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)

The pleiotropic proinflammatory cytokine, interleukin 18, plays a role in innate immunity and, based on mouse models, influences obesity. We investigated variation within the IL18 gene and its effect on markers of the metabolic syndrome. A tagging single nucleotide polymorphism set of 5 SNPs for the gene encoding interleukin 18 was selected and genotype was determined in 3 separate studies. In 2775 healthy middle-aged men, 6 common haplotypes were seen, but none was associated with body mass index (BMI). In 439 patients who underwent coronary artery bypass graft surgery, Hap2 (frequency, 22%) was present at a lower frequency than in healthy subjects and was associated with higher mean BMI compared with Hap1 (P = .011). In 483 men with type 2 diabetes mellitus, Hap2 was again associated with a higher haplotypic mean BMI (P = .002). Those homozygous for Hap2 had a BMI of 31.2 (1.3) kg/m(2), mean (SE), compared with 28.3 (1.0) kg/m(2) in those not carrying a copy of Hap2. No single SNP could fully explain the effects seen. Therefore, variation within IL18, previously shown to be associated with lower IL18 levels, is influencing measures of obesity both in men with type 2 diabetes mellitus and those with advanced coronary heart disease.
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PMID:A common interleukin 18 haplotype is associated with higher body mass index in subjects with diabetes and coronary heart disease. 1744 42

This study investigated the effects of rimonabant (SR141716), an antagonist of the cannabinoid receptor type 1 (CB1), on obesity-associated hepatic steatosis and related features of metabolic syndrome: inflammation (elevated plasma levels of tumor necrosis factor alpha [TNFalpha]), dyslipidemia, and reduced plasma levels of adiponectin. We report that oral treatment of obese (fa/fa) rats with rimonabant (30 mg/kg) daily for 8 weeks abolished hepatic steatosis. This treatment reduced hepatomegaly, reduced elevation of plasma levels of enzyme markers of hepatic damage (alanine aminotransferase, gamma glutamyltransferase, and alkaline phosphatase) and decreased the high level of local hepatic TNFalpha currently associated with steatohepatitis. In parallel, treatment of obese (fa/fa) rats with rimonabant reduced the high plasma level of the proinflammatory cytokine TNFalpha and increased the reduced plasma level of the anti-inflammatory hormone adiponectin. Finally, rimonabant treatment also improved dyslipidemia by both decreasing plasma levels of triglycerides, free fatty acids, and total cholesterol and increasing the HDLc/LDLc ratio. All the effects of rimonabant found in this study were not or only slightly observed in pair-fed obese animals, highlighting the additional beneficial effects of treatment with rimonabant compared to diet. These results demonstrate that rimonabant plays a hepatoprotective role and suggest that this CB1 receptor antagonist potentially has clinical applications in the treatment of obesity-associated liver diseases and related features of metabolic syndrome.
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PMID:Rimonabant reduces obesity-associated hepatic steatosis and features of metabolic syndrome in obese Zucker fa/fa rats. 1759 67

Metabolic syndrome includes most widely distributed clinical conditions such as obesity, hypertension, dislipidemia, and diabetes. Pomegranate fruit extract (PFE), rich in polyphenolic antioxidants, reduces the expression of oxidation-sensitive genes at the sites of perturbed shear-stress. The aim of this study was to evaluate the effect of PFE in comparison to regular pomegranate juice (PJ) and seed oil on the biological actions of nitric oxide (NO) and the arterial function in obese Zucker rats, a model of metabolic syndrome. Our results indicated that supplementation with PFE or PJ significantly decreased the expression of vascular inflammation markers, thrombospondin (TSP), and cytokine TGFbeta1 (P<0.05), whereas seed oil supplementation had a significant effect only on TSP-1 expression (P <0.05). Plasma nitrate and nitrite (NO(x)) levels were significantly increased by PFE and PJ (P<0.05). Furthermore, the effect of PFE in increasing endothelial NO synthase (eNOS) expression was comparable to that of PJ. These data highlight possible clinical applications of PFE in metabolic syndrome.
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PMID:The influence of pomegranate fruit extract in comparison to regular pomegranate juice and seed oil on nitric oxide and arterial function in obese Zucker rats. 1755 10

Adipocyte cytokines regulate glucose metabolism and insulin resistance and adiponectin is thought to have a protective effect against atherosclerosis. Studies have shown that adiponectin expression is decreased in obese subjects and those with metabolic syndrome or diabetes mellitus. The purpose of this study was to investigate the relationship between circulating adipocyte cytokine concentrations and angiographic coronary artery disease (CAD) progression in patients with chest pain. Patients with stable angina pectoris who underwent repeat coronary angiograms and had serum samples at the time of first catheterization between March 1999 and January 2004 were enrolled. A modified Gensini scoring system was used to define angiographic coronary artery progression between the index and follow-up angiograms. Those who had significant angiographic progression of coronary lesions were classified into the progression group (N=55). Those who did not have CAD progression were classified into the non-progression group (N=102). Univariate analysis showed that CAD progression was associated with male gender (93% vs. 78%, p=0.038), higher baseline total cholesterol (187+/-43 vs. 173+/-39 mg/dl, p=0.037) and higher baseline fasting blood glucose (128+/-57 vs. 110+/-40 mg/dl, p=0.037). Patients in the progression group had a significantly lower serum adiponectin level (14.3+/-7.9 vs. 18.9+/-13.2 mug/ml, p=0.007) than, but resistin (28.9+/-13.4 vs. 34.4+/-26.0 ng/ml, p=0.142) and leptin (7.4+/-4.6 vs. 7.7+/-6.5 ng/ml, p=0.675) levels similar to, those in the non-progression group. In a multivariate binary logistic regression model, male gender (odds ratio 4.283, p=0.015), higher serum cholesterol (odds ratio 1.010, p=0.032) and lower serum adiponectin (odds ratio 0.959, p=0.030) were all significant independent predictors of CAD progression. In conclusion, we found that a decreased circulating level of adiponectin is associated with angiographic CAD progression in patients with angina pectoris.
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PMID:Decreased circulating protective adiponectin level is associated with angiographic coronary disease progression in patients with angina pectoris. 1917 15

Type 2 diabetes is associated with excessive food intake and a sedentary lifestyle. Local inflammation of white adipose tissue induces cytokine-mediated insulin resistance of adipocytes. This results in enhanced lipolysis within these cells. The fatty acids that are released into the cytosol can be removed by mitochondrial beta-oxidation. The flux through this pathway is normally limited by the rate of ADP supply, which in turn is determined by the metabolic activity of the adipocyte. It is expected that the latter does not adapt to an increased rate of lipolysis. We propose that elevated fatty acid concentrations in the cytosol of adipocytes induce mitochondrial uncoupling and thereby allow mitochondria to remove much larger amounts of fatty acids. By this, release of fatty acids out of adipocytes into the circulation is prevented. When the rate of fatty acid release into the cytosol exceeds the beta-oxidation capacity, cytosolic fatty acid concentrations increase and induce mitochondrial toxicity. This results in a decrease in beta-oxidation capacity and the entry of fatty acids into the circulation. Unless these released fatty acids are removed by mitochondrial oxidation in active muscles, these fatty acids result in ectopic triacylglycerol deposits, induction of insulin resistance, beta cell damage and diabetes. Thiazolidinediones improve mitochondrial function within adipocytes and may in this way alleviate the burden imposed by the excessive fat accumulation associated with the metabolic syndrome. Thus, the number and activity of mitochondria within adipocytes contribute to the threshold at which fatty acids are released into the circulation, leading to insulin resistance and type 2 diabetes.
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PMID:Fatty acid-induced mitochondrial uncoupling in adipocytes as a key protective factor against insulin resistance and beta cell dysfunction: a new concept in the pathogenesis of obesity-associated type 2 diabetes mellitus. 1809 47

The metabolic syndrome is associated with a dysregulated adipose tissue; in part a consequence of adipose cell enlargement and the associated infiltration of macrophages. Adipose cell enlargement leads to a proinflammatory state in the cells with reduced secretion of adiponectin and with increased secretion of several cytokines and chemokines including interleukin (IL)-6, IL-8, and MCP-1. MCP-1 has been shown to play an important role for the associated recruitment of macrophages into the adipose tissue. The increased release of cytokines leads to an impaired differentiation of the preadipocytes with reduced lipid accumulation and induction of adiponectin, thus promoting ectopic lipid storage. In particular tumor necrosis factor (TNF) alpha, but also IL-6, has been shown to induce these effects in preadipocytes and this is associated with an increased Wnt signaling maintaining the cells in an undifferentiated and proinflammatory state. The proinflammatory state in the adipose tissue also leads to a local insulin resistance including an impaired inhibitory effect of insulin on FFA release. The insulin resistance further supports the proinflammatory state because insulin, by itself, is both antilipolytic and antiinflammatory by antagonizing cytokine-induced activation of STAT signaling.
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PMID:Inflamed adipose tissue: a culprit underlying the metabolic syndrome and atherosclerosis. 1790 71

The adipocyte metabolism has been shown to change during the fat enlargement process associated to obesity. Several procoagulant proteins such as plasminogen activator inhibitor type 1, tissue factor or factor VII and also inducible nitric oxide synthase show higher expression in adipose tissue of obese people in comparison to lean. This overexpression could explain at least a part of the atherogenic and cardiovascular risk associated with obesity. In addition to cytokine secretion, many other features have been observed to be common to adipocyte and monocyte/macrophage lines: for example, phagocytic and microbicidal activities, and possibly a cellular plasticity of adipose precursors. Overweight and obesity are associated with an increased risk of such metabolic abnormalities as dyslipidemia, hypertension or type 2 diabetes mellitus and cardiovascular diseases, common features of the metabolic syndrome. Initially, insulin resistance or hyperinsulinemia was suggested as the origin of these abnormalities. More recent studies indicate that adipokynes have an important role in obesity-associated metabolic complications, and suggest that chronically elevated local or systemic concentrations of adipokynes contribute to the development of complications associated with obesity and metabolic syndrome. Considering all the evidence relating to diet and inflammation, the best diet for protecting against the metabolic derangements associated with obesity and metabolic syndrome would be high in fibre-rich cereals, fruit, vegetables, fish, virgin olive oil and nuts; moderate in wine; and low in meat, processed meat foods and trans-fatty acids.
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PMID:Inflammation, obesity and comorbidities: the role of diet. 1790 26

Adipose tissue is a target for cardiotrophin-1 (CT-1), a cytokine member of the IL-6 family of cytokines that is involved in cardiac growth and dysfunction. However, it is unknown whether adipocytes are a source of CT-1 and whether CT-1 is overexpressed in diseases characterized by increased fat depots [i.e., the metabolic syndrome (MS)]. Thus this work aimed 1) to test whether adipose tissue expresses CT-1 and whether CT-1 expression can be modulated and 2) to compare serum CT-1 levels in subjects with and without MS diagnosed by National Cholesterol Education Program Adult Treatment Panel III criteria. Gene and protein expression of CT-1 was determined by real-time RT-PCR, ELISA, and Western blotting. CT-1 expression progressively increased, along with differentiation time from preadipocyte to mature adipocyte in 3T3-L1 cells. CT-1 expression was enhanced by glucose in a dose-dependent manner in these cells. mRNA and protein CT-1 expression was also demonstrated in human adipose biopsies. Immunostaining showed positive staining in adipocytes. Finally, increased CT-1 serum levels were observed in patients with MS compared with control subjects (127 +/- 9 vs. 106 +/- 4 ng/ml, P < 0.05). Circulating levels of CT-1 were associated with glucose levels (r = 0.2, P < 0.05). Taken together, our data suggest that adipose tissue can be recognized as a source of CT-1, which could account for the high circulating levels of CT-1 in patients with MS.
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PMID:Cardiotrophin-1 is expressed in adipose tissue and upregulated in the metabolic syndrome. 1794 Feb 13

Obstructive sleep apnea (OSA), often concomitant with obesity, increases the risk for the metabolic syndrome. One mechanism that may participate in this association is upregulation of inflammatory pathways. We used structural equation modeling to assess the interrelations between childhood obesity, OSA, inflammation, and metabolic dysfunction. One hundred and eighty-four children (127 boys, mean age: 8.5 +/- 4.1 years) had height and weight measured, underwent overnight polysomnography and had fasting blood taken. The blood was analyzed for insulin, glucose, lipids, leptin, and cytokines [interferon (IFN)-gamma, granulocyte macrophage-colony stimulating factor, interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor-alpha]. Structural equation modeling (SEM) was used to evaluate associations between the outcomes of interest including hypoxia, arousal (related to respiratory and spontaneous), obesity, metabolic dysfunction, and inflammatory markers. Two cytokine factors and one metabolic factor were derived for the SEM. These factors provided good fit in the structural equation model (chi(2)/df = 2.855; comparative fit index = 0.90, root mean squared error of approximation = 0.10) and all factor loadings were significantly different from zero (P < or = 0.01). Overall, our results indicate that while obesity (as measured by body mass index z-score) has a major influence on the metabolic dysfunction associated with OSA, arousal indices, and cytokine markers may also influence this association. Our results support the hypothesis that OSA is a contributor to the mechanisms that link sleep, systemic inflammation and insulin resistance, and show that the interrelations may begin in childhood.
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PMID:Structural equation modeling of sleep apnea, inflammation, and metabolic dysfunction in children. 1803 84

Obesity-induced chronic inflammation is a key component in the pathogenesis of insulin resistance and the Metabolic syndrome. In this review, we focus on the interconnection between obesity, inflammation and insulin resistance. Pro-inflammatory cytokines can cause insulin resistance in adipose tissue, skeletal muscle and liver by inhibiting insulin signal transduction. The sources of cytokines in insulin resistant states are the insulin target tissue themselves, primarily fat and liver, but to a larger extent the activated tissue resident macrophages. While the initiating factors of this inflammatory response remain to be fully determined, chronic inflammation in these tissues could cause localized insulin resistance via autocrine/paracrine cytokine signaling and systemic insulin resistance via endocrine cytokine signaling all of which contribute to the abnormal metabolic state.
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PMID:Inflammation and insulin resistance. 1805 12


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