endothelial Leptin Receptor-Dependent Increases in NADPH Oxidase 1 (Nox1), C-C Chemokine Receptor Type 5 (CCR5), and Inflammation.

BackgroundCardiovascular disease is currently the leading cause of death in patients with human immunodeficiency virus on combination antiretroviral therapy. Although the use of the protease inhibitor ritonavir has been associated with increased prevalence of cardiovascular disease, the underlying mechanisms remain ill‐defined. Herein, we tested the hypothesis that ritonavir‐mediated lipoatrophy causes endothelial dysfunction via reducing endothelial leptin signaling.Methods and ResultsLong‐term (4 weeks) but not short‐term (3 days) treatment with ritonavir reduced body weight, fat mass, and leptin levels and induced endothelial dysfunction in mice. Moreover, ritonavir increased vascular NADPH oxidase 1, aortic H2O2 levels as well as interleukin‐1β, GATA3 (GATA binding protein 3), the macrophage marker (F4/80), and C‐C chemokine receptor type 5 (CCR5) expression. Reactive oxygen species scavenging with tempol restored endothelial function, and both NADPH oxidase 1 and CCR5 deletion in mice protected from ritonavir‐mediated endothelial dysfunction and vascular inflammation. Remarkably, leptin infusion markedly improved endothelial function and significantly reduced vascular NADPH oxidase 1, interleukin‐1β, GATA3, F4/80, and CCR5 levels in ritonavir‐treated animals. Selective deficiency in endothelial leptin receptor abolished the protective effects of leptin infusion on endothelial function. Conversely, selective increases in endothelial leptin signaling with protein tyrosine phosphatase deletion blunted ritonavir‐induced endothelial dysfunction.ConclusionsAll together, these data indicate that ritonavir‐associated endothelial dysfunction is a direct consequence of a reduction in adiposity and leptin secretion, which decreases endothelial leptin signaling and leads to a NADPH oxidase 1–induced, CCR5‐mediated reduction in NO bioavailability. These latter data also introduce leptin deficiency as an additional contributor to cardiovascular disease and leptin as a negative regulator of CCR5 expression, which may provide beneficial avenues for limiting human immunodeficiency virus infection.

Short-term administration of spexin in rats reduces obesity by affecting lipolysis and lipogenesis: An in vivo and in vitro study

The present study aimed to characterize the role of spexin (SPX) in maintaining glucose and lipid homeostasis in vivo in rats with diet-induced obesity. The in vitro effect of spexin on metabolic and endocrine functions of adipocytes isolated from obese rats was also investigated. The in vivo experiment was conducted on rats with diet-induced obesity and administered with SPX for 7 days. Lipid and carbohydrate parameters, liver markers, and hormonal profile were measured. In in vitro studies, adipocytes isolated from obese rats were used. The effect of SPX on lipolysis, lipogenesis, and leptin secretion from fat cells was assessed. The results showed that short-term administration of SPX causes weight loss, increases insulin sensitivity, and improves the metabolic state of obese rats. The in vitro experiments showed that spexin and its receptors, namely galanin receptor 2 (GALR2) and galanin receptor 3 (GALR3), were expressed in various fat depots and in adipocytes from obese rats. We also found that the addition of spexin increased the basal and isoproterenol-stimulated lipolysis and reduced the basal and insulin-stimulated lipogenesis in adipocytes isolated from obese rats. Molecular analysis showed that SPX activated hormone-sensitive lipase (HSL) phosphorylation and upregulated perilipin and HSL mRNA expression. These results suggest that SPX regulates metabolism of obese rats by affecting lipolysis and lipogenesis in adipocytes. Moreover, the present study for the first time demonstrates that SPX modulates leptin synthesis and secretion from isolated adipocytes.

OBEZ HASTALARDA LEPTİN DÜZEYİNİN VE D VİTAMİNİ İLİŞKİSİNİN DEĞERLENDİRİLMESİ

Introduction: Adipocyte-induced hormone leptin, nutrition and energy play an important role in homeostasis. Leptin regulates central or peripheral complex biological effects through its receptors. The mechanisms linking obesity and associated leptin resistance remain largely unclear. Also noncalcaemic effects of Vit D, perspective role is played on hormonal regulation of glucose metabolism and synthesis of adipokines by fat tissue. The aim of our study is to show the role of vitamin D levels on obesity and the activity of leptin levels during Vitamin D differentiation on obese patients. Material and Methods: 40 obese and healthy patients were included this research to analyze Vit D levels. While seen low-Vit D level in individuals, 4 weeks Vit D treatment has been completed. Whole experimental groups were taken blood for leptin measurement. Results: Our findings were indicated that leptin expression was decreased when vitamin D level in low. However, during vitamin D uptake, leptin levels in obese patients were increased correlated to deficiency. That means, leptin is known significant marker to detect obesity which has direct relation with Vitamin D level. Conclusion: These results highlight that reduction serum Vit D levels leads to improved leptin sensitivity. Future clinical trials should be tested Vit D alteration might be diagnostic factor for obesity treatment to leptin secretion.

Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity.

Leptin influences food intake by informing the brain about the status of body fat stores. Rare LEP mutations associated with congenital leptin deficiency cause severe early-onset obesity that can be mitigated by administering leptin. However, the role of genetic regulation of leptin in polygenic obesity remains poorly understood. We performed an exome-based analysis in up to 57,232 individuals of diverse ancestries to identify genetic variants that influence adiposity-adjusted leptin concentrations. We identify five novel variants, including four missense variants, in LEP, ZNF800, KLHL31, and ACTL9, and one intergenic variant near KLF14. The missense variant Val94Met (rs17151919) in LEP was common in individuals of African ancestry only, and its association with lower leptin concentrations was specific to this ancestry (P = 2 × 10-16, n = 3,901). Using in vitro analyses, we show that the Met94 allele decreases leptin secretion. We also show that the Met94 allele is associated with higher BMI in young African-ancestry children but not in adults, suggesting that leptin regulates early adiposity.

Obesity as a contributor to immunopathology in pregnant and non-pregnant adults with COVID-19.

The ongoing coronavirus disease 2019 (COVID‐19) pandemic has led to a global public health emergency with the need to identify vulnerable populations who may benefit from increased screening and healthcare resources. Initial data suggest that overall, pregnancy is not a significant risk factor for severe coronavirus disease 2019 (COVID‐19). However, case series have suggested that maternal obesity is one of the most important comorbidities associated with more severe disease. In obese individuals, suppressors of cytokine signaling are upregulated and type I and III interferon responses are delayed and blunted leading to ineffective viral clearance. Obesity is also associated with changes in systemic immunity involving a wide range of immune cells and mechanisms that lead to low‐grade chronic inflammation, which can compromise antiviral immunity. Macrophage activation in adipose tissue can produce low levels of pro‐inflammatory cytokines (TNF‐α, IL‐1β, IL‐6). Further, adipocyte secretion of leptin is pro‐inflammatory and high circulating levels of leptin have been associated with mortality in patients with acute respiratory distress syndrome. The synergistic effects of obesity‐associated delays in immune control of COVID‐19 with mechanical stress of increased adipose tissue may contribute to a greater risk of pulmonary compromise in obese pregnant women. In this review, we bring together data regarding obesity as a key co‐morbidity for COVID‐19 in pregnancy with known changes in the antiviral immune response associated with obesity. We also describe how the global burden of obesity among reproductive age women has serious public health implications for COVID‐19.

Baicalin-Copper Complex Modulates Gut Microbiota, Inflammatory Responses, and Hormone Secretion in DON-Challenged Piglets.

Simple SummaryDeoxynivalenol (DON) is the most common mycotoxin contaminant in the agriculture industry worldwide. Copper is very efficacious in promoting growth performance and improving feed remuneration, and baicalin may alleviate oxidative stress and inflammatory responses in humans and animals. We speculated that the combined effect of baicalin and copper would have some effect in DON-challenged piglets. The present study examined the effects of a baicalin-copper complex on inflammatory responses, hormone secretion, and gut microbiota in DON challenged piglets. These findings provide new application prospects in piglets involving the combination of baicalin and copper.The present experiment assessed the inflammatory responses, hormone secretion, and gut microbiota of weanling piglets administered baicalin-copper complex (BCU) or deoxynivalenol (DON) supplementation diets. Twenty-eight piglets were randomly assigned to four groups: control diet (Con group), a 4 mg DON/kg diet (DON group), a 5 g BCU/kg diet (BCU group), a 5 g BCU + 4 mg DON/kg diet (DBCU group). After 14 days, the results showed that dietary BCU supplementation remarkably increased the relative abundance of Clostrium bornimense and decreased the relative abundance of Lactobacillus in the DBCU group (p < 0.05). BCU decreased the serum concentration of IgG, IL-2, IFN-γ, and IgA in DON treated piglets (p < 0.05), and promoted the serum concentration of IL-1β, IgG, IL-2, IFN-γ, IgA, IL-6, IgM, and TNFα in normal piglets (p < 0.05). BCU increased the concentrations of serum IGF1, insulin, NPY, GLP-1, and GH, and decreased the concentrations of serum somatostatin in no DON treated piglets (p < 0.05). Dietary BCU supplementation significantly promoted the secretion of somatostatin, and inhibited the secretion of leptin in piglets challenged with DON (p < 0.05). BCU regulated the expression of food intake-related genes in the hypothalamus and pituitary of piglets. Collectively, dietary BCU supplementation alleviated inflammatory responses and regulated the secretion of appetite-regulating hormones and growth-axis hormones in DON challenged piglets, which was closely linked to changes of intestinal microbes.