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)

Atherosclerosis is a vascular disease, appearing early in life, and developing gradually and progressively, from the initial local inflammatory lesions, a stage at which endothelial dysfunction is already present, to the ultimate stage, culminating in atherosclerotic plaque rupture followed by thrombogenesis. Glitazones, specific agonists for the nuclear receptor PPARgamma, act at each stage of the atherogenesis process, and therefore are likely to convey cardioprotective activities in type 2 diabetic patients as well as in non-diabetic patients at high cardiovascular risk (glucose intolerant subjects with or without associated metabolic syndrome). In this review, we summarize the main stages of atherosclerosis progression and their pathophysiological mechanisms, and the results of studies carried out with glitazones, either in in vitro experimental models or in vivo in various animal models, as well as results of recent studies in type 2 diabetic patients, which support the concept for a cardioprotective action of glitazones.
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PMID:[Glitazones and atherosclerosis]. 1595 2

Nonalcoholic steatohepatitis (NASH) is a condition characterized by excessive deposition of fat in the liver (steatosis), inflammation and hepatocellular necrosis. While steatosis alone is generally a benign and stable condition, NASH can have a dire prognosis in a minority of patients, mainly because of fibrosis occurrence and progression to cirrhosis. Life-threatening complications such as liver failure and hepatocellular carcinoma have been described in NASH-induced cirrhosis. Insulin resistance is almost universally found in patients with NASH and the main risk factors for this condition are overweight and diabetes. Improvement in insulin sensitivity, whether achieved by diet, exercise and/or pharmacological interventions, results in a dramatic reduction of liver fat and inflammation and fibrosis as well. Therefore NASH should be viewed as the hepatic phenotypic manifestation of insulin resistance and a bona fide component of the metabolic syndrome. Liver injury should be assessed in diabetic and/or obese patients and the mechanisms by which insulin resistance promotes liver damage needs to be elucidated. The encouraging results of the use of PPARgamma agonists and, in particular, rosiglitazone, in human or experimental models of NASH, justifies future large-scale, randomized controlled trials.
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PMID:[Nonalcoholic steatohepatitis]. 1595 6

Previous investigations have demonstrated a marked effect of soy protein on the metabolic syndrome (MS). The purpose of this preliminary study was to identify the effects of soy-based diets on male obese ZDFxSHHF (fa/ fa-cp/?) rats. Animals were randomly assigned to one of four diets: control, casein (C); low-isoflavone (LIS) soy protein; high-isoflavone (HIS) soy protein; or casein + rosiglitazone (CR). Physiological, biochemical, and molecular parameters were determined at sacrifice. Body weight (p < 0.01) and food intake (p < 0.05) were lower in LIS-fed rodents. Rosiglitazone-treated animals had higher body weight and adiposity (p < 0.05). LIS and CR groups exhibited better glycemic control (p < 0.05), but with a limited effect in rosiglitazone-treated animals. HIS fed rats had higher glucose and triacylglyceride levels (p < 0.01), and lower plasma insulin (p < 0.01). Renal function parameters with the exception of an increase in systolic blood pressure (p < 0.05) were all suppressed in the LIS group (p < 0.01). The CR group had twofold PPARalpha and PPARgamma mRNA abundance (p < 0.01). LIS-fed animals also exhibited greater abundance of PPARgamma mRNA (p < 0.001), and nearly threefold FAS and CPT-1 mRNA levels (p < 0.05). HIS-fed rats also had higher abundance of CPT-1 mRNA, as well as a lower abundance of ACC mRNA (p < 0.05). Soy-based diets, influenced by isoflavone content and distinct from rosiglitazone, improved several metabolic parameters in obese ZDFxSHHF rats.
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PMID:Soy protein influences the development of the metabolic syndrome in male obese ZDFxSHHF rats. 1597 Nov 56

The metabolic syndrome (MSX), characterized by obesity, insulin resistance, dyslipidemia and hypertension, increases the risk of cardiovascular morbidity and mortality. It has recently been hypothesized that MSX and type 2 diabetes are caused by triglyceride and long-chain fatty acid accumulation in liver, muscle, pancreatic islets and selected brain areas. This lipocentric approach is integrated with analysis of inflammation associated with end-organ damage, including the vascular wall. Genes and proteins contributing to insulin resistance, beta cell dysfunction and vascular wall damage have been identified. Transcription factors and coactivators, including peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator-1 are crucial in mediating insulin resistance and accelerating vascular wall inflammation, and represent promising therapeutic targets. New pharmacological strategies include dual PPARalpha/gamma agonists, drugs with pleiotropic effects or combination therapies.
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PMID:New therapeutic options for the metabolic syndrome: what's next? 1600 3

Puerarin is an isoflavone extracted from Chinese plant, Pueraria lobata (Wild.) Ohwi. It has been reported to have comprehensive pharmacological action in treatment of diabetes and cardiovascular diseases. The purpose of this study was to link the scattered effects of puerarin and to find the common mechanisms underlying. We investigated the effect of puerarin on the pivotal common pathogenic factors of metabolic syndrome, which includes obesity, Type II diabetes and cardiovascular diseases. Recently, a large body of evidence indicates that there is a complicated interplay among insulin resistance, adipocytes and endothelial dysfunction that links the abnormalities of metabolic syndrome. Results of present study showed that puerarin could potentiate insulin-induced preadipocyte differentiation, promote glucose-uptake of adipocytes that have been induced insulin resistance by high glucose, and prevent TNF-a-induced apoptosis and viability loss of endothelial cells. Furthermore, we found that these effects are probably due to promote PPARgamma expression and partly through inhibiting abnormal TNF-a-induced intracellular-free Ca(2+) accumulation of endothelial cells. Overall, our synthetical study links the comprehensive pharmacological actions of puerarin to the recognized common pathogenesis of metabolic syndrome, and provides a new insight into the mechanism of puerarin effect.
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PMID:The study of anti-metabolic syndrome effect of puerarin in vitro. 1600 72

Evidence for a genetic basis for type 2 diabetes and the metabolic syndrome has been derived from studies of families, twins and populations with genetic admixture. Identification of genes associated with disease pathogenesis is now underway using techniques such as genome scanning by positional cloning and the candidate gene approach. Genome scanning in several different ethnic groups has identified chromosome regions harbouring type 2 diabetes susceptibility genes such as the novel gene, calpain 10 (CAPN10). The hepatic nuclear factor 4alpha (HNF4alpha) gene partly explains the linkage peak on chromosome 20, while the upstream transcription factor (USF1) is associated with familial combined hyperlipidaemia (FCHL) and maps close to the type 2 diabetes associated 1q peak. Peroxisome proliferator-activated receptor gamma (PPARgamma) was identified as a candidate gene based on its biology. A Pro12Ala variant of this gene has been associated with an increased risk of type 2 diabetes. Many genes accounting for monogenic forms of diabetes have been identified--such as maturity onset diabetes of the young (MODY); glucokinase (GCK) and HNF1alpha mutations being the most common causes of MODY. GCK variants result in 'mild' diabetes or impaired glucose tolerance (IGT) and relatively few cardiovascular complications, while HNF1alpha-associated MODY is more typical of type 2 diabetes, frequently being treated with sulphonylureas or insulin and resulting in microvascular complications. Testing for single gene disorders associated with type 2 diabetes and obesity may determine cause, prognosis and appropriate treatment; however, for the more common polygenic diseases this is not the case. In type 2 diabetes, molecular genetics has the potential to enhance understanding of disease pathogenesis, and help formulate preventative and treatment strategies.
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PMID:Searching for genes in diabetes and the metabolic syndrome. 1603 91

Cardiovascular disease (CVD) remains the leading cause of mortality in developed countries. Several risk factors are associated with CVD, including type 2 diabetes, obesity, insulin resistance, dyslipidaemia and hypertension. Different pharmacological therapies have been developed to control these risk factors. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors, which belong to the nuclear receptor superfamily that controls lipid and glucose metabolism as well as inflammatory risk factors for CVD. PPARalpha agonists, such as the fibrates, correct dyslipidaemia, thus decreasing CVD risk. PPARgamma agonists, such as the glitazones, increase insulin sensitivity and decrease plasma glucose levels in patients with diabetes. Moreover, both PPARalpha and PPARgamma agonists exert anti-inflammatory activities in liver, adipose and vascular tissues. In this review, we focus on the mode of action of PPARalpha and PPARalpha agonists, illustrating the potential of the newly developed dual PPAR agonists for the treatment of global risk in patients with the metabolic syndrome or type 2 diabetes.
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PMID:Inflammation, dyslipidaemia, diabetes and PPars: pharmacological interest of dual PPARalpha and PPARgamma agonists. 1603 93

Previous observations by us have clarified that proteins modified by advanced glycation end products (AGEs) are recognized as effective ligands by CD36-overexpressed CHO cells and undergo receptor-mediated endocytosis. CD36, a member of the class B scavenger receptor family, also acts as a fatty acid transporter in adipocytes. Oxidized low-density lipoprotein (Ox-LDL), a ligand for CD36, is known to upregulate CD36 by activating peroxisome proliferator-activated receptor gamma (PPAR-gamma) in macrophages, whereas PPAR-gamma ligands such as troglitazone and 15-deoxy-delta12,14-prostaglandin J2 decrease leptin secretion from adipocytes. The purpose of this study was to examine effects of AGE ligands on leptin expression in adipocytes. Glycolaldehyde-modified bovine serum albumin (GA-BSA) decreased leptin expression at both the protein and mRNA levels in 3T3-L1 adipocytes and mouse epididymal adipocytes. The binding to and subsequent endocytic degradation of GA-BSA by 3T3-L1 adipocytes were effectively inhibited by a neutralizing anti-CD36 antibody. These results indicate that the ligand interaction of GA-BSA with CD36 leads to downregulation of leptin expression in 3T3-L1 adipocytes, suggesting that AGE-induced leptin downregulation is linked to reduction of the insulin sensitivity in metabolic syndrome.
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PMID:Glycolaldehyde-modified bovine serum albumin downregulates leptin expression in mouse adipocytes via a CD36-mediated pathway. 1603 95

Peroxisome proliferator-activated receptors (PPARs) play key roles in the regulation of energy homeostasis and inflammation, and agonists of PPARalpha and -gamma are currently used therapeutically. Fibrates, first used in the 1970s for their lipid-modifying properties, were later shown to activate PPARalpha. These agents lower plasma triglycerides and VLDL particles and increase HDL cholesterol, effects that are associated with cardiovascular benefit. Thiazolidinediones, acting via PPARgamma, influence free fatty acid flux and thus reduce insulin resistance and blood glucose levels. PPARgamma agonists are therefore used to treat type 2 diabetes. PPARalpha and -gamma agonists also affect inflammation, vascular function, and vascular remodeling. As knowledge of the pleiotropic effects of these agents advances, further potential indications are being revealed, including roles in the management of cardiovascular disease (CVD) and the metabolic syndrome. Dual PPARalpha/gamma agonists (currently in development) look set to combine the properties of thiazolidinediones and fibrates, and they hold considerable promise for improving the management of type 2 diabetes and providing an effective therapeutic option for treating the multifactorial components of CVD and the metabolic syndrome. The functions of a third PPAR isoform, PPARdelta, and its potential as a therapeutic target are currently under investigation.
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PMID:Therapeutic roles of peroxisome proliferator-activated receptor agonists. 1604 15

The peroxisome proliferator-activated receptor (PPAR) family comprises three distinct isotypes: PPARalpha, PPARbeta/delta and PPARgamma. PPARs are nuclear hormone receptors that mediate the effects of fatty acids and their derivatives at the transcriptional level. Until recently, the characterisation of the important role of PPARalpha in fatty acid oxidation and of PPARgamma in lipid storage contrasted with the sparse information concerning PPARbeta/delta. However, evidence is now emerging for a role of PPARbeta/delta in tissue repair and energy homeostasis. Experiments with tissue-specific overexpression of PPARbeta/delta or treatment of mice with selective PPARbeta/delta agonists demonstrated that activation of PPARbeta/delta in vivo increases lipid catabolism in skeletal muscle, heart and adipose tissue and improves the serum lipid profile and insulin sensitivity in several animal models. PPARbeta/delta activation also prevents the development of obesity and improves cholesterol homeostasis in obesity-prone mouse models. These new insights into PPARbeta/delta functions suggest that targeting PPARbeta/delta may be helpful for treating disorders associated with the metabolic syndrome. Although these perspectives are promising, several independent and contradictory reports raise concerns about the safety of PPARbeta/delta ligands with respect to tumourigenic activity in the gut. Thus, it appears that further exploration of PPARbeta/delta functions is necessary to better define its potential as a therapeutic target.
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PMID:Peroxisome proliferator-activated receptor beta/delta as a therapeutic target for metabolic diseases. 1608 48


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