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

Angiotensin II regulates blood pressure and may affect adipogenesis and adipocyte metabolism. Angiotensin II is produced by cleavage of angiotensinogen by renin and angiotensin-converting enzyme in the circulation. In addition, angiotensin II may be produced in various tissues by enzymes of the renin-angiotensin system (RAS) or the nonrenin-angiotensin system (NRAS). We have analyzed the expression of angiotensinogen and enzymes required for its conversion to angiotensin II in human adipose tissue. Northern blot demonstrated angiotensinogen expression in adipose tissue from nine obese subjects. Western blot revealed a distinct band of expected size of the angiotensinogen protein (61 kDa) in isolated adipocytes. RT-PCR, followed by Southern blot, demonstrated renin expression in human adipose tissue. Angiotensin-converting enzyme messenger RNA was detected by RT-PCR, and the identity of the PCR products was verified by restriction enzyme cleavage. Transcripts for cathepsin D and cathepsin G, components of the NRAS, were detected by RT-PCR, verified by restriction enzyme cleavage. We conclude that human adipose tissue expresses angiotensinogen and enzymes of RAS and NRAS. This opens the possibility that angiotensinogen-derived peptides, produced in adipose tissue itself, may affect adipogenesis and play a role in the pathogenesis of obesity.
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PMID:Human adipose tissue expresses angiotensinogen and enzymes required for its conversion to angiotensin II. 981 70

While the prevalence of hypertension is clearly increased among the overweight persons, the pathophysiological mechanisms underlying this frequent association of obesity and hypertension are still poorly understood. The expansion of extracellular volume, inducing hypervolaemia and increased cardiac output, represents the characteristic haemodynamic feature of the obesity-related hypertension. The maintenance of hypervolemia in the face of elevated blood pressure, indicates a resetting of pressor natriuresis toward higher blood pressure. The development of hypertension also indicates an increase in peripheral vascular resistance, thus the lack of physiological adaptation of peripheral resistance to increased cardiac output. The mechanisms underlying these changes in renal function and vascular reactivity can no longer be attributed to hyperinsulinaemia as such, but might be related to insulin resistance responsible for the enhancement in pressor activity of noradrenaline and angiotensin II. This increased reactivity to pressor factors may be due to an inadequate nitric oxide generation by vascular endothelium and to increased sodium and calcium concentration in vascular smooth muscle cells. The role of increased neuropeptide Y (NPY) activity, may also be involved. As to enhancement of tubular sodium reabsorption, it could be related to histological changes within the renal medulla, leading to compression of tubules and vasa recta, hence a more efficient sodium reabsorption. As to the therapeutic approach, the low-energy sodium-restricted diet associated with increased physical activity, represents the cornerstones of treatment for the obesity-related hypertension. If this approach fails, the pharmacological treatment becomes necessary, and the use of the converting enzyme inhibitors seems to be the most appropriate choice of drug therapy for hypertensive obese patients.
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PMID:Obesity and hypertension: from pathophysiology to treatment. 1019 61

Left ventricular (LV) size in childhood closely parallels body size, whereas in adulthood LV mass is increasingly affected by effects of obesity, hypertension, the level of cardiac volume load, and the level of LV myocardial contractility. Recently, additional independent associations of diabetes, arterial structure and function and as yet unknown genes with higher LV mass have been defined; angiotensin II and insulin have also been suggested to be additive stimuli to LV hypertrophy. Consideration of the level of LV mass and of the LV wall thickness/chamber radius ratio (relative wall thickness) has identified four different geometric patterns of LV adaptation to hypertension, including concentric LV hypertrophy (increased mass and wall thickness), eccentric hypertrophy (increased mass, normal relative wall thickness), concentric remodeling (increased relative wall thickness with normal mass) and normal LV geometry. Concentric hypertrophy is associated with especially high arterial pressure while eccentric hypertrophy is associated with obesity and elevated volume load. Numerous studies show that increased LV mass predicts cardiovascular events and death independently of all conventional risk factors; initial studies have also identified adverse implications of low LV midwall function and high relative wall thickness. Pioneer studies strongly suggest that reversal of LV hypertrophy is associated with an improved prognosis.
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PMID:Left ventricular hypertrophy in hypertension: stimuli, patterns, and consequences. 1022 44

In the C57BL/6J mice model, we investigated whether obesity affects the function or expression of components of the tissue renin-angiotensin system and whether endothelin (ET)-1 contributes to these changes. ACE activity (nmol. L His-Leu. mg protein(-1)) was measured in lung, kidney, and liver in control (receiving standard chow) and obese animals treated for 30 weeks with a high-fat, low cholesterol diet alone or in combination with LU135252, an orally active ET(A) receptor antagonist. ACE mRNA expression was measured in the kidney, and the effects of LU135252 on purified human ACE were determined. Aortic and renal tissue ET-1 protein content was measured, and the vascular contractility to angiotensin II was assessed. Obesity was associated with a tissue-specific increase in ACE activity in the kidney (55+/-4 versus 33+/-3 nmol/L) but not in the lung (34+/-2 versus 32+/-2 nmol/L). Long-term LU135252 treatment completely prevented this activation (13.3+/-0.3 versus 55+/-4 nmol/L, P<0.05) independent of ACE mRNA expression, body weight, or renal ET-1 protein but did not affect pulmonary or hepatic ACE activity. Obesity potentiated contractions in response to angiotensin II in the aorta (from 6+/-2% to 33+/-5% KCl) but not in the carotid artery (4+/-1% to 3.6+/-1% KCl), an effect that was completely prevented with LU135252 treatment (6+/-0.4% versus 33+/-5% KCl). No effect of LU135252 on purified ACE was observed. Thus, obesity is associated with the activation of renal ACE in vivo independent of its mRNA expression and enhanced vascular contractility to angiotensin II. These effects are regulated by ET in an organ-specific manner, providing novel mechanisms by which ET antagonists may exert organ protection.
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PMID:Obesity is associated with tissue-specific activation of renal angiotensin-converting enzyme in vivo: evidence for a regulatory role of endothelin. 1064 20

Essential hypertension is a complex disease influenced by different genetic and environmental factors. The renin-angiotensin system (RAS) is implicated in blood pressure regulation. Angiotensinogen (AGT) is the precursor of the biologically active angiotensin II (Ang II). Initial studies on hypertensive siblings and case-control studies indicated the important role of the angiotensinogen gene (AGT) for the predisposition to essential hypertension, preeclampsia and obesity-related hypertension. Recently, different AGT polymorphisms had been identified and analyzed in case-control studies. The aim of present studies is the analysis of potentially functional AGT variants (C-532T, G-6A), which might be responsible for the regulation of gene expression and therefore AGT generation. The A-6 allele is in complete linkage disequilibrium with the T235 allele and is associated with higher AGT expression in vitro. Segregation linkage analysis demonstrated that the C-532T polymorphism influences plasma AGT variability more significantly than the G-6A variant. Since the C-532T polymorphism is located within a AP-2 consensus element, functional promoter analyses are required. The understanding of the molecular basis of RAS in essential hypertension may provide us with new and more specific pharmacological agents and perhaps the ability to individualize antihypertensive treatment.
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PMID:[Role of the angiotensinogen gene for essential hypertension]. 1071 6

The renin-angiotensin system has long been recognized as an important regulator of systemic blood pressure and renal electrolyte homeostasis, and local renin-angiotensin systems have also been implicated in pathological changes of organ structure and function by modulation of gene expression, growth, fibrosis, and inflammatory response. Recently, substantial data have been accumulated in support of the notion that adipose tissue, besides other endocrine functions, also hosts a local renin-angiotensin system. In the first part of this review, we describe the components of the adipose tissue renin-angiotensin system in human and rodent animal models with respect to regulation of angiotensinogen expression and secretion, formation of angiotensin peptides, and the existence of angiotensin II receptors. In the second part, we describe the role of the adipose tissue renin-angiotensin system in the process of adipogenic differentiation and in the regulation of body weight. We also detail the differential regulation of the adipose tissue renin-angiotensin system in obesity and hypertension and thereby also speculate on its possible role in the development of obesity-associated hypertension. Although some findings on the adipose tissue renin-angiotensin system appear to be confusing, its involvement in the physiology and pathophysiology of adipose tissue has been confirmed by several functional studies. Nevertheless, future studies with more carefully described phenotypes are necessary to conclude whether obesity (by stimulation of adipogenic differentiation) and hypertension are associated with changes of renin-angiotensin system activity in adipose tissue. If so, the physiological relevance of this system in animal models and humans may warrant further interest.
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PMID:Physiology and pathophysiology of the adipose tissue renin-angiotensin system. 1085 76

Risk factors contributing to the potential inter-relationship between obesity and hypertension include insulin, fatty acids, and angiotensin II. All of these mediators are either produced by or act on adipocytes, influence fat cell metabolism, and have effects on the cardiovascular system. Moreover, these three mediators have several potential sites for positive feedback interaction, thus exacerbating the influence of any single risk factor. The purpose of this review is to highlight recent advances in our understanding of the influence of insulin, fatty acids, and angiotensin II on fat cell metabolism. Special emphasis is placed on potential adipose-related mechanisms of these factors, which would predictably elevate blood pressure. Given the prevalence of obesity and hypertension in the American population, delineation of potential pharmacologic targets that would influence both of these disease states is of primary importance to the successful treatment of these diseases of the metabolic syndrome X.
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PMID:Fat cell metabolism: insulin, fatty acids, and renin. 1098 Nov 39

Recent clinical and experimental data have radically modified the concept of adipose tissue as one solely devoted to energy storage and release. Adipose tissue is a target organ for glucocorticoids. Several studies of the function of the hypothalamic-pituitary-adrenal axis in obese subjects have failed to reach conclusive results. An innovative finding is that adipose tissue produces cortisol from its inactive precursor, cortisone. Identification of leptin, a hormone synthesised by adipose tissue, has ushered in the modern view that it is a true endocrine organ. Leptin is produced by subcutaneous and to a lesser extent by visceral adipose tissue. It has a central role in body weight and especially fat stores regulation, but is also involved in several complex functions, including the physiological processes associated with puberty. Angiotensinogen (AGT), another hormone synthesised in abundance by adipose tissue, is produced in larger amounts by visceral than subcutaneous fat. In addition, in man and animals adipose tissue appears to possess the whole renin-angiotensin system (RAS), suggesting that angiotensin II, the final effector of the system, is locally produced. The function of adipose RAS is not well known; besides participating, together with other hormones and substances, in adipocyte differentiation and fat tissue growth, it could be involved in the pathogenesis of the complications of obesity. All these findings have opened interesting prospects and are expected to yield further stimulating insights into the physiopathology of the adipose organ.
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PMID:Adipose tissue as an endocrine organ? A review of some recent data. 1108 90

Obesity is a major public health problem in Western countries, and >55% of adult Americans are overweight or obese. A major contributor to the epidemic of obesity is the current environment, which is characterized by increased availability of high energy foods and decreased physical activity. Several studies also demonstrated that genetic susceptibility contributes to obesity in some populations. Obesity research has focused primarily on the role of the hypothalamus in neuroendocrine regulation of food intake. However, a growing number of studies support a potential contribution of adipose tissue, via its newly discovered secretory function, to the pathogenesis of obesity and co-morbid conditions including cardiovascular disease, diabetes and hypertension. This paper will review the role of four factors secreted by adipose tissue (leptin, agouti, angiotensin II and prostaglandins) and their functions in the regulation of energy balance and whole-body homeostasis. Several other peptide and nonpeptide substances are secreted from adipose tissue; their function and regulation have been documented extensively.
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PMID:Secretory, endocrine and autocrine/paracrine function of the adipocyte. 1111 Aug 81

Using Otsuka Long Evans Tokushima Fatty (OLETF) rats, a model of human non-insulin-dependent diabetes mellitus (NIDDM) that exhibits hypertension, obesity, hyperglycemia and hyperlipidemia, the role of local angiotensin II in cardiovascular complications at early stages of NIDDM was characterized. OLETF rats were given an angiotensin converting enzyme (ACE) inhibitor, cilazapril (10 mg/kg/day) or vehicle from the age of 5 weeks to 20 weeks. Arteriolar, intermediate and venular capillary proportions were determined by the double-staining method and levels of collagen and non-collagenous proteins were determined by the selective dye-binding method in heart tissues. In OLETF rats at 20 weeks of age, capillary network remodeling (i.e., an increase in arteriolar portions and a decrease in venular portions) and an increase in collagen content were detected. Cilazapril not only exerted favorable effects on markers of diabetes, but also prevented capillary network remodeling and ameliorated the increase in collagen content. These results suggest that 1) capillary network remodeling and increase in extracellular matrix protein levels precede the onset of overt NIDDM in OLETF rats, and 2) angiotensin II may be involved in the pathogenesis of cardiac complications in the early stages of NIDDM.
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PMID:Coronary capillary remodeling in non-insulin-dependent diabetic rats: amelioration by inhibition of angiotensin converting enzyme and its potential clinical implications. 1121 33


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