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

Regular exercise offers protection against all-cause mortality, primarily by protection against cardiovascular disease and Type 2 diabetes mellitus. The latter disorders have been associated with chronic low-grade systemic inflammation reflected by a two- to threefold elevated level of several cytokines. Adipose tissue contributes to the production of TNF-alpha, which is reflected by elevated levels of soluble TNF-alpha receptors, IL-6, IL-1 receptor antagonist, and C-reactive protein. We suggest that TNF-alpha rather than IL-6 is the driver behind insulin resistance and dyslipidemia and that IL-6 is a marker of the metabolic syndrome, rather than a cause. During exercise, IL-6 is produced by muscle fibers via a TNF-independent pathway. IL-6 stimulates the appearance in the circulation of other anti-inflammatory cytokines such as IL-1ra and IL-10 and inhibits the production of the proinflammatory cytokine TNF-alpha. In addition, IL-6 enhances lipid turnover, stimulating lipolysis as well as fat oxidation. We suggest that regular exercise induces suppression of TNF-alpha and thereby offers protection against TNF-alpha-induced insulin resistance. Recently, IL-6 was introduced as the first myokine, defined as a cytokine that is produced and released by contracting skeletal muscle fibers, exerting its effects in other organs of the body. Here we suggest that myokines may be involved in mediating the health-beneficial effects of exercise and that these in particular are involved in the protection against chronic diseases associated with low-grade inflammation such as diabetes and cardiovascular diseases.
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PMID:The anti-inflammatory effect of exercise. 1577 55

An increasing number of researchers of the metabolic syndrome assume that many mechanisms are involved in its complex pathophysiology such as an increased sympathetic activity, disorders of the hypothalamo-pituitary-adrenal axis, the action of chronic subclinical infections, proinflammatory cytokines, and the effect of adipocytokines or psychoemotional stress. An increasing body of scientific research in this field confirms the role of the neurotrophins and mastocytes in the pathogenesis of inflammatory and immune diseases. Recently it has been proved that neurotrophins and mastocytes have metabotrophic effects and take part in the carbohydrate and lipid metabolism. In the early stage of the metabolic syndrome we established a statistically significant increase in the plasma levels of the nerve growth factor. In the generalized stage the plasma levels of the neutrophines were statistically decreased in comparison to those in the healthy controls. We consider that the neurotrophin deficit is likely to play a significant pathogenic role in the development of the metabolic anthropometric and vascular manifestations of the generalized stage of MetSyn. We suggest a hypothesis for the etiopathogenesis of the metabolic syndrome based on the neuro-immuno-endocrine interactions. The specific pathogenic pathways of MetSyn development include: (1) increased tissue and plasma levels of proinflammatory cytokines Interleukin-1(IL-1), Interleukin-6 (IL-6 ) and tumor necrosis factor - alpha (TNF-alpha) caused by inflammatory and/or emotional distress; (2) increased plasma levels of neurotrophin - nerve growth factor (NGF) caused by the high IL-1, IL-6 and TNFalpha levels; (3) high plasma levels of NGF which enhance activation of: the autonomous nerve system--vegetodystonia (disbalance of neurotransmitters); Neuropeptide Y (NPY)--enhanced feeding, obesity and increased leptin plasma levels; hypothalamo-pituitary-adrenal axis--increased corticotropin-releasing hormone (CRH) and cortisol (hormonal disbalance); immune cells--increased number and degranulation of mastocytes (MC)--immunological disbalance; (4) as a result of 1-3 insulin resistance is exhibited leading to diabetes mellitus. The hypothesis is confirmed by results obtained after 6-month nonsteroid anti-inflammatory treatment of patients with MetSyn. These results are reported in a separate publication.
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PMID:Metabolic syndrome--neurotrophic hypothesis. 1654 15

Atherosclerosis is a long-term chronic inflammatory disease associated with increased concentrations of inflammatory hepatic markers, such as CRP and fibrinogen, and of peripheral origin, such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-6. Peroxisome proliferator-activated receptor (PPAR-)-alpha is a ligand-activated transcription factor that regulates expression of key genes involved in lipid homeostasis and modulates the inflammatory response both in the vascular wall and the liver. PPAR-alpha is activated by natural ligands, such as fatty acids, as well as the lipid-lowering fibrates. PPAR-alpha agonists impact on different steps of atherogenesis: (1) early markers of atherosclerosis, such as vascular wall reactivity, are improved, (2) however, reduced expression of adhesion molecules on the surface of endothelial cells, accompanied by decreased levels of inflammatory cytokines, such as TNF-alpha, IL-1, and IL-6, leads to a decreased leukocyte recruitment into the arterial wall; (3) in later stages of the atherosclerotic process, PPAR-alpha agonists may promote plaque stabilization and reduce cardiovascular events, via effects on metalloproteinases, such as MMP9. Moreover, PPAR-alpha activation by fibrates also impairs proinflammatory cytokine-signaling pathways in the liver resulting in the modulation of the acute phase response reaction via mechanisms independent of changes in lipoprotein levels. Effective coronary artery disease (CAD) prevention requires the use of agents that act beyond low-density lipoprotein cholesterol-lowering. PPAR-alpha agonists appear to comprehensively address some of the abnormalities of the most common clinical phenotypes of the high CAD risk patient of the 21st century such as in the metabolic syndrome and type 2 diabetes: low high-density lipoprotein cholesterol, high triglycerides, small, dense low-density lipoprotein, and a proinflammatory, procoagulant state.
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PMID:Modulation of hepatic inflammatory risk markers of cardiovascular diseases by PPAR-alpha activators: clinical and experimental evidence. 1642 52

The immune and neuroendocrine systems are closely involved in the regulation of metabolism at peripheral and central hypothalamic levels. In both physiological (meals) and pathological (infections, traumas and tumors) conditions immune cells are activated responding with the release of cytokines and other immune mediators (afferent signals). In the hypothalamus (central integration), cytokines influence metabolism by acting on nucleus involved in feeding and homeostasis regulation leading to the acute phase response (efferent signals) aimed to maintain the body integrity. Peripheral administration of cytokines, inoculation of tumor and induction of infection alter, by means of cytokine action, the normal pattern of food intake affecting meal size and meal number suggesting that cytokines acted differentially on specific hypothalamic neurons. The effect of cytokines-related cancer anorexia is also exerted peripherally. Increase plasma concentrations of insulin and free tryptophan and decrease gastric emptying and d-xylose absorption. In addition, in obesity an increase in interleukin (IL)-1 and IL-6 occurs in mesenteric fat tissue, which together with an increase in corticosterone, is associated with hyperglycemia, dyslipidemias and insulin resistance of obesity-related metabolic syndrome. These changes in circulating nutrients and hormones are sensed by hypothalamic neurons that influence food intake and metabolism. In anorectic tumor-bearing rats, we detected upregulation of IL-1beta and IL-1 receptor mRNA levels in the hypothalamus, a negative correlation between IL-1 concentration in cerebro-spinal fluid and food intake and high levels of hypothalamic serotonin, and these differences disappeared after tumor removal. Moreover, there is an interaction between serotonin and IL-1 in the development of cancer anorexia as well as an increase in hypothalamic dopamine and serotonin production. Immunohistochemical studies have shown a decrease in neuropeptide Y (NPY) and dopamine (DA) and an increase in serotonin concentration in tumor-bearing rats, in first- and second-order hypothalamic nuclei, while tumor resection reverted these changes and normalized food intake, suggesting negative regulation of NPY and DA systems by cytokines during anorexia, probably mediated by serotonin that appears to play a pivotal role in the regulation of food intake in cancer. Among the different forms of therapy, nutritional manipulation of diet in tumor-bearing state has been investigated. Supplementation of tumor bearing rats with omega-3 fatty acid vs. control diet delayed the appearance of tumor, reduced tumor-growth rate and volume, negated onset of anorexia, increased body weight, decreased cytokines production and increased expression of NPY and decreased alpha-melanocyte-stimulating hormone (alpha-MSH) in hypothalamic nuclei. These data suggest that omega-3 fatty acid suppressed pro-inflammatory cytokines production and improved food intake by normalizing hypothalamic food intake-related peptides and point to the possibility of a therapeutic use of these fatty acids. The sum of these data support the concept that immune cell-derived cytokines are closely related with the regulation of metabolism and have both central and peripheral actions, inducing anorexia via hypothalamic anorectic factors, including serotonin and dopamine, and inhibiting NPY leading to a reduction in food intake and body weight, emphasizing the interconnection of the immune and neuroendocrine systems in regulating metabolism during infectious process, cachexia and obesity.
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PMID:Hypothalamic integration of immune function and metabolism. 1687 87

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

Gout is caused by the deposition of monosodium urate crystals (MSU) in tissue and provokes a local inflammatory reaction. It is the most common form of inflammatory arthritis in the elderly. The formation of MSU crystals is facilitated by hyperuricemia. In the last two decades, both hyperuricemia and gout have increased markedly and similar trends in the epidemiology of the metabolic syndrome have been observed. Recent studies provide new insights into uric acid metabolism in the kidneys as well as possible links between hyperuricemia and hypertension. MSU crystals provoke inflammation by activating leukocytes to produce inflammatory cytokines and other inflammatory mediators. The uptake of MSU crystals by monocytes involves interactions with Toll-like receptors (TLR-2 and TLR-4) and CD14, components of the innate immune system. Intracellularly, MSU crystals activate inflammasomes to activate pro-IL-1 (interleukin 1) processing to yield mature IL-1beta. The inflammatory effects of MSU are IL-1-dependent and can be blocked by IL-1 inhibitors. These advances provide new therapeutic targets to treat hyperuricemia and gout.
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PMID:[New knowledge on the pathophysiology and therapy of gout]. 1792 25

Inflammation is associated with obesity, the metabolic syndrome, and diabetes. No data are available on the effect of weight reduction on the gene expression of cytokines in immune cells in obesity and the metabolic syndrome. We assessed how long-term weight loss affects expression of cytokines in peripheral blood mononuclear cells (PBMCs) in individuals with impaired glucose metabolism and the metabolic syndrome. Data from 34 subjects randomized to either a weight reduction or a control group for a 33-week period were analyzed. The messenger RNA (mRNA) expression of interleukins (ILs) in PBMCs was measured using real-time polymerase chain reaction. Measures of insulin and glucose metabolism (intravenous and oral glucose tolerance tests), body composition, and circulating adipokines and inflammatory markers were also assessed. Weight reduction resulted in a decrease in the mRNA expression of IL-1beta (IL1B), IL-1 receptor antagonist, and tumor necrosis factor alpha (P < .001) and an increase in expression of IL-6 (IL6) and IL-8 (P < .01). The increase in IL6 expression was associated with a decrease in fasting glycemia (r = -0.53, P < .01). Interestingly, the decrease in IL1B expression was correlated with an increase in insulin sensitivity index (r = -0.68, P < .01). In general, a decrease in circulating levels of adipokines and inflammatory markers was also observed after weight loss. Weight loss altered gene expression of cytokines related to inflammation and the immune response in PBMCs. Changes in IL6 mRNA expression were associated with changes in fasting glycemia. The decrease in IL-1 receptor antagonist expression after weight loss and the strong correlation between the decrease in IL1B expression and the increase in insulin sensitivity suggest a contribution of these genes to insulin-resistant states found in obesity and the metabolic syndrome.
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PMID:Effect of weight loss on cytokine messenger RNA expression in peripheral blood mononuclear cells of obese subjects with the metabolic syndrome. 1819 Oct 48

Metabolic syndrome (MetS) is associated with increased incidence of diabetes and cardiovascular disease (CVD). Prospective clinical trials with alpha-tocopherol (AT) have not yielded positive results. Because AT supplementation decreases circulating gamma-tocopherol (GT), we evaluated supplementation with GT (800 mg/day), AT (800 mg/day), the combination or placebo for 6 weeks alone AT and GT concentrations, biomarkers of oxidative stress, and inflammation in subjects with MetS (n=20/group). Plasma AT and GT levels increased following supplementation with AT alone or GT alone or in combination. AT supplementation significantly decreased GT levels. Urinary alpha- and gamma-CEHC, metabolites of the respective Ts, also increased correspondingly, i.e., alpha-CEHC with AT and gamma-CEHC with GT supplementation, compared to placebo. HsCRP levels significantly decreased in the combined AT+GT group. LPS-activated whole blood release of IL-1 and IL-6 did not change. There was a significant decrease in TNF with AT alone or in combination with GT. Plasma MDA/HNE and lipid peroxides were significantly decreased with AT, GT, or in combination. Nitrotyrosine levels were significantly decreased only with GT or GT+AT but not with AT compared to placebo. Thus, the combination of AT and GT supplementation appears to be superior to either supplementation alone on biomarkers of oxidative stress and inflammation and needs to be tested in prospective clinical trials to elucidate its utility in CVD prevention.
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PMID:Gamma-tocopherol supplementation alone and in combination with alpha-tocopherol alters biomarkers of oxidative stress and inflammation in subjects with metabolic syndrome. 1819 45

Gout is the most common form of inflammatory arthritis in the elderly. In the last two decades, both hyperuricemia and gout have increased markedly and similar trends in the epidemiology of the metabolic syndrome have been observed. Recent studies provide new insights into the transporters that handle uric acid in the kidney as well as possible links between these transporters, hyperuricemia, and hypertension. The treatment of established hyperuricemia has also seen new developments. Febuxostat and PEG-uricase are two novel treatments that have been evaluated and shown to be highly effective in the management of hyperuricemia, thus enlarging the therapeutic options available to lower uric acid levels. Monosodium urate (MSU) crystals are potent inducers of inflammation. Within the joint, they trigger a local inflammatory reaction, neutrophil recruitment, and the production of pro-inflammatory cytokines as well as other inflammatory mediators. Experimentally, the uptake of MSU crystals by monocytes involves interactions with components of the innate immune system, namely Toll-like receptor (TLR)-2, TLR-4, and CD14. Intracellularly, MSU crystals activate multiple processes that lead to the formation of the NALP-3 (NACHT, LRR, and pyrin domain-containing-3) inflammasome complex that in turn processes pro-interleukin (IL)-1 to yield mature IL-1 beta, which is then secreted. The inflammatory effects of MSU are IL-1-dependent and can be blocked by IL-1 inhibitors. These advances in the understanding of hyperuricemia and gout provide new therapeutic targets for the future.
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PMID:Developments in the scientific and clinical understanding of gout. 1894 74

Consumption of a high-fat diet (HFD) is associated with white adipose tissue (WAT) inflammation, which contributes to key components of the metabolic syndrome, including insulin resistance (IR) and hepatic steatosis (HS). To determine the differential effects of exercise training (EX), low-fat diet (LFD), and their combination on WAT inflammation, Balb/cByJ male mice (n=34) were fed an HFD for 12 wks before they were randomized into one of four intervention groups: HFD-EX, LFD-EX, HFD-sedentary (SED), or LFD-SED. EX mice performed 12 wks of exercise training on a motorized treadmill (1h/d, 5d/wk, 12 m/min, 5% grade, approximately 65% VO(2) max), while SED mice remained sedentary in their home cages. WAT gene expression of adipokines was assessed using rt-PCR. IR was measured using HOMA-IR, and HS via hepatic triglyceride content. EX significantly reduced (53%) WAT gene expression of MCP-1, and LFD significantly reduced (50%) WAT gene expression of the macrophage specific marker, F4/80 as well as the adipocytokine IL-1 ra (25%). EX independently improved IR, while both EX and LFD improved HS. These findings suggest that both diet and exercise have unique beneficial effects on WAT inflammatory markers and the mechanism by which each treatment improves metabolic complications associated with chronic consumption of an HFD may be different.
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PMID:Effects of diet and exercise on metabolic disturbances in high-fat diet-fed mice. 1936 52


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