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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 an active and complex endocrine organ that secretes numerous bioactive substances, including hormones, growth factors, and cytokines. Central obesity, one of the components of metabolic syndrome, is a cardiometabolic risk factor associated with a state of chronic inflammation and coagulation, one in which the expression of certain adipocytokines, including tumor necrosis factor-alpha (TNF-(alpha), interleukin (IL)-6, and plasminogen activator inhibitor-1 (PAI-1) is more abundantly increased, while adiponectin expression is decreased. TNF-alpha initiates and organizes inflammatory changes in vascular tissue. IL-6, an inflammatory cytokine directly implicated in atherogenesis, exerts pleiotropic effects on a variety of tissues. An increased concentration of PAI-1, an important regulator of the endogenous fibrinolytic system, promotes continued clotting. Adiponectin, on the other hand, has potent vasculoprotective, angiogenic, anti-inflammatory, and antiatherogenic properties. Adiponectin levels are low in obese individuals and increase when weight is lost, thereby serving as a marker for cardioprotection. Weight loss has long been promoted as a means to reduce the risk of type 2 diabetes and cardiovascular disease; for example, exercise and a hypocaloric diet have been shown to decrease PAI-1 levels. Weight loss drugs, such as orlistat, a lipase inhibitor, and sibutramine, a serotonin and norepinephrine reuptake inhibitor, have both been shown to produce a decrease in C-reactive protein levels and an increase in serum adiponectin. Rimonabant, a selective cannabinoid 1 receptor antagonist in Phase III studies, also has been shown to increase adiponectin levels. These agents may play a role in the regulation of adipocytokines, which may directly affect the risk for cardiometabolic disease.
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PMID:The relation of adipose tissue to cardiometabolic risk. 1720 62

Obesity and obesity related diseases are a major public health problem. Recent studies have shown that fat tissue is not a simple energy storage organ, but exerts important endocrine and immune functions. These are achieved predominantly through release of adipocytokines, which include several novel and highly active molecules released abundantly by adipocytes like leptin, resistin, adiponectin or visfatin, as well as some more classical cytokines released possibly by inflammatory cells infiltrating fat, like TNF-alpha, IL-6, MCP-1 (CCL-2), IL-1. All of those molecules may act on immune cells leading to local and generalized inflammation and may also affect vascular (endothelial) function by modulating vascular nitric oxide and superoxide release and mediating obesity related vascular disorders (including hypertension, diabetes, atherosclerosis, and insulin resistance) but also cancer or non-alcoholic fatty liver diseases. Present review, in a concise form, focuses on the effects of major adipocytokines, characteristic for adipose tissue like leptin, adiponectin, resistin and visfatin on the immune system, particularly innate and adaptive immunity as well as on blood vessels. Macrophages and T cells are populating adipose tissue which develops into almost an organized immune organ. Activated T cells further migrate to blood vessels, kidney, brain and other organs surrounded by infiltrated fat leading to their damage, thus providing a link between metabolic syndrome, inflammation and cardiovascular and other associated disorders. Ceretain treatments may lead to significant changes in adipocytokine levels. For example include beta-2 adrenoreceptor agonists, thiazolidinediones as well as androgens lead to decrease of plasma leptin levels. Moreover future treatments of metabolic system associated disorders should focus on the regulation of adipocytokines and their modes of action.
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PMID:Adipocytokines - novel link between inflammation and vascular function? 1722 78

Regular exercise offers protection against all cause mortality and there is evidence from randomised intervention studies that physical training is effective as a treatment in patients with chronic heart diseases, type 2 diabetes and symptoms related to the metabolic syndrome. Chronic diseases such as cardiovascular disease, type 2 diabetes and cancer are associated with chronic low-grade systemic inflammation. It has been demonstrated that regular exercise induces anti-inflammatory effects with elevated levels of anti-inflammatory cytokines and suppression of TNF-alpha production. Thereby, exercise offers protection against TNF-alpha-induced insulin resistance. Otherwise, the exercise-induced production and release of IL-6 from myofibers may contribute to abrogate an atherogenic lipid profile, which is often associated with chronic diseases. This review focuses on the anti-inflammatory effects of exercise and how this may contribute to mediate the beneficial health effects of exercise training in patients with chronic diseases associated with chronic low-grade inflammation.
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PMID:The role of IL-6 in mediating the anti-inflammatory effects of exercise. 1724 90

In a prior study, we have shown that tumor necrosis factor (TNF)-alpha neutralization improves inflammatory markers and total adiponectin in patients with the metabolic syndrome, without improving insulin sensitivity. In this study, we sought to extend our understanding of the effects of TNF-alpha neutralization in this human model of obesity by investigating the responses of high-molecular-weight (HMW) adiponectin, resistin, leptin, and muscle adiposity to etanercept in patients with the metabolic syndrome. Fifty-six men and women with the metabolic syndrome enrolled in a double-blind randomized placebo-controlled trial. Circulating concentrations of total and HMW adiponectin, resistin, and leptin were determined at baseline and after 4 wk of treatment with etanercept. Muscle adiposity was measured by computed tomography (CT). Although etanercept increased total adiponectin concentration, the HMW form, which is thought to mediate insulin sensitivity, was unchanged. Thus the ratio of HMW to total adiponectin decreased following etanercept treatment compared with placebo (-0.03 +/- 0.03 vs. 0.06 +/- 0.03, P = 0.02). Resistin tended to decrease in the etanercept-treated group compared with placebo (-0.6 +/- 0.7 vs. 1.2 +/- 0.7 ng/ml, P = 0.06), whereas leptin was not altered. Etanercept decreased muscle attenuation on CT [-0.61 +/- 0.64 Hounsfield units (HU) vs. 1.54 +/- 0.77 HU in placebo, P = 0.04], suggesting an increase in muscle adiposity. Together, these results demonstrate that neutralization of TNF-alpha in obese humans results in differential effects on critical adipokines and body composition indexes. These findings may help to explain the lack of effect on insulin sensitivity and extend our knowledge of the biological effects of TNF-alpha neutralization in obesity.
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PMID:Effects of TNF-alpha neutralization on adipocytokines and skeletal muscle adiposity in the metabolic syndrome. 1737 98

Metabolic syndrome (MS) is a cluster of synergistically interacting cardiovascular risk factors which may have serious consequences for the development of cardiovascular disease and diabetes. In this study, we aimed to estimate the prevalence of MS within presumably healthy French families of the STANISLAS cohort, and to observe biological parameters involved in cardiovascular diseases among the offspring of MS subjects. 371 apparently healthy families (1366 individuals) were examined at two visits with a five-year interval (t0 and t+5). MS prevalence was assessed among parents following the ATP-III definition. Our results show that MS is present in presumably healthy adults of the STANISLAS cohort and increases with age. Moreover, low HDL-C and TNF-alpha may play an important role in the development of MS in childhood, at least in our population. Therefore, a systematic tracking of MS appears to be all the more important as it will permit early management of MS in parents and the installation of efficient preventive measures in children including specific advice for diet and physical activity.
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PMID:[A prospective study on the prevalence of metabolic syndrome among healthy French families: the importance of plasma concentration of TNF-alpha in addition to its genetic polymorphism]. 1748 78

The peroxisome proliferator-activated receptors (PPARs) are nuclear fatty acid receptors that have been suggested to play crucial roles in metabolic diseases such as hyperlipidemia, insulin resistance, and diabetes. The three PPAR subtypes, alpha, beta, and beta/delta, have distinct expression patterns. We have investigated the role of PPARgamma in the pathogenesis of type 2 diabetes. Heterozygous PPARgamm-deficient mice were protected from the development of insulin resistance due to adipocyte hypertrophy on a high-fat diet. A Pro12Ala polymorphism in the human PPARgamma2 gene, which has been reported to cause a reduction in PPARy activity, was associated with a decreased risk of type 2 diabetes in various ethnic groups including Japanese subjects. Consistent with these results, moderate reduction of PPARgamma activity by RXR antagonist decreased the triglyceride content of white adipose tissue (WAT)/muscle/liver, due to an increase in fatty-acid combustion and a decrease in lipogenesis, thereby ameliorating high-fat diet-induced obesity and insulin resistance. By contrast, potent activation of PPARy by thiazolidinedione (TZD) stimulated adipocyte differentiation and apoptosis, thereby preventing adipocyte hypertrophy, which is associated with the alleviation of insulin resistance, presumably due to decreases in FFA, and TNFa, and the up-regulation of adiponectin. TZD increased the triglyceride content of WAT, but decreased that of the liver/muscle, leading to the amelioration of insulin resistance at the expense of obesity. It should also be noted that TZD has an anti-atherogenic effect in vivo. Uncovering the regulatory mechanisms and transcriptional targets of PPARgamma will provide insights into the pathogenesis of metabolic syndrome and offer valuable information for rational drug design.
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PMID:[PPARgamma and metabolic syndrome]. 1759 90

We examined the hypothesis that insulin resistance in skeletal muscle promotes the development of atherogenic dyslipidemia, associated with the metabolic syndrome, by altering the distribution pattern of postprandial energy storage. Following ingestion of two high carbohydrate mixed meals, net muscle glycogen synthesis was reduced by approximately 60% in young, lean, insulin-resistant subjects compared with a similar cohort of age-weight-body mass index-activity-matched, insulin-sensitive, control subjects. In contrast, hepatic de novo lipogenesis and hepatic triglyceride synthesis were both increased by >2-fold in the insulin-resistant subjects. These changes were associated with a 60% increase in plasma triglyceride concentrations and an approximately 20% reduction in plasma high-density lipoprotein concentrations but no differences in plasma concentrations of TNF-alpha, IL-6, adiponectin, resistin, retinol binding protein-4, or intraabdominal fat volume. These data demonstrate that insulin resistance in skeletal muscle, due to decreased muscle glycogen synthesis, can promote atherogenic dyslipidemia by changing the pattern of ingested carbohydrate away from skeletal muscle glycogen synthesis into hepatic de novo lipogenesis, resulting in an increase in plasma triglyceride concentrations and a reduction in plasma high-density lipoprotein concentrations. Furthermore, insulin resistance in these subjects was independent of changes in the plasma concentrations of TNF-alpha, IL-6, high-molecular-weight adiponectin, resistin, retinol binding protein-4, or intraabdominal obesity, suggesting that these factors do not play a primary role in causing insulin resistance in the early stages of the metabolic syndrome.
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PMID:The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndrome. 1764 Sep 6

It has long been recognized the epidemiological association of psoriasis, especially the most severe forms, with several diseases that share a common pathogenic substrate involving TNF-alpha and different target organs (arthritis and Crohn's disease, for example), as well as an increased risk of coronary heart disease and occlusive cardiovascular disease. In the patient with severe psoriasis there is also an increased prevalence of obesity, dyslipemia, adult diabetes mellitus, alcohol abuse and tobacco habit which contribute to the increased risk of mortality associated with atherosclerosis. Recently it has been identified the so-called metabolic syndrome, characterized by the association of abdominal obesity, atherogenic dyslipemia, hypertension, insulin resistance with or without glucose intolerance and a proinflammatory and prothrombotic state as a risk factor for cardiovascular disease. There is evidence that in rheumatoid arthritis as well as in psoriasis, chronic inflammation has a pathogenic role in the metabolic syndrome and associated comorbidities, and its adequate treatment may contribute to revert it. The dermatologist should recognize the elements of the metabolic syndrome and propose the patient with psoriasis, in addition to the optimal dermatologic treatment, changes in life habits and appropriate drug therapy to reduce the risk of cardiovascular morbi-mortality.
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PMID:[Psoriasis, a systemic disease?]. 1766 29

Dietary conjugated linoleic acid (CLA) and the antihypertensive drug, telmisartan, have both been shown to modify cardiovascular risks. The effects of a combination of these two agents have, however, not been investigated. This 20 week study sought to assess the therapeutic potential of a CLA/telmisartan co-administration in rats fed a high-fructose high-fat diet. Thirty-three male Sprague-Dawley rats were randomly assigned to five experimental groups, including control, losartan, telmisartan, CLA, and CLA + telmisartan-treated animals. Body weight, blood pressure, and blood levels of lipids, glucose, insulin, and inflammatory markers were measured. Co-administration of CLA and telmisartan resulted in significant (P < 0.05) reductions in body weight, visceral fat, serum total cholesterol, triglycerides, glucose, plasma insulin concentrations, and systolic blood pressure compared with those in the control group. Moreover, plasma levels of IL1-alpha and IFN-gamma were reduced and levels of IL1-beta, IL-4, IL-6, and IL-10, plus TNF-alpha were increased in the co-therapy group, compared with controls. In conclusion, this study suggests that a combination of CLA with telmisartan may modify several risk factors of cardiovascular disease commonly seen in metabolic syndrome. This combination of nutraceuticals and pharmaceuticals may be a safe and cost-effective strategy in a number of high-risk subjects. Future studies will further document clinical benefits of such combination therapy.
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PMID:The effects of simultaneous administration of dietary conjugated linoleic acid and telmisartan on cardiovascular risks in rats. 1768 Feb 92

In this cross-sectional study, we evaluate potential predictors of Metabolic Syndrome (MS) in a group of 54 Caucasian chronically HIV-infected patients with lipodystrophy. According to ATP-III criteria, 22 patients were affected by MS and 32 were not. The mean age of the sample was 41.2+/-8.6 years, and most patients were males (74.1%); the two groups were homogeneous for gender, age, viro-immunologic status and the duration of antiviral therapy. The independent association between MS and several factors including demographic characteristics, type of highly-active antiviral therapy (HAART), viro-immunologic response, common cardiovascular risk factors (including Framingham scores), and selected cytokines (IFN-gamma, TNF-alpha, IL-2, IL-4, IL-6, IL-10 and IL-18), was investigated using stepwise forward logistic regression. At multivariate analysis, the only independent predictors of the metabolic syndrome were triglycerides and IL-18. A 10 mg/dL increase in triglycerides corresponds to an adjusted risk ratio for MS of 1.11 (95 percent IC: 1.04-1.19); and patients in the top tertile of IL-18 (those with IL-18 >/= 530 pg/L) had more than three times the likelihood of MS, as compared to the bottom and medium tertiles of IL-18 (patients with IL-18< 530 pg/L). This relationship was not attenuated by the inclusion of any other variable in the multivariate model. However, the association between metabolic syndrome and IL-18 is no longer significant when IL-18 is treated as a continuous variable (trend p = 0.087). Our results on HIV patients with lipodystrophy confirm previous findings on a strong independent association between IL-18 and MS in the general population. Further research is needed to clarify the mechanism of this association and its role in the development of cardiovascular disease in HIV patients.
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PMID:Metabolic syndrome and cardiovascular risk in HIV-infected patients with lipodystrophy. 1788 Jul 65


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