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

Peroxisome proliferator-activated receptors (PPARs) have been implicated in metabolic diseases, such as obesity, diabetes, and atherosclerosis, due to their activity in liver and adipose tissue on genes involved in lipid and glucose homeostasis. Here, we show that the PPARalpha and PPARgamma forms are expressed in differentiated human monocyte-derived macrophages, which participate in inflammation control and atherosclerotic plaque formation. Whereas PPARalpha is already present in undifferentiated monocytes, PPARgamma expression is induced upon differentiation into macrophages. Immunocytochemistry analysis demonstrates that PPARalpha resides constitutively in the cytoplasm, whereas PPARgamma is predominantly nuclear localized. Transient transfection experiments indicate that PPARalpha and PPARgamma are transcriptionally active after ligand stimulation. Ligand activation of PPARgamma, but not of PPARalpha, results in apoptosis induction of unactivated differentiated macrophages as measured by the TUNEL assay and the appearance of the active proteolytic subunits of the cell death protease caspase-3. However, both PPARalpha and PPARgamma ligands induce apoptosis of macrophages activated with tumor necrosis factor alpha/interferon gamma. Finally, PPARgamma inhibits the transcriptional activity of the NFkappaB p65/RelA subunit, suggesting that PPAR activators induce macrophage apoptosis by negatively interfering with the anti-apoptotic NFkappaB signaling pathway. These data demonstrate a novel function of PPAR in human macrophages with likely consequences in inflammation and atherosclerosis.
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PMID:Activation of proliferator-activated receptors alpha and gamma induces apoptosis of human monocyte-derived macrophages. 974 21

Obesity and non-insulin-dependent diabetes mellitus (NIDDM) are closely linked. They frequently occur together in patients, and body mass index (BMI) is the strongest risk factor for the development of NIDDM. Both obesity and NIDDM are also major causes of morbidity and mortality from atherogenic macrovascular disease, and they are independent risk factors for coronary heart disease. The risk of developing NIDDM and cardiovascular disease is affected by the regional distribution of body fat. Visceral obesity is associated with a higher degree of risk than peripheral obesity. The metabolic and circulatory changes associated with visceral obesity lead to the development of insulin resistance and increased lipoprotein synthesis. For example, the change in the population profile of lipoproteins in the blood, and alterations in the levels of oxidative stress lead to an increased cardiovascular and macrovascular risk. The changes in lipid metabolism also affect haemorrheological function. They have been linked to decreased fibrinolysis (a serious cardiovascular risk factor) through elevated levels of plasminogen activator inhibitor factor, high blood viscosity, and increased erythrocyte aggregability. Increased BMI also appears to be associated with endothelial dysfunction, which is a major factor in atheroma plaque formation and development of thrombosis. Visceral obesity therefore adds a significant burden to the already increased cardiovascular risk inherent in NIDDM. However, even moderate weight loss may successfully reverse the majority of changes seen with visceral obesity.
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PMID:Relationship between obesity and the increased risk of major complications in non-insulin-dependent diabetes mellitus. 977 22

Acute coronary syndromes (ACS) such as unstable angina, myocardial infarction, or sudden ischemic death evolve from coronary thrombosis consequence of atherosclerotic plaque disruption. Plaque stabilization is an important therapeutic strategy in the prevention of ACS. Coronary risk factors include age, male sex, cigarette smoking, hypertension, dislipidemia, diabetes mellitus, insulin resistance and/or hyper insulinemia, obesity, sedentary lifestyle, stress, and the morning surge of sympathetic activity. New risk factors are emerging such as high homocystein, inflammation, and some kinds of infection. Control of blood pressure and cholesterol clearly reduce the risk of coronary events and mortality although the effects of antihypertensive therapy have been less than expected. The benefits of smoking cessation, moderate alcohol consumption, low-dose aspirin prophylaxis, estrogen-replacement therapy in postmenoposal women have also been shown.
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PMID:[Risk factors and prevention of acute coronary syndrome]. 979 37

The objective of this study was to determine the prevalence of carotid atherosclerosis in black Cameroonian adults presenting cardiovascular risk factors (CVRF). It was based on 77 subjects over the age of 40 years (50 men and 27 women) with at least one major CVRF, such as hypertension (HT), smoking, dyslipidaemia or diabetes mellitus. Obesity [body mass index (BMI), waist/hips ratio (W/H)] and hyperuricaemia were also taken into account. Duplex ultrasound examination of the carotid arteries was performed with a Siemens apparatus equipped with a 7.5 MHz transducer array. An atheromatous plaque was defined as medio-intimal thickening > or = 1.5 mm, with either protrusion or hyperechogenicity. Risk factors were distributed as follows in our serie: HT: 82%, Obesity: 49% (W/H) and 32% (BMI); Diabete: 32%; Smoking: 23%; Hyperuricaemia: 21%; Hypercholesterolaemia: 13%. 19 subjects (25%) (12 men and 7 women with a mean age of 63 years) presented one or more atheromatous plaques in the carotid arteries. Hyperuricaemia and hypercholesterolaemia were significantly correlated with the presence of plaques, with a marked tendency in subjects over the age of 70. In this study, hyperuricaemia and advanced age appeared to be independent arterial risk factors on multivariate analysis. In conclusion, our data show that carotid atherosclerosis does exist in our populations, especially in elderly subjects with cardiovascular risk factors. The particular role of hyperuricaemia as a predictive factor of atheromatous plaques in black Cameroonian subjects needs to be defined.
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PMID:[Ultrasonic demonstration of carotid atherosclerosis in black Cameroonian adults with cardiovascular risk]. 992 49

In normal isolated beta-cells, the response to glucose is heterogeneous and characterized by an increasing number of secretory cells as glucose concentration rises (Pipeleers DG, Kiekens R, Ling Z, Wilikens A, Schuit F: Physiologic relevance of heterogeneity in the pancreatic beta-cell population. Diabetologia 37 (Suppl. 2):S57-S64, 1994). We hypothesized that fasting hyperinsulinemia in obesity might be explained by altered beta-cell heterogeneity of signal transduction mechanisms, possibly involving exocytotic proteins. Insulin secretion from individual beta-cells sorted according to the size of the islet donor (<125 microm, >250 microm, and intermediate diameter) was measured by reverse hemolytic plaque assay. Beta-cells from fa/fa rats were hypertrophied 25-40%, independent of donor islet size. This was accompanied by an increased proportion of secretory cells (recruitment) at 5.5-11.0 mmol/l glucose, increased secretion per cell at 2.8 mmol/l glucose, and decreased insulin content after acute glucose exposure without an increase in secretion per cell. Decreased expression of exocytotic (soluble N-ethylmaleimide-sensitive fusion protein receptor [SNARE]) proteins, vesicle-associated membrane protein isoform 2 (VAMP-2), synaptosomal protein of 25 kDa (SNAP-25), and syntaxin-1 and -2 in fa/fa beta-cells may contribute to the failure to sustain excessive plaque size at higher glucose concentrations. Fasting hyperinsulinemia may be maintained by increased recruitment and an exaggerated secretory response in all fa-derived islet populations. Glucose regulates beta-cell responsiveness in the short term, and these effects may involve altered expression of SNARE proteins.
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PMID:Beta-cell hypertrophy in fa/fa rats is associated with basal glucose hypersensitivity and reduced SNARE protein expression. 1033 3

Uncoupling protein 2 (UCP-2) mRNA expression has been shown to be altered by metabolic conditions such as obesity in humans, but its functional significance is unknown. The expression of UCP-2 mRNA and protein in normal rat islets was established by reverse transcriptase-polymerase chain reaction and immunocytochemistry in pancreatic islets and tissue, respectively. Intense immunostaining of UCP-2 correlated with insulin-positive ,-cells. Overexpression of UCP-2 in normal rat islets was accomplished by infection with an adenovirus (AdEGI-UCP-2) containing the full-length human UCP-2 coding sequence. Induction of the AdEGI-UCP-2 gene resulted in severe blunting of glucose-stimulated insulin secretion (GSIS) without affecting islet insulin content or the ability of the calcium ionophore A23187 to increase insulin secretion from AdEGI-UCP-2-expressing islets. Therefore, UCP-2 overexpression affects signal transduction proximal to Ca2+-mediated steps, including exocytosis. Insulin secretion from single beta-cells to 16.5 mmol/l glucose examined by reverse hemolytic plaque assay was nearly ablated if UCP-2 was overexpressed. Thus, a direct, causal relationship between overexpression of UCP-2 and inhibition of GSIS in normal islets has been established. These data suggest that increased expression of UCP-2 has the potential to cause the lack of a glucose effect on insulin secretion in type 2 diabetes.
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PMID:Overexpression of uncoupling protein 2 inhibits glucose-stimulated insulin secretion from rat islets. 1038 58

The different diseases associated with the insulin resistance syndrome--diabetes mellitus or impaired carbohydrate tolerance, atherogenic lipoprotein phenotype, arterial hypertension and central type of obesity are the main risk factors of atherosclerosis. The reduced sensitivity of target tissues to the metabolic action of insulin (insulin resistance) is considered at present a separate risk factor. The authors analyze on the basis of a group of 210 coronarographic patients the influence of insulin resistance and associated etiopathogenetic risk factors on coronary lesions evaluated by the method of quantitative coronarography. From the results of the investigation ensues that insulin resistance is the most frequent metabolic deviation in patients with coronary disease whereby in the macrovascular group it was found in 74.3% and in the group with microvascular angina pectoris in 64.3% of the patients. Changes in the lipoprotein spectrum were a more frequent and earlier manifestation of insulin resistance than impaired carbohydrate metabolism. The change from functional changes of the vascular wall (impaired endothelium-dependent vasodilatation) to the development of an atheromatous plaque depends on the total number of cholesterol conveying lipoproteins assessed by means of the apoprotein B level and on the capacity of the reverse cholesterol transport, whereby both mechanisms are greatly influenced by insulin sensitivity. The degree of coronary affection evaluated by means of a coronary score, is in patients with manifest diabetes comparable with the affection in patients with insulin resistance without manifest diabetes and these two groups differ very significantly as to the extent and degree of affection from patients with a normal sensitivity to the effect of insulin.
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PMID:[Insulin resistance and the coronary syndrome]. 1042 19

Previous studies showed that the 139H strain of scrapie injected intra-cerebrally in hamsters caused obesity, and extensive histopathological changes in islets of Langerhans and pituitaries. In the current study, we report that an abnormal granular substance, which stained positively with periodic acid-Schiff (PAS-positive substance; PPS), was found in the islets of Langerhans, pituitaries, adrenal glands, in the lumens of blood vessel cores (BVCs) and in blood vessels in 139H-infected hamsters, but not in either 263K-infected or control hamsters. This substance was found in the endocrine organs, forming grape-like or plaque-like structures, which were small, round to ovoid, and homogenous measuring up to 7 microns in diameter and usually grouped in clusters. PPS was not found in the brains of control or scrapie-infected hamsters. Using immunostaining for amyloid protein (PrP, beta A4), as well as Congo red and thioflavin-S stains, no evidence was found of amyloid plaque formation in the islets of Langerhans, the adrenal glands, or the pituitaries of 139H- or 263K-infected hamsters. PPS might relate to the pathological changes in the endocrine organs in 139H-infected hamsters.
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PMID:Abnormal periodic acid-Schiff (PAS)-positive substance in the islets of Langerhans, pituitaries and adrenal glands of 139H scrapie-infected hamsters. 1042 34

Cardiovascular disease remains a frequent cause of morbidity and mortality in industrialized countries, particularly in subjects with hypertension, diabetes mellitus, and dyslipidemia, conditions frequently associated with central obesity. Identification of early morphological and/or functional alterations of the cardiovascular system may help target individuals most likely to benefit from preventive measures. The literature data and our own experience suggest that parameters that are direct expressions of cardiovascular damage, can be identified at an early stage. For example, diastolic dysfunction may precede the clinical expression of several cardiac diseases, left ventricular hypertrophy is one of the first manifestations of cardiac involvement in hypertension, central obesity and diabetes mellitus, and a carotid plaque may point to concomitant coronary artery disease. Other early manifestations of cardiovascular involvement are microalbuminuria and endothelial dysfunction. Insulin resistance and alterations of the renin-angiotensin-aldosterone system play an important physiopathogenic role in the development of cardiovascular damage in obese subjects, and their association with risk and cardiovascular disease has been confirmed in numerous studies. Since all these changes generally precede overt clinical manifestations and are closely related to cardiovascular morbidity, they may help identify individuals at the highest risk of cardiovascular events.
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PMID:Early markers of cardiovascular damage in obese subjects. 1072 13

The raised fatty streak (fatty plaque) is the gross term for the lesion intermediate between the juvenile (flat) fatty streak and the raised lesion of atherosclerosis. We measured the percentage of intimal surface involved with flat fatty streaks, raised fatty streaks, and raised lesions in the aortas and right coronary arteries of 2876 autopsied persons aged 15 through 34 years who died of external causes. Raised fatty streaks were present in the abdominal aortas of approximately 20% of 15- to 19-year-old subjects, and this percentage increased to approximately 40% for 30- to 34-year-old subjects. Raised fatty streaks were present in the right coronary arteries of approximately 10% of 15- to 19-year-old subjects, and this percentage increased to approximately 30% for 30- to 34-year-old subjects. The percent intimal surface involved with raised fatty streaks increased with age in both arteries and was associated with high non-high density lipoprotein (HDL) and low HDL cholesterol concentrations in the abdominal aorta and right coronary artery, with hypertension in the abdominal aorta, with obesity in the right coronary artery of men, and with impaired glucose tolerance in the right coronary artery. Associations of risk factors with raised fatty streaks became evident in subjects in their late teens, whereas associations of risk factors with raised lesions became evident in subjects aged >25 years. These results are consistent with the putative transitional role of raised fatty streaks and show that coronary heart disease risk factors accelerate atherogenesis in the second decade of life. Thus, long-range prevention of atherosclerosis should begin in childhood or adolescence.
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PMID:Associations of coronary heart disease risk factors with the intermediate lesion of atherosclerosis in youth. The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. 1093 23


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