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)

Psoriasis is a chronic and debilitating inflammatory disease associated with serious comorbidities. Psoriasis can have a significant impact on a patient's quality of life and is associated with loss of productivity, depression, and an increased prevalence of malignancy. Emerging comorbidities of psoriasis include cardiovascular disease and metabolic syndrome. Psoriasis patients have an increased prevalence of the core components of metabolic syndrome, including obesity, dyslipidemia, and insulin resistance. The relationship between psoriasis and comorbidities such as metabolic syndrome and cardiovascular disease is likely linked to the underlying chronic inflammatory nature of psoriasis. The molecular mechanisms involved in psoriasis-associated dysregulation of metabolic function are believed to be due, in large part, to the action of increased levels of proinflammatory factors, such as tumor necrosis factor-alpha, that are central to the pathogenesis of psoriasis. Recent studies investigating the effects of tumor necrosis factor antagonists on the treatment of cardiovascular disease and metabolic syndrome support this concept.
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PMID:Psoriasis comorbidities. 1827 20

It is unclear whether an association between familial combined hyperlipidemia (FCHL) and inflammatory markers exists, independently of age, sex, body weight, insulin resistance, and metabolic syndrome. Serum concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1), monocyte chemoattractant protein 1, interleukin 6, tumor necrosis factor-alpha (TNF-alpha), and high-sensitive C-reactive protein were determined in 135 probands with FCHL and in 146 normolipidemic, normotensive, normoglycemic healthy subjects. Insulin resistance was evaluated using homeostasis model assessment (HOMA). All inflammatory parameters, except interleukin 6, were significantly higher in FCHL according to medians or mean comparisons. After adjustment for age, sex, body mass index, and HOMA, only TNF-alpha remained an independent predictor of FCHL status by binary logistic regression (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.07-1.31; P = .001). In particular, elevated levels of TNF-alpha (above the 90th and 95th percentiles of the value observed in the control group, 9.6 and 9.8 pg/mL, respectively) were independent predictors of FCHL status: for TNF-alpha above the 90th percentile, OR was 7.91 (95% CI, 3.27-19.13; P < .001), and for TNF-alpha above 95th percentile, OR was 13.08 (95% CI, 4.60-37.15; P < .0001). The independent role of TNF-alpha as predictor of FCHL status was confirmed after adjustment for components of the metabolic syndrome (P = .007 and P = .003, for TNF-alpha values above 90th and 95th percentiles, respectively). In conclusion, among the inflammatory markers most commonly measured, only TNF-alpha was associated with FCHL independently of age, sex, body mass index, and HOMA. The association of TNF-alpha with FCHL was also independent of the metabolic syndrome.
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PMID:Tumor necrosis factor-alpha is a marker of familial combined hyperlipidemia, independently of metabolic syndrome. 1832 61

Adiponectin, an abundant adipocyte-derived plasma protein that modulates vascular function in type 2 diabetes, has been shown to provide cytoprotection to both pancreatic and vascular systems in diabetes. Therefore, we examined whether up-regulation of heme oxygenase (HO)-1 ameliorates the levels of inflammatory cytokines and influences serum adiponectin in Zucker fat (ZF) rats. ZF rats displayed a decrease in both HO activity and HO-1 and HO-2 protein levels and an increase in tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 compared with Zucker lean (ZL) rats. Treatment of ZF animals with 2 mg/kg cobalt protoporphyrin IX (CoPP) increased protein levels of HO-1 and HO activity, but HO-2 was unaffected. The increase in HO-1 was associated with a decrease in superoxide levels (p < 0.05) and an increase in plasma adiponectin (p < 0.005), compared with untreated ZF rats. CoPP treatment decreased visceral and s.c. fat content, and it reduced weight gain (p < 0.01). In addition, the inflammatory cytokines TNF-alpha and IL-6 were decreased (p < 0.04 and p < 0.008, respectively). Treatment of human bone marrow-derived adipocytes cultured with CoPP resulted in an increase in HO-1 and a decrease in superoxide levels. Up-regulation of HO-1 caused adipose remodeling, smaller adipocytes, and increased adiponectin secretion in the culture medium of human bone marrow-derived adipocytes. In summary, this study demonstrates that the antiobesity effect of HO-1 induction results in an increase in adiponectin secretion, in vivo and in vitro, a decrease in TNF-alpha and IL-6, and a reduction in weight gain. These findings highlight the pivotal role and symbiotic relationship of HO-1 and adiponectin in the modulation of the metabolic syndrome phenotype.
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PMID:Heme oxygenase-mediated increases in adiponectin decrease fat content and inflammatory cytokines tumor necrosis factor-alpha and interleukin-6 in Zucker rats and reduce adipogenesis in human mesenchymal stem cells. 1833 66

Studies performed during the last decade indicate that adipose tissue is not only a site of triglyceride storage but also an active endocrine organ which secretes many biologically active mediators referred to as "adipokines". In contrast to many adipokines which are overproduced in obese individuals and exert deleterious effects on insulin sensitivity, lipoprotein metabolism and cardiovascular system, such as leptin, tumor necrosis factor-alpha, plasminogen activator inhibitor-1, resistin, etc., adiponectin seems to be a unique adipokine which is produced in lower amounts in obese than in lean subjects and possesses predominantly beneficial activities, i.e. increases insulin sensitivity, stimulates fatty acid oxidation, inhibits inflammatory reaction and induces endothelium-dependent nitric oxide-mediated vasorelaxation. Adiponectin binds two receptors, AdipoR1 and AdipoR2. Adiponectin knockout mice exhibit various manifestations of the metabolic syndrome such as insulin resistance, glucose intolerance, hyperlipidemia, impaired endothelium-dependent vasorelaxation and hypertension, as well as augmented neointima formation after vascular injury. Clinical studies indicate that plasma adiponectin concentration is lower in patients with essential hypertension and ischemic heart disease. Raising endogenous adiponectin level or increasing the sensitivity to this hormone may be a promising therapeutic strategy for patients with metabolic and cardiovascular diseases. Among currently used drugs, thiazolidinediones (peroxisome proliferator activated receptor gamma agonists) are most effective in elevating adiponectin level.
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PMID:Adiponectin and its role in cardiovascular diseases. 1833 52

Tristetraprolin (TTP/zinc finger protein 36) family proteins have antiinflammatory effects by destabilizing proinflammatory mRNA. TTP expression is reduced in fats of obese people with metabolic syndrome and brains of suicide victims and is induced by insulin and cinnamon polyphenol extract (CPE) in adipocytes, by lipopolysaccharide (LPS) in macrophages, and by green tea polyphenol extract in rats. CPE was reported to improve immune function against microorganisms, but the mechanism is unknown. This study tested the hypothesis that CPE regulates immune function involving genes encoding TTP, proinflammatory cytokines, and glucose transporter (GLUT) families and compared the effects of CPE to those of insulin and LPS in mouse RAW264.7 macrophages. CPE increased TTP mRNA and protein levels, but its effects were less than LPS. CPE (100 mg/L, 0.5-4 h) increased TTP and tumor necrosis factor (TNF) mRNA levels by up to 2- and 6-fold that of the control, respectively, and the base level of TTP was 6-fold that of TNF. LPS (0.1 mg/L, 4 h) increased TTP, TNF, granulocyte-macrophage colony-stimulating factor, cyclooxgenase-2, and interleukin 6 mRNA levels by 39-1868 fold. CPE and LPS increased GLUT1 expression (the major GLUT form in macrophages) to 3- and 2-fold that of the control, respectively. Insulin (100 nmol/L, 0.5-4 h) did not exhibit major effects on the expression of these genes. CPE increased TTP expression more rapidly than those of proinflammatory cytokines and the net increases of TTP mRNA levels were larger than those of proinflammatory cytokines. These results suggest that CPE can affect immune responses by regulating anti- and proinflammatory and GLUT gene expression.
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PMID:Cinnamon polyphenol extract affects immune responses by regulating anti- and proinflammatory and glucose transporter gene expression in mouse macrophages. 1842 88

Subjects with metabolic syndrome--a constellation of cardiovascular risk factors of which central obesity and insulin resistance are the most characteristic--are at increased risk for developing diabetes mellitus and cardiovascular disease. In these subjects, abdominal adipose tissue is a source of inflammatory cytokines such as tumor necrosis factor-alpha, known to promote insulin resistance. The presence of inflammatory cytokines together with the well-documented increased risk for cardiovascular diseases in patients with inflammatory arthritides and systemic lupus erythematosus has prompted studies to examine the prevalence of the metabolic syndrome in an effort to identify subjects at risk in addition to that conferred by traditional cardiovascular risk factors. These studies have documented a high prevalence of metabolic syndrome which correlates with disease activity and markers of atherosclerosis. The correlation of inflammatory disease activity with metabolic syndrome provides additional evidence for a link between inflammation and metabolic disturbances/vascular morbidity.
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PMID:Metabolic syndrome in rheumatic diseases: epidemiology, pathophysiology, and clinical implications. 1849 18

We investigated for evidence of early metabolic syndrome irrespective of body mass index (BMI) in subjects with premature pubarche (PP). Ten children with PP were compared with controls matched for age, sex, ethnicity, and BMI. Congenital adrenal hyperplasia and other known causes of PP were excluded by standard methods. Anthropometry, blood pressure (BP), dual-energy x-ray absorptiometry body scan, fasting blood lipid profile, and cytokines were obtained. The children were divided into 2 groups: (1) the total group of children with PP, and their age-, sex-, ethnicity-, and BMI-matched controls and (2) those with PP and normal BMI (<19 kg/m(2)) and their matched controls selected from the original groups. The PP subjects with normal BMI (S(1)) showed significantly higher systolic BP (P = .028), diastolic BP (P = .028), and mean arterial pressure (P = .018) compared with matched controls (C(1)). Nevertheless, for both groups, all the above parameters were statistically not significant when corrected for height. Fat distribution in PP subjects indicated significantly higher android (P = .047) and android-gynoid ratio (P = .013). Normal-BMI PP children had significantly higher android-gynoid ratio fat distribution compared with their matched controls (P = .037). Trunk fat percentage (p: 0.04) and trunk fat (grams) (P = .007) were significantly elevated in PP children compared with matched controls. Again, for both groups, all the above parameters were not statistically significant when corrected for height. The PP subjects had significantly higher tumor necrosis factor (TNF)-alpha (P = .038) and interleukin-8 (picograms per milliliter) (P = .05) compared with matched controls. Normal-BMI PP children also had higher TNF-alpha (P = .028) compared with matched controls. When corrected for height, TNF-alpha was higher in the total (P = .037) and normal-BMI (P = .043) PP children. Premature pubarche can be linked to markers of the metabolic syndrome in lean children.
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PMID:Evidence of metabolic syndrome in lean children with premature pubarche at diagnosis. 1850 54

The metabolic syndrome (MetS) is associated with an increased incidence of diabetes and coronary heart disease. Postprandial lipemia is a prominent feature of dyslipidemia in both type 2 diabetes mellitus and MetS and is also associated with coronary heart disease. Oxidative stress and inflammation are pivotal in all stages of atherosclerosis; however, there is a paucity of data on postprandial oxidative stress and inflammation in subjects with MetS. Thus, the primary aim of this study was to compare the postprandial effects of an energy-dense, high-fat, fast-food-style (FFS) meal with an American Heart Association (AHA)-recommended heart-healthy meal on biomarkers of oxidative stress and inflammation in subjects with MetS. A total of 11 subjects with MetS completed the study. Glucose levels were significantly increased 2 hours after both FFS and AHA diets (P < .0001), and high-density lipoprotein cholesterol levels significantly decreased in FFS diet but not in the AHA diet (P for interaction < .05). Total triglyceride levels significantly increased postprandially only in the FFS meal but not in the AHA meal (P for interaction = .03). Plasma thiobarbituric acid reactive substances and malondialdehyde + hydroxynonenal increased significantly with time in both dietary groups, and the postprandial increase was greater in the FFS diet compared to the AHA diet (P < .0005). Serum high-sensitivity C-reactive protein, interleukin 6, and tumor necrosis factor levels did not change with time or dietary treatment. The postprandial increase in interleukin 1b was significantly higher with the FFS meal, thus resulting in significant differences between both treatments (P for interaction = .03). Thus, in subjects with MetS, consumption of an energy-dense, fatty meal (FFS breakfast) results in increased postprandial oxidative stress compared to a heart-healthy meal (AHA).
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PMID:High-fat, energy-dense, fast-food-style breakfast results in an increase in oxidative stress in metabolic syndrome. 1850 72

It is well known that the relative risk of developing type 2 diabetes mellitus increases with increasing body mass index. The presence of not only excessive body fat but also the pattern of fat distribution (central obesity) is important for other metabolic abnormalities included in the metabolic syndrome. The possible mechanisms linking obesity to type 2 diabetes including high concentrations of free fatty acids, altered adipokines expression (low adiponectin levels and high expression of tumor necrosis factor-alpha), and low-grade inflammation are reviewed. Finally, the author refers to the theory that the primary defect is beta-cell failure that leads to diabetes as well as to obesity.
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PMID:The road from obesity to type 2 diabetes. 1850 43

Psoriasis is a chronic immune-inflammatory-mediated disease that can predispose patients to other inflammatory conditions. For example, individuals with psoriasis are at increased risk for insulin resistance, obesity, dyslipidemia, and hypertension--components that characterize the metabolic syndrome. The metabolic syndrome is an important driver of adverse cardiovascular outcomes. Proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), and other factors that are overproduced in patients with psoriasis likely contribute to the increased risk for development of metabolic syndrome. This article reviews the association of psoriasis with metabolic syndrome, as well as the impact of biologic agents that are currently used to treat psoriasis (ie, TNF antagonists) on risk factors for metabolic syndrome.
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PMID:Psoriasis and the metabolic syndrome. 1856 88


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