Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Visfatin is a newly discovered adipocyte hormone with a direct relationship between plasma visfatin level and type 2 diabetes mellitus. Visfatin binds to the insulin receptor at a site distinct from that of insulin and causes hypoglycaemia by reducing glucose release from liver cells and stimulating glucose utilization in adipocytes and myocytes. Visfatin is upregulated by hypoxia, inflammation and hyperglycaemia and downregulated by insulin, somatostatin and statins. This hormone is found in the cytoplasm as well as the nucleus of cells and has been identified in many tissues and organs including the brain, kidney, lung, spleen and testis but preferentially expressed in visceral adipose tissue and upregulated in some animal models of obesity. Visceral adipose tissue is regarded to be more pernicious than subcutaneous adipose tissue. Visfatin is an endocrine, autocrine as well as paracrine peptide with many functions including enhancement of cell proliferation, biosynthesis of nicotinamide mono- and dinucleotide and hypoglycaemic effect. Visfatin, also known as a pre-B cell colony-enhancing factor, consists of 491 amino acids (aa) in human, chimpanzee, cattle, pig, rat and mouse, 490 aa in rhesus monkey, 285 aa in sheep, 587 in opossum and 588 aa in canines. Visfatin gene is well preserved during evolution. For example, the canine visfatin protein sequence is 96% and 94% identical to human and rodent visfatin, respectively. Since evidence of a direct link between visfatin genotype and human type 2 diabetes mellitus is still weak, more molecular, physiological and clinical studies are needed to determine the role of visfatin in the etiology and pathogenesis of type 2 diabetes mellitus.
 ...
PMID:Visfatin: structure, function and relation to diabetes mellitus and other dysfunctions. 1869 Oct 43

Recent researches have shown that adipocytokines secreted by adipose tissue play an important role in inflammation which is considered to be a crucial step in the pathogenesis of atherosclerosis. Leptin, one of the earlier adipocytokines, is known to play a major role in cardiovascular disease and recent observations suggest that leptin is an independent risk factor for coronary heart disease. Resistin, another recently discovered adipocytokine, has been related to risk factors of atherosclerosis, and in diabetic individuals serum resistin levels correlate well with inflammatory markers and are predictive for the development of cardiovascular disease. Adiponectin, another adipocytokine of interest in recent years, seems to be the most promising one studied to date. In contrast to leptin and resistin, adiponectin seems to be beneficial for health and it is a protective factor and decreased in obesity. However, many other factors derived from adipose tissue have also been discovered, such as interleukin-6, tumor necrosis factor alpha, monocyte chemoattractant protein 1, apelin, visfatin and probably others awaiting discovery in the near future. In this paper, we discussed the role of adipocytokines in the pathogenesis of atherosclerotic cardiovascular disease.
 ...
PMID:A new frame in thromboembolic cardiovascular disease: Adipocytokine. 1837 21

The aim of the study were to answer the question 1.) Whether circulating pro-inflammatory markers of endothelial dysfunction and due to chronic low-grade inflammation of obesity, are altered in untreated lean, young relatively healthy polycystic ovary syndrome (PCOS) patients in comparison with healthy controls; 2.) Whether postprandial plasma concentration pattern of ghrelin and PYY can be predictable as risk factors for atherosclerosis and depend of obesity. Forty young women with PCOS were divided in two groups: 19 lean and 21 obese. The control group included 20 lean, healthy volunteers. Plasma total and active ghrelin, total PYY and PYY(3-36), serum adiponectin and insulin were measured using RIA technique, serum sCD40L, visfatin, sP-, sE-selectins, resistin by EIA. Composition of test meal was: 527 kcal total and consisted of 24.1% fat, 54.4% carbohydrate and 21.5% protein. Total and active ghrelin and total PYY were significantly lower in obese PCOS women, whereas active ghrelin was also significantly lower in lean PCOS women compared to controls. Postprandial plasma total ghrelin levels decrease were blunted in lean and obese compared to controls (12.8 % and 18.2% vs 28.2 %). Postprandial plasma active ghrelin decreased in lean and obese PCOS groups (49.9 % and 44.1 %) and controls (63.8 %). PCOS subjects exhibited smaller rises in postprandial levels of total PYY. Postprandial plasma PYY(3-36) levels increased in obese PCOS women (30.9 %) and controls (41%), whereas lean PCOS women exhibited blunted increase (11.5%). sCD40L levels increased, whereas adiponectin decreased in PCOS groups independently, whereas rise in visfatin, sE- and sP-selectin and the fall in adiponectin was associated with obesity. sP- and sE -selectins correlated positively with obesity. In summary, our study provides the first evidence that lean untreated young PCOS women contribute to the so called "pancreatic islet adaptation to insulin resistance" because of ghrelin and PYY profiles. We confirmed existing of low-grade chronic inflammation in early stage of visceral obesity in lean PCOS patients. The lost endogenous "islet adaptation to insulin resistance" may lead to endothelial dysfunction and promote acceleration of atherosclerosis.
 ...
PMID:Postprandial response of ghrelin and PYY and indices of low-grade chronic inflammation in lean young women with polycystic ovary syndrome. 1881 36

Macrostemonoside A, a newly found compound, is derived from Allium macrostemon Bung. However, investigation into its nature is lacking. In this study, the effects of macrostemonoside A on hyperglycemia, hyperlipidemia, visceral fat accumulation, and related enzyme activities in high-fat diet-fed C57BL/6 mice are examined. The results showed that mice fed with a high-fat diet had a significant increase in fasting blood glucose, liver glycogen, serum total cholesterol, and visceral fat accumulation, but were mildly or moderately inhibited by macrostemonoside A at a dose of 4 mg/kg/d after 30 days of treatment. This hypoglycemic effect might be associated with the potential increase in insulin sensitivity and visfatin expression, although it needs further validation in future studies. Its anti-obesity effect might be associated with elevated total lipase activity in visceral adipose cells. The up-regulation in the expression of peroxisome proliferators-activated receptor gamma 2 might be responsible for the increased lipase activity in visceral adipose cells. Furthermore, we supposed that its action mechanisms might promote energy metabolism in muscles. Macrostemonoside A, with its steroid-like structure, has no significant cortisone-like side effects on the immune system but has potential cardiovascular protective effects. These results suggested that a potential compound to treat hyperglycemia, hyperlipidemia, and visceral obesity could be developed. However, its underlying mechanisms need further investigation in future studies.
 ...
PMID:Novel effects of macrostemonoside A, a compound from Allium macrostemon Bung, on hyperglycemia, hyperlipidemia, and visceral obesity in high-fat diet-fed C57BL/6 mice. 1893 Jul 25

The newly discovered adipokine visfatin has been hypothesized to be related to obesity and insulin resistance. In this study, we investigate if the 2 single nucleotide polymorphisms rs4730153 and G-948T are associated with obesity and/or related traits and whether they influence the messenger RNA (mRNA) levels of PBEF1 (originally the abbreviation for pre-B-cell colony-enhancing factor 1) in visceral and subcutaneous adipose tissue (VAT and SAT). We found that obese carriers of the PBEF1 G-948T variant allele had significantly higher levels of high-density lipoprotein cholesterol (GG, 1.1 [0.97-1.3] mmol/L; GT + TT, 1.3 [1.0-1.5] mmol/L; P = .02). Other than that, neither rs4730153 nor G-948T had any major impact on any of the obesity-related phenotypes. There was no difference in mRNA expression between VAT and SAT (2.08 +/- 0.17 and 2.09 +/- 0.14, respectively; P = .26), but there was a nonsignificant trend toward higher PBEF1 mRNA levels in the variant allele carriers concerning both VAT and SAT for both single nucleotide polymorphisms. A significant correlation was observed between body mass index and PBEF1 mRNA expression in SAT (R = 0.37, P = .03) but not in VAT (R = 0.26, P = .12). In conclusion, PBEF1 G-948T is associated with increased high-density lipoprotein cholesterol; but genetic variation in PBEF1 does not seem to have a major impact on the development of obesity or on the expression of the gene.
 ...
PMID:The visfatin (PBEF1) G-948T gene polymorphism is associated with increased high-density lipoprotein cholesterol in obese subjects. 1894 Mar 94

Macrophages play key roles in obesity-associated pathophysiology, including inflammation, atherosclerosis, and cancer, and processes that affect the survival-death balance of macrophages may have an important impact on obesity-related diseases. Adipocytes and other cells secrete a protein called extracellular nicotinamide phosphoribosyltransferase (eNampt; also known as pre-B cell colony enhancing factor or visfatin), and plasma levels of eNampt increase in obesity. Herein we tested the hypothesis that eNampt could promote cell survival in macrophages subjected to endoplasmic reticulum (ER) stress, a process associated with obesity and obesity-associated diseases. We show that eNampt potently blocks macrophage apoptosis induced by a number of ER stressors. The mechanism involves a two-step sequential process: rapid induction of interleukin 6 (IL-6) secretion, followed by IL-6-mediated autocrine/paracrine activation of the prosurvival signal transducer STAT3. The ability of eNampt to trigger this IL-6/STAT3 cell survival pathway did not depend on the presence of the Nampt enzymatic substrate nicotinamide in the medium, could not be mimicked by the Nampt enzymatic product nicotinamide mononucleotide (NMN), was not blocked by the Nampt enzyme inhibitor FK866, and showed no correlation with enzyme activity in a series of site-directed mutant Nampt proteins. Thus, eNampt protects macrophages from ER stress-induced apoptosis by activating an IL-6/STAT3 signaling pathway via a nonenzymatic mechanism. These data suggest a novel action and mechanism of eNampt that could affect the balance of macrophage survival and death in the setting of obesity, which in turn could play important roles in obesity-associated diseases.
 ...
PMID:Extracellular Nampt promotes macrophage survival via a nonenzymatic interleukin-6/STAT3 signaling mechanism. 1894 71

Obesity is associated with an array of health problems in adult and pediatric populations. Understanding the pathogenesis of obesity and its metabolic sequelae has advanced rapidly over the past decades. Adipose tissue represents an active endocrine organ that, in addition to regulating fat mass and nutrient homeostasis, releases a large number of bioactive mediators (adipokines) that signal to organs of metabolic importance including brain, liver, skeletal muscle, and the immune system--thereby modulating hemostasis, blood pressure, lipid and glucose metabolism, inflammation, and atherosclerosis. In the present review, we summarize current data on the effect of the adipose tissue-derived hormones adiponectin, chemerin, leptin, omentin, resistin, retinol binding protein 4, tumor necrosis factor-alpha and interleukin-6, vaspin, and visfatin on insulin resistance.
 ...
PMID:Adipokines and insulin resistance. 1900 16

Over the last few years, it has become obvious that obesity and insulin resistance are linked by a variety of proteins secreted by adipocytes. Visfatin/PBEF (pre-B-cell colony-enhancing factor) has recently been identified as a novel adipokine with insulin-mimetic effects. Furthermore, an enzymatic function has been reported that reveals visfatin/PBEF as Nampt (nicotinamide phosphoribosyltransferase; EC 2.4.2.12.). Moreover, reports on the structure and hormonal regulation of visfatin/PBEF/Nampt have given further insights into its potential physiological role. The present review summarizes studies on visfatin/PBEF/Nampt as a novel adipokine.
 ...
PMID:Visfatin/PBEF/Nampt: structure, regulation and potential function of a novel adipokine. 1901 57

Osteoarthritis (OA) is a multifactorial disease. Different risk factors have been identified such as aging and obesity and different models have been used to study the impact of obesity and overweight in this pathology. The field the more studied is in vitro cartilage submitted to mechanical stresses. Four different stresses can be applied on this tissue: shear stress, loading, tensile stress (stretching) and hydrostatic pressure. The signal transduction to the chondrocyte and to the nucleus of the cell is a large field of investigation named mechano-transduction. The response of cartilage depends on quality of subchondral bone as well. So, more and more teams are studying the impact of mechanical stresses on bone, mainly by stretching osteoblasts or by submitting them to a fluid shear stress. Recently, a new model of bone compression has been set up, with osteoblasts in their own extracellular matrix. Finally the third field studied is the role of adipokines, mediators playing a key role in obesity, on the aetiology of OA. Adipokines like leptin, resistin, adiponectin and visfatin, seems to play a pro-inflammatory role in arthritis. Studying the role of obesity in OA could be more complex than expected. The link between OA and obesity may not simply be due to high mechanical stresses applied on the tissues, but soluble mediators may play an important role in the onset of OA in obese patients.
 ...
PMID:Osteoarthritis and obesity: experimental models. 1902 97

Inflammatory cytokines have been linked to obesity-related insulin resistance. To investigate the effect of TNF-alpha, an inflammatory cytokine, on insulin action, C57BL/6J mice were treated with TNF-alpha for 7 days after which we examined the in vivo effects of TNF-alpha on glucose tolerance and insulin sensitivity with IV glucose tolerance tests and hyperinsulinemic-euglycemic clamps. In addition, we analyzed the in vivo effect of TNF-alpha on several metabolism-related genes and adipocytokines implicated in the development of insulin resistance. TNF-alpha treatment resulted in markedly increased fasting blood glucose, insulin and free fatty acids (FFA) levels and reduced glucose tolerance. During the clamps, the rates insulin-stimulated whole body (G(Rd)) and skeletal muscle glucose uptake (MGU) and insulin's ability to suppress hepatic glucose production (HGP) were decreased in TNF-alpha treated animals, indicating insulin resistance. In addition, both PPARgamma and ATGL mRNA expression in adipose tissues as well as ATGL protein levels in plasma were downregulated. Moreover, adipose mRNA expression and plasma protein levels of adiponectin and visfatin were significantly down-regulated. We conclude that the alterations of PPARgamma, ATGL, adiponectin and visfatin may contribute to the development of insulin resistance mediated by TNF-alpha.
 ...
PMID:The adipose triglyceride lipase, adiponectin and visfatin are downregulated by tumor necrosis factor-alpha (TNF-alpha) in vivo. 1902 57


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>