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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inflammation plays a key role in the pathogenesis of a number of chronic inflammatory systemic diseases (CISDs), including psoriasis, rheumatoid arthritis, systemic lupus erythematosus and Crohn's disease, and also in the pathogenesis of atherosclerosis. CISDs and cardiovascular diseases, such as atherosclerosis, share common pathogenic features, and cardiovascular disease is an important cause of morbidity and mortality in patients with CISDs. Activated inflammatory cells and pro-inflammatory cytokines contribute to the development of psoriatic lesions and play an important role in the breakdown of atherosclerotic plaques. Psoriasis and atherosclerosis also have similar histological characteristics involving T cells, macrophages and monocytes. In particular, the extravasation of T cells through the epithelium is characteristic of both psoriatic and atherosclerotic plaques. Cardiovascular disease is an important cause of morbidity and mortality in patients with psoriasis, which is associated with an increased cardiovascular risk profile compared with the general population. Patients with psoriasis are at increased risk of arterial hypertension, coronary heart disease, hyperlipidaemia, obesity and type II diabetes, which are more prevalent than in control patients. This increased risk could be due to the effects of chronic inflammatory changes, particularly the infiltration of T cells and subsequent secretion of pro-inflammatory cytokines. Some drugs used in the treatment of cardiovascular disease, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and angiotensin-converting enzyme inhibitors have anti-inflammatory activity. In addition, systemic treatments for psoriasis may, by decreasing inflammation, reduce the risk of cardiovascular disease. It is suggested, therefore, that an integrated approach to the treatment of the inflammatory processes underlying both psoriasis and atherosclerosis may be beneficial in reducing cardiovascular risk in patients with psoriasis. The newer targeted biological therapies, such as efalizumab and infliximab, which offer the potential for long-term disease control in psoriasis, may be of particular use in this setting.
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PMID:Inflammation in atherosclerosis and psoriasis: common pathogenic mechanisms and the potential for an integrated treatment approach. 1870 Sep 10

Visceral (intra-abdominal) obesity is associated with a cluster of cardiovascular risk factors that together promote macrovascular and microvascular disease. An atherogenic dyslipidemia, characterized by an increase in serum triglyceride-rich lipoproteins, a decrease in plasma levels of high-density lipoprotein cholesterol and increased prevalence of small, dense low-density lipoprotein particles (although low-density lipoprotein cholesterol levels are normal or only modestly elevated), as well as chronic inflammation, play key roles in the pathogenesis of visceral obesity-related complication. These abnormalities may be consequent to a global metabolic effect of insulin resistance. Pharmacological treatments, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, fibric acid derivatives, insulin sensitizers and cannabinoid receptor type 1 blockers, are often required to correct the dyslipidemia of visceral obesity. The basis for a multiple approach to correcting dyslipoproteinemia in visceral obesity and the metabolic syndrome relies on understanding the mechanisms of action of the individual therapeutic components.
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PMID:[Dyslipidemia in visceral obesity: pathophysiological mechanisms, clinical implications and therapy]. 1877 49

Atherosclerosis develops over the course of 50 years, beginning in the early teenage years. The causes of this process appear to be lipid retention, oxidation, and modification, which provoke chronic inflammation at susceptible sites in the walls of all major conduit arteries. Initial fatty streaks evolve into fibrous plaques, some of which develop into forms that are vulnerable to rupture, causing thrombosis or stenosis. Erosion of the surfaces of some plaques and rupture of a plaque's calcific nodule into the artery lumen also may trigger thrombosis. The process of plaque development is the same regardless of race/ethnicity, sex, or geographic location, apparently worldwide. However, the rate of development is faster in patients with risk factors such as hypertension, tobacco smoking, diabetes mellitus, obesity, and genetic predisposition. Clinical trial data demonstrate that treatment with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) favorably alters plaque size, cellular composition, chemical composition, and biological activities centered on inflammation and cholesterol metabolism, as well as the risk of clinical events due to atherosclerosis. Even with advanced atherosclerosis, statins begin to improve clinical risk within 4 months. During long-term follow-up in clinical trials for up to 11 years with or without further treatment, clinical benefit remains significant, indicating the durability of treatment-induced changes in the development of plaque. Thus, atherosclerosis, a disease heretofore viewed as inevitably progressive, can be treated to significantly alter arterial lesions and reduce their clinical consequences.
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PMID:The pathology of atherosclerosis: plaque development and plaque responses to medical treatment. 1911 86

The aim of this study was to investigate the metabolic effects of a dietary supplement of powdered rose hip to C57BL/6J mice fed a high-fat diet (HFD). Two different study protocols were used; rose hip was fed together with HFD to lean mice for 20 wk (prevention study) and to obese mice for 10 wk (intervention study). Parameters related to obesity and glucose tolerance were monitored, and livers were examined for lipids and expression of genes and proteins related to lipid metabolism and gluconeogenesis. A supplement of rose hip was capable of both preventing and reversing the increase in body weight and body fat mass imposed by a HFD in the C57BL/6J mouse. Oral and intravenous glucose tolerance tests together with lower basal levels of insulin and glucose showed improved glucose tolerance in mice fed a supplement of rose hip compared with control mice. Hepatic lipid accumulation was reduced in mice fed rose hip compared with control, and the expression of lipogenic proteins was downregulated, whereas AMP-activated protein kinase and other proteins involved in fatty acid oxidation were unaltered. Rose hip intake lowered total plasma cholesterol as well as the low-density lipoprotein-to-high-density lipoprotein ratio via a mechanism not involving altered gene expression of sterol regulatory element-binding protein 2 or 3-hydroxymethylglutaryl-CoA reductase. Taken together, these data show that a dietary supplement of rose hip prevents the development of a diabetic state in the C57BL/6J mouse and that downregulation of the hepatic lipogenic program appears to be at least one mechanism underlying the antidiabetic effect of rose hip.
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PMID:Rose hip exerts antidiabetic effects via a mechanism involving downregulation of the hepatic lipogenic program. 2095 31

Reciprocal relationships between endothelial dysfunction and insulin resistance suggest that therapies improving endothelial dysfunction will simultaneously improve insulin sensitivity and other metabolic parameters. However, previous studies with some statins either did not alter insulin sensitivity or promoted insulin resistance despite significant improvements in endothelial dysfunction and decreases in circulating pro-inflammatory markers. This may be due to pleiotropic or off-target effects of some statins to cause insulin resistance by diverse mechanisms unrelated to endothelial dysfunction. Indeed, there is evidence of other differential metabolic actions of distinct statins including effects on hydroxymethylglutaryl-CoA reductase inhibition, isoprotenoid synthesis, calcium release, glucose transport, insulin secretion, and/or insulin resistance. Pravastatin increases expression of adiponectin mRNA, enhances adiponectin secretion, increases plasma levels of adiponectin, and enhances insulin sensitivity in mice and humans. Clinical studies including large scale randomized controlled trials demonstrate potential differences between individual statins, with pravastatin promoting risk reduction for new onset of diabetes. Conversely, other statins including atorvastatin, rosuvastatin, and simvastatin all promote significant increase in this risk. Given the frequent concordance of metabolic diseases including diabetes, obesity, and metabolic syndrome with cardiovascular diseases associated with hyperlipidemia, it is important to understand the potential metabolic risks and benefits of therapies with distinct statins. In this review, we discuss these differential effects of statins on metabolic homeostasis and insulin sensitivity.
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PMID:Differential metabolic effects of distinct statins. 2113 Apr 54

The early lesions of atherosclerosis begin in childhood and are related to antecedent cardiovascular disease (CVD) risk factors. Environmental and genetic factors (eg, diet, obesity, exercise, and certain inherited dyslipidemias) influence progression of such lesions. Identification of youth at risk for atherosclerosis includes an integrated assessment of these predisposing factors. Treatment starts with a diet low in total and saturated fat and cholesterol, use of water-soluble fiber, plant stanols and plant sterols, weight control, and exercise. Drug therapy, for example, with inhibitors of hydroxymethylglutaryl-CoA reductase, bile acid sequestrants, and cholesterol absorption inhibitors, can be considered in those with a positive family history of premature CVD and low-density lipoprotein cholesterol >160 mg/dL after dietary and hygienic measures. Candidates for drug therapy often include those with familial hypercholesterolemia, familial combined hyperlipidemia, the metabolic syndrome, polycystic ovarian syndrome, type 1 diabetes, and the nephrotic syndrome. Such dietary and drug therapy appears safe and efficacious. Early identification and treatment of youth with CVD risk factors and dyslipidemia are likely to retard the atherosclerotic process. Optimal detection and treatment of high-risk children either from the general population or from families with premature CVD will require a comprehensive universal screening and evaluation program.
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PMID:Clinical and laboratory assessment of cardiovascular risk in children: Guidelines for screening, evaluation, and treatment. 2129 41

Obesity is known to be associated with a number of effects on skin physiology. KKA(y) obese mouse is a model of type 2 diabetes characterized by systemic oxidative stress because of severe obesity, hypertriglyceridaemia, hyperglycaemia and hyperinsulinaemia. We investigated lipid peroxidation and vascular endothelial growth factor (VEGF) expression in the skin of KKA(y) obese mice. We also investigated the effect of lipid peroxidation derivatives on VEGF production and proliferation in human epidermal keratinocyte cell line (HaCaT). The lipid peroxidation level in the mouse skin tissue was determined by measuring the levels of thiobarbituric acid-reactive substances. The levels of VEGF expression, p44/p42 mitogen-activated protein kinase (MAPK) activation and CD36 expression were analysed by Western blot. Their localization was examined by immunofluorescence. For the in vitro experiments, an enzyme-linked immunosorbent assay was utilized to measure VEGF secretion in the medium. In vitro experiments demonstrated that lipid peroxidation derivatives increased VEGF production in HaCaT cells, which was blocked by a p44/p42 MAPK inhibitor and anti-CD36 antibody. We observed increased levels of lipid peroxidation derivatives, p44/p42 MAPK activation and VEGF expression in the skin of KKA(y) obese mice. Notably, pitavastatin, an inhibitor of competitive 3-hydroxy-3-methylglutaryl coenzyme A reductase, suppressed all of these processes. Our results suggest that lipid peroxidation induces VEGF expression via CD36 and p44/p42 MAPK pathway in the skin of obese mice.
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PMID:Lipid peroxidation-induced VEGF expression in the skin of KKAy obese mice. 2135 88

Many biological activities of green tea have been attributed to a major constituent, (minus;)-epigallocatechin gallate (EGCG). We previously reported that EGCG and an EGCG-free fraction derived from green tea modulated the gene expression of gluconeogenic enzymes, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, in the mouse liver. EGCG is also known to affect the gene expression of enzymes related to lipid metabolism. However, it remains to be examined whether or not a constituent other than EGCG contributes to the change in gene expression of these enzymes. In this study, we prepared an EGCG-free water-soluble fraction (GT-W), and examined its effects on the hepatic gene expression of lipogenic enzymes in mice. The results of quantitative real-time PCR assays indicated that the dietary administration of GT-W for 4 weeks reduced the hepatic gene expression of lipogenic enzymes: fatty acid synthase, hydroxymethylglutaryl coenzyme A reductase, and acetyl-coenzyme A carboxylase alpha. Also, the gene expression of sterol regulatory element-binding transcription factor (Srebf)1 and/or Srebf2 was reduced, suggesting that the reduction of Srebfs contributed to the down-regulation of the lipogenic enzymes, since these transcription factors bind the promoter region to enhance their expression. The plasma levels of triglycerides and cholesterol were reduced with statistical significance in the group given a diet containing GT-W. These results suggest that in addition to EGCG, green tea contains some component(s) which may help to prevent arteriosclerosis and obesity.
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PMID:Effects of a catechin-free fraction derived from green tea on gene expression of enzymes related to lipid metabolism in the mouse liver. 2236 81

The protective effects of Houttuynia cordata aqueous extract (HCAE) in mice consuming a high saturated fat diet (HFD) were examined. HCAE, at 0.5, 1, or 2%, was supplied in drinking water for 8 weeks. HCAE was rich in phenolic acids and flavonoids. HCAE intake at 1 and 2% decreased body weight, epididymal fat, insulin resistance, triglyceride and total cholesterol contents in plasma and liver from HFD-treated mice (p < 0.05). HFD enhanced hepatic activity of malic enzyme, fatty acid synthase (FAS) and 3-hydroxy-3-methylglutaryl coenzyme A reductase; and augmented the hepatic level of saturated fatty acids (p < 0.05). HCAE intake at 2% reduced malic enzyme and FAS activities, and lowered saturated fatty acids content in liver (p < 0.05). HCAE suppressed HFD induced oxidative and inflammatory stress in the heart and liver via reducing the malondialdehyde level, retaining glutathione content and glutathione peroxidase activity, decreasing tumor necrosis factor-alpha, interleukin (IL)-1beta and IL-6 production (p < 0.05). These results support that Houttuynia cordata is a potent food against HFD induced obesity, and oxidative and inflammatory injury.
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PMID:Protective effects of Houttuynia cordata aqueous extract in mice consuming a high saturated fat diet. 2316 92

The liver plays a central role in regulating cholesterol homeostasis. High fat diets have been shown to induce obesity and hyperlipidemia. Despite considerable advances in our understanding of cholesterol metabolism, the regulation of liver cholesterol biosynthesis in response to high fat diet feeding has not been fully addressed. The aim of the present study was to investigate mechanisms by which a high fat diet caused activation of liver 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) leading to increased cholesterol biosynthesis. Mice were fed a high fat diet (60% kcal fat) for 5weeks. High fat diet feeding induced weight gain and elevated lipid levels (total cholesterol and triglyceride) in both the liver and serum. Despite cholesterol accumulation in the liver, there was a significant increase in hepatic HMG-CoA reductase mRNA and protein expression as well as enzyme activity. The DNA binding activity of sterol regulatory element binding protein (SREBP)-2 and specific protein 1 (Sp1) were also increased in the liver of mice fed a high fat diet. To validate the in vivo findings, HepG2 cells were treated with palmitic acid. Such a treatment activated SREBP-2 as well as increased the mRNA and enzyme activity of HMG-CoA reductase leading to intracellular cholesterol accumulation. Inhibition of Sp1 by siRNA transfection abolished palmitic acid-induced SREBP-2 and HMG-CoA reductase mRNA expression. These results suggest that Sp1-mediated SREBP-2 activation contributes to high fat diet induced HMG-CoA reductase activation and increased cholesterol biosynthesis. This may play a role in liver cholesterol accumulation and hypercholesterolemia.
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PMID:Activation of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase during high fat diet feeding. 2365 31


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