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

The metabolic syndrome is a cluster of cardiovascular risk factors, and visceral adiposity is a central component that is also strongly associated with insulin resistance. Both visceral obesity and insulin resistance are important risk factors for the development of type 2 diabetes. It is likely that adipose tissue, particularly in the intra-abdominal depot, is part of a complex interplay involving several tissues and that dysregulated hormonal, metabolic and neural signalling within and between organs can trigger development of metabolic disease. One attractive hypothesis is that many factors leading to insulin resistance are mediated via the generation of abnormal amounts of reactive oxygen species (ROS). There is much evidence supporting that detrimental effects of glucose, fatty acids, hormones and cytokines leading to insulin resistance can be exerted via such a common pathway. This review paper mainly focuses on metabolic and other 'stress' factors that affect insulin's target cells, in particular adipocytes, and it will highlight oxidative stress as a potential unifying mechanism by which these stress factors promote insulin resistance and the development and progression of type 2 diabetes.
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PMID:Metabolic stress in insulin's target cells leads to ROS accumulation - a hypothetical common pathway causing insulin resistance. 1762 46

We examined the effect of exercise on postprandial hypertriglyceridemia (PHTG) and insulin resistance in individuals with metabolic syndrome. Subjects were 10 hypertriglyceridemic men with insulin resistance [age = 35.0 +/- 1.8 yr, body weight = 90.7 +/- 3.3 kg, fasting triglyceride (TG) = 2.6 +/- 0.4 mmol/l, peak oxygen consumption ((.)Vo(2peak)) = 36.0 +/- 1.3 ml(-1).kg(-1).min(-1), and homeostatic model assessment of insulin resistance (HOMA-IR)= 3.1 +/- 0.3]. Each participant performed a control trial (Ctr; no exercise) and three exercise trials at 60% of their (.)Vo(2peak) for 30 min (30 min-Ex), 45 min (45 min-Ex) and 60 min (60 min-Ex). All subjects had a fat meal in each trial. In the exercise trials, the subject jogged on a treadmill for a designated duration of 12 h before ingestion of a fat meal. Blood samples were taken at 0 h (before the meal) and at 2, 4, 6, and 8 h after the meal. The plasma TG, area score under TG concentration curve over an 8-h period (TG AUC) after the meal, and HOMA-IR were analyzed. The TG AUC scores in both the 45 min-Ex and 60 min-Ex were 31 and 33% lower, respectively, than Ctr (P < 0.02). There were no significant differences in TG AUC scores between the 30 min-Ex and the Ctr (P > 0.05). There were no trial differences in the fasting plasma glucose concentration (P > 0.05). HOMA-IR values in the 30 min-Ex, 45 min-Ex, and 60 min-Ex trials were lower than the Ctr (P < 0.03), but no significant differences were found in HOMA-IR among the exercise trials. The results suggest that for physically inactive individuals with metabolic syndrome, exercising at moderate intensity for 45 min effectively attenuates PHTG while exercise for 30 min is sufficient to improve insulin action.
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PMID:Effect of exercise duration on postprandial hypertriglyceridemia in men with metabolic syndrome. 1764 Dec 15

The mechanisms of reduced cardiorespiratory fitness (CF) in renal transplant recipients (RTR) have not been studied closely. This study evaluated the relationships between CF and specific cardiovascular risk factors (metabolic syndrome [MS], physical inactivity, myocardial ischemia, and atherosclerotic burden) in glucose-intolerant RTR. Data were recorded on 71 glucose-intolerant RTR (mean age 55 yr; 55% male; median transplant duration 5.7 yr). MS was defined using National Cholesterol Education Programme Adult Treatment Panel III criteria. Resting and exercise stress echocardiography were performed, and myocardial ischemia was identified by new or worsening wall motion abnormalities. Cardiorespiratory fitness was determined using peak oxygen uptake (VO(2)) by expired gas analysis. Atherosclerotic burden was assessed by carotid intima-media thickness (IMT). Mean peak VO(2) was 19 +/- 7 ml/kg per min and was significantly lower than predicted peak VO(2) (29 +/- 6 ml/kg per min; P < 0.001). Patients with MS (63%) had reduced CF (17 +/- 6 versus 22 +/- 8 ml/kg per min; P = 0.001) and were more likely to be physically inactive (76 versus 48%; P = 0.02). CF was reduced in 14 patients with myocardial ischemia (15 +/- 3 versus 20 +/- 7 ml/kg per min; P = 0.05). CF was positively correlated with male gender, height, and physical activity and inversely correlated with number of MS risk factors and IMT (adjusted R(2) = 0.66). Carotid IMT added incremental value to clinical variables in determining VO(2) (adjusted R(2) = 0.65 versus 0.63; P = 0.04). Reduced CF is associated with physical inactivity, MS, and atherosclerotic burden in glucose-intolerant RTR. Further studies should address whether increasing exercise and modifying MS risk factors improve CF in RTR.
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PMID:Cardiorespiratory fitness is related to physical inactivity, metabolic risk factors, and atherosclerotic burden in glucose-intolerant renal transplant recipients. 1769 59

Mitochondria are energy-producing organelles that conduct other key cellular tasks. Thus, mitochondrial damage may impair various aspects of tissue functioning. Mitochondria generate oxygen- and nitrogen-derived oxidants, being themselves major oxidation targets. Dysfunctional mitochondria seem to contribute to the pathophysiology of hypertension, cardiac failure, the metabolic syndrome, obesity, diabetes mellitus, renal disease, atherosclerosis, and aging. Mitochondrial proteins and metabolic intermediates participate in various cellular processes, apart from their well-known roles in energy metabolism. This emphasizes the participation of dysfunctional mitochondria in disease, notwithstanding that most evidences supporting this concept come from animal and cultured-cell studies. Mitochondrial oxidant production is altered by several factors related to vascular pathophysiology. Among these, angiotensin-II stimulates mitochondrial oxidant release leading to energy metabolism depression. By lowering mitochondrial oxidant production, angiotensin-II inhibition enhances energy production and protects mitochondrial structure. This seems to be one of the mechanisms underlying the benefits of angiotensin-II inhibition in hypertension, diabetes, and aging rodent models. If some of these findings can be reproduced in humans, they would provide a new perspective on the implications that RAS-blockade can offer as a therapeutic strategy. This review intends to present available information pointing to mitochondria as targets for therapeutic Ang-II blockade in human renal and CV disease.
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PMID:From mitochondria to disease: role of the renin-angiotensin system. 1778 64

Although the biochemical steps linking insulin resistance with the metabolic syndrome have not been completely clarified, mounting experimental and clinical evidence indicate oxidative stress as an attractive candidate for a central pathogenic role since it potentially explains the appearance of all risk factors and supports the clinical manifestations. In fact, metabolic syndrome patients exhibit activation of biochemical pathways leading to increased delivery of reactive oxygen species, decreased antioxidant protection and increased lipid peroxidation. The described associations between increased abdominal fat storage, liver steatosis and systemic oxidative stress, the diminished concentration of nitric oxide derivatives and antioxidant vitamins and the endothelial oxidative damages observed in subjects with the metabolic syndrome definitively support oxidative stress as the common second-level event in a unifying pathogenic view. Moreover, it has been observed that oxidative stress regulates the expression of genes governing lipid and glucose metabolism through activation or inhibition of intracellular sensors. Diet constituents can modulate redox reactions and the oxidative stress extent, thus also acting on nuclear gene expression. As a consequence of the food-gene interaction, metabolic syndrome patients may express different disease features and extents according to the different pathways activated by oxidative stress-modulated effectors. This view could also explain family differences and interethnic variations in determining risk factor appearance. This review mechanistically focused on oxidative stress events leading to individual disease factor appearance in metabolic syndrome patients and their setting for a more helpful clinical approach.
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PMID:Oxidative stress-induced risk factors associated with the metabolic syndrome: a unifying hypothesis. 1785 68

The metabolic syndrome (MetS) phenotype is typically characterized by visceral obesity, insulin resistance, atherogenic dyslipidemia involving hypertriglyceridemia and subnormal levels of high density lipoprotein-cholesterol (HDL-C), oxidative stress and elevated cardiovascular risk. The potent antioxidative activity of small HDL3 is defective in MetS [Hansel B, et al. J Clin Endocrinol Metab 2004;89:4963-71]. We evaluated the functional capacity of small HDL3 particles from MetS subjects to protect endothelial cells from apoptosis induced by mildly oxidized low-density lipoprotein (oxLDL). MetS subjects presented an insulin-resistant obese phenotype, with hypertriglyceridemia, elevated apolipoprotein B and insulin levels, but subnormal HDL-C concentrations and chronic low grade inflammation (threefold elevation of C-reactive protein). When human microvascular endothelial cells (HMEC-1) were incubated with oxLDL (200 microg apolipoprotein B/ml) in the presence or absence of control HDL subfractions (25 microg protein/ml), small, dense HDL3b and 3c significantly inhibited cellular annexin V binding and intracellular generation of reactive oxygen species. The potent anti-apoptotic activity of small HDL3c particles was reduced (-35%; p<0.05) in MetS subjects (n=16) relative to normolipidemic controls (n=7). The attenuated anti-apoptotic activity of HDL3c correlated with abdominal obesity, atherogenic dyslipidemia and systemic oxidative stress (p<0.05), and was intimately associated with altered physicochemical properties of apolipoprotein A-I (apoA-I)-poor HDL3c, involving core cholesteryl ester depletion and triglyceride enrichment. We conclude that in MetS, apoA-I-poor, small, dense HDL3c exert defective protection of endothelial cells from oxLDL-induced apoptosis, potentially reflecting functional anomalies intimately associated with abnormal neutral lipid core content.
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PMID:Metabolic syndrome features small, apolipoprotein A-I-poor, triglyceride-rich HDL3 particles with defective anti-apoptotic activity. 1786 79

Metabolic syndrome is common in the general population, but there is little information available on the underlying signaling mechanisms regulating triglyceride (TG) content in the body. In the current study, we have uncovered a role for protein kinase Cbeta (PKCbeta) in TG homeostasis by studying the consequences of a targeted disruption of this kinase. PKCbeta(-/-) mutant mice were considerably leaner and the size of white fat depots was markedly decreased compared with wild-type littermates. TG content in the liver and skeletal muscle of PKCbeta(-/-) mice was also significantly low. Interestingly, mutant animals were hyperphagic and exhibited higher food intake and reduced feed efficiency versus wild type. The protection from obesity involves elevated oxygen consumption/energy expenditure and increased fatty acid oxidation in adipose tissue with concurrent increased mitochondria genesis, up-regulation of PGC-1alpha and UCP-2, and down-regulation of perilipin. The ability of PKCbeta deficiency to promote fat burning in adipocytes may suggest novel therapeutic strategies for obesity and obesity-related disorders.
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PMID:Protein kinase C deficiency increases fatty acid oxidation and reduces fat storage. 1796 98

We evaluated the linkage between oxygen uptake at the ventilatory threshold (VT) and muscle strength in subjects with and without metabolic syndrome. We used data of 226 Japanese men with metabolic syndrome and 265 Japanese men without the syndrome. Metabolic syndrome has recently been defined by a new criterion in Japan. Oxygen uptake at VT and muscle strength, i.e. grip strength and leg strength were measured. Oxygen uptake at VT and muscle strength/body weight were found to be significantly lower in subjects with metabolic syndrome than in those without the syndrome. However, the differences did not reach significant levels after adjusting for leg strength/body weight or oxygen uptake at VT. A combination of aerobic exercise and resistance training might be considered for preventing and improving metabolic syndrome.
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PMID:Linkage between oxygen uptake at ventilatory threshold and muscle strength in subjects with and without metabolic syndrome. 1797 42

Insulin Resistance along with endothelial dysfunction give rise to a constellation of syndromes designated as IRS/MBS metabolic syndrome. Endothelial dysfunction starts early in life much before the development of structural atherosclerosis. Recent insights into vascular biology enable us to understand the molecular mechanisms underlying endothelial dysfunction, and the scope and need for prevention of "pre-clinical" coronary atherosclerosis through lifestyle modification; diet, exercise and stress management. Diminished production of nitric oxide (NO) and/or increased inactivation of NO through oxidative stress (reactive oxygen species ROS and reactive nitrogen species (RNS) are the basis of endothelial dysfunction hence increasing the bioavailability of NO and decreasing its inactivation is the aim of prevention and reversal of endothelial dysfunction. Insulin regulates constitutive NOS gene expression in endothelial cells in vivo; vasodilation is an important component of Insulin-stimulated whole body glucose uptake. Successful strategies are: PPAR alpha and gamma agonists which increase NO production in endothelium; anti-oxidants such as vit. E and C; supplementation with L-arginine, tetrahydrobiopterin-BH4 or sepiapterin (precursor of BH4), SOD mimetic tempol, statins which apart from lowering cholesterol improve NO production, selective beta1 adrenoreceptor antagonists such as nebivolol; suppression of angiotensin-mediated endothelin production by ACE inhibitors and ATR blockers; CB1 receptor blockers, PKCb inhibitors, nitric oxide donors (glyceryl trinitrate and isosorbide dinitrate), dietary supplements of EPA/DHA and regular physical exercise and control of mental stress.
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PMID:Causation, prevention and reversal of vascular endothelial dysfunction. 1805 38

Oxidative stress is a continuous level of oxidative damage in animal cells, which is caused by an overabundance of reactive oxygen species or a decline in antioxidant ability against them. Oxidative stress increases with individual risk factors of atherosclerosis such as obesity, hypertension, hyperlipidemia, diabetes and smoking. Thus, oxidative stress is considered to play a key role in the pathogenesis of atherosclerosis. This review discusses the relationship between oxidative stress and atherosclerosis based on findings from our research group. We have found that atherosclerotic lesions are formed in the aorta of mice fed a high-cholesterol and high-linoleic diet, in parallel with elevated serum lipid peroxide levels. This model is useful for primary screening of antiatherosclerotic agents with antioxidative activity. One notable factor in the development of atherosclerosis is oxidized low-density lipoprotein (OxLDL). In order to examine OxLDL levels in blood, we have developed anion-exchange HPLC methods using stepwise elution. Using these methods, we have found that OxLDL markedly increases in a rat model of metabolic syndrome, in animals exposed to cigarette smoke and in smokers in parallel with other oxidative stress markers. These oxidative stress markers have been attenuated by administration of several antioxidants. In addition, we have found that smoking accelerates atherogenesis in the aorta of apoE-deficient mice and this acceleration can be ameliorated by administration of vitamin E. These observations suggest that antioxidant supplementation may be an effective therapeutic strategy for metabolic syndrome and smoking-induced diseases in which elevated oxidative stress plays a pivotal role.
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PMID:[Oxidative stress and atherosclerosis]. 1805 88


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