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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 fat-derived protein adiponectin is an important insulin-sensitizing adipocytokine which is downregulated in insulin resistance and obesity. Recently, two receptors of this adipose-expressed protein called adiponectin receptor 1 (AdipoR1) and 2 (AdipoR2) have been cloned. To clarify expression and regulation of these receptors in fat cells, AdipoR1 and AdipoR2 mRNA was measured by quantitative real-time reverse transcription-polymerase chain reaction during differentiation of 3T3-L1 adipocytes and after treatment with various hormones known to induce insulin resistance. Interestingly, AdipoR2 synthesis was significantly increased up to 4.8-fold during differentiation of 3T3-L1 preadipocytes, whereas AdipoR1 expression was only augmented up to 1.4-fold. Furthermore, growth hormone (GH) induced AdipoR2, but not AdipoR1 mRNA by up to 2.4-fold in a dose- and time-dependent fashion with significant stimulation detectable at concentrations as low as 5 ng/ml GH and as early as 2 h after effector addition. The positive effect of GH on AdipoR2 expression could be reversed by withdrawal of the hormone for 24 h. In contrast, other key hormones involved in the regulation of insulin resistance and energy metabolism such as insulin, isoproterenol, dexamethasone, triiodothyronine, angiotensin 2, tumor necrosis factor alpha, and interleukin-6 did not influence AdipoR1 and AdipoR2 synthesis in vitro. Taken together, our results suggest that AdipoR2 expression is differentiation-dependent and selectively regulated by GH implying a potential role of this hormone in adiponectin-associated alterations of insulin sensitivity and energy homeostasis.
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PMID:Growth hormone is a positive regulator of adiponectin receptor 2 in 3T3-L1 adipocytes. 1475 11

5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR) can be used as an experimental tool to activate 5'-AMP-activated protein kinase (AMPK) and has been shown to improve insulin sensitivity. In parallel adiponectin also seems to activate AMPK and to improve insulin sensitivity. We have investigated the effects of AICAR on the gene expression of adiponectin and on gene expression and release of cytokines in human adipose tissue in vitro. AICAR stimulated AMPK alpha1 activity 3-4-fold (p<0.001), and dose-dependently increased adiponectin mRNA levels with significant stimulation (2-4-fold) at AICAR concentrations of 0.5-2mM (p<0.05). The adipose tissue protein release of tumor necrosis factor-alpha (TNF- alpha) and interleukin-6 (IL-6) was decreased by AICAR (p<0.05). In conclusion, AICAR stimulated adipose tissue AMPK alpha1 activity and adiponectin gene expression, while attenuating the release of TNF-alpha and IL-6. Reduced concentrations of these cytokines and increased levels of adiponectin might play a role for the insulin sensitizing effects of AICAR.
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PMID:AICAR stimulates adiponectin and inhibits cytokines in adipose tissue. 1503 79

That obesity is associated with insulin resistance and type II diabetes mellitus is well accepted. Overloading of white adipose tissue beyond its storage capacity leads to lipid disorders in non-adipose tissues, namely skeletal and cardiac muscles, pancreas, and liver, effects that are often mediated through increased non-esterified fatty acid fluxes. This in turn leads to a tissue-specific disordered insulin response and increased lipid deposition and lipotoxicity, coupled to abnormal plasma metabolic and (or) lipoprotein profiles. Thus, the importance of functional adipocytes is crucial, as highlighted by the disorders seen in both "too much" (obesity) and "too little" (lipodystrophy) white adipose tissue. However, beyond its capacity for fat storage, white adipose tissue is now well recognised as an endocrine tissue producing multiple hormones whose plasma levels are altered in obese, insulin-resistant, and diabetic subjects. The consequence of these hormonal alterations with respect to both glucose and lipid metabolism in insulin target tissues is just beginning to be understood. The present review will focus on a number of these hormones: acylation-stimulating protein, leptin, adiponectin, tumour necrosis factor alpha, interleukin-6, and resistin, defining their changes induced in obesity and diabetes mellitus and highlighting their functional properties that may protect or worsen lipid metabolism.
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PMID:Diabetes, lipids, and adipocyte secretagogues. 1505 36

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

The aim of the present study was to examine the relationship between adiponectin and the systemic inflammatory response in weight-losing patients with non-small cell lung cancer (NSCLC). Measurement of anthropometry, acute phase proteins, interleukin-6, leptin (total and free) and adiponectin were carried out on healthy subjects (n = 13) and non-small cell lung cancer patients with weight loss (n = 20). The groups were age and sex matched. Compared with the controls the cancer group had a lower BMI (p < 0.01), mid-upper arm circumference (p < 0.001), triceps skinfold thickness (p < 0.05) and circulating concentrations of albumin (p < 0.001), haemoglobin (p < 0.05), free and total leptin (p < 0.05) and adiponectin (p < 0.01). In contrast, the cancer group had elevated circulating concentrations of interleukin-6 and C-reactive protein concentrations (p < 0.001). In the cancer group circulating adiponectin concentrations were significantly inversely correlated with both free (rs = -0.675, p = 0.001) and total leptin concentrations (rs = -0.690, p = 0.001). However, neither weight loss, interleukin-6 or C-reactive protein concentrations were correlated with either adiponectin, free or total leptin concentrations in the cancer group. These results suggest that adipokine production is normal and is unlikely to play a major role in the abnormal fat metabolism in weight-losing cancer patients.
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PMID:Adiponectin and the systemic inflammatory response in weight-losing patients with non-small cell lung cancer. 1524 98

The adipocytokines are biologically active polypeptides that are produced either exclusively or substantially by the adipocytes, and act by endocrine, paracrine, and autocrine mechanisms. Most have been associated with obesity, hyperinsulinaemia, type 2 diabetes, and chronic vascular disease; in addition, six adipocytokines--vascular endothelial growth factor, hepatocyte growth factor, leptin, tumour necrosis factor-alpha, heparin-binding epidermal growth factor-like growth factor, and interleukin-6--promote angiogenesis while one, adiponectin, is inhibitory. Obesity and insulin resistance have both been identified as risk factors for breast cancer and are associated with late-stage disease and poor prognosis. Angiogenesis is essential for breast cancer development and progression, and so it is plausible that obesity-related increases in adipocytokine production and a reduction in adiponectin may adversely affect breast cancer outcome by their angiogenesis-related activities. There is also experimental evidence that some adipocytokines can act directly on breast cancer cells to stimulate their proliferation and invasive capacity. Thus, adipocytokines may provide a biological mechanism by which obesity and insulin resistance are causally associated with breast cancer risk and poor prognosis. Both experimental and clinical studies are needed to develop this concept, and particularly in oestrogen-independent breast cancers where preventive and therapeutic options are limited.
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PMID:Obesity, adipocytokines, and insulin resistance in breast cancer. 1524 84

Patients with end-stage renal disease (ESRD) are at high risk from potentially devastating cardiovascular sequelae due to the unique clustering of risk factors in these patients. Inflammation is believed to play a key role in the pathogenesis of these cardiovascular lesions. Both pro- and anti-inflammatory cytokines produced from monocytes, and also from adipocytes, have been studied in this regard. Pro-inflammatory cytokines, although cytoprotective acutely, correlate with increased risk of cardiovascular disease (CVD) in chronic situations. Conversely, elevated levels of anti-inflammatory mediators are associated with increased patient survival times. Statistical modelling, calculation of relative risk and cost considerations indicate that determination of serum C-reactive protein levels may be a useful predictor of CVD in ESRD patients. Adipocytes are a rich source of many of the same cytokines produced by monocytes, including interleukin-6, tumour necrosis factor-alpha, as well as adipocyte-specific proteins, leptin and adiponectin (ADPN). ADPN, which is produced in much greater quantities than leptin, is inversely related to body mass index and to insulin resistance, suggesting a possible role in type 2 diabetes. Additionally, ADPN has been shown to modulate the endothelial inflammatory response in vitro. Plasma ADPN levels are an inverse predictor of cardiovascular outcomes among patients with ESRD. Furthermore, ADPN is related to several metabolic risk factors in a manner consistent with the hypothesis that this protein acts as a protective factor for the cardiovascular system.
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PMID:Inflammatory proteins as predictors of cardiovascular disease in patients with end-stage renal disease. 1528 63

The adipose tissue produces a vast number of molecules called adipokines such as leptin, tumoral necrosis factor (TNFalpha), interleukins and adiponectin. Many of the metabolic disturbances associated with obesity and the metabolic syndrome may be due to citokine production by adipocytes. The adipose tissue increases the soluble fractions of TNFalpha leading to a rise in its biological activity. The activation of TNFalpha system causes insulin resistance through different mechanisms such as defects in receptor fosforilation and reduction in insulin-sensitive glucose transporters. TNFalpha is also involved in the pathophysiology of hypertension and dyslipidaemia associated with obesity and insulin resistance. More than one third of interleukin-6 (IL-6) concentrations come from the adipocytes. It has been demonstrated a role for IL-6 in the development of hyperlipidemia, diabetes and hypertension. In contrast to the rest of adipokines, adiponectin is reduced in obesity, diabetes or cardiovascular disease. Adiponectin improves insulin resistance, dyslipidaemia and adhesion to endothelial cells protecting from atherosclerosis development. Thus, adipokines have an important role in the pathophysiology of metabolic syndrome by different mechanisms involving metabolic and vascular effects.
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PMID:[Obesity and inflammation]. 1538 13

Chronic inflammation is prevalent in dialysis patients. We investigated the relationship between inflammation and newly identified adipokines: leptin and adiponectin in this population. A total of 129 chronic hemodialysis patients were collected. Serum high sensitivity C-reactive protein (CRP), interleukin-6 (IL-6), leptin and adiponectin levels were determined as well as other metabolic variables. Correlation studies and multiple regression analysis were performed among variables. Our results showed that hemodialysis patients had elevated levels of inflammatory markers, leptin and adiponectin. Diabetic subjects had higher serum CRP and lower albumin levels than non-diabetics. Serum CRP levels were positively correlated with IL-6 levels and negatively correlated with albumin levels. Serum leptin levels were directly related to CRP levels while adiponectin levels were inversely related to CRP levels. A significant negative correlation was observed between serum leptin and adiponectin levels. Serum IL-6 levels were the single independent factor affecting CRP levels. Body mass index can predict both serum leptin and adiponectin levels. We conclude that hemodialysis patients are at an increased risk of chronic inflammation and diabetes patients are even more susceptible to this status. Both serum leptin and adiponectin levels are associated with inflammatory markers. As adipose tissue is the major secreting site of these adipokines, our results suggest that adipose tissue plays an important role in the pathogenesis of chronic inflammation in dialysis patients.
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PMID:The relationship between inflammatory markers, leptin and adiponectin in chronic hemodialysis patients. 1556 Jun 77


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