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

The role of the adipose tissue in immunity has recently emerged, and there is now ample evidence that this role is elucidated by a number of cytokine-like hormones produced by adipocytes - called adipokines. The most relevant adipokines are leptin, adiponectin and visfatin, and all have marked effects on metabolic and immune function. The discovery of adipokines has led to the development of a novel concept that the pathogenesis of atherosclerosis can be associated with low-degree inflammation associated with slow (auto)immune attack of the endothelial wall of arteries. This model considers therefore adipokines as the bridge between atherosclerosis, inflammation and immunity. We review here the most recent advances on adipokine research, with a particular emphasis on the model that considers atherosclerotic lesions as effects of the (auto)immune-mediated damage of the endothelium that is sustained by low-degree chronic inflammation typical of obesity and metabolic syndrome.
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PMID:Leptin and adipocytokines: bridging the gap between immunity and atherosclerosis. 1822 Aug 5

Adipose tissue is the source of soluble mediators (adipokines), secreted mainly by adipocytes. Leptin acts on the brain and peripheral organs to regulate energy homeostasis and the neuroendocrine axis. Adiponectin regulates glucose and lipid metabolism by targeting the liver and skeletal muscle. Adiposederived proinflammatory cytokines, vasoactive peptides, coagulation and complement factors, visfatin, vaspin and retinol-binding protein signal through paracrine and hormonal mechanisms. Understanding the biology of adipose tissue and the rapidly growing list of adipokines provides new insights into normal physiological regulation, as well as the pathogenesis and treatment of obesity, diabetes and disorders of lipid metabolism and cardiovascular system.
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PMID:Adipokines in obesity. 1823 Sep 3

Visfatin has recently been identified as a novel visceral adipokine which may be involved in obesity-related vascular disorders. However, it is not known whether visfatin directly contributes to endothelial dysfunction. Here, we investigated the effect of visfatin on vascular inflammation, a key step in a variety of vascular diseases. Visfatin induced leukocyte adhesion to endothelial cells and the aortic endothelium by induction of the cell adhesion molecules, ICAM-1 and VCAM-1. Promoter analysis revealed that visfatin-mediated induction of CAMs is mainly regulated by nuclear factor-kappaB (NF-kappaB). Visfatin stimulated IkappaBalpha phosphorylation, nuclear translocation of the p65 subunit of NF-kappaB, and NF-kappaB DNA binding activity in HMECs. Furthermore, visfatin increased ROS generation, and visfatin-induced CAMs expression and NF-kappaB activation were abrogated in the presence of the direct scavenger of ROS. Taken together, our results demonstrate that visfatin is a vascular inflammatory molecule that increases expression of the inflammatory CAMs, ICAM-1 and VCAM-1, through ROS-dependent NF-kappaB activation in endothelial cells.
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PMID:Visfatin enhances ICAM-1 and VCAM-1 expression through ROS-dependent NF-kappaB activation in endothelial cells. 1824 74

Visfatin was recently identified as an adipocytokine and has insulin mimetic properties, but its role in adolescents remains largely unknown. In this study, we examined the impact of adolescent obesity on circulating visfatin levels and the relationship between visfatin and anthropometric indices, insulin sensitivity, and blood lipids in Chinese adolescents (11-18 years). Serum visfatin, adiponectin, leptin, and blood lipids were measured in 76 non-obese and 72 obese adolescents. The medians of serum visfatin levels were significantly higher in obese subjects of 34.68ng/ml than in non-obese subjects of 28.67ng/ml (P=0.002). There were no significant correlations in the non-obese group between the serum visfatin concentration and the anthropometric indices or the lipid parameters. However, visfatin levels were negatively correlated with age, early insulin secretion index (EISI), Tanner stage, and positively correlated with HDL-c in the obese adolescents. These relationships, except that for EISI and Tanner stage, remained significant (P<0.05) after adjusting for age, gender, and body mass index. Moreover, unlike adiponectin and leptin, visfatin concentration did not correlate with testosterone in non-obese and obese boys. In conclusion, visfatin levels may decrease with age and be related to the HDL metabolism in obese adolescents.
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PMID:Serum visfatin concentrations in obese adolescents and its correlation with age and high-density lipoprotein cholesterol. 1824 53

The melanocortin (MC) system is a pivotal component of the hypothalamo-pituitary-adrenal (HPA) stress axis and plays an important role in the pathogenesis of obesity and the metabolic syndrome. Adipose dysfunction is implicated in the pathogenesis of these disorders. We investigated direct ACTH effects on adipose functions in immortalised murine white and brown adipocytes. MC receptor types 2 and 5 were expressed at the mRNA and protein levels and were strongly up-regulated during differentiation. Chronic ACTH stimulation did not affect adipogenesis. Insulin-induced glucose uptake in white adipocytes was acutely and transiently reduced by 45% upon ACTH treatment. Visfatin and adiponectin gene expression was reduced by about 50% in response to ACTH, while interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) mRNA levels were acutely up-regulated by 2100 and 60% respectively. Moreover, IL-6 secretion was increased by 1450% within 4 h of ACTH treatment. In brown adipocytes, stimulation with ACTH caused a 690% increase in uncoupling protein (UCP)-1 mRNA levels within 8 h, followed by a 470% increase in UCP-1 protein concentrations after 24 h. Consistently, p38 mitogen-activated protein kinase (MAPK) phosphorylation was acutely increased by 1800% in response to ACTH stimulation, and selective inhibition of p38 MAPK abolished the ACTH-mediated UCP-1 protein increase. Taken together, ACTH acutely promotes an insulin-resistant, pro-inflammatory state and transiently enhances energy combustion. In conditions characterised by a dysregulation of the HPA stress axis such as the metabolic syndrome, direct MC interaction with adipocytes may contribute to dysregulated energy balance, insulin resistance and cardiometabolic complications.
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PMID:Melanocortin crosstalk with adipose functions: ACTH directly induces insulin resistance, promotes a pro-inflammatory adipokine profile and stimulates UCP-1 in adipocytes. 1831 Apr 42

Visfatin was recently identified as a novel adipokine highly enriched in visceral adipose tissue and suggested to play a role in the pathophysiology of obesity and type 2 diabetes mellitus. However, the biological role of visfatin remains elusive since subsequent studies failed to repeat some of the original findings. We report here the cloning of six porcine visfatin transcript variants, resulting from alternate polyadenylation or alternate splicing of exons. It is further demonstrated that the porcine visfatin gene and protein expression measured in fat tissues correlate negatively with subcutaneous (s.c.), visceral and total body fat tissue weights. Moreover, there was no correlation between visfatin mRNA or protein levels and fasting glucose or insulin. No correlation could be found between circulating visfatin and any of the carcass and metabolic parameters. Our results also demonstrate that the tumor necrosis factor (TNF)alpha increases porcine visfatin gene expression in stromal-vascular (SV) cell cultures, thus suggesting an intermediary role for TNFalpha in visfatin response. In conclusion, our results demonstrate that the porcine visfatin gene cannot be considered as a marker of fat accumulation since the highest visfatin expression levels were associated with the leaner animals.
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PMID:Visfatin expression is not associated with adipose tissue abundance in the porcine model. 1834 25

In order to investigate whether weight loss can lead to improvement of the mononuclear cell (MNC) proinflammatory state, 21 nondiabetic obese women with mean age 34+/-2 years (mean+/-s.e.m.) and BMI 32.5+/-1.2 kg/m2 were enrolled in a 12-week caloric restriction and light exercise-based weight loss program. Ten lean women served as controls. Reverse transcription-PCR of proinflammatory cytokines and adipocytokines as well as homeostasis model assessment of insulin resistance (HOMA-IR) were determined before and after weight reduction. Nuclear factor kappaB (NF-kappaB) binding to DNA and inhibitors of NF-kappaB (IkappaB-alpha and IkappaB-beta) obtained from peripheral MNCs were measured. Overall, subjects lost a mean of 4.0+/-0.4 kg (5.0+/-0.3% of their initial body weight) (P<0.01). In addition to significant reductions in BMI, fasting glucose and insulin concentrations, mean serum high-sensitivity C-reactive protein (hs-CRP), migration inhibitor factor (MIF), leptin and visfatin levels decreased by 49.0, 66.6, 17.2, and 50.2%, respectively (all P<0.05), while adiponectin concentrations rose by 33.9% (P<0.05). The DNA binding of the transcriptionally active NF-kappaB from (p65/p50) decreased by 38.1% (P<0.05). Elevated levels of mRNA of NF-kappaB related proinflammatory genes, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), MIF, and matrix metalloproteinase-9 (MMP-9), decreased significantly after weight loss. Although mRNA expression of Rel-A, p105, IkappaB-alpha, IkappaB-beta decreased significantly, their protein levels did not change after weight loss. As a group, NF-kappaB binding activity correlated with HOMA-IR (r=0.332, P=0.049) and marginally with values of BMI (r=0.308, P=0.059). In conclusion, weight loss by 5% of initial weight in nondiabetic obese women led to significant improvement in activated intranuclear NF-kappaB binding as well as several transcriptions of proinflammatory genes regulated by NF-kappaB.
Obesity (Silver Spring) 2008 May
PMID:Effect of weight loss on proinflammatory state of mononuclear cells in obese women. 1939 76

Retinol-binding protein 4 (RBP4) and nicotinamide phosphoribosyltransferase/visfatin (Nampt/visfatin) are adipocyte-secreted proteins (adipokines) whose relevance to the metabolic syndrome and regulation in obesity remain controversial. Here, we tested the hypothesis that adipose tissue expression and circulating levels of these two adipokines are elevated in obesity by analyzing their changes in both a genetic and a diet-induced model of obesity in the rat (obese FA/ FA Zucker rats and Wistar rats fed a cafeteria diet, respectively). Compared with lean controls, obese FA/ FA rats were hyperleptinemic, hyperinsulinemic, and insulin resistant and had reduced RBP4 serum levels and mRNA levels in adipose depots, unchanged Nampt/visfatin serum levels, and reduced Nampt/visfatin mRNA levels selectively in the inguinal adipose depot. Cafeteria diet-induced obesity resulted in increased fed blood glucose levels, a variable degree of insulin resistance, unchanged serum Nampt/visfatin and RBP4 levels, and reduced mRNA levels of both adipokines in several adipose depots. Hence, increases in RBP4 or Nampt/visfatin do not accompany obesity and insulin resistance in the models examined.
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PMID:Retinol-binding protein 4 and nicotinamide phosphoribosyltransferase/visfatin in rat obesity models. 1840 39

Obesity is characterized by systemic low-grade inflammation in which adipose tissue, especially the omental depot, is thought to play a key role. We have previously shown that inflammation impairs 3T3-L1 preadipocyte cell line differentiation. To explore whether this interaction also takes place in vivo, the expression of several genes related to inflammation and adipocyte differentiation was assessed in human samples. Paired adipose tissue biopsies (from omental and subcutaneous depots) were obtained from 24 women: 6 lean normoglycemic and 18 obese volunteers with different glycemic states (normoglycemic, glucose-intolerant, or type 2 diabetic). The expression levels of CD14, IL-18, leptin, adiponectin, sterol regulatory element binding transcription factor 1 (SREBP1), peroxisome proliferator-activated receptor gamma (PPARgamma), pre-B-cell colony enhancing factor 1 (PBEF1) (or visfatin), glycerol-3-phosphate dehydrogenase 1 (soluble) (GPD1), lipoprotein lipase (LPL), fatty acid binding protein 4, adipocyte (FABP4), and hypoxia-inducible factor 1alpha were determined by quantitative real-time PCR. CD14 and IL-18 were overexpressed in omental adipose tissue compared with the subcutaneous depot, irrespective of the subject's obesity or diabetes status. A significant decrease of LPL, GPD1, and leptin expression was observed in omental tissue, and an inverse correlation between expression of CD14 and IL-18 and that of PPARgamma, LPL, and FABP4 was observed. The underexpression of omental lipogenic markers was more accentuated in the presence of glucose intolerance. Furthermore, adiponectin and SREBP1 expression was also significantly decreased in omental tissue of type 2 diabetic patients. PBEF1 and HIF1alpha expression remained comparable in all samples. Therefore, in humans, inflammation is increased in the omental depot, as evidenced by CD14 and IL-18 expression. In this localization, the inflammatory state is associated with a decreased expression of lipogenic markers, which is more pronounced in diabetic subjects.
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PMID:Inflammation is associated with a decrease of lipogenic factors in omental fat in women. 1883 93

Adipocytokines, fat tissue derived factors with regulatory properties, are involved in the pathophysiology of atheromatous and metabolic illnesses such as: ischemic heart disease, insulin resistance, obesity, dyslipidemia and diabetes mellitus. Enlargement of visceral adipose tissue depots determines a worse evolution for those complaints. Drugs as angiotensin converting enzyme inhibitors (ACEI), thiazolidinediones (glitazones) or angiotensin-II receptor antagonists, generally associated with the adequate hypolipidemic (statins, fibrates) or antiobesity (orlistat, sibutramine, rimonabant) medication, would increase those adipocytokines with anti-inflammatory and insulin-sensitizing properties (i.e. adiponectin or visfatin), while reducing pro-inflammatory and thrombogenic cytokines (as leptin, tumor necrosis factor [TNF]-alpha, plasminogen activator inhibitor 1 [PAI-1]). Thus, these pharmacologic therapeutic approaches would have a beneficial effect in order to diminish morbidity-mortality and improve the prognosis of patients with said diseases, all of them related to high cardiovascular risk.
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PMID:[Adipocytokines: implications in the prognosis and drug treatment of cardiovascular diseases]. 1845 36


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