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

Adipose tissue is not simply a store of excess energy, but also secretes a variety of proteins into circulating blood that influence systemic metabolism. These include tumor necrosis factor (TNF-alpha), plasminogen activator inhibitor type 1 (PAI-1), leptin, resistine and adiponectin. These are collectively known as adipocytokines. Adiponectin (also referred to as AdipoQ, Acrp 30, apM1 or GBP28) is a novel adipose-specific protein. A recent genome study mapped a susceptibility locus for type 2 diabetes and the metabolic syndrome on chromosome 3q27, where the adiponectin gene is located. Adiponectin is a peculiar adipocytokine because in contrast to the markedly increased levels of many others, as leptin or TNF-alpha, its level is reduced in obesity and type 2 diabetes. The administration of thiazolidinediones, which are synthetic PPARs-gamma ligands, significantly increases the plasma adiponectin concentrations, an effect that could improve insulin sensitivity. Thus, the administration of adiponectin may provide a novel treatment modality for insulin resistance and type 2 diabetes.
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PMID:[Adiponectin: a new adipocytokine]. 1462 49

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

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

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

Most studies describe the association between one particular inflammatory marker and insulin resistance (IR), features of the metabolic syndrome, or progression to type 2 diabetes. We aimed to build an Inflammation Score as a tool to measure IR-associated inflammatory activity and to evaluate the ability of different surrogate indexes of IR to reflect the inflammatory state. We studied 81 subjects, aged 47.7 +/- 12 yr with a body mass index of 28.3 +/- 4 kg/m(2). The Inflammation Score was composed of: white blood cell count, erythrocyte sedimentation rate, C-reactive protein, and soluble fraction of TNF-alpha receptors 1 and 2. All the subjects underwent a frequently sampled iv glucose tolerance test, an oral glucose tolerance test, and surrogate indexes of IR were calculated. Each increase in the Inflammation Score was associated with a progressive increase in IR. We found significant differences across categories (0-1, 2, 3, and 4-5 points in the score) in age (P = 0.048), waist circumference (P = 0.015), body mass index (P = 0.013), blood pressure (P = 0.005), and uric acid (P = 0.031). The Inflammation Score was significantly associated with all but three of the surrogate IR indexes [2-h insulin glucose ratio, Gutt's insulin sensitivity (SI) index, and Avignon's 2-h SI index]. Surrogate indexes obtained from basal values showed a similar correlation with the Inflammation Score than the SI from frequently sampled iv glucose tolerance test. In summary, the Inflammation Score is a useful tool in the evaluation of IR-associated inflammatory activity. The surrogate indexes obtained using fasting glucose and insulin appear to better reflect this inflammatory state. Basal rather than stimulated indexes should be used in the evaluation of therapeutic measures aimed at modifying IR-associated inflammatory activity.
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PMID:An inflammation score is better associated with basal than stimulated surrogate indexes of insulin resistance. 1548 52

The purpose of this study was to investigate whether aerobic fitness, body composition, body fat distribution, and inflammation are different in obese postmenopausal women with and without the metabolic syndrome (MS), and whether the severity of MS is associated with these characteristics. Fifty-eight women (age, 59 +/- 1 yr; body mass index, 33.0 +/- 0.6 kg/m2)completed testing of maximal aerobic capacity, body composition (fat mass, lean mass, and percent body fat), body fat distribution (sc and visceral fat areas, and regional adipocyte sizes), and inflammation (C-reactive protein, IL-6, and TNF-alpha,and their soluble receptors). Lean mass (44.4 +/- 0.9 vs. 41.2 +/- 0.9 kg; P < 0.05), visceral fat area (180 +/- 10 vs. 135 +/- 7 cm2; P <0.001), and plasma soluble TNF receptor 1 (sTNFR1; 860 +/- 25 vs. 765 +/- 42 pg/ml; P < 0.05) were higher in women with the MS(n = 27) than in those without the MS (n = 31). The number of MS components was directly related to weight, body mass index, fat mass, lean mass, visceral fat area, and plasma sT-NFR1. We conclude that obese older women with the MS are characterized by high lean mass, high visceral fat, and elevated sTNFR1, and the severity of the MS is associated with body composition, visceral adiposity, and inflammation.
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PMID:The metabolic syndrome in obese postmenopausal women: relationship to body composition, visceral fat, and inflammation. 1548 17

Large longitudinal studies showed the epidemiological link between obesity and hypertension. During last years, multiple possible mechanisms involved in this association were identified. Adipose tissue has an important role in the genesis of hypertension in obese patients through several pathways: insulin resistance, leptin, renin-angiotensin-aldosteron system and mediators of inflammation (TNF-alpha, IL-6). Adipocyte may be the major player in the development of insulin resistance and hypertension, elements of the metabolic syndrome, responsible for the cardiovascular complications.
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PMID:Hypertension in obese patients: a dysmetabolic hypertension with a possible adipocyte dysfunction mechanism. 1552 95

The focus of current diabetes research is the clarification of the pathogenetic relationships between subclinical inflammation, diabetes and arteriosclerosis. Even minimal disturbances in glucose tolerance are associated with a chronic, generalized inflammatory reaction that links components of the metabolic syndrome and contributes to the development of diabetic complications as well as to the development and progression of arteriosclerosis. The most important mediators and markers of this inflammation cascade are NF-kappaB, TNF-alpha, IL-6, CRP and PAI-1. For the treatment of subclinical inflammation, substances with anti-inflammatory properties such as statins or ACE inhibitors are of increasing importance.
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PMID:[Inflammation and diabetes]. 1554 May 36

Chronic hypoxia, viral infections/bacterial toxins, inflammation states, biochemical disorders, and genetic abnormalities are the most likely trigger of sudden infant death syndrome (SIDS). Autopsy studies have shown increased pulmonary density of macrophages and markedly more eosinophils in the lungs accompanied by increased T and B lymphocytes. The elevated levels of immunoglobulins, about 20% more muscle in the pulmonary arteries, increased airway smooth muscle cells, and increased fetal hemoglobin and erythropoietin are evidence of chronic hypoxia before death. Other abnormal findings included mucosal immune stimulation of the tracheal wall, duodenal mucosa, and palatine tonsils, and circulating interferon. Low normal or higher blood levels of cortisol often with petechiae on intrathoracic organs, depleted maternal IgG antibodies to endotoxin core (EndoCAb) and early IgM EndoCAb triggered, partial deletions of the C4 gene, and frequent IL-10-592*A polymorphism in SIDS victims as well as possible hypoxia-induced decreased production of antiinflammatory, antiimmune, and antifibrotic cytokine IL-10, may be responsible for the excessive reactions to otherwise harmless infections. In SIDS infants, during chronic hypoxia and times of infection/inflammation, several proinflammatory cytokines are released in large quantities, sometimes also representing a potential source of tissue damage if their production is not sufficiently well controlled, eg, by pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP). These proinflammatory cytokines down-regulate gene expression of major cytochrome P-450 and/or other enzymes with the specific effects on mRNA levels, protein expression, and enzyme activity, thus affecting metabolism of several endogenous lipophilic substances, such as steroids, lipid-soluble vitamins, prostaglandins, leukotrienes, thromboxanes, and exogenous substances. In SIDS victims, chronic hypoxia, TNF-alpha and other inflammatory cytokines, and arachidonic acid (AA) as well as n-3 polyunsaturated fatty acids (FA), stimulated and/or augmented superoxide generation by polymorphonuclear leukocytes, which contributed to tissue damage. Chronic hypoxia, increased amounts of nonheme iron in the liver and adrenals of these infants, enhanced activity of CYP2C9 regarded as the functional source of reactive oxygen species (ROS) in some endothelial cells, and nicotine accumulation in tissues also intensified production of ROS. These increased quantities of proinflammatory cytokines, ROS, AA, and nitric oxide (NO) also resulted in suppression of many CYP450 and other enzymes, eg, phosphoenolpyruvate carboxykinase (PEPCK), an enzyme important in the metabolism of FA during gluconeogenesis and glyceroneogenesis. PEPCK deficit found in SIDS infants (caused also by vitamin A deficiency) and eventually enhanced by PACAP lipolysis of adipocyte triglycerides resulted in an increased FA level in blood because of their impaired reesterification to triacylglycerol in adipocytes. In turn, the overproduction and release of FA into the blood of SIDS victims could lead to the metabolic syndrome and an early phase of type 2 diabetes. This is probably the reason for the secondary overexpression of the hepatic CYP2C8/9 content and activity reported in SIDS infants, which intensified AA metabolism. Pulmonary edema and petechial hemorrhages often present in SIDS victims may be the result of the vascular leak syndrome caused by IL-2 and IFN-alpha. Chronic hypoxia with the release of proinflammatory mediators IL-1alpha, IL-1beta and IL-6, and overloading of the cardiovascular and respiratory systems due to the narrowing airways and small pulmonary arteries of these children could also contribute to the development of these abnormalities. Moreover, chronic hypoxia of SIDS infants induced also production of hypoxia-inducible factor 1alpha (HIF-1alpha), which stimulated synthesis and release of different growth factors by vascular endothelial cells and intensified subclinical inflammatory reactions in the central nervous system, perhaps potentiated also by PACAP and VIP gene mutations. These processes could lead to the development of brainstem gliosis and disorders in the release of neuromediators important for physiologic sleep regulation. All these changes as well as eventual PACAP abnormalities could result in disturbed homeostatic control of the cardiovascular and respiratory responses of SIDS victims, which, combined with the nicotine effects and metabolic trauma, finally lead to death in these often genetically predisposed children.
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PMID:Possible pathomechanisms of sudden infant death syndrome: key role of chronic hypoxia, infection/inflammation states, cytokine irregularities, and metabolic trauma in genetically predisposed infants. 1554 94

Adipose tissue is a major source of inflammatory and thrombotic cytokines. This study investigated the relationship of abdominal subcutaneous adipose tissue cytokine gene expression to body composition, fat distribution, and metabolic risk during obesity. We determined body composition, abdominal fat distribution, plasma lipids, and abdominal subcutaneous fat gene expression of leptin, TNF-alpha, IL-6, PAI-1, and adiponectin in 20 obese, middle-aged women (BMI, 32.7 +/- 0.8 kg/m2; age, 57 +/- 1 yr). A subset of these women without diabetes (n = 15) also underwent an OGTT. In all women, visceral fat volume was negatively related to leptin (r = -0.46, P < 0.05) and tended to be negatively related to adiponectin (r = -0.38, P = 0.09) gene expression. Among the nondiabetic women, fasting insulin (r = 0.69, P < 0.01), 2-h insulin (r = 0.56, P < 0.05), and HOMA index (r = 0.59, P < 0.05) correlated positively with TNF-alpha gene expression; fasting insulin (r = 0.54, P < 0.05) was positively related to, and 2-h insulin (r = 0.49, P = 0.06) tended to be positively related to, IL-6 gene expression; and glucose area (r = -0.56, P < 0.05) was negatively related to, and insulin area (r = -0.49, P = 0.06) tended to be negatively related to, adiponectin gene expression. Also, adiponectin gene expression was significantly lower in women with vs. without the metabolic syndrome (adiponectin-beta-actin ratio, 2.26 +/- 0.46 vs. 3.31 +/- 0.33, P < 0.05). We conclude that abdominal subcutaneous adipose tissue expression of inflammatory cytokines is a potential mechanism linking obesity with its metabolic comorbidities.
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PMID:Abdominal adipose tissue cytokine gene expression: relationship to obesity and metabolic risk factors. 1556 50


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