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 aim of this study was to investigate the possible role of resistin in obese women with and without insulin resistance. We compared serum concentrations of resistin with interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), soluble TNF receptors 1 and 2, and certain anthropometric and metabolic parameters in 26 obese women (body mass index [BMI], 35.8 +/- 4.12 kg/m2) and 15 healthy control women (BMI, 22.32 +/- 1.89 kg/m2). Fasting serum resistin and inflammatory cytokine levels were measured by enzyme immunoassay. Insulin resistance was measured by the homeostasis model assessment of insulin resistance (HOMA-R) formula. Compared with lean controls, obese women showed higher HOMA-R values and levels of insulin and increased values of TNF-alpha, soluble TNF receptors, and IL-6. There was no significant difference in resistin levels between the investigated groups of obese women and lean subjects. The results showed that serum resistin concentrations did not correlate with BMI, HOMA, fasting plasma glucose level, or fasting plasma insulin level. Serum resistin correlated with fat mass and IL-6 in the group with impaired glucose tolerance (obese group) (r = 0.51, P < .05, and r = 0.37, P < .05, respectively) and with low-density lipoprotein cholesterol (r = -0.39, P < .05) in the same group. The groups we examined are relatively small; it is likely that with a larger number of subjects, the correlation in other obese women groups may achieve statistical significance. It seems that resistin may be linked with inflammation and obesity and, indirectly, with insulin resistance.
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PMID:Relationship between serum resistin concentration and proinflammatory cytokines in obese women with impaired and normal glucose tolerance. 1704 52

Insulin resistance in skeletal muscle is linked to an elevated adipose tissue mass, as is found in obesity, but can also be observed in lipodystrophy, in which adipose tissue is greatly reduced. Adipose tissue releases endocrine and metabolic mediators and is actively involved in crosstalk with skeletal muscle, a process that precedes and underlies the development of insulin resistance in muscles. Adipokines including tumor necrosis factor alpha, interleukin-6, leptin and adiponectin influence insulin signaling in skeletal muscle. Free fatty acids, their metabolites and ectopic fat in muscle also contribute to insulin resistance. Recent research indicates inflammation, endoplasmic reticulum stress and oxidative stress could be underlying mechanisms at the center of the development of insulin resistance. Insights into the role of macrophages in adipose tissue add to the complicated interplay between adipose tissue and skeletal muscle.
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PMID:The adipocyte-myocyte axis in insulin resistance. 1708 39

Definitions of the metabolic syndrome (MetS) include obesity, dyslipidemia, elevated levels of fasting blood glucose, and blood pressure as criteria, but it is also known that the MetS is associated with chronic, subclinical inflammation. Hyperglycemia (fasting and postprandial) may be important in exacerbating this proinflammatory state. We aimed to assess the impact of oral glucose challenge and in vitro glucose-stimulation on gene expression and secretion of inflammatory parameters in peripheral blood leukocytes and to investigate whether presence of the MetS could "prime" leukocytes to up-regulate proinflammatory markers in response to glucose. Using quantitative real-time PCR, we could show that the expression of intercellular adhesion molecule 1 (ICAM-1), tumor necrosis factor alpha (TNF-alpha), and interleukin 6 (IL-6) significantly increased in peripheral blood leukocytes from "MetS" subjects (n=39) compared to "no MetS" subjects (n=35) 2 h after an oral glucose tolerance test (ICAM-1 +52%, TNF-alpha +107%, and IL-6 +38%) and also in vitro after 72 h cultivation in high-glucose medium (ICAM-1 +74%, TNF-alpha +71%, and IL-6 +44%). Using ELISA and Luminex technique, we further observed a trend towards increased immune mediator concentrations in the corresponding cell culture supernatants from MetS patients (ICAM-1 +21%, TNF-alpha +31%, and IL-6 +175%). Thus, the MetS may support peripheral inflammation by sensitizing leukocytes to up-regulate proinflammatory markers in response to glucose, which in turn increases the risk for type-2 diabetes mellitus and cardiovascular disease.
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PMID:The metabolic syndrome sensitizes leukocytes for glucose-induced immune gene expression. 1716 Jun 70

The endocannabinoid system modulates many pathophysiological functions, including the brain pathways involved in the regulation of body weight and adipose tissue function. The selective cannabinoid CB(1) receptor antagonist, rimonabant, has undergone phase III clinical testing as anti-obesity drug. Obesity is considered a mild inflammatory condition and predisposes individuals to an increased risk of developing many diseases. It has been recently suggested that a successful intervention to treat obesity is a therapy combining weight-reducing drugs with anti-inflammatory ones. In this scenario, rimonabant's anti-obesity action is accompanied by favorable changes in markers for insulin resistance, C-reactive protein, adiponectin, tumor necrosis factor alpha (TNFalpha). The results reported by Croci and Zarini in this issue highlight the anti-inflammatory and anti-hyperalgesic effect of rimonabant in obese animals, so suggesting that it could provide a more general and aggressive strategy to protect obese patients from many pathological risks.
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PMID:Rimonabant: more than an anti-obesity drug? 1724 60

Recent studies associate obesity and insulin resistance in horses with development of abnormal reproductive function and debilitating laminitis. The factors contributing to insulin resistance in obese horses are unknown. However, human studies provide evidence that elevated inflammatory cytokines such as tumor necrosis factor alpha (TNFalpha), IL1, and IL6 play direct roles in development of obesity-associated insulin resistance. Thus, inflammation may be a key link between obesity and insulin resistance in horses. The aim of the current investigation was to examine possible relationships between obesity, inflammatory cytokines, and insulin sensitivity (IS) in the horse. Age was recorded and BCS and percent body fat (% FAT) were determined as measures of obesity in 60 mares. In addition, blood mRNA expression of IL1, IL6, and TNFalpha and circulating concentrations of TNFalpha protein (TNFp) were determined in each mare. Finally, fasted concentrations of insulin were determined, and IS was determined using the hyperinsulinemic, euglycemic clamp. Significant correlations between several variables provided evidence for the design of 4 population regression models to estimate relationships between measures of obesity, inflammatory factors, and IS in the sample population. The results of these analyses revealed that IS decreased as BCS and % FAT increased (P < 0.001) in the sample population. Additionally, increased IL1 (P < 0.05) and TNFp (P < 0.01) were associated with decreased IS. However, increased TNFalpha (P < 0.001) was associated with decreased IS only in mares 20 yr of age and older. Increased BCS and % FAT were associated with increased expression of TNFalpha (P = 0.053) and IL1 (P < 0.05), and increased TNFp (P < 0.05). Surprisingly, increased BCS and % FAT were associated with decreased IL6 expression (P = 0.05) in mares <20 yr of age. Finally, evaluation of the influence of obesity and inflammatory cytokines on IS within the same model suggested that BCS and % FAT (P < 0.001) with TNFalpha [mRNA (P = 0.07) and protein (P < 0.05)] are inversely associated with IS independently of one another. Combined, these results provide the first evidence associating obesity with increased inflammatory factors in the horse. Furthermore, the results suggest that an interrelationship exists among obesity, inflammatory cytokines, and IS in the horse and emphasize the need for further studies to elucidate the nature of these relationships.
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PMID:Relationships among inflammatory cytokines, obesity, and insulin sensitivity in the horse. 1726 35

Gaucher disease (glucocerebrosidase deficiency) is characterized by massive accumulation of lipid-laden macrophages in various tissues. Patients with Gaucher disease show a hitherto unexplained increase in hepatic glucose output. Because adiponectin is thought to influence hepatic glucose output, we studied its serum concentration in a cohort of patients with Gaucher disease. Serum adiponectin was indeed found to be markedly reduced in patients (median value, 3.1 microg/mL; range, 1.4-6.3 microg/mL) as compared with healthy subjects (median value 5.6 microg/mL range, 1.9-14.0 microg/mL). Successful treatment of patients was accompanied by an increase in serum adiponectin, from 3.1 to 3.6 microg/mL (P = .002). In healthy individuals, low levels of circulating adiponectin are generally associated with obesity. In patients with Gaucher disease, however, adiponectin levels did not correlate with body mass index. The hypoadiponectinemia in Gaucher patients is most likely attributable to their low-grade chronic inflammation. The characteristic storage macrophages produce inflammatory cytokines such as tumor necrosis factor alpha that is known to suppress adiponectin production. It is of interest that the very low adiponectin levels in Gaucher patients are not accompanied by hyperglycemia, contrary to their effect in obese individuals. It is hypothesized that the excessive hepatic glucose production in these patients balances the assumed increased glucose consumption by the massive amounts of storage macrophages. Hypoadiponectemia may play a regulatory role in preventing hypoglycemia in this condition.
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PMID:Very low serum adiponectin levels in patients with type 1 Gaucher disease without overt hyperglycemia. 1729 18

Although the vast majority of heavy drinkers and individuals with obesity, insulin resistance, and the metabolic syndrome have steatosis, only a minority ever develop steatohepatitis, fibrosis, and cirrhosis. Genetic and environmental risk factors for advanced alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) seem likely to include factors that influence the severity of steatosis and oxidative stress, the cytokine milieu, the magnitude of the immune response, and/or the severity of liver fibrosis. For ALD, the dose and pattern of alcohol intake, coffee intake, and dietary and other lifestyle factors leading to obesity are the most important environmental determinants of disease risk. For NAFLD, dietary saturated fat and antioxidant intake, small bowel bacterial overgrowth, and obstructive sleep apnea syndrome may play a role. Family studies and interethnic variations in susceptibility suggest that genetic factors are important in determining disease risk. For ALD, functional polymorphisms in the ADH and ALDH alcohol metabolizing genes play a role in determining susceptibility in Oriental populations. No genetic associations with advanced NAFLD have been replicated in large studies. Preliminary data suggest that polymorphisms in the genes encoding microsomal triglyceride transfer protein, superoxide dismutase 2, the CD14 endotoxin receptor, tumor necrosis factor alpha, transforming growth factor beta, and angiotensinogen may be associated with steatohepatitis or hepatic fibrosis or both.
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PMID:Genetics of alcoholic liver disease and nonalcoholic fatty liver disease. 1729 76

Obesity-associated, system-wide elevations in free fatty acids, tumor necrosis factor alpha, and glucocorticoids increase intracellular lipid metabolites and promote insulin resistance. In this issue, Holland et al. (2007) provide pharmacological and genetic evidence that ceramide plays a key role in the development of insulin resistance induced by these factors.
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PMID:The path to insulin resistance: paved with ceramides? 1733 25

Obesity is associated with increased cardiovascular morbidity and mortality. Although obesity-associated hypertension, dyslipidemia and insulin resistance account in part for this association, it becomes increasingly apparent that a systemic and local pro-inflammatory response of adipose tissue might also be a contributing factor. White adipose tissue (WAT) is a highly active organ secreting various peptides such as cytokines, chemokines and hormone-like proteins. Besides the visceral and subcutaneous depots, WAT is also found in the close vicinity of blood vessels (perivascular adipose tissue), where it secretes cytokines such as interleukin-1, tumor necrosis factor alpha, pro-atherogenic chemokines, and pro-angiogenic peptides. These factors appear to contribute directly to alterations of the function and structure of the vascular wall, including chronic inflammation, alterations of vascular tone, proliferation of smooth muscle cells, neo-angiogenesis and hence to the development of atherosclerosis and cardiovascular complications.
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PMID:Local adipose tissue depots as cardiovascular risk factors. 1741 12

Adrenal incidentalomas (AIs) have been associated with an increased incidence of several cardiovascular risk factors, similar to overt Cushing syndrome. Data about the involvement of the adipokines in the development of insulin resistance and atherosclerosis in AI are completely lacking. The aim of the present study was to evaluate plasma interleukin 6 (IL-6), adiponectin, resistin, tumor necrosis factor alpha (TNF-alpha), and monocyte chemoattractant protein 1 (MCP-1) levels in patients with AI. Plasma IL-6, adiponectin, resistin, TNF-alpha, and MCP-1 levels were measured in 20 healthy subjects (6 males; 14 females; age, 58.5 +/- 2.2 years; body mass index, 28.1 +/- 0.9 kg/m(2)) and in 20 patients (5 males; 15 females; age, 57.9 +/- 2.0 years; body mass index, 28.0 +/- 0.8 kg/m(2)) with AI and typical computed tomographic features of cortical adenoma, who were not affected by diabetes mellitus, hypertension, or other relevant diseases. All patients underwent anthropometric measurements and determination of basal corticotropin, cortisol, and urinary free cortisol excretion. Overnight dexamethasone test and 250-microg corticotropin test were performed in all cases. A subclinical Cushing syndrome was found in 3 patients, whereas the others had apparently nonfunctioning masses. Plasma IL-6, adiponectin, resistin, TNF-alpha, and MCP-1 levels were higher in patients than in controls (64.4 +/- 2.8 vs 5.5 +/- 0.6 pg/mL, 13.7 +/- 1.3 vs 3.6 +/- 0.5 microg/mL, 12.5 +/- 1.9 vs 5.1 +/- 0.2 ng/mL, 27.0 +/- 1.5 vs 22.2 +/- 1.5 pg/mL, 172.5 +/- 20.0 vs 104.4 +/- 19.5 pg/mL, respectively; P < .05) and apparently not affected by the presence of visceral obesity. Plasma IL-6 levels were negatively correlated with urinary free cortisol (r = -0.461, P < .05), and TNF-alpha levels were positively correlated with cortisol after the administration of 1 mg dexamethasone (r = 0.636, P < .01). In conclusion, patients with AI may show increased levels of adipokines (apparently not related to the presence of diabetes, hypertension, or obesity), which may be affected by the presence of the adrenal adenoma. For some adipokines, a direct production from the adrenal gland may be hypothesized even if other studies are needed to better investigate the role of adipokines in states of altered cortisol secretion.
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PMID:Adipokine levels and cardiovascular risk in patients with adrenal incidentaloma. 1744 45


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