Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fat tissue is a significant source of endogenous tumor necrosis factor alpha (TNFalpha), the pluripotent cytokine that plays an important role as a mediator of the peripheral insulin resistance found in obesity. The majority of evidence for this role of TNFalpha is from studies in animal models of obesity. To explore further the role of TNFalpha in the pathogenesis of obesity-related insulin resistance in humans, we compared plasma levels of TNFalpha and the other main endocrine cytokine, interleukin-6 ([IL-6] both measured by enzyme-linked immunosorbent assay), in 26 obese women (body mass index [BMI] > 30 kg/m2) and 13 female controls (BMI < 26 kg/m2) without a history of recent or active infection. Glucose and insulin levels were measured at 0, 1, and 2 hours after a 75-g oral glucose load. There was no significant difference in plasma TNFalpha or IL-6 levels between obese and non-obese subjects overall (2.10 +/- 0.19 v 1.65 +/- 0.18 pg/mL and 2.06 +/- 0.29 v 1.50 +/- 0.17 pg/mL, respectively). However, TNFalpha levels were significantly elevated in obese subjects with a 2-hour glucose level more than 140 mg/dL (n = 8) compared with the other obese subjects (n = 18) and the non-obese controls (2.88 +/- 0.46 v 1.75 +/- 0.10 and 1.65 +/- 0.18 pg/mL, respectively, P < .01). Furthermore, the TNFalpha level correlated significantly with the waist to hip ratio ([WHR] r = .53, P < .01) and fasting and post-oral glucose tolerance test (OGTT) insulin levels (r = .47, P < .02), but not with the BMI, and was higher in obese women with a WHR more than 0.90 (n = 14) in comparison to those with a WHR less than 0.90 (n = 12, 2.47 +/- 0.29 v 1.66 +/- 0.18 pg/mL, respectively, P < .03). The corresponding plasma leptin level was significantly higher in obese women versus the control group (41.6 +/- 2.5 v22.3 +/- 2.9 ng/mL, P < .001) and was related to the BMI (r = .60, P < .01) but not to TNFalpha or the WHR. There were no significant differences in the corresponding IL-6 concentration between groups, and IL-6 did not correlate with TNFalpha, leptin, BMI, WHR, or insulin levels. In conclusion, circulating TNFalpha levels are higher in abdominal obesity compared with peripheral obesity, and may contribute to the insulin resistance that more commonly complicates the former pattern of fat distribution.
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PMID:Circulating tumor necrosis factor alpha concentrations are higher in abdominal versus peripheral obesity. 1053

The prevalence of overweight and obesity continues to increase rapidly in the United States, with more than half of all adults currently overweight or obese. In general, people become obese because of a combination of inherited genes and a lifestyle consisting of low levels of physical activity and consumption of excess calories. Obesity, especially the central or visceral type, is a predisposing factor for the development of type 2 diabetes mellitus, hypertension, and cardiovascular disease (CVD). Obesity and type 2 diabetes are associated with insulin resistance. The relation among obesity, insulin resistance, and CVD appears to develop at a relatively young age. Central obesity is linked with hyperinsulinemia, insulin resistance, dyslipidemia, and proinflammatory and prothrombotic clinical states. Adipose tissue synthesizes and secretes biologically active molecules that may affect CVD risk factors. These chemical messengers include adiponectin, resistin, leptin, plasminogen activator inhibitor-1, tumor necrosis factor-alpha, and interleukin-6. In overweight and obese individuals, weight loss may improve insulin sensitivity, leading to reduction in risk factors for CVD and, consequently, the potential for cardiovascular events. Agents that improve insulin sensitivity, such as the thiazolidinediones, have been shown to reduce visceral obesity. Decreases in visceral adipose tissue contribute to improvements in insulin sensitivity and blood pressure, and weight loss reduces serum levels of triglycerides and low-density lipoprotein cholesterol while increasing serum levels of high-density lipoprotein cholesterol. Reduction of risk factors suggests that the development of cardiovascular disease will be reduced by the improvement of insulin sensitivity and weight loss.
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PMID:Obesity as a cardiovascular risk factor. 1467 64

The level of interleukin-6 (IL-6), a cytokine with prothrombotic properties, and its associations with metabolic, coagulation and fibrinolytic parameters were investigated in 68 young women (23-49 years, mean 40 years old) six months to six years after myocardial infarction (MI, N=22), lacunar cerebral infarction (LACI, N=16) and deep vein thrombosis (VT, N=30); all women were in the reproductive period, aged <45 years at the time of acute thrombotic event. Forty-seven age-matched women comprised a control group. Basic and multivariate analysis disclosed different patterns of IL-6 increase in all three groups of patients. In the MI group IL-6 was significantly elevated independently of factors known to increase IL-6 levels; the increase was most pronounced in patients with high lipoprotein(a). This result suggests a prothrombotic association of lipoprotein(a) with IL-6. In the whole LACI group IL-6 was not significantly increased. However, patients with elevated levels of IL-6 had abdominal obesity and elevated fibrinogen, suggesting the possibility that this combination might represent a specific risk profile. In VT group elevated IL-6 level was found in the group of previous users of oral contraceptives (OC). This might be relevant, since it is known that OC could importantly increase (previously elevated) IL-6 level in selected women. Our results suggest the hypothesis that the role of IL-6 might be vascular-bed-specific and further propose that increased IL-6 level might represent a novel, non-classical risk factor for development of MI, LACI and VT in specific subgroups of young women, which have to be clarified in further studies.
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PMID:Possible vascular-bed-specific role of interleukin-6 in young women with a history of myocardial infarction, lacunar cerebral infarction and deep vein thrombosis. 1503 42

Adipose tissue (AT) is not considered anymore as a passive depot for storing excess energy in the form of triglycerides but as an active organ secreting several hormones or adipokines. With the exception of adiponectin the serum levels of adipokines are increased in obesity. Leptin regulates food intake, reproductive and immune system. Adiponectin decreases insulin resistance and has antiinflammatory properties. On the contrary, resisting, tumor necrosis factor and Interleukin-6 are diabetogenic and induce inflammatory reactions. It is believed that atherosclerosis is due to the inflammation induced by oxydized LDL-cholesterol in vessels. Abdominal obesity is associated with increased incidence of metabolic disorders and insulin resistance. The role of adipokines in these disorders is described as well as their role in the antidiabetic effect of thiazo-linedinediones. AT contains also enzymes responsible for the aromatization of androstenedione into estrone, which could explain an increase of breast and uterus cancer in obese people.
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PMID:[Adipose tissue: a real endocrine gland synthesizing hormones and cytokines: clinical implications]. 1509 64

Persistent low-grade inflammation, as indicated by higher circulating levels of inflammatory mediators such as C-reactive protein, interleukin-6 and tumour necrosis factor-alpha, is a strong risk factor for several chronic diseases. There are data indicating that decreasing energy intake and increasing physical activity may be effective therapies for reducing overall inflammation. Evidence is strong that circulating levels of inflammatory markers are elevated with total and abdominal obesity, possibly owing to a higher secretion rate of cytokines by adipose tissue in obese people. Moreover, very-low-energy dietary weight loss reduces both circulating markers of inflammation and adipose-tissue cytokine production. Data from several large population-based cohorts show an inverse association between markers of systemic inflammation and physical activity or fitness status; small-scale intervention studies support that exercise training diminishes inflammation. Dietary weight loss plus exercise is likely more effective than weight reduction alone in reducing inflammation. To date, data from randomized, controlled trails designed to definitively test the effects of weight loss or exercise training, or both, on inflammation are limited. Future studies are required to define the amount of weight loss needed for clinically meaningful reductions of inflammation; in addition, fully powered and controlled studies are necessary to clarify the effect of exercise training on chronic, systemic inflammation.
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PMID:Behavioural treatments for chronic systemic inflammation: effects of dietary weight loss and exercise training. 1624 6

It is proposed that metabolic syndrome X is initiated in the perinatal period as a low-grade systemic inflammatory condition. Increased consumption of energy-dense diets by pregnant women and lactating mothers suppresses the activities of Delta-6 and Delta-5 desaturases not only in maternal tissues but also in fetal liver and the placenta, resulting in decreased plasma and tissue concentrations of long-chain polyunsaturated fatty acids omega-6 arachidonic acid (AA), omega-3 eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). EPA, DHA, and AA have negative feedback control on tumor necrosis factor-alpha and IL-6 synthesis. Hence, EPA, DHA, and AA deficiencies induced by an energy-dense diet increase generation of tumor necrosis factor-alpha and interleukin-6, markers of inflammation that in turn decrease production of endothelial nitric oxide and adiponectin to induce insulin resistance in maternal and fetal tissues. Increased concentrations of tumor necrosis factor-alpha and interleukin-6 enhance expression and activity of 11beta-hydroxysteroid dehydrogenase type 1 enzyme, which produces abdominal obesity, insulin resistance, hyperlipidemia, hyperphagia, and hyperleptinemia, characteristic features of metabolic syndrome X. Continued consumption of an energy-dense diet in childhood aggravates these molecular events. This implies that supplementation of long-chain polyunsaturated fatty acids (especially AA, EPA, and DHA in appropriate ratios) from the perinatal period through adulthood could prevent, arrest, or postpone development of metabolic syndrome X.
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PMID:Pathophysiology of metabolic syndrome X and its links to the perinatal period. 1592 3

The associations of inflammatory markers (high-sensitivity C-reactive protein [hs-CRP], interleukin-6 [IL-6], tumor necrosis factor-alpha, and fibrinogen) with anthropometric and metabolic variables were examined in a sample of 112 postmenopausal women not receiving hormone therapy. Body fat distribution was measured by computed tomography, and insulin sensitivity was determined by an euglycemic-hyperinsulinemic clamp. hs-CRP (0.10 < or = r(2) < or =0.37) and IL-6 (0.06 < or = r(2) < or =0.31) were significantly associated with anthropometric and metabolic variables, including visceral and subcutaneous adipose tissue, systolic and diastolic blood pressure, triglycerides, high-density lipoprotein (HDL) cholesterol, and insulin sensitivity (p <0.05). Women with greater hs-CRP concentrations showed deterioration in their metabolic risk profiles, including abdominal obesity, greater triglyceride and lower HDL cholesterol concentrations, and lower insulin sensitivity compared with women with lower hs-CRP levels. Fifty-nine percent of women with high hs-CRP concentrations had the metabolic syndrome as recently defined by the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. After adjustment for visceral adipose tissue, most of the differences in the plasma lipid-lipoprotein profile were eliminated between women with high hs-CRP levels and women with low hs-CRP levels, whereas some differences in blood pressure variables, insulin sensitivity, and inflammatory markers (IL-6 and fibrinogen) remained significant. In conclusion, these results suggest that increased visceral adipose tissue levels appear to be a determinant covariable of the association between high hs-CRP concentrations and alteration in the metabolic profile.
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PMID:Relation of high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-alpha, and fibrinogen to abdominal adipose tissue, blood pressure, and cholesterol and triglyceride levels in healthy postmenopausal women. 1597 42

Metabolic syndrome is a cluster of metabolic abnormalities consisting essentially of obesity, especially abdominal obesity. Metabolic syndrome has been highlighted as a risk factor for cardiovascular and other chronic diseases. Obesity has been implicated in various gastrointestinal diseases such as gastroesophageal reflux diseases and colorectal cancer. Recently, abdominal obesity has been shown to be more important than obesity as expressed by an elevated body mass index as a causative factor for the development of these diseases. In addition to the mechanical effects of obesity, such as an increase in intra-abdominal pressure from large amounts of adipose tissue, substances that adipose tissues secrete, such as tumor necrosis factor-alpha, interleukin-6, leptin, and insulin-like growth factor-1, have been proposed to be pathogenic links to these diseases. In this review, we discuss the association of metabolic syndrome or the individual components of metabolic syndrome, focusing on obesity and abdominal obesity, with gastrointestinal diseases.
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PMID:Metabolic syndrome and gastrointestinal diseases. 1746 54

Although obesity has been consistently linked to an increased risk of several malignancies, including cancers of the colon, gallbladder, kidney, and pancreas, its role in prostate cancer etiology remains elusive. Data on the association between obesity and prostate cancer incidence are inconsistent, and in some studies obesity is associated with an increase in risk of high-grade prostate cancer but with a decrease in risk of low-grade tumors. In contrast, obesity has been consistently associated with an increased risk of prostate cancer aggressiveness and mortality. The differential effects of obesity on subtypes of prostate cancer suggest etiologic heterogeneity in these tumors and complex interactions between androgen metabolism and several putative risk factors, including insulin resistance, diabetes, inflammation, and genetic susceptibility, on prostate cancer risk. Data on the role of abdominal obesity, insulin resistance, and metabolic syndrome in prostate cancer etiology are limited. Obesity has been shown to be associated with a state of low-grade chronic inflammation, and insulin resistance and the metabolic syndrome are associated with adverse metabolic profiles and with higher circulating concentrations of inflammation-related markers, including leptin, interleukin-6, and tumor necrosis factor-, many of which have been shown to enhance tumor growth. Thus, whether obesity and metabolic syndrome modulate the risk of prostate cancer through chronic inflammation needs to be investigated further. Given that the prevalence of obesity and metabolic syndrome is increasing worldwide and that the world population is aging, the roles of obesity and metabolic syndrome in prostate carcinogenesis warrant further clarification.
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PMID:Obesity, metabolic syndrome, and prostate cancer. 1826 78

It has been known for about 50 years that different obesity phenotypes do exist. Nonetheless, how abdominal, namely visceral, obesity is burdened by metabolic and cardiovascular diseases has been established only in recent years. The association between abdominal obesity and diabetes, which is well documented, has been mainly explained by the lower insulin sensitivity of subjects with excess visceral fat. However, more recent studies support the hypothesis that several molecules released in greater or lower amount by visceral adipocytes can exert also a detrimental role on beta-cell function. Among these molecules free fatty acids and adipokines should be mentioned. The latter include inflammatory cytokines, such as tumor necrosis factor-alpha and interleukin-6 and hormones synthesized by adipocytes, such as adiponectin, leptin and resistin. Visceral obesity is also associated with an excessive depot of triglycerides and other lipid products (e.g., ceramide) within the key organs of glucose metabolism (liver, skeletal muscle, pancreatic islets). This phenomenon seems to contribute to both insulin resistance and beta-cell dysfunction, favoring abnormalities of glucose homeostasis.
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PMID:[Abdominal obesity and diabetes]. 1877 50


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