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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The adipose tissue produces and secretes many bioactive substances, which we conceptualized as Adipocytokines (Nature Medicine 1996). Adiponectin is a novel adipocytokine, which we identified by screening the adipose-specific genes from human fat. Adiponectin is a secreted protein, the concentration of which reaches as high as 5-15 micrograms/ml in human plasma. Adiponectin mRNA is expressed exclusively in adipose tissues. The adiponectin mRNAs and its plasma levels are reduced in obesity, type 2 diabetes and atherosclerosis. Hyperinsulinemic euglycemic clamp studies in humans and monkeys, and several recent studies from others revealed that adiponectin is an insulin-sensitizing hormone. Furthermore, adiponectin exhibited anti-atherogenic moieties, decreasing the attachment of monocytes to endothelial cells through inhibiting the expression levels of adhesion molecules. It reduced the lipid accumulation in macrophages through reducing the expression of scavenger receptor, and inhibited the cytokine-stimulated proliferation of smooth muscle cells. The genetic mutation of the adiponectin gene accompanying hypoadiponectinemia was strongly associated with the incidence of type 2 diabetes and atherosclerosis in Japanese subjects. Hypoadiponectinemia was the strongest predictor for the development of type 2 diabetes in humans. Adiponectin knockout mice exhibited diet-induced diabetes and severer atherosclerotic response by vascular injury. Adiponectin supplement reversed the insulin resistance syndrome including diabetes and atherosclerotic change in the knockout mice. We conclude that "Hypoadiponectinemia" stands upstream of the pathophysiology of metabolic syndrome, hence, can be a direct target of drug intervention to tackle life style-related disease rampant in developed countries.
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PMID:[Adipocytokines and life style-related disease]. 1467 87

Genome-wide scanning is a powerful tool to identify susceptible chromosome loci, however, individual chromosomal regions still have many candidate genes. Although cDNA microarray analysis provides valuable information for identifying genes involved in pathogenesis, expression levels of many genes are changed. A novel approach for identification of therapeutic targets is the combination of genome-wide scanning and the use of DNA chips, as shown in Fig. (1). Using DNA chips, we screened for secreted molecules, the expressions of which were changed in adipose tissues from mice rendered insulin resistance. Decreased expression of one of these molecules, adiponectin/Acrp30, correlates strongly with insulin resistance. Interestingly, recent genome-wide scans have mapped a susceptibility locus for type 2 diabetes and metabolic syndrome to chromosome 3q27, where adiponectin gene is located. Decreasing serum adiponectin levels are associated with increased risk for type 2 diabetes. Interestingly, adiponectin was decreased in insulin resistant rodent models both of obesity and lipoatrophy, and replenishment of adiponectin ameliorated their insulin resistance. Moreover, adiponectin transgenic mice ameliorated insulin resistance and diabetes Adiponectin knockout mice showed insulin resistance and glucose intolerance. In muscle and liver, adiponectin activated AMP kinase and PPARalpha pathways thereby increasing beta-oxidation of lipids, leading to decreased TG content, which ameliorated insulin resistance under a high-fat diet. Despite similar plasma glucose and lipid levels on an apoE deficient background, adiponectin transgenic apoE deficient mice showed amelioration of atherosclerosis, which was associated with decreased expressions of class A scavenger receptor and tumor necrosis factor alpha. Finally, cDNA encoding adiponectin receptors (AdipoR1 and R2) have been identified by expression cloning, which facilitates the understanding of molecular mechanisms of adiponectin actions and obesity-linked diseases such as diabetes and atherosclerosis and the designing of novel antidiabetic and anti-atherogenic drugs with AdipoR1 and R2 as molecular targets.
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PMID:Dual roles of adiponectin/Acrp30 in vivo as an anti-diabetic and anti-atherogenic adipokine. 1468 55

Adiponectin, a newly discovered adipose-tissue-specific protein, is thought to be involved in the regulation of insulin action. The aim of the present study was to determine whether adiponectin contributes to the improvement in insulin sensitivity during very-low-calorie diet (VLCD). Biopsies of sc abdominal adipose tissue and blood sampling for analysis of plasma adiponectin and related hormones and metabolites were performed before and at the end of a 4-wk VLCD in 33 nonmorbidly obese women (body mass index, 34.4 +/- 4.1 kg/m(2)). VLCD produced a decrease in weight (7.1 +/- 0.4 kg) and in insulin and leptin levels and led to an improvement in insulin sensitivity. Adiponectin gene expression and plasma levels were not modified during calorie restriction. Before VLCD, we found negative correlations between plasma adiponectin and variables related to the metabolic syndrome. Adiponectin mRNA levels showed a negative correlation with lipoprotein a plasma values. The correlations observed before VLCD were not found after VLCD. The data suggest that adiponectin is related to the protection against the metabolic syndrome but is not involved in the regulation of VLCD-induced improvement of insulin sensitivity.
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PMID:Adiponectin gene expression and plasma values in obese women during very-low-calorie diet. Relationship with cardiovascular risk factors and insulin resistance. 1476 92

Adiponectin, which is secreted specifically from adipocyte, is thought to play a key role in the metabolic syndrome. We studied the associations of plasma adiponectin concentrations with blood cells and hepatopancreatic enzymes in 339 women aged 54.0 +/- 0.8 (mean +/- SE) years. Plasma adiponectin before and after adjustment for body composition or calculated insulin resistance increased in slight anemic women (372.6 +/- 2.6 x 10(4)/mm3) compared with non-anemic subjects (471.1 +/- 1.7) (all p < 0.0001), and were inversely associated with red blood cells (RBC), hemoglobin, hematocrit, white blood cells and platelet values (p < 0.0001-0.02), independent of age, diastolic blood pressure, body mass index, serum triglyceride, insulin resistance or blood urea nitrogen. Age and adiponectin/body fat mass (%) were negative, and blood pressure and insulin resistance were positive significant independent determinants of RBC in step-wise regression analysis. Moreover, adiponectin before and after adjustment were inversely associated with serum ALAT, gammaGTP and ChE, and positively with amylase levels (p < 0.0001-0.02). These results indicate the possibility that increased adiponectin may contribute to the suppressive bone marrow function in vivo. Combined with the leptin's data, adipocyte derived proteins were related to the hematopoiesis, therefore it has shown the possible existence of adipose tissue/ bone marrow function linkage more clearly. Furthermore, hepatopancreatic enzyme associations with this protein may indicate the possibility that adiponectin will regulate the hepatopancreatic function in health and disease.
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PMID:Relationships between plasma adiponectin and blood cells, hepatopancreatic enzymes in women. 1496 Nov 65

Adiponectin is a novel adipocytokine negatively correlated with parameters of the metabolic syndrome, such as body mass index (BMI), body fat mass (BFM), and circulating insulin levels. Furthermore, metabolic actions directly on the liver have been described. The aim of the present study was to characterize circulating adiponectin levels, hepatic turnover, and the association of adiponectin with key parameters of hepatic as well as systemic metabolism in cirrhosis, a catabolic disease. Circulating adiponectin levels and hepatic turnover were investigated in 20 patients with advanced cirrhosis. Hepatic hemodynamics [portal pressure, liver blood flow, hepatic vascular resistance, indocyanine green (ICG) half-life], body composition, resting energy expenditure, hepatic free fatty acids (FFA) and glucose turnover, and circulating levels of hormones (catecholamines, insulin, glucagon) and proinflammatory cytokines (IL-1beta, TNF-alpha, IL-6) were also assessed. Circulating adiponectin increased dependently on the clinical stage in cirrhosis compared with controls (15.2 +/- 1.7 vs. 8.2 +/- 1.1 microg/ml, respectively, P < 0.01), whereas hepatic extraction decreased. Adiponectin was negatively correlated with parameters of hepatic protein synthesis (prothrombin time: r = -0.62, P = 0.003; albumin: r = -0.72, P < 0.001) but not with transaminases or parameters of lipid metabolism. In addition, circulating adiponectin increased with portal pressure (r = 0.67, P = 0.003), hepatic vascular resistance (r = 0.60, P = 0.008), and effective hepatic blood flow (ICG half-life: r = 0.69, P = 0.001). Adiponectin in cirrhosis was not correlated with BMI, BFM, parameters of energy metabolism, insulin levels, hepatic FFA and glucose turnover, and circulating proinflammatory cytokines. These results demonstrate that 1) adiponectin plasma levels in cirrhosis are significantly elevated, 2) the liver is a major source of adiponectin extraction, and 3) adiponectin levels in cirrhosis do not correlate with parameters of body composition or metabolism but exclusively with reduced liver function and altered hepatic hemodynamics.
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PMID:Elevated circulating adiponectin levels in liver cirrhosis are associated with reduced liver function and altered hepatic hemodynamics. 1501 Mar 38

The plasma concentration of the adipocyte-derived peptide adiponectin is decreased in patients with obesity and type 2 diabetes. The adiponectin gene is located on chromosome 3q27, where a diabetes susceptibility locus has been mapped. Adiponectin gene polymorphisms (single nucleotide polymorphisms [SNPs]) have been associated with BMI, insulin sensitivity, and type 2 diabetes in some cross-sectional studies. Our aim was to assess the contribution of these SNPs in the development of features of the insulin resistance syndrome in a 3-year prospective study in approximately 4,500 French Caucasian subjects from the Epidemiologic Data on the Insulin Resistance Syndrome (DESIR) cohort. For subjects who were normoglycemic at baseline, the 3-year risk of becoming hyperglycemic (diabetes or impaired fasting glucose) was affected by two SNPs: G-11391A and T45G. For G-11391A, the risk was increased in GA carriers (odds ratio [OR] adjusted for sex [versus GG] = 1.60 [95% CI 1.16-2.20]; P = 0.004). For T45G, it was increased in GG carriers (OR [versus TT] = 2.71 [1.31-5.60]; P = 0.007). After 3 years, GG subjects had a greater increase in BMI (P = 0.009) and waist-to-hip ratio (P = 0.007). Adiponectin levels at baseline were associated with the development of hyperglycemia (P = 0.005), but the predictive effects on the risk for hyperglycemia were independent of adiponectin genotypes. In conclusion, in the DESIR study, variations at the adiponectin locus affect body weight gain, body fat distribution, and onset of hyperglycemia, as well as adiponectin levels. Adiponectin gene SNPs may have several phenotypic effects that co-occur with the development of the metabolic syndrome.
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PMID:Adiponectin gene polymorphisms and adiponectin levels are independently associated with the development of hyperglycemia during a 3-year period: the epidemiologic data on the insulin resistance syndrome prospective study. 1504 34

Adiponectin is one of the key molecules in the metabolic syndrome, and its concentration is decreased in obesity, type-2 diabetes, and coronary artery disease. Genetic investigation has revealed that 2 polymorphisms (I164T and G276T) are related to adiponectin concentration and diabetes. To examine whether adiponectin affects hypertension genetically or biologically, we performed a case-control study. A total of 446 diagnosed cases of hypertension (HT) in men and 312 normotensive (NT) men were enrolled in this study. Plasma adiponectin concentration was measured using an enzyme-linked immunosorbent assay system. Single nucleotide polymorphisms were determined by TaqMan polymerase chain reaction method. After adjustment for confounding factors, adiponectin concentration was significantly lower in HT (HT: 5.2+/-0.2 microg/mL; NT: 6.1+/-0.2 microg/mL; P<0.001). Furthermore, multiple regression analysis indicated that hypoadiponectinemia was an independent risk factor for hypertension (P<0.001). Blood pressure was inversely associated with adiponectin concentration in normotensives regardless of insulin resistance. In subjects carrying the TC genotype of the I164T polymorphism, adiponectin concentration was significantly lower (TC: 2.6+/-0.9 microg/mL; TT: 5.5+/-0.1 microg/mL; P<0.01), and most of them had hypertension. In contrast, the G276T polymorphism was not associated with adiponectin concentration or hypertension. In conclusion, hypoadiponectinemia is a marker for predisposition to hypertension in men.
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PMID:Hypoadiponectinemia is an independent risk factor for hypertension. 1512 70

Severe obesity increases the prevalence of the metabolic syndrome, and moderate acute weight loss with a very low-calorie diet in obese subjects with the metabolic syndrome leads to significant metabolic benefits. Adiponectin has been implicated in both the pathogenesis of obesity-related insulin resistance and increased inflammation. We analyzed the relationship of the adipocyte-derived hormone adiponectin with indices of inflammation, adiposity, and insulin resistance in obese subjects with (MS+, n = 40) and without (MS-, n = 40) the metabolic syndrome and examined the acute effects of rapid weight loss. MS+ subjects had significantly lower adiponectin (7.6 +/- 0.6 vs. 10.4 +/- 0.6 microg/ml; P = 0.003) and significantly higher TNF-alpha (3.3 +/- 0.2 vs. 2.8 +/- 0.3 pg/ml; P = 0.004) levels compared with MS- subjects matched for age and body mass index. Plasma adiponectin and TNF-alpha levels were inversely related to the number of metabolic syndrome factors in a stepwise manner. After 4-6 wk of weight loss, there was marked improvement in glucose, insulin, leptin, and triglycerides, whereas adiponectin and TNF-alpha concentrations did not change. Thus, increases in plasma levels of adiponectin or reductions in TNF-alpha are not required for marked improvements in glucose/insulin and lipid metabolism with acute weight loss.
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PMID:Adiponectin, inflammation, and the expression of the metabolic syndrome in obese individuals: the impact of rapid weight loss through caloric restriction. 1518 Oct 44

Here we investigated the biological functions of adiponectin, a fat-derived hormone, by disrupting the gene encodes it in mice. Adiponectin knockout mice (KO) exhibited severe diet-induced insulin resistance with reduced IRS-1-associated P13-kinase activity in muscle. KO also revealed severe neo-intimal thickening in response to vascular-injury and hypertension induced by salt diet. Carbon-tetrachloride induced severe liver fibrosis in KO with the elevated gene expression of growth factors. These phenotypes in KO were reversed by viral-mediated production of adiponectin. Our results indicate that adiponectin should be one of key molecule of the metabolic syndrome and may be a new therapeutic target for the metabolic syndrome.
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PMID:[Adiponectin knockout mice]. 1520 43

Recent progress in adipocyte-biology shows that adipocytes are not merely fat-storing cells but that they secrete a variety of hormones, cytekines, growth factors and other bioactive substabces, conceptualized as adipocytokines. These include plasminogen activator inhibitor 1(PAI-1), tumor necrosis factor(TNF-alpha), leptin and adiponectin. Dysregulated productions of these adipocytekines participate in the pathogenesis of obesity-associated metabolic syndrome such as insulin resistance, type 2 diabetes, hyperlipidemia, and vascular diseases. Increased productions of PAI-1 and TNF-alpha from accumulated fat contribute to the formation of thrombosis and insulin resistance in obesity, respectively. Lack of leptin causes metabolic syndrome. Adiponectin exerts insulin-sensitizing and anti-atherogenic effects, hence decrease of plasma adiponectin is causative for insulin resistance and atherosclerosis in obesity.
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PMID:[Adipocytokines and metabolic syndrome--molecular mechanism and clinical implication]. 1520 45


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