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

The aims of the present study was to examine how overweight and obesity affect serum concentrations nitric oxide (NO) metabolites and to determine whether there is association between serum concentrations tumor necrosis factor (TNF)-alpha and TNF soluble receptors (sTNF-R) in subjects with overweight and obesity. The study groups involved 154 women: 102 obese (81 obese with body mass index [BMI] 30 to 40 kg/m2 and 21 obese with BMI > 40 kg/m2), 24 overweight patients, and 28 lean controls. Serum concentrations of NO metabolites and of TNF-alpha and its soluble receptors (sTNF-R1, sTNFR-2) were measured by enzyme-linked immunosorbent assay (ELISA) kits. Serum concentration of insulin was measured by radioimmunoassay (RIA). Plasma glucose, cholesterol, high-density lipoprotein (HDL)-cholesterol, and triglicerydes were determined by enzymatic procedure. Body composition was determined by impedance analysis using Bodystat (Douglas, British Isles). Serum concentrations of NO in the overweight group (35.1 +/- 12.1 micromol/L) and the obese groups with BMI 30 to 40 kg/m2 (32.8 +/- 9.3 micromol/L) and with BMI greater than 40 kg/m2 (33.3 +/- 8.5 micromol/L) were significantly higher when compared to controls (28.2 +/- 8.1 micromol/L): P < .05; P < .01, and P < .01, respectively. There was no difference in levels of NO between the overweight group and both obese groups. Serum concentration of TNF-alpha was also significantly higher in the group with overweight (6.5 +/- 3.1 pg/mL), in the obese group with BMI 30 to 40 kg/m2 (6.8 +/- 3.1 pg/mL), and in the obese group with BMI greater than 40 kg/m2 (7.4 +/- 2.6 pg/mL) when compared to controls (2.9 +/- 2.2 pg/mL): P < .00005; P < .00005, and P < .0000001, respectively. However, serum concentrations of sTNF-R1 and -R2 did not differ significantly between the overweight group, both obese groups, and controls. In conclusion, we observed increased serum concentrations of TNF-alpha and NO in overweight and obese women. It seems that there is an association between serum concentrations of TNF-alpha and NO; however, this relationship depends on the degree of obesity.
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PMID:Serum concentrations of nitric oxide, tumor necrosis factor (TNF)-alpha and TNF soluble receptors in women with overweight and obesity. 1537 81

Obese (f/f) Koletsky rats lack the leptin receptor (LR), whereas their lean (F/?) counterparts bear a fully functional LR. By using f/f and F/? rats, we studied whether the LR is involved in lipopolysaccharide (LPS)-induced fever and hypothermia. The body temperature responses to LPS (10 or 100 microg/kg iv) were measured in Koletsky rats exposed to a thermoneutral (28 degrees C) or cool (22 degrees C) environment. Rats of both genotypes responded to LPS with fever at 28 degrees C and with dose-dependent hypothermia at 22 degrees C. The fever responses of the f/f and F/? rats were identical. The hypothermic response of the f/f rats was markedly prolonged compared with that of the F/? rats. The prolonged hypothermic response to LPS in the f/f rats was accompanied by enhanced NF-kappaB signaling in the hypothalamus and an exaggerated rise in the plasma concentration of tumor necrosis factor (TNF)-alpha. The f/f rats did not respond to LPS with an increase in the plasma concentration of corticosterone or adrenocorticotropic hormone, whereas their F/? counterparts did. The hypothermic response to TNF-alpha (80 microg/kg iv) was markedly prolonged in the f/f rats. These data show that the LR is essential for the recovery from LPS hypothermia. LR-dependent mechanisms of the recovery from LPS hypothermia include activation of the anti-inflammatory hypothalamo-pituitary-adrenal axis, inhibition of both the production and hypothermic action of TNF-alpha, and suppression of inflammatory (via NF-kappaB) signaling in the hypothalamus.
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PMID:A new function of the leptin receptor: mediation of the recovery from lipopolysaccharide-induced hypothermia. 1538 70

Since the discovery of leptin, the adipocyte and its products have been the subject of intensive research. Thus, it has been demonstrated that adipose tissue plays a central role in energy homeostasis, behaving as an endocrine organ that expresses molecules involved in regulation of metabolism; alterations in the expression or activity of those molecules have a fundamental role in pathologies such as obesity and insulin resistance. However, little is known about the role played by another tissue, skeletal muscle, which may have similar functions regarding metabolism control. Indeed, some molecules expressed in this tissue have recently been shown to modulate adipose metabolism. The present review considers the metabolic interrelationships and cross-talk of signals derived from both skeletal muscle and adipose tissue. It is suggested that cytokines derived from both tissues may have an important role in maintaining an adequate ratio of skeletal muscle to fat and thus may play an important role in the control of body weight. IL-15 (a cytokine highly-expressed in skeletal muscle), TNF-alpha, and leptin could play a decisive role in the suggested "conversation" between adipose tissue and skeletal muscle.
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PMID:Cross-talk between skeletal muscle and adipose tissue: a link with obesity? 1538 34

Increased circulating levels of liver enzymes emerging during treatment with psychotropic drugs are frequently encountered and, in general, attributed to drug metabolism or toxic effects. Because obesity was shown to be associated with elevated liver enzyme levels in different non-psychiatric study samples, we hypothesized that drug-induced weight gain might be an additional causative factor. We tested this hypothesis in 67 inpatients who received psychopharmacological treatment across five weeks. Stepwise linear regression was used to predict changes in the serum levels of aspartate-amino transferase (ASAT) and alanine-amino transferase (ALAT) by changes in the body mass index (BMI), by changes in other biological parameters related to body weight (tumor necrosis factor-alpha [TNF-alpha], soluble TNF receptors [sTNF-R], interleukin-6 [IL-6], leptin plasma levels) and by the respective liver enzyme baseline level. BMI changes from baseline to endpoint were significantly associated with the changes in ALAT and ASAT levels across five weeks of treatment and with ALAT and ASAT levels at the end point of the study. The baseline levels of ALAT and ASAT also had a significant impact on these liver enzyme level changes, whereas all other variables had not. These results suggest that weight gain-associated metabolic changes occurring during treatment with psychotropic drugs have consistent and clinically relevant effects on the liver.
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PMID:Elevation of liver enzyme levels during psychopharmacological treatment is associated with weight gain. 1550 22

Metabolic alterations such as insulin resistance are thought to underlie the endothelial dysfunction and low grade inflammation found in morbid obesity. Twenty-six morbidly obese patients, aged 39.0 +/- 10.0 (mean +/- sd), were evaluated before and 4.2 +/- 0.8 months after bariatric surgery. A marked increment in the insulin sensitivity index (S(I)) and the endothelium-dependent vasodilatory response in a dorsal hand vein was observed after weight loss following bariatric surgery. Circulating levels of E-selectin, P-selectin, plasminogen activator inhibitor-1, and von Willebrand factor, which were higher than those in the control group, decreased significantly after surgery. Plasma vascular cell adhesion molecule-1, angiotensin-converting enzyme, intercellular adhesion molecule-1, thrombomodulin, and plasma and intraplatelet cGMP levels did not change after weight loss. All inflammatory markers were higher in morbidly obese patients. After surgery, C- reactive protein and sialic acid diminished, whereas circulating levels of IL-6, TNF-alpha, and its soluble receptors did not. Positive correlations were found between changes in adiposity and S(I) and changes in C-reactive protein and between changes in sialic acid and changes in endothelial function. In conclusion, a marked improvement in S(I), endothelial function, and low grade inflammation was observed in the weight-losing, morbidly obese patients after bariatric surgery. S(I) and adiposity appear to play roles in obesity-related, low grade inflammation that contribute to the endothelial dysfunction observed in morbid obesity.
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PMID:Effects of changes in body weight and insulin resistance on inflammation and endothelial function in morbid obesity after bariatric surgery. 1550 18

Resistin is an adipocyte-secreted hormone proposed to link obesity with insulin resistance and diabetes, but no previous study has performed a joint quantitative evaluation of white adipose tissue (WAT) resistin mRNA expression and serum levels in relation to insulinemia and glycemia in mice. We have thus comparatively assessed WAT resistin mRNA expression and serum resistin levels in lean C57BL/6J mice and various mouse models of obesity, including diet-induced obese (DIO) C57BL/6J mice, high fat-fed TNF-alpha-/- mice, and brown adipose tissue (BAT)-deficient uncoupling protein-diphtheria toxin A chain (UCP1-DTA) mice. We also studied whether treatment with the weight-reducing and insulin-sensitizing compounds, MTII, an alpha-melanocyte-stimulating hormone analog, or CNTF(Ax15), a ciliary neurotrophic factor analog, alters resistin mRNA expression and/or circulating levels in lean and DIO C57BL/6J mice. We find that resistin mRNA expression is similar in DIO and lean C57BL/6J mice, as well as in TNF-alpha-/- and wild-type (WT) mice. Circulating resistin levels, however, are higher in DIO C57BL/6J, high fat-fed TNF-alpha-/-, and UCP1-DTA mice compared with lean controls. Moreover, although resistin mRNA expression is upregulated by MTII treatment for 24 h and downregulated by CNTF(Ax15) treatment for 3 or 7 days, circulating resistin levels are not altered by MTII or CNTF(Ax15) treatment. In addition, serum resistin levels, but not resistin mRNA expression levels, are correlated with body weight, and neither resistin mRNA expression nor serum resistin levels are correlated with serum insulin or glucose levels. We conclude that transcriptional regulation of resistin in WAT does not correlate with circulating resistin levels and that circulating resistin is unlikely to play a major endocrine role in insulin resistance or glycemia in mice.
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PMID:Circulating resistin in lean, obese, and insulin-resistant mouse models: lack of association with insulinemia and glycemia. 1552 96

Large longitudinal studies showed the epidemiological link between obesity and hypertension. During last years, multiple possible mechanisms involved in this association were identified. Adipose tissue has an important role in the genesis of hypertension in obese patients through several pathways: insulin resistance, leptin, renin-angiotensin-aldosteron system and mediators of inflammation (TNF-alpha, IL-6). Adipocyte may be the major player in the development of insulin resistance and hypertension, elements of the metabolic syndrome, responsible for the cardiovascular complications.
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PMID:Hypertension in obese patients: a dysmetabolic hypertension with a possible adipocyte dysfunction mechanism. 1552 95

Adipose tissue is a major source of inflammatory and thrombotic cytokines. This study investigated the relationship of abdominal subcutaneous adipose tissue cytokine gene expression to body composition, fat distribution, and metabolic risk during obesity. We determined body composition, abdominal fat distribution, plasma lipids, and abdominal subcutaneous fat gene expression of leptin, TNF-alpha, IL-6, PAI-1, and adiponectin in 20 obese, middle-aged women (BMI, 32.7 +/- 0.8 kg/m2; age, 57 +/- 1 yr). A subset of these women without diabetes (n = 15) also underwent an OGTT. In all women, visceral fat volume was negatively related to leptin (r = -0.46, P < 0.05) and tended to be negatively related to adiponectin (r = -0.38, P = 0.09) gene expression. Among the nondiabetic women, fasting insulin (r = 0.69, P < 0.01), 2-h insulin (r = 0.56, P < 0.05), and HOMA index (r = 0.59, P < 0.05) correlated positively with TNF-alpha gene expression; fasting insulin (r = 0.54, P < 0.05) was positively related to, and 2-h insulin (r = 0.49, P = 0.06) tended to be positively related to, IL-6 gene expression; and glucose area (r = -0.56, P < 0.05) was negatively related to, and insulin area (r = -0.49, P = 0.06) tended to be negatively related to, adiponectin gene expression. Also, adiponectin gene expression was significantly lower in women with vs. without the metabolic syndrome (adiponectin-beta-actin ratio, 2.26 +/- 0.46 vs. 3.31 +/- 0.33, P < 0.05). We conclude that abdominal subcutaneous adipose tissue expression of inflammatory cytokines is a potential mechanism linking obesity with its metabolic comorbidities.
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PMID:Abdominal adipose tissue cytokine gene expression: relationship to obesity and metabolic risk factors. 1556 50

A role for high leptin levels in the proinflammatory state associated with obesity has been proposed on the basis of observational studies, but a recent interventional study employing administration of long-acting pegylated leptin resulting in very high pharmacologic levels in obese subjects did not support this idea. These interventional studies have not yet been independently confirmed, however, and varying levels and duration of hyperleptinemia as well as the presence of comorbidities such as diabetes have not yet been investigated as potential effect modifiers. We performed three interventional studies involving administration of recombinant methionyl human leptin (r-metHuLeptin) to lean, otherwise healthy obese, and obese diabetic subjects to investigate whether increasing circulating leptin levels over a wide spectrum of values (from low physiologic to high pharmacologic) would alter serum levels of inflammatory markers and other cytokines important in the T helper cell response. Increasing leptin levels from low physiologic to high physiologic in lean men and from higher physiologic to low pharmacologic in obese men over 3 d did not alter serum interferon-gamma, IL-10, TNF-alpha, monocyte chemoattractant protein-1, or soluble intercellular adhesion molecule-1. In obese subjects with type 2 diabetes mellitus, the administration of r-metHuLeptin for 4 or 16 wk, resulting in high pharmacologic leptin levels, did not activate the TNF-alpha system or increase cytokines or inflammatory markers, including IL-10, IL-6, C-reactive protein, monocyte chemoattractant protein-1, and soluble intercellular adhesion molecule-1. These findings do not support an etiopathogenic role for leptin in proinflammatory states associated with leptin excess such as obesity and have direct relevance for the potential future therapeutic use of r-metHuLeptin in humans.
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PMID:Recombinant methionyl human leptin administration to achieve high physiologic or pharmacologic leptin levels does not alter circulating inflammatory marker levels in humans with leptin sufficiency or excess. 1591 91

We show that NF-kappaB and transcriptional targets are activated in liver by obesity and high-fat diet (HFD). We have matched this state of chronic, subacute 'inflammation' by low-level activation of NF-kappaB in the liver of transgenic mice, designated LIKK, by selectively expressing constitutively active IKK-b in hepatocytes. These mice exhibit a type 2 diabetes phenotype, characterized by hyperglycemia, profound hepatic insulin resistance, and moderate systemic insulin resistance, including effects in muscle. The hepatic production of proinflammatory cytokines, including IL-6, IL-1beta and TNF-alpha, was increased in LIKK mice to a similar extent as induced by HFD in in wild-type mice. Parallel increases were observed in cytokine signaling in liver and mucscle of LIKK mice. Insulin resistance was improved by systemic neutralization of IL-6 or salicylate inhibition of IKK-beta. Hepatic expression of the IkappaBalpha superrepressor (LISR) reversed the phenotype of both LIKK mice and wild-type mice fed an HFD. These findings indicate that lipid accumulation in the liver leads to subacute hepatic 'inflammation' through NF-kappaB activation and downstream cytokine production. This causes insulin resistance both locally in liver and systemically.
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PMID:Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB. 1568 73


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