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)

Visceral adipose tissue (VAT) imaged by computed tomography (CT) or magnetic resonance imaging (MRI) is associated with the metabolic syndrome features, being morphologically and functionally different from subcutaneous adipose tissue (SAT). Insulin effect is lower and catecholamine effect higher in visceral adipose tissue, with its metabolites and its secretions draining through portal system, partially at least, to the liver. Thus, visceral cells transfer and release fatty acids more extensively, have increased glucocorticoid and reduced thiazolidinedione responses, produce more angiotensinogen, interleukin-6 and plasminogen activator inhibitor-1, and secrete less leptin and adiponectin than SAT. Furthermore, there are regional differences in the intrinsic characteristics of the preadipocytes, with those of SAT presenting greater differentiation and fat cell gene expression but less apoptosis than that of VAT. All features contribute to the morbidity associated with increased VAT. To evaluate the relationship between VAT and components of the metabolic syndrome, 55 non-diabetic women, 11 lean (VAT < 68 cm 2) and 44 obese were studied. The obese with VAT within the normal range (VAT < or = 68 cm 2) had higher BMI, WHR, BP and resistance to FFA suppression during oGTT in comparison to the lean controls. The obese with VAT > 68 cm 2 compared to those with VAT < or = 68 cm 2 had similar body mass index (BMI) but significantly higher in vivo homeostasis model assessment for insulin resistance (HOMA IR ) results and triglycerides. By pooling all data, correlation analysis indicated that VAT contributes more to insulin resistance (HOMA IR ) than SAT does, but not when insulin-suppressed plasma free fatty acids during oral glucose tolerance test as an index of insulin resistance are taken into consideration.
 ...
PMID:Depot-specific hormonal characteristics of subcutaneous and visceral adipose tissue and their relation to the metabolic syndrome. 1266 Aug 70

Abdominal obesity has been linked to the development of insulin resistance and Type 2 diabetes mellitus (DM2). By surgical removal of visceral fat (VF) in a variety of rodent models, we prevented insulin resistance and glucose intolerance, establishing a cause-effect relationship between VF and the metabolic syndrome. To characterize the biological differences between visceral and peripheral fat depots, we obtained perirenal visceral (VF) and subcutaneous (SC) fat from 5 young rats. We extracted mRNA from the fat tissue and performed gene array hybridization using Affymetrix technology with a platform containing 9 000 genes. Out of the 1 660 genes that were expressed in fat tissue, 297 (17.9 %) genes show a two-fold or higher difference in their expression between the two tissues. We present the 20 genes whose expression is higher in VF fat (by 3 - 7 fold) and the 20 genes whose expression is higher in SC fat (by 3 - 150 fold), many of which are predominantly involved in glucose homeostasis, insulin action, and lipid metabolism. We confirmed the findings of gene array expression and quantified the changes in expression in VF of genes involved in insulin resistance (PPARgamma leptin) and its syndrome (angiotensinogen and plasminogen activating inhibitor-1, PAI-1) by real-time PCR (qRT-PCR) technology. Finally, we demonstrated increased expression of resistin in VF by around 12-fold and adiponectin by around 4-fold, peptides that were not part of the gene expression platform. These results indicate that visceral fat and subcutaneous fat are biologically distinct.
 ...
PMID:Differential gene expression between visceral and subcutaneous fat depots. 1266 Aug 71

Overfeeding of rodents leads to increased local formation of angiotensin II due to increased secretion of angiotensinogen from adipocytes. Whereas angiotensin II promotes adipocyte growth and preadipocyte recruitment, increased secretion of angiotensinogen from adipocytes also directly contributes to the close relationship between adipose-tissue mass and blood pressure in mice. In contrast, angiotensin II acts as an antiadipogenic substance in human adipose tissue, and the total increase in adipose-tissue mass may be more important in determining human plasma angiotensinogen levels than changes within the single adipocyte. However, as increased local formation of angiotensin II in adipose tissue may be increased especially in obese hypertensive subjects, a contribution of the adipose-tissue renin-angiotensin system to the development of insulin resistance and hypertension is conceivable in humans, but not yet proven. Insulin resistance may be aggravated by the inhibition of preadipocyte recruitment, which results in the redistribution of triglycerides to the liver and skeletal muscle, and blood pressure may be influenced by local formation of angiotensin II in perivascular adipose tissue. Thus, although the mechanisms are still speculative, the beneficial effects of ACE-inhibition and angiotensin-receptor blockade on the development of type 2 diabetes in large clinical trials suggest a pathophysiological role of the adipose-tissue renin-angiotensin system in the metabolic syndrome.
 ...
PMID:The adipose-tissue renin-angiotensin-aldosterone system: role in the metabolic syndrome? 1267 68

Obesity is closely associated with the metabolic syndrome, a combination of disorders including insulin resistance, diabetes, dyslipidemia, and hypertension. A role for local glucocorticoid reamplification in obesity and the metabolic syndrome has been suggested. The enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) regenerates active cortisol from inactive 11-keto forms, and aP2-HSD1 mice with relative transgenic overexpression of this enzyme in fat cells develop visceral obesity with insulin resistance and dyslipidemia. Here we report that aP2-HSD1 mice also have high arterial blood pressure (BP). The mice have increased sensitivity to dietary salt and increased plasma levels of angiotensinogen, angiotensin II, and aldosterone. This hypertension is abolished by selective angiotensin II receptor AT-1 antagonist at a low dose that does not affect BP in non-Tg littermates. These findings suggest that activation of the circulating renin-angiotensin system (RAS) develops in aP2-HSD1 mice. The long-term hypertension is further reflected by an appreciable hypertrophy and hyperplasia of the distal tubule epithelium of the nephron, resembling salt-sensitive or angiotensin II-mediated hypertension. Taken together, our findings suggest that overexpression of 11beta-HSD1 in fat is sufficient to cause salt-sensitive hypertension mediated by an activated RAS. The potential role of adipose 11beta-HSD1 in mediating critical features of the metabolic syndrome extends beyond obesity and metabolic complications to include the most central cardiovascular feature of this disorder.
 ...
PMID:Transgenic amplification of glucocorticoid action in adipose tissue causes high blood pressure in mice. 1284 62

In obese humans and rodents there is increased expression of the key glucocorticoid (GC) regenerating enzyme, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), in adipose tissue. This increased expression appears to be of pathogenic importance because transgenic mice overexpressing 11beta-HSD1 selectively in adipose tissue exhibit a full metabolic syndrome with visceral obesity, dyslipidemia, insulin-resistant diabetes, and hypertension. In this model, while systemic plasma GC levels are unaltered, GC delivery to the liver via the portal vein is increased. 11beta-HSD1 is most highly expressed in liver where inhibition or deficiency of its activity improves glucose and lipid homeostasis. To determine the potential contribution of elevated intrahepatic GCs alone toward development of insulin-resistant syndromes we generated transgenic mice expressing increased 11beta-HSD1 activity selectively in the liver under transcriptional control of hepatic regulatory sequences derived from the human apoE gene (apoE-HSD1). Transgenic lines with 2- and 5-fold-elevated 11beta-HSD1 activity exhibited mild insulin resistance without altered fat depot mass. ApoE-HSD1 transgenic mice exhibited fatty liver and dyslipidemia with increased hepatic lipid synthesis/flux associated with elevated hepatic LXRalpha and PPARalpha mRNA levels as well as impaired hepatic lipid clearance. Further, apoE-HSD1 transgenic mice have a marked, transgene-dose-associated hypertension paralleled by incrementally increased liver angiotensinogen expression. These data suggest that elevated hepatic expression of 11beta-HSD1 may relate to the pathogenesis of specific fatty liver, insulin-resistant, and hypertensive syndromes without obesity in humans as may occur in, for example, myotonic dystrophy, and possibly, the metabolically obese, normal-weight individual.
 ...
PMID:Metabolic syndrome without obesity: Hepatic overexpression of 11beta-hydroxysteroid dehydrogenase type 1 in transgenic mice. 1511 95

Increased visceral adiposity is a pivotal component of the metabolic syndrome. Differential gene expression patterns of fat-derived peptides (FDPs) in visceral fat and subcutaneous fat have been characterized in the fasting state. Here we examined whether delivery of nutrients differentially affects the expression of FDPs in visceral fat versus subcutaneous fat (in the fed state). We increased the rate of glucose flux into adipose tissue of normal rats (n = 16) by hyperglycemia or hyperinsulinemia using the clamp technique. Glucose uptake was associated with increased expression of FDPs, including resistin ( approximately 5-fold), adiponectin ( approximately 2-fold), leptin ( approximately 15-fold), plasminogen activating inhibitor-1 ( approximately 10-fold), and angiotensinogen ( approximately 4-fold) in visceral fat, but markedly less in subcutaneous fat. Cytokine expression derived mainly from vascular/stromal/macrophage components of adipose tissue was less dramatically increased. Infusion of glucosamine amplified the results obtained by increasing glucose uptake into adipose tissue, suggesting that flux through the hexosamine biosynthetic pathway may serve as a mechanism for "nutrient sensing." Nutrient-dependent expression of FDPs in visceral fat was also associated with increased plasma levels of several FDPs. Because a biologic sensing pathway can dynamically couple daily food intake to abnormal plasma levels of important FDPs, we challenge the practice of obtaining plasma levels after fasting to assess risk factors for metabolic syndrome.
 ...
PMID:Differential responses of visceral and subcutaneous fat depots to nutrients. 1573 42

Epidemiological reports show that about half of all adults suffer from hypertension, and the incidence of diabetes mellitus, dyslipidemia and obesity is markedly increasing in Japan. Recent progress in gene determination has shown that lifestyle-related diseases, including hypertension, are multigenetic diseases. In particular, renin-angiotensin genes play an important role in the pathogenesis of hypertension. Upregulation of the transcription of angiotensinogen and angiotensin-converting enzyme genes increases blood pressure and cardiovascular organ damage through increased levels of angiotensin II. In this review, I first introduce the history of the recognition, understanding and the development of treatment for hypertension. Secondly, the basic relationship of the pathogenesis between hypertension and the new concept of metabolic syndrome will be shown, and the usefulness of angiotensin II receptor antagonist for hypertensive patients with obesity and/or metabolic syndrome. Finally, I will reveal the utility of gene diagnosis for acute myocardial infarction and cerebral infarction by detecting the polymorphism of renin-angiotensin genes. On the other hand, the positive correlation between blood pressure and body mass index is affected by the Gln27Glu genotype of the beta2-adrenoceptor gene. These studies investigating the gene-environmental relationship will contribute to the development of tailor-made medicine in the future.
 ...
PMID:[Increasing menace of cardiovascular diseases in the era of obesity]. 1654 38

Excess body weight may be associated with various functional/structural lesions of the kidney. The spectrum ranges from glomerulomegaly with or without focal or segmental glomerulosclerosis, to diabetic nephropathy, to carcinoma of the kidney and nephrolithiasis. The first sign of renal injury is microalbuminuria or frank proteinuria, in particular in the presence of hypertension. The occurrence of microalbuminuria and/or chronic kidney insufficiency (glomerular filtration rate < 60 mL/min/1.73 m2) is related to the increasing number of components of the metabolic syndrome, ie, central obesity, elevated fasting blood glucose level, hypertriglycerides, low high-density lipoprotein cholesterol, and hypertension. In the long run, end-stage renal failure may develop. An increased body mass index is particularly harmful in patients with reduced renal functional mass (unilateral renal agenesis or nephrectomy) and other renal diseases (immunoglobulin A nephritis and chronic graft dysfunction after kidney transplantation). In the pathogenesis of obesity-associated glomerulopathy, hyperfiltration is of fundamental importance. The factors involved are energy intake (high protein and salt), hyperinsulinemia, and enhanced tubuloglomerular feedback because of increased sodium reabsorption. The adrenergic and renin-angiotensin-aldosterone systems as well as glucocorticoids are stimulated. In addition, several active proteins generated in the central adipose tissue, such as leptin, proinflammatory cytokines, plasminogen activator inhibitor-1, angiotensinogen, and growth factors (transforming growth factor-beta1), as well as low levels of the protective adiponectin, may contribute to renal injury. Of greatest importance is the development of hypertension and of diabetes, which are directly related to the severity of central obesity. Obesity-associated renal disease should be prevented or retarded by weight reduction following lifestyle modification (salt restriction, hypocaloric diet, aerobic exercise), or eventually by antiobesity medication or bariatric surgery. In the presence of glomerulopathy and/or hypertension, angiotensin converting enzyme inhibitors or angiotensin II type I receptor blockers are the drugs of choice to improve glomerular hyperfiltration.
 ...
PMID:Renal disease in obesity: the need for greater attention. 1682 23

Adipose tissue contains various types of cells that include preadipocytes and adipocytes. Studies have emphasized that (i) preadipocytes secrete factors involved in their own differentiation and (ii) adipocytes acquire the ability to communicate systemically with other organs (brain, liver, skeletal muscle) and locally with other cells (preadipocytes, endothelial cells and monocytes/macrophages). Adipocytes secrete proteins exhibiting either beneficial (leptin, adiponectin) or deleterious effects (angiotensinogen). Associated to the effect of secretory products from macrophages (cytokines), a disturbance in the balance between these various secreted factors leads to the development of a metabolic syndrome.
 ...
PMID:Adipose tissue as a secretory organ: from adipogenesis to the metabolic syndrome. 1686 Feb 75

While the vast majority of heavy drinkers and individuals with obesity, insulin resistance, and the metabolic syndrome will have steatosis, only a minority will ever develop steatohepatitis, fibrosis, and cirrhosis. Genetic and environmental risk factors for advanced alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) seem likely to include factors that influence the severity of steatosis and oxidative stress, the cytokine milieu, the magnitude of the immune response, and/or the severity of fibrosis. For ALD, the dose and pattern of alcohol intake, along with obesity are the most important environmental factors determining disease risk. For NAFLD, dietary saturated fat and antioxidant intake and small bowel bacterial overgrowth may play a role. Family studies and interethnic variations in susceptibility suggest that genetic factors are important in determining disease risk. For ALD, functional polymorphisms in the alcohol dehydrogenases and aldehyde dehydrogenase alcohol metabolising genes play a role in determining susceptibility in Oriental populations. No genetic associations with advanced NAFLD have been replicated in large studies. Preliminary data suggest that polymorphisms in the genes encoding microsomal triglyceride transfer protein, superoxide dismutase 2, the CD14 endotoxin receptor, TNF-alpha, transforming growth factor-beta, and angiotensinogen may be associated with steatohepatitis and/or fibrosis.
 ...
PMID:Genes or environment to determine alcoholic liver disease and non-alcoholic fatty liver disease. 1703 1


1 2 3 4 Next >>