Important Regulator Of Body Weight Research Articles

Kisspeptin and body weight homeostasis in relation to phenotypic features of polycystic ovary syndrome; metabolic regulation of reproduction

BackgroundPolycystic ovary syndrome (PCOS) is a heterogeneous disorder characterized by a diverse collection of reproductive and metabolic abnormalities. kisspeptin (KISS) is novel peptides associated with regulation of metabolism, food intake, puberty and reproduction. The aim of the present study was to estimate KISS level in patients with PCOS, and to evaluate the possible relationship between KISS level with anthropometric measures as well as clinic-morphological features of PCOS. Materials and methodscross section control study enrolled 90 control group and 105 patients with PCOS and they were stratified according to their body mass index (BMI) to; underweight (n = 9, BMI ˂19), normal weight (n = 25, BMI = 19.1–25), over weight (n = 34,BMI = 25.1–30), obese grade I (n = 12, BMI = 30.1–35) , obese grade II (n = 13, BMI 35.1–40) and obese grade III (n = 12, BMI˃40).Circulating KISS levels were measured using ELISA. ResultsOur results revealed that, KISS levels were higher in PCOS patients compared to controls. Among PCOS group, there were significant lower level of KISS levels in underweight, overweight and obese compared to normal weight group. Even more importantly, KISS levels decreased with increasing of BMI as the following, grade I, grade II and grade III. Moreover, it was negatively correlated to anthropometric measures, glycemic, lipid profile and positively correlated the phenotype characteristics of PCOS. Linear regression test observed that hirsutism score, HOMA-IR and LH were the main predictors of KISS levels in PCOS.Conclusion: circulating KISS is an important regulator of body weight and reproduction especially in PCOS women.

Lipoprotein lipase in hypothalamus is a key regulator of body weight gain and glucose homeostasis in mice.

Regulation of energy balance involves the participation of many factors, including nutrients, among which are circulating lipids, acting as peripheral signals informing the central nervous system of the energy status of the organism. It has been shown that neuronal lipoprotein lipase (LPL) participates in the control of energy balance by hydrolysing lipid particles enriched in triacylglycerols. Here, we tested the hypothesis that LPL in the mediobasal hypothalamus (MBH), a well-known nucleus implicated in the regulation of metabolic homeostasis, could also contribute to the regulation of body weight and glucose homeostasis. We injected an adeno-associated virus (AAV) expressing Cre-green fluorescent protein into the MBH of Lpl-floxed mice (and wild-type mice) to specifically decrease LPL activity in the MBH. In parallel, we injected an AAV overexpressing Lpl into the MBH of wild-type mice. We then studied energy homeostasis and hypothalamic ceramide content. The partial deletion of Lpl in the MBH in mice led to an increase in body weight compared with controls (37.72±0.7g vs 28.46±0.12, p<0.001) associated with a decrease in locomotor activity. These mice developed hyperinsulinaemia and glucose intolerance. This phenotype also displayed reduced expression of Cers1 in the hypothalamus as well as decreased concentration of several C18 species of ceramides and a 3-fold decrease in total ceramide intensity. Conversely, overexpression of Lpl specifically in the MBH induced a decrease in body weight. Our study shows that LPL in the MBH is an important regulator of body weight and glucose homeostasis.

Effect of tuberculosis treatment on leptin levels, weight gain, and percentage body fat in Indonesian children.

PurposeTuberculosis (TB) remains a problem in the community. TB patients usually experience malnutrition, which is characterized by both decreased body weight (BW) and body fat percentage (BFP). Leptin, an important regulator of BW, also plays an important role in cellular immunity, which is integral to defense against Mycobacterium tuberculosis infection. We analyzed the effect of an anti-TB treatment regimen on the leptin level, BW, and BFP of children with TB.MethodsThe design of this study was a group interrupted time series. The subjects were children with probable TB according to clinical criteria based on an Indonesian scoring system adopted from the Consensus of Expert Panel. BW; BFP; energy intake; fat and protein intake; and leptin levels before, 2 months after (intensive phase), and 6 months after (continuation phase) anti-TB treatment, were measured. About 40 children, aged 5–14 years, participated in this study.ResultsThe BW, BFP and leptin level increased from before treatment to after completion of the intensive phase and still showed an increased during the continuation phase: BW 18.65 kg, 19.75 kg, and 20.85 kg; BFP 18.3%, 19.5%, and 20.2%; and leptin level 1.9 mg/dL, 3.07 mg/dL, and 3.4 mg/dL, respectively (P<0.01).ConclusionLeptin level, BW, and BFP increased throughout the course of anti-TB treatment, compared with pretreatment values. Further research is needed to compare the results with data for healthy children.

Shp2 signaling in POMC neurons is important for leptin's actions on blood pressure, energy balance, and glucose regulation.

Previous studies showed that Src homology-2 tyrosine phosphatase (Shp2) is an important regulator of body weight. In this study, we examined the impact of Shp2 deficiency specifically in proopiomelanocortin (POMC) neurons on metabolic and cardiovascular function and on chronic blood pressure (BP) and metabolic responses to leptin. Mice with Shp2 deleted in POMC neurons (Shp2/Pomc-cre) and control mice (Shp2(flox/flox)) were implanted with telemetry probes and venous catheters for measurement of mean arterial pressure (MAP) and leptin infusion. After at least 5 days of stable control measurements, mice received leptin infusion (2 μg·kg(-1)·day(-1) iv) for 7 days. Compared with Shp2(flox/flox) controls, Shp2/Pomc-cre mice at 22 wk of age were slightly heavier (34 ± 1 vs. 31 ± 1 g) but consumed a similar amount of food (3.9 ± 0.3 vs. 3.8 ± 0.2 g/day). Leptin infusion reduced food intake in Shp2(flox/flox) mice (2.6 ± 0.5 g) and Shp2/Pomc-cre mice (3.2 ± 0.3 g). Despite decreasing food intake, leptin infusion increased MAP in control mice, whereas no significant change in MAP was observed in Shp2/Pomc-cre mice. Leptin infusion also decreased plasma glucose and insulin levels in controls (12 ± 1 to 6 ± 1 μU/ml and 142 ± 12 to 81 ± 8 mg/100 ml) but not in Shp2/Pomc-cre mice. Leptin increased V̇o2 by 16 ± 2% in controls and 7 ± 1% in Shp2/Pomc-cre mice. These results indicate that Shp2 signaling in POMC neurons contributes to the long-term BP and antidiabetic actions of leptin and may play a modest role in normal regulation of body weight.

Association of melanocortin-4 receptor gene polymorphisms with obesity-related parameters in Malaysian Malays

Background: Melanocortin-4 receptor (MC4R) is an important regulator of body weight and energy intake. Genetic polymorphisms of the MC4R gene have been found to be linked to obesity in many recent studies across the globe.Aim: This study aimed to examine the effects of MC4R polymorphisms on obesity parameters, Linkage disequilibrium (LD) pattern and haplotypes in Malaysian Malays.Methods: The study subjects were 652 Malaysian Malays. Genomic DNA was extracted from buccal swabs. Genotyping was performed using Sequenom MassARRAY® iPLEX platform. Anthropometric and blood lipid profiles were measured.Results: MC4R rs571312 SNP was associated with logBMI (p = 0.008) and systolic blood pressure (p = 0.005), while MC4R rs2229616 SNP was associated with total cholesterol (TC) levels (p = 0.016). The MC4R rs7227255 SNP did not show any association with obesity parameters.Conclusions: The strength of LD of the MC4R gene region is low and the haplotypes were not associated with obesity in Malaysian Malays.

Biology and pharmacology of bombesin receptor subtype-3

This review summarizes the results of recent studies regarding the biology and pharmacology of novel synthetic agonists and antagonists of the bombesin receptor subtype-3 (BRS-3). All three mammalian bombesin receptors including gastrin-releasing peptide receptor, the neuromedin B receptor, and the BRS-3 have been shown to regulate energy balance and appetite and satiety. Studies indicate that the orphan BRS-3 is an important regulator of body weight, energy expenditure, and glucose homeostasis. Endogenous bombesin-like peptides bombesin, gastrin-releasing peptide, and neuromedin B receptor do not bind to BRS-3 and the endogenous BRS-3 ligand remains unknown. The novel synthesis of selective, high-affinity BRS-3 agonists and antagonists has recently been accomplished and showed that BRS-3 regulates energy balance independent of other established pathways and glucose-stimulated insulin secretion in the pancreatic islet cells. The availability of new BRS-3 selective agonists and antagonists will facilitate further elucidation of its role in energy homeostasis, and provides a potential approach for the pharmacological treatment of obesity and type 2 diabetes. The native ligand of the G protein-coupled BRS-3 has not been identified as of now. However, novel synthesis of small-molecule, high-affinity agonists and antagonists on the BRS-3 was used in the recent studies and demonstrated an important role of BRS-3 in the regulation of energy homeostasis and glucose metabolism.

Anti-obesity effects of the methanolic extract and chakasaponins from the flower buds of Camellia sinensis in mice

The methanolic extract from the flower buds of Camellia sinensis cultivated in Fujian Province showed inhibitory effects on body weight gain and the weight of visceral fats in high-fat diet-fed mice and/or Tsumura Suzuki Obese Diabetic (TSOD) mice. A suppressive effect of the extract on food intake was suggested to contribute to the anti-obesity effect. The n-butanol (BuOH)-soluble fraction also reduced food intake in normal diet-fed mice. A principal constituent, chakasaponin II, inhibited gastric emptying (GE) as well as food intake. These inhibitory effects were partly reduced by pretreatment with a high dose of capsaicin. The n-BuOH-soluble fraction and chakasaponin II suppressed mRNA levels of neuropeptide Y (NPY), an important regulator of body weight through its effects on food intake and energy expenditure, in the hypothalamus. Furthermore, chakasaponin II enhanced the release of serotonin (5-HT) from the isolated ilea of mice in vitro. These findings suggested that the active saponins suppressed the appetite signals in the hypothalamus through stimulation of the capsaicin-sensitive sensory nerves, probably vagal afferent nerves, or enhancement of 5-HT release from the ilea, leading to reduced food intake and body weight gain.

The CIDEA Gene V115F Polymorphism Is Associated With Obesity in Swedish Subjects

The cell death-inducing DFFA (DNA fragmentation factor-alpha)-like effector A (CIDEA) gene is implicated as an important regulator of body weight in mice and humans and is therefore a candidate gene for human obesity. Here, we characterize common CIDEA gene polymorphisms and investigate them for association with obesity in two independent Swedish samples; the first comprised 981 women and the second 582 men. Both samples display a large variation in BMI. The only detected coding polymorphism encodes an exon 4 V115F amino acid substitution, which is associated with BMI in both sexes (P = 0.021 for women, P = 0.023 for men, and P = 0.0015 for joint analysis). These results support a role for CIDEA alleles in human obesity. CIDEA-deficient mice display higher metabolic rate, and the gene cross-talks with tumor necrosis factor-alpha (TNF-alpha) in fat cells. We hypothesize that CIDEA alleles regulate human obesity through impact on basal metabolic rate and adipocyte TNF-alpha signaling.

Short sleep duration is associated with reduced leptin, elevated ghrelin, and increased body mass index.

BackgroundSleep duration may be an important regulator of body weight and metabolism. An association between short habitual sleep time and increased body mass index (BMI) has been reported in large population samples. The potential role of metabolic hormones in this association is unknown.Methods and FindingsStudy participants were 1,024 volunteers from the Wisconsin Sleep Cohort Study, a population-based longitudinal study of sleep disorders. Participants underwent nocturnal polysomnography and reported on their sleep habits through questionnaires and sleep diaries. Following polysomnography, morning, fasted blood samples were evaluated for serum leptin and ghrelin (two key opposing hormones in appetite regulation), adiponectin, insulin, glucose, and lipid profile. Relationships among these measures, BMI, and sleep duration (habitual and immediately prior to blood sampling) were examined using multiple variable regressions with control for confounding factors.A U-shaped curvilinear association between sleep duration and BMI was observed. In persons sleeping less than 8 h (74.4% of the sample), increased BMI was proportional to decreased sleep. Short sleep was associated with low leptin (p for slope = 0.01), with a predicted 15.5% lower leptin for habitual sleep of 5 h versus 8 h, and high ghrelin (p for slope = 0.008), with a predicted 14.9% higher ghrelin for nocturnal (polysomnographic) sleep of 5 h versus 8 h, independent of BMI.ConclusionParticipants with short sleep had reduced leptin and elevated ghrelin. These differences in leptin and ghrelin are likely to increase appetite, possibly explaining the increased BMI observed with short sleep duration. In Western societies, where chronic sleep restriction is common and food is widely available, changes in appetite regulatory hormones with sleep curtailment may contribute to obesity.

Abnormalities of the hypothalamo-pituitary-thyroid axis in the pro-opiomelanocortin deficient mouse

The melanocortin system is an important regulator of body weight and the hypothalamo-pituitary-thyroid (HPT) axis. The pro-opiomelanocortin (POMC)-null mouse, deficient in all POMC-derived peptides, including alpha-melanocyte stimulating hormone (α-MSH), has an obese phenotype. We studied the HPT axis of POMC-null mice, which has not been previously investigated. Because α-MSH has a stimulatory effect on the HPT axis, we hypothesised that these mice would have a down-regulated thyroid axis, consistent with a recent study of POMC-null humans. The activity of the HPT axis was studied by collecting blood, pituitaries and hypothalami from ad libitum fed, adult POMC-null, heterozygous and wild-type mice. POMC-null mice had significantly elevated plasma total T 4 (TT 4) and free T 3 (fT 3) with reduced plasma thyroid stimulating hormone (TSH), pituitary TSH content and hypothalamic thyrotrophin stimulating hormone (TRH) content compared to wild-type mice. No significant differences between heterozygous and wild-type mice were observed. POMC-null mice have an abnormal HPT axis, which may contribute to their hyperphagia and obesity. These abnormalities are in contrast to those observed in POMC-null humans. These findings support a role for the melanocortin system in the regulation of the HPT axis.