Aging ; genetics ; metabolism ; Animals ; Diabetes Mellitus ; enzymology ; metabolism ; Humans ; Longevity ; genetics ; physiology ; Neoplasms ; enzymology ; metabolism ; Neurodegenerative Diseases ; enzymology ; metabolism ; Obesity ; enzymology ; metabolism ; Sirtuins ; genetics ; metabolism

Visfatin, also named nicotinamide phosphoribosyl transferase (NAMPT), is a cytokine secreted from adipose tissue. Visfatin can regulate immune action and is involved in the NAD+ salvage pathway. In addition, recent researches have shown that visfatin helps the regulation of glucose and lipid metabolism, especially in exercise-induced weight reduction for obesity. The aim of this review is to provide an overview of the contribution of visfatin gene polymorphisms to glucose and lipid metabolism and exercise-induced weight reduction in obesity.
Exercise ; physiology ; Glycolipids ; metabolism ; Humans ; Nicotinamide Phosphoribosyltransferase ; genetics ; physiology ; Obesity ; genetics ; metabolism ; Polymorphism, Genetic ; Weight Loss ; genetics

OBJECTIVETo investigate the expression of GIRK4 gene in the kidney tissues of obese rats.

METHODSObese rat models were established using diet-induced method. The GIRK4 protein expression in kidney tissues was determined in 20 obese rats and 10 normal rats using Western blot analysis.

RESULTSThe relative expression level of GIRK4 protein in the kidney tissues of obese rat (1.75±0.42) was significantly lower than that in normal rats (3.37±0.68, P<0.05).

CONCLUSIONGIRK4 has a low protein expression in the kidney tissues of obese rat.

Animals ; Female ; Gene Expression ; Kidney ; metabolism ; Male ; Obesity ; genetics ; metabolism ; Potassium Channels, Inwardly Rectifying ; genetics ; metabolism ; Rats

This paper aims to study the effect of Xiangqin Jiere Granules(XQ) on lipid metabolism and chronic inflammation in different obesity model mice. The monosodium glutamate(MSG) obese mouse model was established by subcutaneous injection of MSG in newborn mice, and the high fat diet(HFD) obese mouse model was established by feeding adult mice with HFD. The normal mice were assigned into the control group; the MSG obese mice were assigned into MSG model group, XQ4.5 group(Xiangqin Jiere Granu-les, 4.5 g·kg~(-1)), XQ22.5 group(Xiangqin Jiere Granules, 22.5 g·kg~(-1)); the HFD obese mice were assigned into HFD model group, XQ4.5 group, and XQ22.5 group. The mice were intragastrically administrated with saline or XQ for 5 weeks. After that, the body weight, visceral fat mass, liver and thymus weight, and the organ indexes in each group were measured. The levels of triglyceride(TG), total cholesterol(TC), and low-density lipoprotein cholesterol(LDL-c) in serum and liver tissue were detected by the kits. The mRNA expression levels of acetyl CoA carboxylase 1(ACC1), fatty acid synthetase(FAS), diacylgycerol acyltransferase 1(DGAT1) and hepatic lipase(HTGL) involved in lipid metabolism in mouse liver tissue were detected by quantitative real-time PCR(qPCR). The protein levels of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in serum were detected by ELISA, and the mRNA levels of TNF-α and IL-6 in liver tissue were detected by qPCR. Compared with the control group, MSG and HFD mice showed increased body weight, abdominal circumference, Lee index and visceral fat mass as well as elevated levels of TG, TC, and LDL-c in serum. The model mice had up-regulated gene levels of ACC1, FAS and DGAT1 while down-regulated gene level of HTGL in the liver. Furthermore, the mRNA and protein levels of IL-6 increased in the model mice. Compared with the model mice, XQ treatment decreased the body weight, abdominal circumference, Lee index, and visceral fat mass, lowered the levels of TG, TC, and LDL-c in se-rum, down-regulated the gene levels of ACC1, FAS, and DGAT1 in liver tissue, up-regulated the gene level of HTGL, and down-regulated the mRNA and protein levels of IL-6. To sum up, XQ has good therapeutic effect on different obesity model mice. It can improve lipid metabolism and reduce fat accumulation in obese mice by regulating the enzymes involved in lipid metabolism, and alleviate obesity-related chronic low-grade inflammation.
Animals ; Inflammation/metabolism* ; Lipid Metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Obesity/genetics*

PURPOSE: Obesity is a risk factor for asthma and type II diabetes. Peroxisome proliferator-activated receptor (PPAR)-gamma has been suggested to regulate inflammatory responses in diabetes and asthma. We investigated whether PPAR-alpha, PPAR-gamma, adiponectin receptors (AdipoR1, AdipoR2), leptin, and tumor necrosis factor (TNF)-alpha are expressed in rat lung tissues and whether the expression differs between obese Otsuka Long-Evans Tokushima Fatty (OLETF) and lean Long Evans Tokushima Otsuka (LETO) rats. MATERIALS AND METHODS: Obese and lean rats were given with a high fat diet or a 30% restricted diet for 32 weeks, and their blood glucose levels and weights were monitored. After 32 weeks, mRNA levels of PPAR-alpha, PPAR-gamma, AdipoR1, AdipoR2, leptin, and TNF-alpha in lung tissues were measured using real time PCR. RESULTS: PPAR-alpha, PPAR-gamma, AdipoR1, AdipoR2, leptin, and TNF-alpha were expressed in both obese and lean rat lung tissues. Increased serum glucose levels on intraperitoneal glucose tolerance testing and a higher weight gain at 32 weeks were observed in OLETF control rats compared to OLETF diet restricted rats. PPAR-gamma expression was markedly elevated in obese control and diet restricted rats compared to lean rats, although PPAR-gamma expression in obese rats was not affected by diet restriction. Leptin was highly expressed in OLETF rats compared to LETO rats. TNF-alpha expression was enhanced in OLETF control rats compared LETO diet restricted rats, and decreased by diet restriction. PPAR-alpha, AdipoR1, and AdipoR2 expression were not significantly different between obese and lean rats. CONCLUSION: PPAR-gamma was highly expressed in the lung tissues of obese rats and may be a novel treatment target for regulating lung inflammation associated with obesity.
Animals ; Body Weight ; Glucose Tolerance Test ; Leptin/genetics/metabolism ; Lung/*metabolism ; Male ; Obesity/genetics/*metabolism ; PPAR gamma/genetics/*metabolism ; RNA, Messenger/metabolism ; Rats ; Rats, Long-Evans ; Receptors, Adiponectin/genetics/metabolism ; Tumor Necrosis Factor-alpha/genetics/metabolism

The worldwide prevalence of obesity is steadily increasing, nearly doubling between 1980 and 2008. Obesity is often associated with insulin resistance, a major risk factor for type 2 diabetes mellitus (T2DM): a costly chronic disease and serious public health problem. The underlying cause of T2DM is a failure of the beta cells of the pancreas to continue to produce enough insulin to counteract insulin resistance. Most current T2DM therapeutics do not prevent continued loss of insulin secretion capacity, and those that do have the potential to preserve beta cell mass and function are not effective in all patients. Therefore, developing new methods for preventing and treating obesity and T2DM is very timely and of great significance. There is now considerable literature demonstrating a link between inhibitory guanine nucleotide-binding protein (G protein) and G protein-coupled receptor (GPCR) signaling in insulin-responsive tissues and the pathogenesis of obesity and T2DM. These studies are suggesting new and emerging therapeutic targets for these conditions. In this review, we will discuss inhibitory G proteins and GPCRs that have primary actions in the beta cell and other peripheral sites as therapeutic targets for obesity and T2DM, improving satiety, insulin resistance and/or beta cell biology.
Animals ; Diabetes Mellitus, Type 2/drug therapy/*metabolism ; GTP-Binding Protein alpha Subunits/genetics/*metabolism ; Humans ; Insulin-Secreting Cells/metabolism ; Obesity/drug therapy/*metabolism ; Receptor, Melatonin, MT2/genetics/*metabolism ; Receptors, Adrenergic, alpha-1/genetics/*metabolism ; Receptors, Prostaglandin/genetics/*metabolism

Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disease initially reported by Bardet and Biedl in the 1920s. BBS is a pleiotropic and genetically heterogeneous disorder characterized by retinopathy, obesity, polydactyly, renal malformations and functional abnormalities, learning disabilities and hypogenitalism. BBS patients are also prone to diabetes mellitus, hypertension and congenital heart disease. To date, 16 BBS genes (BBS1-BBS16) have been identified. However, the molecular etiology of BBS is not yet entirely clear. In this article, we have reviewed recent research on BBS and discussed its implications for understanding of ciliopathology.
Animals ; Bardet-Biedl Syndrome ; complications ; genetics ; metabolism ; Biomedical Research ; Humans ; Obesity ; etiology

The prevalence of obesity has increased worldwide in recent decades. Genetic factors are now known to play a substantial role in the predisposition to obesity and may contribute up to 70% of the risk for obesity. Technological advancements during the last decades have allowed the identification of many hundreds of genetic markers associated with obesity. However, the transformation of current genetic variant-obesity associations into biological knowledge has been proven challenging. Genomics and proteomics are complementary fields, as proteomics extends functional analyses. Integrating genomic and proteomic data can help to bridge a gap in knowledge regarding genetic variant-obesity associations and to identify new drug targets for the treatment of obesity. We provide an overview of the published papers on the integrated analysis of proteomic and genomic data in obesity and summarize four mainstream strategies: overlap, colocalization, Mendelian randomization, and proteome-wide association studies. The integrated analyses identified many obesity-associated proteins, such as leptin, follistatin, and adenylate cyclase 3. Despite great progress, integrative studies focusing on obesity are still limited. There is an increased demand for large prospective cohort studies to identify and validate findings, and further apply these findings to the prevention, intervention, and treatment of obesity. In addition, we also discuss several other potential integration methods.
Humans ; Proteome/metabolism* ; Proteomics ; Prospective Studies ; Obesity/genetics* ; Genomics ; Genome-Wide Association Study

The current epidemic of obesity and its associated metabolic syndromes impose unprecedented challenges to our society. Despite intensive research on obesity pathogenesis, an effective therapeutic strategy to treat and cure obesity is still lacking. Exciting studies in last decades have established the importance of the leptin neural pathway in the hypothalamus in the regulation of body weight homeostasis. Important hypothalamic neuropeptides have been identified as critical neurotransmitters from leptin-sensitive neurons to mediate leptin action. Recent research advance has significantly expanded the list of neurotransmitters involved in body weight-regulating neural pathways, including fast-acting neurotransmitters, gamma-aminobutyric acid (GABA) and glutamate. Given the limited knowledge on the leptin neural pathway for body weight homeostasis, understanding the function of neurotransmitters released from key neurons for energy balance regulation is essential for delineating leptin neural pathway and eventually for designing effective therapeutic drugs against the obesity epidemic.
Animals ; Energy Metabolism ; Gene Expression ; Humans ; Hunger ; Hypothalamus ; metabolism ; physiology ; Leptin ; metabolism ; physiology ; Neural Pathways ; metabolism ; Neuropeptides ; genetics ; metabolism ; Obesity ; metabolism

OBJECTIVETo study the effect of beta3 adrenergic receptor (beta3AR) Trp64Arg and peroxisome proliferator activated receptor gamma 2 (PPARgamma2) Prol2Ala polymorphisms on insulin resistance.

METHODSOne hundred and eight dizygotic twin pairs were enrolled in this study. Microsatellite polymorphism was used to diagnose zygosity of twins. Insulin sensitivity was estimated with logarithm transformed homeostasis model assessment (HOMA). PCR-RFLP analysis was performed to detect the variants. As a supplement to the sib-pair method, identity by state (IBS) was used to analyze the association of polymorphisms with insulin sensitivity.

RESULTSThe genotype frequencies of Trp64Trg, Trp64Arg, and Arg64Arg were 72.3%, 23.8%, and 3.9%, respectively, while the genotype frequencies of Prol2Pro, Prol2Ala, and Alal2Ala were 89.9%, 9.6%, and 0.5%, respectively. For beta3AR Trp64Arg the interclass co-twin correlations of Waist-to-hip ratio (WHR), blood glucose (GLU), and insulin (INS), homeostasis model assessment insulin resistance index (HOMA-IR) of the twin pairs sharing 2 alleles of IBS were greater than those sharing 0-1 allele of IBS, and HOMA-IR had statistic significance. For PPARgamma2 Pro12Ala most traits of twin pairs sharing 2 alleles of IBS had greater correlations and statistic significance in body mass index (BMI), WHR, percent of body fat (PBF) and GLU, but there were low correlations of either insulin or HOMA-IR of twin pairs sharing 1 or 2 alleles of IBS. The combined effects of the two variations showed less squared significant twin-pair differences of INS and HOMA-IR among twins sharing 4 alleles of IBS.

CONCLUSIONSBeta3AR Trp64Arg and PPARgamma2 Pro12Ala polymorphisms might be associated with insulin resistance and obesity, and there might be slight synergistic effects between this two gene loci, and further studies are necessary to confirm this finding.

Adolescent ; Child ; Child, Preschool ; Genotype ; Humans ; Insulin Resistance ; genetics ; Obesity ; genetics ; PPAR gamma ; genetics ; Polymorphism, Genetic ; Receptors, Adrenergic, beta-3 ; genetics ; Twins, Dizygotic ; genetics ; metabolism