Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adiponectin, a major adipose cytokine, plays a crucial role in the inhibition of metabolic syndrome by acting on such cell types as muscle cells and hepatocytes. Furthermore, evidence suggests that adiponectin may influence cancer pathogenesis. Adiponectin occurs in non-proteolytic (full-length adiponectin: f-adiponectin) and proteolytic (globular adiponectin: g-adiponectin) forms in various oligomeric states. Different forms of adiponectin show distinct biological effects through differential activation of downstream signaling pathways. Here we identify c-Jun NH(2)-terminal kinase (JNK), and signal transducer and activator of transcription 3 (STAT3) as common downstream effectors of f- and g-adiponectin. f- and g-adiponectin both stimulate JNK activation in prostate cancer DU145, PC-3, and LNCaP-FGC cells, hepatocellular carcinoma HepG2 cells, and C2C12 myoblasts. Furthermore, both f- and g-adiponectin drastically suppress constitutive STAT3 activation in DU145 and HepG2 cells. These suggest that JNK and STAT3 may constitute a universal signaling pathway to mediate adiponectin's pathophysiological effects on metabolic syndrome and cancer.
 ...
PMID:Adiponectin activates c-Jun NH2-terminal kinase and inhibits signal transducer and activator of transcription 3. 1593 15

The adiponectin paralog CORS-26 (collagenous repeat-containing sequence of 26kDa protein) is a member of the C1q/TNF-alpha molecular superfamily. CORS-26 is a secreted protein and baculovirus-produced CORS-26 released in the supernatant of insect cells forms stable trimers. Adiponectin exerts anti-inflammatory effects in LPS-treated monocytic cells and CORS-26 also reduces IL-6 and TNF-alpha secretion but does not increase IL-10. Suppression of NFkappaB signalling may explain the anti-inflammatory actions of CORS-26. Furthermore CORS-26 protein was detected in human monocytic and dendritic cells. The present data demonstrate for the first time that CORS-26 forms trimers, exerts anti-inflammatory properties and that it is expressed in monocytic cells. Therefore CORS-26 may provide a new target for pharmacological drugs in inflammatory diseases like the metabolic syndrome.
 ...
PMID:The adiponectin paralog CORS-26 has anti-inflammatory properties and is produced by human monocytic cells. 1621 90

Fibric acid is a synthetic ligand of the nuclear receptor peroxisome proliferator-activated receptor (PPAR)-alpha that is highly expressed in skeletal muscle and heart, where it promotes beta-oxidation of fatty acids to mediate hypolipidemic actions. PPAR-alpha regulates expression of key proteins involved in atherogenesis, vascular inflammation, plaque instability, and thrombosis. Thus, PPAR-alpha may exert direct antiatherogenic actions in the vascular wall. Endothelial dysfunction associated with the metabolic syndrome and other insulin-resistant states is characterized by impaired insulin-stimulated nitric oxide production from the endothelium and decreased blood flow to skeletal muscle. Thus, improvement in insulin sensitivity leads to improved endothelial function. This may be an additional mechanism whereby fibrates decrease the incidence of coronary heart disease. Adiponectin is a protein secreted specifically by adipose cells that may couple regulation of insulin sensitivity with energy metabolism and serve to link obesity with insulin resistance. In this review, we discuss the mechanisms underlying the vascular and metabolic effects of fibrates that may act synergistically to prevent or regress atherosclerosis and coronary heart disease.
 ...
PMID:Beneficial vascular and metabolic effects of peroxisome proliferator-activated receptor-alpha activators. 1623 May 15

Adiponectin is a serum protein secreted by adipocytes and accounts for approximately 0.01% of total plasma protein. In healthy patient populations adiponectin can be found in concentrations of 7-12 mg/l. Unlike other adipocyte products, adiponectin correlates with decreased free fatty acid blood concentrations and reduced body mass index or body weight. Adiponectin protects from vascular diseases by inhibiting local proinflammatory signals, preventing preatherogenic plaque formation, and by impeding arterial wall thickening. Proinflammatory state and endothelial dysfunction are nominators of the metabolic syndrome, a complex set of risk factors including vascular and metabolic insulin resistance with hyperglycemia, hypertension, and dyslipidemia. Over the past years, thiazolidinediones, like rosiglitazone or pioglitazone, became known as a therapeutic option for patients suffering from the metabolic syndrome. It is considered that insulin sensitizers exert their benefit through indirect induction of adiponectin expression. Clinical studies have confirmed that treatment with thiazolidinediones may increase adiponectin concentrations in patients with type 2 diabetes independent from improvements in blood glucose control or parallel treatment with insulinotropic drugs. These findings suggest that adiponectin may have a diagnostic value and can be used especially for monitoring treatment success. This review summarizes recent biological and clinical data indicating that adiponectin may be the molecular link between obesity and insulin resistance and may serve as a biomarker for the metabolic syndrome.
 ...
PMID:Biological background and role of adiponectin as marker for insulin resistance and cardiovascular risk. 1628 70

Adiponectin circulates in human plasma mainly as a 180-kDa low molecular weight (LMW) hexamer and a high molecular weight (HMW) multimer of approximately 360 kDa. We comprehensively examined the relationships between circulating levels of total adiponectin, adiponectin multimers, and the relative distribution (i.e., ratio) of multimeric forms with key features of the metabolic syndrome. Total adiponectin (r = 0.45), HMW (r = 0.47), LMW (r = 0.31), and HMW-to-total adiponectin ratio (r = 0.29) were significantly correlated with insulin-stimulated glucose disposal rate. Similarly, total (r = -0.30), HMW (r = -0.38), and HMW-to-total adiponectin ratio (r = -0.34) were correlated with central fat distribution but not with total fat mass or BMI. Regarding energy metabolism, although there were no effects on resting metabolic rate, total (r = 0.41) and HMW (r = 0.44) were associated with increasing rates of fat oxidation. HMW-to-total adiponectin ratio increased as a function of total adiponectin, and it was HMW quantity (not total or HMW-to-total adiponectin ratio or LMW) that was primarily responsible for all of these relationships. Impact on nuclear magnetic resonance lipoprotein subclasses was assessed. HMW and total adiponectin were correlated with decreases in large VLDL (r = -0.44 and -0.41); decreases in small LDL (r = -0.41 and -0.36) and increases in large LDL (r = 0.36 and 0.30) particle concentrations accompanied by increased LDL particle size (r = 0.47 and 0.39); and increases in large HDL (r = 0.45 and 0.37) and HDL particle size (r = 0.53 and 0.47). Most of these correlations persisted after adjustment for metabolic covariables. In conclusion, first, serum adiponectin is associated with increased insulin sensitivity, reduced abdominal fat, and high basal lipid oxidation; however, it is HMW quantity, not total or HMW-to-total adiponectin ratio, that is primarily responsible for these relationships. Second, reduced quantities of HMW independently recapitulate the lipoprotein subclass profile associated with insulin resistance after correcting for glucose disposal rate and BMI. Finally, HMW adiponectin is an important factor in explaining the metabolic syndrome.
 ...
PMID:Adiponectin multimeric complexes and the metabolic syndrome trait cluster. 1638 May

Adiponectin, an adipose-derived plasma protein, has been well established to be an important biomarker for metabolic syndrome and its complications after exhausted studies in humans. Animal and cell culture experiments also support most claims from human observations of its roles in the metabolic syndrome. Reproducible results of human genetic studies of diverse ethnic origin and by different investigators may provide the evidence for its causative roles in the pathogenesis of the metabolic syndrome and further insight into the genetic constitutions of the metabolic syndrome. Some of the common polymorphisms in the promoter region, exon and intron 2, and the rare nonsynonymous mutations in exon 3 of the human adiponectin gene were repeatedly shown in many studies from many different ethnic populations to associate with the phenotypes related to body weight, glucose metabolism, insulin sensitivity, and risk of type 2 diabetes mellitus and coronary artery disease. The association of adiponectin genetic variations with dyslipidemia and blood pressure was less explored. The common polymorphisms and rare mutations of the human adiponectin gene itself were demonstrated to associate with differential expression of adiponectin at the plasma protein level and mRNA level in adipose tissue. The PPARgamma2 Pro12Ala variants were also shown to influence insulin sensitivity in interaction with adiponectin genotype or to influence plasma adiponectin levels. However, the results were not consistent. Three genome-wide scans for the loci that regulate plasma adiponectin concentration suggest further exploration on chromosomes 5, 9, 14, 15, and 18 is required. These human genetic studies on adiponectin and the metabolic syndrome strongly suggest that adiponectin is one of the causative factors in its pathogenesis and provide significant insights into the genetic makeup of the metabolic syndrome. Extension from these studies may accelerate the discovery of new molecular targets for future therapeutic interventions.
 ...
PMID:Human genetics of adiponectin in the metabolic syndrome. 1638 53

Several studies have reported an association between markers of liver injury, including elevated concentrations of alanine aminotransferase (ALT) aspartate aminotransferase (AST), and prospective risk of type 2 diabetes. We therefore examined the relationship between ALT and AST on the one hand, and serum adiponectin and highly sensitive CRP on the other, both of which have been reported to be associated with prospective risk of type 2 diabetes; we also tested for variable components of metabolic syndrome in 198 male college students aged 18-20 years. ALT showed a positive relationship with percentage body fat (r = 0.19, p = 0.02), serum leptin (r = 0.21, p = 0.01), LDL cholesterol (r = 0.29, p = 0.0003), triglyceride (r = 0.28, p = 0.0004) and apolipoprotein B (r = 0.35, p < 0.0001) even after adjustment for body mass index (BMI). Although there was a significant relationship with serum insulin, adiponectin (inversely), homeostasis model assessment of insulin resistance, systolic and diastolic blood pressure, HDL cholesterol (inversely) and LDL particle diameter in simple regression analysis, significance disappeared after adjustment for BMI. In contrast, CRP (r = 0.16, p = 0.04) was associated with ALT after adjustment for BMI, although simple regression analysis revealed no association between the two. Relationships were smaller for AST, and significance disappeared after adjustment for BMI. Multiple regression analysis excluding lipid variables revealed significant and independent associations of ALT with adiponectin and percentage body fat. In a model including lipid variables, apolipoprotein B emerged as an independent predictor of ALT in addition to adiponectin and percentage body fat. These variables explained 29 % of ALT variability. In conclusion, serum ALT levels were associated with leptin and CRP as well as many components of the insulin resistance syndrome in young healthy men. Adiponectin, apolipoprotein B and percentage body fat emerged as significant and independent predictors of ALT. Since adiponectin and chronic subclinical inflammation have been reported to predict the development of type 2 diabetes and since abnormalities in apolipoprotein B metabolism occur in the early course of insulin resistance, these findings may be compatible with the association between liver markers and risk of diabetes.
 ...
PMID:Serum alanine aminotransferase is associated with serum adiponectin, C-reactive protein and apolipoprotein B in young healthy men. 1652 13

The increasing prevalence of obesity and metabolic syndrome/insulin resistance has attracted considerable interest due to their identification as risk factors for cardiovascular disease and, hence, targets for cardiovascular disease prevention. This review focuses on adiponectin, the most profusely secreted protein from adipose tissue, which itself is being increasingly recognised as an important and very active endocrine organ, secreting a wide range of biologically active substances known as adipokines or adipocytokines. Adiponectin has been demonstrated to have insulin sensitising effects, and secretion of adiponectin is reduced as adipose tissue mass increases. Adiponectin has also been demonstrated to have anti-inflammatory and anti-atherogenic properties, and is independently associated with cardiovascular disease. The evidence that suggests adiponectin plays a role in the relationship between obesity and insulin resistance, and also insulin resistance and cardiovascular disease, is examined. Variation in the adiponectin gene is one tool to determine whether this relationship is causal. The association of identified variants with human disease, specifically obesity and its consequences, type 2 diabetes and cardiovascular disease is reviewed. This data may enable patients at greater risk of the adverse effects of obesity to be identified and, as such, benefit from more targeted therapy of its consequences.
 ...
PMID:Adiponectin and its gene variants as risk factors for insulin resistance, the metabolic syndrome and cardiovascular disease. 1658 Oct 78

To elucidate the role of visceral fat accumulation in the metabolic syndrome, differences in the pathology of the metabolic syndrome with or without visceral fat accumulation were investigated. A total of 472 prediabetic Japanese men (mean age, 47.5 +/- 7.2 yr) with impaired fasting glycemia (IFG) levels of 110-125 mg/dL were eligible for participation in the study. The study subjects were divided into the following four groups, and intergroup comparisons were made: group I without visceral fat area [VFA] > or = 100 cm2 but presenting with fewer than two other risk factors (i.e., TG > or =150 mg/dL, HDL-C < 40 mg/dL, BP > or = 130/ > or = 85 mmHg, or FPG > or = 110 mg/dL) (n = 231); group II without VFA of > or = 100 cm2 but presenting with three or more other risk factors (n = 57); group III with VFA of > or = 100 cm2 accompanied by FPG 110 mg/dL alone (n = 27); and group IV with VFA > or =100 cm2 and two or more other risk factors (n = 157). The prevalence of patients who had three or more risk factors with or without VFA > or = 100 cm2 was 45.3% (214 out of 472 patients), while that of those with VFA > or = 100 cm2 who had two or more other risk factors was 33% (157 out of 472 patients). Group II had significantly higher VFA values than group I (p < 0.05), and group IV had significantly higher VFA values than group II (p < 0.001). While no significant differences in HOMA-R values were seen between groups I and II, these values were significantly higher in group IV compared to groups I and II (p < 0.001 and p < 0.05, respectively). Furthermore, group IV showed significantly higher 2-h insulin levels after glucose loading compared to group I (p < 0.001). While no significant differences were seen between groups II and IV, insulin levels tended to be higher in group IV. Adiponectin levels showed an incremental fall in VFA from group I through groups II and III to group IV. Groups III and IV showed significantly lower adiponectin levels compared to group I (p < 0.05, p < 0.001, respectively); and group IV showed significantly lower adiponectin levels than group II (p < 0.05). A logistic regression analysis using VFA, TG and HDL-C, and BP as explanatory variables showed that the relative risk for high HOMAR values were 2.65 (p < 0.001) for patients with VFA > or =100 cm2; 1.64 (p < 0.05) for those with TG > or = 150 mg/dL and HDL < 40 mg/dL; and 1.79 (p < 0.01) for those with BP > or = 130/ > or = 85 mmHg. These findings demonstrate that the degree of insulin resistance and the risk of arteriosclerosis vary depending on whether or not the metabolic syndrome accompanied by a clustering of risk factors has visceral fat accumulation as an underlying pathology, strongly suggesting a crucial role for visceral fat accumulation in the metabolic syndrome.
 ...
PMID:Differences in the pathology of the metabolic syndrome with or without visceral fat accumulation: a study in pre-diabetic Japanese middle-aged men. 1662 4

Adiponectin is a recently described adipokine that has been recognized as a key regulator of insulin sensitivity and tissue inflammation. It is produced by adipose tissue (white and brown) and circulates in the blood at very high concentrations. It has direct actions in liver, skeletal muscle and the vasculature, with prominent roles to improve hepatic insulin sensitivity, increase fuel oxidation [via up-regulation of adenosine monophosphate-activated protein kinase (AMPK) activity] and decrease vascular inflammation. Adiponectin exists in the circulation as varying molecular weight forms, produced by multimerization. Recent data indicate that the high-molecular weight (HMW) complexes have the predominant action in the liver. In contrast to other adipokines, adiponectin secretion and circulating levels are inversely proportional to body fat content. Levels are further reduced in subjects with diabetes and coronary artery disease. Adiponectin antagonizes many effects of tumour necrosis factor-alpha(TNF-alpha) and this, in turn, suppresses adiponectin production. Furthermore, adiponectin secretion from adipocytes is enhanced by thiazolidinediones (which also act to antagonize TNF-alpha effects). Thus, adiponectin may be the common mechanism by which TNF-alpha promotes, and the thiazolidinediones suppress, insulin resistance and inflammation. Two adiponectin receptors, termed AdipoR1 and AdipoR2, have been identified and these are ubiquitously expressed. AdipoR1 is most highly expressed in skeletal muscle and has a prominent action to activate AMPK, and hence promote lipid oxidation. AdipoR2 is most highly expressed in liver, where it enhances insulin sensitivity and reduces steatosis via activation of AMPK and increased peroxisome-proliferator-activated receptor alpha ligand activity. T-cadherin, which is expressed in endothelium and smooth muscle, has been identified as an adiponectin-binding protein with preference for HMW adiponectin multimers. Given the low levels of adiponectin in subjects with the metabolic syndrome, and the beneficial effect of the adipokine in animal studies, there is exciting potential for adiponectin replacement therapy in insulin resistance and related disorders.
 ...
PMID:Adiponectin--a key adipokine in the metabolic syndrome. 1663 86


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>