Decreased Leptin Concentrations Research Articles

Investigation of Adiponectin, Leptin and Ghrelin Levels and Evaluation of Metabolic Profiles in the Periparturient Period in Romanov Sheep

The periparturient period is very important especially in terms of pregnancy-related herd-based diseases. In this period, especially for early diagnosis of subclinical diseases, a metabolic profile test is used. In the periparturient period, important changes occur in adipose tissue. Blood samples were collected from 16 Romanov sheep in the periparturient in serum tubes on the 21st, 14th, 7th, and postpartum days, and 7th, 14th, and 21st days after delivery. Metabolic profile and Adiponectin, Leptin and Ghrelin parameters evaluated from the blood samples. In the periparturient period, ELISA analyzes of TNF-α were performed for inflammatory evaluation. As a result of the analyzes, Prenatal increase in NEFA concentrations, postpartum decrease in cholesterol concentrations, postpartum increase and decrease in AST concentrations, postpartum increase in GGT concentrations, prenatal and postnatal increases in total protein concentrations, postpartum increase in BUN and creatinine concentrations, postpartum decrease in magnesium concentrations, Prenatal increase in adiponectin concentrations and postpartum decrease, postpartum decrease in leptin concentrations and prenatal increase in ghrelin concentrations occurred. With the results obtained, it was concluded that the evaluation of metabolic profile and adipose tissue is important in the diagnosis of diseases in the periparturient period.

Exploring the rare variants associated with Type 2 Diabetes Mellitus in Indian population and its disease-drug association studies: an in-silico approach

The diversified eating habits and religious culture of Indian population may be one of the reasons they largely contribute to the global diabetes burden. In the present investigation, an in-silico approach was carried out to explore hub genes in the Indian population with Type 2 Diabetes Mellitus (T2DM) that are scantily reported in the GWAS catalogue and probable potential anti-diabetic drugs from plants. This computational approach unwrapped LEP (leptin) as the hub gene among 170 genes analyzed with 14 non-synonymous single nucleotide polymorphisms (nsSNPs) with MAF < 0.01. The mutation of the LEP gene leads to a decrease in leptin concentration, which increases the risk of obesity and T2DM. According to the DUET webserver, 11 of 14 mutations examined were found to destabilize the LEP protein. Among 14, four barely reported LEP variants rs781301976 (I45N), rs776443424 (S52F), rs200915360 (D76Y), and rs1191666811 (D162N) were unzipped to be associated with T2DM, which may be the probable potential drug targets. The virtual screening revealed Vescalagin as having the highest binding energy among 336 natural compounds. Molecular docking of Vescalagin depicted higher binding energy (-9.0 kcal/mol) against mutated LEP [rs200915360 (D76Y)] compared to wild (-8.9 kcal/mol) and LEP-Metformin complexes. The trajectory analysis of MD simulations revealed that Vescalagin was more effective than Metformin in stabilizing the system. The present study suggests that the associations of the investigated nsSNPs in LEP [rs200915360 (D76Y)] and others can be key factors in the predominant role of T2DM morbidity in the Indian population that can be used as potential markers and drug targets for T2DM therapeutics. Communicated by Ramaswamy H. Sarma

Impact of Two Types of Exercise Interventions on Leptin and Omentin Concentrations and Indicators of Lipid and Carbohydrate Metabolism in Males with Metabolic Syndrome.

Leptin (LEP) and omentin (OMEN) are proteins whose concentrations change with the development of the metabolic syndrome (MetS). There are few intervention studies using various forms of physical activity in people with MetS that aim to determine the impact of physical exercise on the fluctuations of the presented hormones, and their results are contradictory. The present study aimed to examine the effect of two types of exercise intervention on LEP and OMEN concentrations and indicators of lipid and carbohydrate metabolism in males with MetS. The study included 62 males with MetS (age 36.6 ± 6.9 years, body mass 110.31 ± 17.37 kg), randomly allocated to EG1, the examined group with aerobic training (n = 21); EG2, the examined group with combined aerobic and resistance training (n = 21), both for 12 weeks, and the control group (CG) without interventions (n = 20). Anthropometric measurements, body composition (body fat [BF], android body fat [ANDR]), as well as a biochemical blood analysis (omentin [OMEN], leptin [LEP], quantitative insulin sensitivity check index [QUICKI], high-density lipoprotein cholesterol [HDL-C] and nonHDL-C) were performed at baseline, and at 6 and 12 weeks of interventions and after 4 weeks after ending intervention (follow-up). Intergroup and intragroup comparisons were performed. In the intervention groups EG1 and EG2, a decrease in BF was observed as well as an improvement in carbohydrate metabolism parameters. In the EG1 group, the level of ANDR was reduced. In EG2 a decrease in LEP concentration between measurements was confirmed. However, no significant changes were found in the concentration of OMEN in any groups. Combined aerobic and resistance exercises led to a higher reduction of LEP concentration than applying only aerobic training in males with MetS.

Pheophorbide A isolated from Gelidium amansii inhibits adipogenesis by regulating adipogenic transcription factors and AMPK in 3T3-L1 adipocytes

Adipocyte lipid accumulation causes adipocyte hypertrophy and adipose tissue increment, leading to obesity. As part of our efforts to isolate antiobesity agents from natural products, we first isolated the active compound from the extract of Gelidium amansii through bioassay-guided fractionation. We then hypothesized that pheophorbide A isolated from G amansii inhibits adipogenesis by downregulating adipogenic transcription factors; therefore, the antiadipogenic effects of pheophorbide A were investigated in 3T3-L1 adipocytes. On differentiation of 3T3-L1 preadipocytes into adipocytes, they were treated with pheophorbide A (0-83 µM). Pheophorbide A inhibited triglyceride accumulation (half maximal inhibitory concentration = 114.2 µM) and stimulated glycerol release in a dose-dependent manner in 3T3-L1 adipocytes. In addition, pheophorbide A significantly decreased leptin concentrations in 3T3-L1 adipocytes. Pheophorbide A inhibited adipogenesis by suppressing the expression of adipogenic transcriptional factors including peroxisome proliferator-activated receptor γ, CCATT/enhancer binding protein α, sterol regulatory element binding protein 1c, and fatty acid synthase. It also induced the expression of phosphorylation of AMP-activated protein kinase. Therefore, these results suggest that pheophorbide A may be useful for preventing or treating obesity because of its inhibitory effect on adipogenesis.

Effects of tramadol abuse on plasma concentration of leptin and agouti related protein (AgRP)

The current study is a trial to understand the effect of one of the most commonly used analgesics and also one of the most abused drugs “tramadol” on the hormones regulating the appetite and subsequently the body weight “Leptin and AgRP”. This study included 40 participants, classified into four groups, 10 participants each. Group I (GI) and group II (GII) composed of control healthy volunteer males having confirmed negative tramadol and des-methy-tramadol in their blood. GI participants aged 38.67 ± 2.35 years and have normal weight with Body Mass Index (BMI) equal 21.9 ± 0.67. GII participants aged 37.40 ± 2.67 years and having BMI equal 33.93 ± 0.57. Group III (GIII) and group IV (GIV) had positive tramadol and des-methyl- tramadol in their blood confirmed by gas chromatography-mass spectrometry. GIII participants have normal weight with BMI equal 22.55 ± 0.88 and age equal 37.66 ± 2.30 years. GIV participants were obese with BMI equal 33.83 ± 0.81 and age equal to 36.40 ± 2.60 years. All subjects with hypertension and diabetes mellitus were excluded. Human leptin hormone was measured depending on immunoradiometric assay IRMA; the human AgRP hormone was measured by using a quantitative sandwich enzyme immunoassay technique. Leptin concentration in obese non tramadol users (GII) is increased (14.78 ± 0.74) in comparison to the normal weight non tramadol users (GI) (6.96 ± 0.43) but it is lower than the obese tramadol users (GIV) (17.68 ± 0.6) while the normal weight tramadol users (GIII) showed increased leptin concentration (14.02 ± 0.83) in comparison to the normal weight non tramadol users (GI) (6.96 ± 0.43) and decreased leptin concentration in comparison to the obese tramadol users (GIV) (17.68 ± 0.6). Regarding the blood concentration of AgR P, it was higher in GII (17.12 ± 1.14) than GIV (11.85 ± 0.79) and lower in GIII (17.33 ± 0.98) than GI (25.05 ± 0.72). So it can be concluded that using tramadol was associated with an increase in leptin concentration either on comparing the normal weight groups or the high BMI groups. An opposite effect was seen on AgRP concentration. There is positive correlation between leptin and BMI in the control groups (GI and GII) and negative correlations in the tramadol users in groups (GIII and GIV) meanwhile there was a negative correlation between AgRP and BMI in the control groups (GI and GII) and positive correlations in the tramadol users in groups (GIII and GIV). A negative correlation between leptin and AgRP in all the studied groups. It is concluded that tramadol abuses increased leptin concentration in both normal weight and obese cases in comparison to non-abusers either normal weight or obese. Meanwhile, it decreased AgRP concentration in both normal weight and obese cases in comparison to non-abusers either normal weight or obese. Also, the review of the literature concluded that they are also altered in different cases of drug abuse so it is recommended to study the effect of other abused drugs on these hormones.

The role of leptin in monitoring training loads during rowing: a systematic review

Objective: In competitive sports, too small or too large loads lead to poor sports results. Situation of overload are particularly dangerous to the body, which may lead to overtraining. In this work, the literature on the possibility of assessing training loads with the use of leptin concentration measurement in men and women practicing rowing was analysed. Materials and methods: A systematic review was performed using the Scopus, Pubmed and Google Scholar databases between 1995-2020. After an initial analysis of 56 articles and taking the analysed topics into account, 25 articles were included in this review. As part of the review, data for 75 rowers were analysed. The usefulness of leptin - a hormone produced by adipose tissue - as a marker of training loads in several sports disciplines, with particular emphasis on rowing, was evaluated. Within this context, the role of leptin may be to control these loads due to its relatively high sensitivity in response to increases in training intensity or volume. The presented general characteristics of rowing and the physiological basis of exercise are the background for considerations on the possibility of using leptin as a burden marker in this discipline. Results: Due to the fact that the concentration of leptin correlates with the content of adipose tissue and BMI (Body Mass Index), its changes may inform about training loads directly related to the amount of energy expenditure. A review of the literature from the last 25 years, i.e. from the moment when this hormone was discovered, allowed to formulate the thesis that leptin may be a marker of training loads, however, determining its concentration makes sense when the same factors that may affect its secretion are taken into account each time. Conclusions: Training in rowing, that involves high training loads, causes significant changes in blood leptin levels. Training periods with high exercise load, associated with a significant increase in energy expenditure, lead to a decrease in resting leptin concentration, while periods with less load increase it. The main factor determining changes in leptin concentration during training is the amount of energy expenditure, which in the case of rowing involving very large muscle groups, is very high. Although the amount of energy expenditure in training, leading to a decrease in leptin concentration is difficult to determine, the energy expenditure cannot be less than 800 kcal in a single training unit.

Effects of poor maternal nutrition during gestation on ewe and offspring plasma concentrations of leptin and ghrelin

Poor maternal nutrition during gestation can negatively affect offspring growth, development, and health. Leptin and ghrelin, key hormones in energy homeostasis and appetite control, may mediate these changes. We hypothesized that restricted- and over-feeding during gestation would alter plasma concentrations of leptin and ghrelin in ewes and offspring. Pregnant ewes (n = 37) were fed 1 of 3 diets starting on d 30 ± 0.02 of gestation until necropsy at d 135 of gestation or parturition: restricted- [RES; 60% National Research Council (NRC) requirements for total digestible nutrients, n = 13], control- (CON; 100% NRC, n = 11), or over-fed (OVER; 140% NRC, n = 13). Blood samples were collected from pregnant ewes at days 20, 30, 44, 72, 100, 128, and 142 of gestation. Offspring blood samples were collected within 24 h after birth (n = 21 CON, 25 RES, 23 OVER). Plasma leptin and ghrelin concentrations were determined by RIA. Ewe data were analyzed using the MIXED procedure in SAS with ewe as the repeated subject. Offspring data were analyzed using the MIXED procedure. Correlations between BW and leptin and ghrelin concentrations were identified using PROC CORR. At d 100, RES (5.39 ± 2.58 ng/mL) had decreased leptin concentrations compared with OVER (14.97 ± 2.48 ng/mL; P = 0.008) and at d 128, RES (6.39 ± 2.50 ng/mL) also had decreased leptin concentrations compared with OVER (13.61 ± 2.47 ng/mL; P = 0.04). At d 142, RES (0.26 ± 0.04 ng/mL) had increased ghrelin concentrations compared with CON (0.15 ± 0.04 ng/mL; P = 0.04). Leptin and ghrelin concentrations were also altered between days of gestation within a dietary treatment. In CON ewes, plasma concentrations of leptin were increased at d 30 (19.28 ± 7.43 ng/mL) compared with d 44 (5.20 ± 3.10 ng/mL; P = 0.03), and the plasma concentrations of ghrelin at d 128 (0.20 ± 0.03 ng/mL) were increased compared with d 30 (0.16 ± 0.03 ng/mL; P = 0.01) and d 100 (0.17 ± 0.03 ng/mL; P = 0.04). Maternal diet did not alter plasma ghrelin or leptin concentrations in the offspring (P > 0.50). There were no strong, significant correlations between ewe BW and leptin (r < 0.33; P > 0.06) or ghrelin (r > -0.47; P > 0.001) concentrations or lamb BW and leptin or ghrelin concentrations (r > -0.32, P > 0.06). Maternal alterations in circulating leptin and ghrelin may program changes in energy balance that could result in increased adiposity in adult offspring. Alterations in energy homeostasis may be a mechanism behind the long-lasting changes in growth, body composition, development, and metabolism in the offspring of poorly nourished ewes.

Anti-Oxidant potential of Herbal formulation (Sahaj Vati) Modulating Leptin, Insulin activity

Obesity increased at alarming rate considered as serious health risks and World Health Organization wish to halt rise of obesity. Therefore, search for treatment, dietary interventions is necessary to attenuate and/or prevent the obesity. Sahaj Vati was prepared by Shilajeet , Curcuma longa , Plumbago zeylanica, Commiphora mukul and might be reduces obesity. Twenty four albino rats were randomized into four equal groups were selected as control, positive control, as standard (orlistate) and Sahaj Vati treated group, respectively. Monosodium glutamate (MSG) was administered at dose of 10 mg/kg body weight for 10 days and Sahaj Vati &amp; orlistate was administered orally at dose of 200 and 10 mg/kg body weight respectively for four week. After four week, body weight of animals, serum leptin, insulin, total oxidant, total antioxidant and oxidative stress index were estimated. It was observed that body weight was significantly increased by MSG whereas body weight, was significantly decreased by orlistat and Sahaj Vati . Sahaj Vati significantly increased insulin concentration, total anti-oxidant status and decreased total oxidant status &amp; oxidative stress and significantly decreased leptin concentration. Thus, Sahaj Vati decreases body weight by modulating leptin &amp; insulin concentration as well as total oxidant status, total anti-oxidant status &amp; oxidative stress.

The Effect of Omega-3 Fatty Acid Supplementation on Serum Adipocytokines, Lipid Profile and Biochemical Markers of Inflammation in Recreational Runners.

Background: The study aimed to evaluate the effects of a 3-week ω-3 PUFA supplementation on serum adipocytokines (i.e., adiponectin, leptin), neuregulin-4 (NRG4) and erythrocyte omega-3 (ω-3) fatty acid content, as well as the blood antioxidant defense capacity in non-elite endurance runners. Methods: Twenty-four runners were randomized into two groups: the supplemented group, who received omega free fatty acids extract containing 142 mg of EPA, 267 mg of DHA, 12 mg of vitamin E and 5 µg of vitamin D, each administrated at a dose of six capsules twice a day for three weeks, or the placebo group. Venous blood samples were withdrawn at the start and at the end of the study protocols to estimate serum biochemical variables. Results: A significantly higher ω-3 index and lower AA/EPA ratio was observed after ω-3 PUFA compared to pre-supplementation levels (p < 0.001 and p < 0.001, respectively). An increase in baseline adiponectin and NRG4 levels, as well as a decrease of leptin concentration and lipid profile improvement, were observed in subjects after a ω-3 PUFA diet. The increased ω-3 index had a significant effect on TNFα levels and a serum marker of antioxidant defense. Conclusions: The ω-3 PUFA extract with added vitamin E and D supplementation may have a positive effect on the function of the adipocyte tissue, as well as the ability to prevent cardiovascular complications in athletes.

PSIV-28 Program Chair Poster Pick: The Effects of Poor Maternal Nutrition During Gestation on Ewe and Offspring Plasma Concentrations of Leptin and Ghrelin

Abstract Poor maternal nutrition (restricted- and over-feeding) during gestation may alter leptin and ghrelin, key hormones in energy homeostasis and appetite control. They may also have a regulatory role in maternal metabolic adaptations critical during gestation to ensure optimal offspring growth and development. We hypothesized that restricted- and over-feeding during gestation would alter plasma concentrations of leptin and ghrelin in ewes and their offspring. Pregnant Western White-faced ewes were individually fed 60% (RES; n = 13), 100% (CON; n = 11), or 140% (OVER; n = 13) of NRC requirements for TDN starting on d 30±0.02 of gestation. Blood samples were collected in the morning from fasted pregnant ewes weekly from d 20 of gestation until parturition and from offspring (n = 31) within 24 hours after birth. Leptin and ghrelin concentrations were determined by radioimmunoassay. Data were analyzed using the MIXED procedure in SAS with main effects of treatment, day of gestation and their interaction. Leptin (P &amp;lt; 0.002) and ghrelin (P &amp;lt; 0.015) concentrations were altered in pregnant ewes between treatments within a day of gestation. At d 100 (P = 0.008) and d 128 (P = 0.04), RES ewes (5.392.58 ng/mL; 6.392.50 ng/mL) had decreased leptin concentrations compared with OVER ewes (14.972.48 ng/mL; 13.612.47 ng/mL), with CON ewes intermediate. RES ewes (0.260.04 ng/mL) had increased ghrelin concentrations compared with CON ewes at d 142 (0.150.04 ng/mL; P = 0.042), with OVER ewes intermediate. Leptin (P &amp;lt; 0.002) and ghrelin (P &amp;lt; 0.015) concentrations were altered between days of gestation within a dietary treatment. Leptin concentration increased across gestation in OVER ewes. In RES ewes, leptin concentration decreased and ghrelin concentration increased over gestation. Leptin (P = 0.5) and ghrelin (P = 0.5) concentrations in lambs were not different at birth. Alterations in leptin and ghrelin in ewes during gestation may disrupt critical metabolic adaptations that may contribute to suboptimal offspring growth and development.

Acute effect of concurrent exercise on serum leptin and resistance insulin response in sedentary men

Aim: This study aimed to determine the delayed effect of one session of concurrent exercise on serum leptin and resistance insulin levels of sedentary men. Materials and Methods: Fifteen healthy young men with a mean age of 22.9 ± 1.7 years and a body mass index of 23.3 ± 1 kg/m2 voluntarily participated in this experimental research. They participated in one session of concurrent exercise including 20 min of aerobic running on a treadmill at 60%–70% maximum oxygen uptake plus a resistance exercise at the intensity of 70% of 1-repetition maximum with ten repetitions per set to second round. Blood serum leptin, glucose, insulin, and insulin resistance index were assessed before, 24, 48, and 72 h after the exercise program.Results: The results showed that leptin level did not change statistically significantly immediately and 72 h after the exercise termination (P > 0.05) but did decrease statistically significantly 24 and 48 h after the exercise program (P ≤ 0.05). The result also showed that insulin and insulin resistance levels decreased statistically significantly immediately after the exercise and lasted for up to 48 h postexercise (P ≤ 0.05); however, it returned to its initial value after 72 h of recovery (P > 0.05). Conclusions: It was concluded that energy use in one session of concurrent exercise might reduce leptin levels up to 48 h of recovery. In addition, a decrease in insulin, a known inducer of leptin expression in adipocytes, occurs before the decrease in leptin. This change may mediate the decrease of leptin concentration.

The Effect of Noninvasive Bariatric Surgery on the Levels of Certain Adipokines and Atherosclerosis Risk Factors in Patients with Metabolic Syndrome

Objective: Besides glucose intolerance, dyslipidemia, and hypertension, visceral obesity is one of the most important atherogenic pathological factors in patients with metabolic syndrome (MetS). The aim of this study is to examine whether weight loss following BioEnterics Intragastric Balloon (BIB-system) therapy affects adipokine concentration and atherosclerosis risk factor profile in patients with MetS.Methods: The study group comprised 30 patients (17 female, BMI = 38.5 ± 8.6 kg/m2; 13 male, BMI = 43.3 ± 7 kg/m2) with MetS qualified to BIB-system therapy. The control group included 18 age matched healthy volunteers (10 female, BMI = 23.3 ± 2.8 kg/m2 and eight male, BMI = 27.3 ± 0.9 kg/m2). Biochemical analyses of blood samples and anthropometric measurements were conducted, before and after six-month BIB system therapy.Results: BIB therapy resulted in a significant drop in body weight, and body fat percentage, and in BMI, VAI, WHtR, BAI, TG, glucose, hsCRP, and leptin levels. In addition Tc/HDL, LDL/HDL, TG/HDL, and leptin/adiponectin ratios fell significantly, and adiponectin concentration increased. All anthropometric parameters apart from Tc and hsCRP, were significantly different post-therapy compared to healthy controls. The therapy induced downregulation of hsCRP which was positively correlated with the reduction in body weight, BMI and BAI. The decrease in leptin concentration correlated positively with the fall in total cholesterol and body weight. The fall in leptin/adiponectin ratio positively correlated with the downregulation of BAI and body fat.Conclusion: BIB therapy appears to have beneficial effects on MetS. This is indicated by amelioration of the pro-inflammatory status related to obesity, demonstrated by an improved lipid profile significant downregulation of hsCRP concentration following therapy.

Neuroinflammation induced by lipopolysaccharide leads to memory impairment and alterations in hippocampal leptin signaling

Peripheral inflammation promotes immune-to-brain communication, mediated by cytokines that affect brain activity. Lipopolysaccharide (LPS) has been widely used to mimic systemic inflammation, and the adipokine leptin, released in this condition, modulates hypothalamic leptin receptors (ObR), contributing to sickness behavior. In this study, we used the intracerebroventricular (ICV) route for LPS administration in an attempt to evaluate an acute and direct of this pathogen-associated molecular pattern on leptin-mediated signaling in the hippocampus, where ObR has been implicated in modulating cognitive response. We used bilateral ICV injection of LPS (25 μg/ventricle) in 60-day-old male Wistar rats and the analysis were performed 48 h after surgery. Neuroinflammation was characterized in the LPS group by an increase in concentration of IL-1β, COX-2 and TLR4 in the hippocampus as well as glial fibrillary acidic protein (GFAP), indicating an astrocyte commitment. Cognitive damage was observed in the animals of the LPS group by an inability to increase the recognition index during the object recognition test. We observed an increase in the concentration of leptin receptors in the hippocampus, which was unaccompanied by changes in the proteins involved in leptin intracellular signaling (p-STAT3 and SOCS3). Moreover, we found a decrease in leptin concentration in the serum of the animals in the LPS group accompanied by an increase in TNF-α levels. Our results showed that neuroinflammation, even in an acute state, can lead to cognitive impairment and may be associated with leptin signaling disturbances in the hippocampus.

Macronutrient Supplements in Preterm and Small-for-Gestational-Age Animals: A Systematic Review and Meta-analysis

Early macronutrient supplementation in preterm and/or small-for-gestational-age (SGA) infants may improve growth but have detrimental effects on later cardio-metabolic health which may be sex-specific. We systematically reviewed the long-term effects of early macronutrient supplementation in preterm and SGA animals and whether these differ by sex. Using Cochrane Neonatal and SYRCLE methodologies we included random or quasi-random studies that allocated non-human mammals to macronutrient supplements or no supplements between birth and weaning and assessed post-weaning outcomes. We used random-effects models to calculate standardized mean differences (SMD) with 95% confidence intervals (CIs). Six studies provided low to very-low-quality evidence that macronutrient supplementation increased weight in juvenile rats (SMD; 95% CI: 2.13; 1.00, 3.25; 1 study, n = 24), increased leptin concentrations in older adults (1.31; 0.12, 2.51; 1 study, n = 14 male rats), but decreased leptin concentrations in young adults (−1.13; −2.21, −0.05; 1 study, n = 16 female rats) and improved spatial learning and memory (qualitative data; 1 study). There was no evidence of sex-specific effects and no overall effect on length, serum lipids, body composition, HOMA-IR, or blood pressure. Macronutrient supplements may affect later growth, metabolism, and neurodevelopment of preterm and SGA animals, but evidence is limited and low quality.

Genetic features of hormonal regulation of energy metabolism (literature review)

Summary: Many chronic diseases are associated with impaired human energy metabolism and its hormonal regulation. According to the WHO, there are more than 300 million people with obesity in the world, 24.1% of the population are suffering from obesity in Ukraine. Being overweight is one of the main factors in the development of type 2 diabetes, cardiovascular and oncological diseases, pathology of the musculoskeletal and digestive systems, as well as reproductive dysfunction. Obesity is a multifactorial disease. According to the results presented in the literature, the accumulation of fat in the subcutaneous and visceral region will lead to a change in the expression of genes encoding proteins that regulate energy metabolism. Leptin belongs to the group of adipocyte hormones of subcutaneous fat. The expression of leptin is regulated by several hormones, including insulin and glucocorticoids, and starvation also leads to a decrease of leptin concentration in plasma. Leptin reduces hunger, activates the use of fats in energy metabolism and inhibits the excessive accumulation of fat reserves. Leptin resistance may occur due to the presence of a mutation or polymorphic variation in its receptor gene. One of the most studied and clinically significant polymorphic variants of the leptin receptor gene (LEPR) is the replacement of glutamine amino acid with arginine at 223 positions (Q223R), which leads to a decrease in the sensitivity of receptors to leptin. Mutations in POMC lead to obesity, which is accompanied by atrophy of the adrenal cortex and multiple disorders. Mutations in MC4R lead to obesity in patients but ensure normal sexual development and adequate functioning of the endocrine glands. Now scientists on the whole world are actively developing methods to fight obesity, based on stimulating the functioning of cascades of leptin-dependent signaling.

The effect of weight change over a 2-year period on inflammatory status in postmenopausal women.

Body fat distribution has been shown to be a predictor of adhesion molecule and inflammatory marker expression albeit the effect of modest weight change on concentrations of adhesion molecules and inflammatory markers in postmenopausal women are not fully understood. The primary aim was to investigate the effects of weight change on adhesion molecules and inflammatory markers over 24 months in postmenopausal women. Body composition was assessed in 254 healthy postmenopausal women using dual-energy X-ray absorptiometry (DXA). Adhesion molecules and inflammatory markers were analysed by multiplex ELISA. Participants weight gain/loss at 24 months was defined as any value that was either above/below the weight value recorded at baseline. Postmenopausal women with an average weight loss of 3% had significantly decreased leptin concentrations by 18% at 24 months (P < 0.01). A 4% increase in body weight or a 9% increase in FMI significantly increased intercellular adhesion molecule-1 (ICAM-1), tumour necrosis factor-α (TNF-α) and leptin concentrations in postmenopausal women at 24 months (P < 0.01). Modest weight loss in postmenopausal women has a lowering effect on leptin concentrations over 24 months which may improve inflammatory status whilst modest weight gain increases ICAM-1, leptin and TNF-α, markers which are associated with a pro-inflammatory state and vascular complications.

Trichosanthes cucumerina extracts enhance glucose uptake and regulate adiponectin and leptin concentrations in 3T3-L1 adipocytes model

Trichosanthes cucumerina (Cucurbitaceae) commonly known as Snake gourd or Labu Ular is considered the largest genre in the Cucurbitaceae family and is mainly found in the southeast areas of Asia. It has been used in Ayurvedic medicine as a treatment for certain diseases such as Diabetes mellitus, but these acclaims lack scientific-based evidence. In this study, water and ethanol extracts of three parts of Trichosanthes cucumerina namely; whole vegetable, peels, and seeds, were assessed for toxicity through a cell viability assay using 3T3-L1 pre-adipocytes model which revealed a maximum toleration concentration of 0.063 mg/mL. The extracts were further tested on adipocytes’ differentiation and positively showed a stimulation of lipid droplets formation during adipogenesis and significantly (p<0.001) increased glycerol release levels (75.34±3.69 µg/ml) during adipolysis. The extracts also significantly (p<0.001) promoted the uptake of glucose into the cells (2636.22±91.33 Bq) in an action similar to that of insulin. Similar results were observed during ELISA assay with a significant increase (p<0.001) in adiponectin concentrations (3593.1±225.25 ng/mL) and a decrease in leptin concentrations (23870±5066.07 pg/mL). The present study results indicate a beneficial effect of Trichosanthes cucumerina extracts on adipogenesis, adipolysis and glucose uptake, in addition to a regulation of adiponectin and leptin concentrations in 3T3-L1 adipocytes which can be of clinical importance in energy regulation which is a key factor in treating diabetes, obesity, and metabolic syndrome.

Caloric Restriction-Induced Decreases in Dopamine Receptor Availability are Associated with Leptin Concentration.

It has been previously reported that early after Roux-en-Y-gastric bypass, dopamine (DA) type 2 and 3 receptor (D2/3R) binding potential (BPND ) was decreased from preoperative levels. The current study aimed to determine whether calorie restriction without weight loss modifies D2/3R BPND and whether such changes are explained by neuroendocrine regulation. Fifteen females with obesity (BMI = 39 ± 6 kg/m2 ) were studied before and after ∼10 days of a very-low-calorie-diet (VLCD). Outcome measures included fasting insulin, leptin, acyl ghrelin, and glucose, and insulin sensitivity and disposition index were estimated using the oral-minimal model (OMM) method. Participants underwent positron emission tomography scanning with the displaceable radioligand [18 F]fallypride to estimate available regional D2/3R levels. Regions of interest included the caudate, putamen, ventral striatum, hypothalamus, and substantia nigra (SN). With the VLCD, weight decreased slightly (-3 kg). Insulin, glucose, and leptin decreased significantly, but there was no change in acyl ghrelin or measures from OMM. SN D2/3R BPND decreased significantly, with trends toward decreased levels in the remaining regions. The decrease in leptin concentration strongly predicted the change in D2/3R BPND in all regions (all P ≤ 0.004). In obesity, reductions in regional D2/3R availability after VLCD are suggestive of increased endogenous DA competing with the radioligand. Changes in regional D2/3R availability were associated with decreases in leptin concentrations that occurred before clinically significant weight loss.

Lep Expression and Its Role in Obesity and Type-2 Diabetes.

Obesity is metabolic disorder that increases the risk of diabetes, heart disease, and other metabolic syndromes in human beings. One sign of diabetes is increased blood glucose levels in the body. Glucose levels increase due to problems with insulin secretion or insulin resistance. Maturity onset of diabetes of the young is more common in adults and occurs due to insulin resistance. Both diabetes and obesity are major problems that are responsible for the death of millions of individuals every year, worldwide. Leptin, a 164-KDa hormone that is secreted by white adipose tissue, is a product of the lep gene. Mutation in lep decreases leptin concentration and increases obesity and type-2 diabetes mellitus. Leptin has been shown to produce positive effects on hunger, energy expenditure, and behavior and is thus useful in the treatment of obesity and type-2 diabetes. Leptin controls appetite through its effect on the hypothalamus in the brain. Both leptin and insulin regulate appetite, body weight, and glucose levels in the body.

Maternal high-fat diet inversely affects insulin sensitivity in dams and young adult male rat offspring.

This study attempts to further clarify the potential effects of maternal high-fat (HF) diet on glucose homeostasis in dams and young adult male rat offspring. Female rats were divided into control (CON dams) and HF (HF dams) diet groups, which received the diet 4 weeks prior to and through pregnancy and lactation periods. Blood samples were taken to determine metabolic parameters, then an intraperitoneal glucose tolerance test (IPGTT) was performed. Maternal HF diet increased intra-abdominal fat mass and plasma corticosterone level, but decreased leptin concentration in dams. In HF offspring intra-abdominal fat mass, plasma leptin, and corticosterone levels decreased. Following IPGTT, the plasma insulin level of HF dams was higher than the controls. In HF offspring plasma insulin level was not significantly different from the controls, but a steeper decrease of their plasma glucose concentration was observed.