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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adipocytes have traditionally been considered to be the primary site for whole body energy storage mainly in the form of triglycerides and fatty acids. This occurs through the ability of insulin to markedly stimulate both glucose uptake and lipogenesis. Conventional wisdom held that defects in fuel partitioning into adipocytes either because of increased adipose tissue mass and/or increased lipolysis and circulating free fatty acids resulted in dyslipidemia, obesity, insulin resistance and perhaps diabetes. However, it has become increasingly apparent that loss of adipose tissue (lipodystrophies) in both animal models and humans also leads to metabolic disorders that result in severe states of insulin resistance and potential diabetes. These apparently opposite functions can be resolved by the establishment of adipocytes not only as a fuel storage depot but also as a critical endocrine organ that secretes a variety of signaling molecules into the circulation. Although the molecular function of these adipocyte-derived signals are poorly understood, they play a central role in the maintenance of energy homeostasis by regulating insulin secretion, insulin action, glucose and lipid metabolism, energy balance, host defense and reproduction. The diversity of these secretory factors include enzymes (lipoprotein lipase (LPL) and adipsin), growth factors [vascular endothelial growth factor (VEGF)], cytokines (tumor necrosis factor-alpha, interleukin 6) and several other hormones involved in fatty acid and glucose metabolism (leptin, Acrp30, resistin and acylation stimulation protein). Despite the large number of molecules secreted by adipocytes, our understanding of the pathways and mechanisms controlling intracellular trafficking and exocytosis in adipocytes is poorly understood. In this article, we will review the current knowledge of the trafficking and secretion processes that take place in adipocytes, focusing our attention on two of the best characterized adipokine molecules (leptin and adiponectin) and on one of the most intensively studied regulated membrane proteins, the GLUT4 glucose transporter.
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PMID:An adipocentric view of signaling and intracellular trafficking. 1239 77

Diabetes mellitus has attained epidemic proportions worldwide. It is suggested that resistin (also called Fizz 3), a cysteine. rich-protein may represent a link between obesity and insulin resistance. Uncoupling proteins are candidate genes for human obesity or type 2 diabetes mellitus. Amylin has a vital role in regulating blood glucose concentration following meals. Gluco watch biographers are safe and effective device to measure glucose every 20 minutes. Islet transplantation has had a remarkable preliminary success. Protein kinase Cbeta inhibitor was shown to reduce albuminuria and decrease statement of TGFbeta and various extracellular matrix proteins in diabetic rats.
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PMID:Current and future perspective in the management of diabetes. 1240 80

Resistin, a novel adipose-derived protein, has been proposed to cause insulin-resistant states in obesity. To evaluate whether an insulin-sensitizing drug, metformin, regulates adipose tissue resistin expression, murine models of obesity and diabetes, db/db mice, were treated with metformin (metformin group), insulin (insulin group), and vehicle (control group) for 4 weeks, followed by analyzing resistin protein expression in their adipose tissues. Unexpectedly, resistin protein expression was increased by 66% in the metformin group relative to the control group, while it did not differ between the insulin and control groups. Hyperinsulinemia was improved in the metformin group, while the insulin group exhibited severe hyperinsulinemia, similar to the control group. Furthermore, in comparison between obese mice (db/db mice) and age-matched lean controls, resistin protein expression was reduced by 58% in the obese mice with severe hyperinsulinemia. These data collectively suggest that resistin expression may be suppressed by hyperinsulinemia and that metformin may upregulate resistin expression via the improvement of hyperinsulinemia in obesity.
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PMID:Effect of metformin on adipose tissue resistin expression in db/db mice. 1241 46

Secreted by white adipose tissue as a hormone, resistin was identified as a possible link between obesity and insulin resistance. High circulating resistin levels were observed to correlate with obesity. Administration of resistin lowered the glucose tolerance threshold and impaired insulin activity; whereas anti-resistin antibodies had the opposite effects. However, contradictory data were subsequently reported in regard to the correlation between resistin expression level and obesity or type 2 diabetes. Two additional proteins that share a highly homologous C-terminus with resistin have been identified in mouse, and one in human, forming a resistin-related protein family. Resistin was shown to dimerize through a disulfide bond formed by the N-terminal-most cysteine (Cys26). Here we demonstrate that while Cys26 is both necessary and sufficient for homodimer formation, all three resistin family members can also interact with one another regardless of the presence of Cys26 through non-covalent interactions. Furthermore, protein crosslinking analysis indicated that resistin and resistin beta, but not resistin alpha, exist as multimers, probably with a dimer as the subunit. The multiple protein complex formation is obviously at a level higher than the Cys26 disulfide bonding. These results suggest the potential importance of considering intermolecular interactions among resistin family members in studying their functions.
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PMID:Differential dimerization and association among resistin family proteins with implications for functional specificity. 1242 47

The objective of this review is to summarize the current evidence of a novel adipocytokine, resistin. Resistin is a novel peptide hormone that belongs to a family of tIssue-specific resistin-like molecules originally named for its resistance to insulin. Although a seminal proposal by Steppan et al. suggested resistin to be a hormone that links obesity to diabetes, several studies have subsequently been published supporting the concept that insulin resistance and obesity are actually associated with a decreased resistin expression. Resistin expression is regulated by a variety of agents and hormones, including thiazolidinediones, insulin, tumor necrosis factor alpha and growth hormone. Studies about their role in the regulation of resistin expression are, however, inconsistent in many cases. Experiments in humans have shown no differences in resistin expression between normal, insulin-resistant or type 2 diabetic samples. However, some recent genetic studies have demonstrated an association between resistin and insulin resistance and obesity. In addition, regional variation in the expression of resistin mRNA and protein levels in humans is an interesting finding with the highest levels found in the abdominal depot. In conclusion, resistin is a fascinating new hormone for which a definite role in metabolism will be revealed in the near future.
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PMID:Resistin - a mediator of obesity-associated insulin resistance or an innocent bystander? 1244 87

Polycystic ovary syndrome (PCOS) is a leading cause of anovulatory infertility and affects approximately 4-7% of reproductive age women in the U.S. It is characterized by hyperandrogenemia and chronic anovulation and is associated with insulin resistance, obesity, and increased risk for type 2 diabetes. In a screen of candidate genes, a region on chromosome 19p13.3 was identified that shows significant evidence for both linkage and association with PCOS. A promising candidate gene for PCOS, resistin, maps to exactly this region. Resistin is a protein hormone thought to modulate glucose tolerance and insulin action. We tested for association between a single nucleotide polymorphism in the promoter region of the resistin gene and three phenotypes: PCOS, obesity, and insulin resistance. We did not find evidence for association with any of the phenotypes. It is therefore unlikely that variation in the resistin gene accounts for the strong association that we observe between chromosome 19p13.3 and PCOS. Instead, this association is most likely due to a gene or genetic element in this region that has not been identified.
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PMID:Variation in resistin gene promoter not associated with polycystic ovary syndrome. 1250 16

Resistin is a cysteine-rich protein postulated to be a molecular link between obesity and type 2 diabetes. The aim of this study was to investigate the role of PPAR gamma in the regulation of resistin expression in human primary macrophages. Fluorescent real-time PCR (Taqman) analysis of resistin expression across a range of human tissues showed that resistin is highly expressed in bone marrow compared to other tissues. Taqman analysis and Western blotting showed that rosiglitazone decreased resistin expression at both the mRNA and protein levels in human primary monocyte-derived macrophages in vitro. Resistin expression was reduced by up to 80% after exposure to 100 nM rosiglitazone for 96 h. Bioinformatics analysis of the genomic sequence upstream of the resistin coding sequence identified several putative PPAR response elements of which one was shown to bind PPAR gamma using electrophoretic mobility shift assays. Our data support a direct role for PPAR gamma in the regulation of resistin expression.
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PMID:Resistin is expressed in human macrophages and directly regulated by PPAR gamma activators. 1250 8

It is now widely accepted that white adipose tissue (WAT) secretes a number of peptide hormones, including leptin, several cytokines, adipsin and acylation-stimulating protein (ASP), angiotensinogen, plasminogen activator inhibitor-1 (PAI-1), adiponectin, resistin etc., and also produces steroids hormones. This newly discovered secretory function has shifted our view of WAT, which is no longer considered only an energy storage tissue but a major endocrine organ, at the heart of a complex network influencing energy homeostasis, glucose and lipid metabolism, vascular homeostasis, immune response and even reproduction. Virtually all known adipose secreted proteins are dysregulated when the WAT mass is markedly altered, either increased in the obese state or decreased in lipoatrophy. This strongly implicates adipose-secreted products in the ethiopathology and/or complications of both obesity and cachexia. This review discusses the physiological relevance of adipose secretion by focusing on protein and steroid hormones. Regulation of WAT secretion by the major regulatory factors impinging on the adipocytes, i.e. insulin, glucocorticoids, catecholamines and thiazolidinediones (TZD) will be addressed. The rationale for therapeutic strategies aimed at compensating adverse effects resulting from overproduction or lack of a specific adipose secretory product will be discussed.
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PMID:Adipose tissue hormones. 1250 47

The adipose-derived hormone resistin is postulated to link obesity to insulin resistance and diabetes. Here, the infusion of either resistin or the resistin-like molecule-beta (RELMbeta) rapidly induced severe hepatic but not peripheral insulin resistance. In the presence of physiologic hyperinsulinemia, the infusion of purified recombinant resistin, increasing circulating resistin levels by approximately twofold to 15-fold, inhibited glucose metabolism such that lower rates of glucose infusion were required to maintain the plasma glucose concentration at basal levels. The effects of resistin and RELMbeta on in vivo insulin action were completely accounted for by a marked increase in the rate of glucose production. These results support the notion that a novel family of fat- and gut-derived circulating proteins modulates hepatic insulin action.
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PMID:Adipose-derived resistin and gut-derived resistin-like molecule-beta selectively impair insulin action on glucose production. 1456 1

High-fat diet and intrauterine growth retardation may predispose to obesity, insulin resistance, and type 2 diabetes. Because prenatal ethanol (ETOH) exposure causes intrauterine growth retardation, we investigated its interactions with postnatal high-fat diet on glucose tolerance and adipocyte-derived hormones in the rat offspring. High-fat-fed offspring had increased adiposity, serum leptin, and muscle uncoupling protein-3, but decreased adiponectin mRNA, compared with corresponding chow-fed groups. ETOH-exposed offspring had normal adiponectin, but increased resistin mRNA and protein, compared with controls, regardless of postnatal diet. Skeletal muscle glucose transporter-4 content was decreased after both ETOH exposure and high-fat feeding. Glycemic and insulin responses to an ip glucose challenge were equally increased in non-ETOH-exposed high-fat-fed offspring and in ETOH-exposed chow-fed offspring, with additive effects of ETOH and high-fat diet. Pancreatic insulin content was elevated only in non-ETOH-exposed high-fat-fed offspring. The data suggest that high-fat diet worsens glucose intolerance in offspring of rats exposed to ETOH. Prenatal ETOH exposure and postnatal high-fat diet might cause insulin resistance through separate mechanisms, involving resistin and adiponectin, respectively.
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PMID:Glucose intolerance and resistin expression in rat offspring exposed to ethanol in utero: modulation by postnatal high-fat diet. 1253 10


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