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

Adiponectin is an adipocyte hormone that links visceral adiposity with insulin resistance and atherosclerosis. It is unique among adipocyte-derived hormones in that its circulating concentrations are inversely proportional to adiposity, and low adiponectin concentrations predict the development of type 2 diabetes and cardiovascular disease. Consequently, in the decade since its discovery, adiponectin has generated immense interest as a potential therapeutic target for the metabolic syndrome and diabetes. This review summarizes current research regarding the regulation of circulating adiponectin concentrations by physiological, pharmacological, and nutritional factors, with an emphasis on human studies. In humans, plasma adiponectin concentrations are influenced by age and gender, and are inversely proportional to visceral adiposity. In vitro studies suggest that adiponectin production may be determined primarily by adipocyte size and insulin sensitivity, with larger, insulin-resistant adipocytes producing less adiponectin. While adiponectin concentrations are unchanged after meal ingestion, they are increased by significant weight loss, such as after bariatric surgery. In addition, adiponectin production is inhibited by a number of hormones, including testosterone, prolactin, glucocorticoids and growth hormone, and by inflammation and oxidative stress in adipose tissue. Smoking decreases, while moderate alcohol consumption increases, circulating adiponectin concentrations. Dietary fatty acid composition in rodents influences adiponectin production via ligand-activated nuclear receptors (PPARs); however, current evidence in humans is equivocal. In addition to PPAR agonists (such as thiazolidinediones and fibrates), a number of pharmacological agents (angiotensin receptor type 1 blockers, ACE inhibitors, and cannabinoid receptor antagonists) used in treatment of the metabolic syndrome also increase adiponectin concentrations in humans.
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PMID:Physiological, pharmacological, and nutritional regulation of circulating adiponectin concentrations in humans. 1851 Apr 34

Adipose tissue that consists of mature and immature adipocytes is suggested to contain mesenchymal stem cells (MSCs), but a culture system for analyzing their cell types within the tissue has not been established. Here we show that three-dimensional collagen gel culture of rat sc adipose tissue fragments maintained viable mature adipocytes for a long term, producing immature adipocytes and MSC-like cells from the fragments, using immunohistochemistry, ELISA, and real time RT-PCR. Bromodeoxyuridine uptake of mature adipocytes was detected. Adiponectin and leptin, and adipocyte-specific genes of adiponectin, leptin, and PPAR-gamma were detected in culture assembly, whereas the lipogenesis factor insulin (20 mU/ml) and inflammation-related agent TNF-alpha (2 nm) increased and decreased, respectively, all of their displays. Both spindle-shaped cell types with oil red O-positive lipid droplets and those with expression of MSC markers (CD105 and CD44) developed around the fragments. The data indicate that adipose tissue-organotypic culture retains unilocular structure, proliferative ability, and some functions of mature adipocytes, generating both immature adipocytes and CD105+/CD44+ MSC-like cells. This suggests that our method will open up a new way for studying both multiple cell types within adipose tissue and the cell-based mechanisms of obesity and metabolic syndrome.
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PMID:A new organotypic culture of adipose tissue fragments maintains viable mature adipocytes for a long term, together with development of immature adipocytes and mesenchymal stem cell-like cells. 1853 1

Adiponectin is one of the most thoroughly studied adipocytokines. Low plasma levels of adiponectin are found to associate with obesity, metabolic syndrome, diabetes and many other human diseases. From animal experiments and human studies, adiponectin has been shown to be a key regulator of insulin sensitivity. In this article, we review the evidence and propose that hypo-adiponectinemia is not a major cause of obesity. Instead, it is the result of obesity-induced insulin resistance in the adipose tissue. Hypo-adiponectinemia then mediates the metabolic effects of obesity on the other peripheral tissues, such as liver and skeletal muscle and may also exert some direct effects on end-organ damage. We propose that deciphering the molecular details governing the adiponectin gene expression and protein secretion will lead us to more comprehensive understanding of the mechanisms of insulin resistance in the adipose tissue and provide us new avenues for the therapeutic intervention of obesity and insulin resistance-related human disorders.
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PMID:Adiponectin: a biomarker of obesity-induced insulin resistance in adipose tissue and beyond. 1853 23

Adiponectin is an insulin-sensitizing adipocytokine, and recently it has been suggested as a biomarker of metabolic syndrome. We studied the relationships between adiponectin and parameters of metabolic syndrome in obese children. Fasting plasma adiponectin, insulin, glucose, lipids, and anthropometric parameters were measured in 180 obese children and 125 non-obese controls. Adiponectin was significantly decreased in obese boys and girls compared to non-obese controls. Adiponectin was inversely related to body mass index, waist circumference (WC), insulin, homeostasis model assessment for insulin resistance, and triglycerides, after adjusting for age in both genders. Adiponectin was correlated with high-density lipoprotein cholesterol (HDL-C) after adjusting for age in both genders. In multiple regression analysis, WC was independently related to adiponectin in boys, and WC and HDL-C were independently related to adiponectin in girls. In conclusion, WC, a simple measure of central adiposity, is a determinant of adiponectin in obese children.
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PMID:Determinants of plasma adiponectin levels in obese children. 1882 73

Adiponectin, an adipokine secreted by the white adipose tissue, plays an important role in regulating glucose and lipid metabolism and controlling energy homeostasis in insulin-sensitive tissues. A decrease in the circulating level of adiponectin has been linked to insulin resistance, type 2 diabetes, atherosclerosis, and metabolic syndrome. Adiponectin exerts its effects through two membrane receptors, AdipoR1 and AdipoR2. APPL1 is the first identified protein that interacts directly with adiponectin receptors. APPL1 is an adaptor protein with multiple functional domains, the Bin1/amphiphysin/rvs167, pleckstrin homology, and phosphotyrosine binding domains. The PTB domain of APPL1 interacts directly with the intracellular region of adiponectin receptors. Through this interaction, APPL1 mediates adiponectin signaling and its effects on metabolism. APPL1 also functions in insulin-signaling pathway and is an important mediator of adiponectin-dependent insulin sensitization in skeletal muscle. Adiponectin signaling through APPL1 is necessary to exert its anti-inflammatory and cytoprotective effects on endothelial cells. APPL1 also acts as a mediator of other signaling pathways by interacting directly with membrane receptors or signaling proteins, thereby playing critical roles in cell proliferation, apoptosis, cell survival, endosomal trafficking, and chromatin remodeling. This review focuses mainly on our current understanding of adiponectin signaling in various tissues, the role of APPL1 in mediating adiponectin signaling, and also its role in the cross-talk between adiponectin/insulin-signaling pathways.
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PMID:APPL1: role in adiponectin signaling and beyond. 1885 21

The clinical relevance of the term "metabolic syndrome", the definition criteria, and predictive power are being disputed. Inclusion of sleep-disordered breathing and sleep apnoea into a definition of metabolic syndrome is also controversial once children and/or adolescents are affected. Nevertheless, along with the increasing prevalence of childhood obesity, the prevalence of the metabolic syndrome in obese children is reported at 30%, irrespective of the definition applied. Moreover, childhood obesity is associated with sleep-disordered breathing. Adipocytokines, cytokines secreted from adipose tissue, are thought to play a major role in the pathophysiology of metabolic syndrome. Leptin was initially suggested as a promising "anti-obesity" hormone. New concepts indicate that in humans leptin and its soluble receptor may be more important in states of energy deficiency rather than a predictor of the metabolic syndrome. Adiponectin, on the other hand, is not only related to obesity and insulin resistance, but appears to be the strongest predictor for metabolic syndrome, even in children. In newborns and infants, both adipocytokines occur in high concentrations, even though this cannot completely explain the increased risk for ensuing metabolic disease later in life. Finally, low-grade systemic inflammation may underlie the clustering of metabolic risk factors. Overall factors from the adipose tissue may constitute not only markers but also mediators of metabolic sequelae of obesity.
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PMID:Metabolic syndrome in children and adolescents--risk for sleep-disordered breathing and obstructive sleep-apnoea syndrome? 1894 84

Adiponectin is an adipose tissue-specific hormone that is commonly decreased in obese subjects. Furthermore, single-nucleotide polymorphisms (SNPs) of the adiponectin gene have been associated with metabolic phenotypes. The present study investigated whether the adiponectin gene promoter variant -11391 G/A (rs17300539) could predict the risk of developing traits characterizing the metabolic syndrome (MetS) and the impact of weight management. The -11391 G/A SNP was genotyped in 180 Spanish volunteers (BMI: 31.4+/-3.2 kg/m (2); age: 35+/-5 years). Clinical measurements were determined at baseline, following an 8-week low-calorie diet (LCD), and at 32 and 60 weeks. At baseline, the GG genotype was associated with higher HOMA-IR, insulin and triacylglyceride concentrations than other genotypes (p<0.05) and was also related with a higher risk of insulin resistance (OR: 2.437, p=0.025) and MetS clinical manifestations (OR: 3.236, p=0.003). Following the LCD, the increased risk in GG subjects compared with others disappeared (p>0.05). By 32 weeks after dietary therapy (n=84), GG carriers had recovered the risk of metabolic comorbidities (OR: 2.420, p=0.043). This risk was even more evident after 60 weeks (OR: 2.875, p=0.014). These data show an increased risk of insulin resistance and MetS complications in obese subjects of the -11391 GG genotype. The risk was markedly reduced during an energy-restricted diet, but was not sustained. Carriage of the A allele therefore confers protection from weight regain, and the effect is particularly evident 32-60 weeks after the dietary intervention, when improvement in GG subjects had disappeared.
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PMID:The - 11391 G/A polymorphism of the adiponectin gene promoter is associated with metabolic syndrome traits and the outcome of an energy-restricted diet in obese subjects. 1894 81

Adiponectin is an important vascular protective substance whose levels are reduced in states of insulin resistance. The relationships between plasma insulin levels and adiponectin are not fully understood, and it is not known whether it is the elevated circulating levels of insulin or insulin resistance that directly affects adiponectin levels. The present study evaluates the direct effect of chronic hyperinsulinemia on plasma adiponectin levels. Male Sprague-Dawley rats were treated with insulin (n=15) administered by a sustained-release implant or were given a sham implantation (n=10) as a control group. Body weight, systolic blood pressure, plasma glucose, triglycerides, insulin, and adiponectin were measured at baseline and after 20 and 40 d of treatment. Insulin-treated rats and controls showed a similar increase in body weight. The insulin-treated group had a significant increase in plasma insulin levels and a decrease in plasma glucose levels compared with the sham group, with no change in blood pressure or triglyceride levels. Adiponectin levels remained unchanged despite the significant increase in insulin levels. High circulating insulin levels do not affect plasma adiponectin levels. These results support the concept that the primary defect that results in insulin resistance and hyperinsulinemia is responsible for the altered plasma adiponectin levels in the metabolic syndrome and type 2 diabetes.
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PMID:The effect of chronic hyperinsulinemia on plasma adiponectin levels in Sprague-Dawley rats. 1894 82

In eukaryotic cells, receptor endocytosis is a key event regulating signaling transduction. Adiponectin receptors belong to a new receptor family that is distinct from G-protein-coupled receptors and has critical roles in the pathogenesis of diabetes and metabolic syndrome. Here, we analyzed the endocytosis of adiponectin and adiponectin receptor 1 (AdipoR1) and found that they are both internalized into transferrin-positive compartments that follow similar traffic routes. Blocking clathrin-mediated endocytosis by expressing Eps15 mutants or depleting K(+) trapped AdipoR1 at the plasma membrane, and K(+) depletion abolished adiponectin internalization, indicating that the endocytosis of AdipoR1 and adiponectin is clathrin-dependent. Depletion of K(+) and overexpression of Eps15 mutants enhance adiponectin-stimulated AMP-activated protein kinase phosphorylation, suggesting that the endocytosis of AdipoR1 might downregulate adiponectin signaling. In addition, AdipoR1 colocalizes with the small GTPase Rab5, and a dominant negative Rab5 abrogates AdipoR1 endocytosis. These data indicate that AdipoR1 is internalized through a clathrin- and Rab5-dependent pathway and that endocytosis may play a role in the regulation of adiponectin signaling.
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PMID:Endocytosis of adiponectin receptor 1 through a clathrin- and Rab5-dependent pathway. 1898 21

Nonalcoholic steatohepatitis (NASH) is the hepatic manifestation of the metabolic syndrome. Currently, there is no established therapy for NASH. The aim of the present study was to evaluate the efficacy of atorvastatin in the treatment of NASH associated with hyperlipidemia. This prospective study included 31 patients with biopsy-proven NASH with hyperlipidemia. Body mass index, serum lipids, liver function tests, fibrosis markers, and adipocytokines (adiponectin, leptin, tumor necrosis factor-alpha) were measured periodically during an open-label study of atorvastatin (10 mg daily) for 24 months. Standard weight-loss counseling was continued during the treatment period. Oral glucose tolerance test and liver density assessed by computerized tomography were performed before and after treatment. Follow-up liver biopsy was performed in 17 patients. All 31 patients had high cholesterol levels at baseline, and 20 also presented high triglyceride levels. The body mass index and serum glucose levels did not change during the treatment. After treatment, 23 patients (74.2%) presented normal transaminase levels. Adiponectin levels were significantly increased, and the levels of tumor necrosis factor-alpha were significantly decreased. However, leptin levels were not changed significantly. The concentration of long-chain fatty acids was decreased; and significant decreases were observed in C18:2,n-6 (linoleic acid, -21%) and C20:4,n-6 (arachidonic acid, -22%). Liver steatosis and nonalcoholic fatty liver disease activity score were significantly improved, whereas 4 patients had increased fibrosis stage. The NASH-related metabolic parameters improved with therapy, including fibrosis in some patients. However, 4 of 17 patients had progression of fibrosis over the 2-year period, with 3 of them progressing to stage 3. It is unclear whether this divergent response represents sampling error, heterogeneity in the population, or untreated postprandial hyperglyceridemia. Controlled trials are needed to further investigate and resolve this.
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PMID:Efficacy of atorvastatin for the treatment of nonalcoholic steatohepatitis with dyslipidemia. 1901 95


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