UMLS:C0028754 - FACTA Search

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

Clinical and experimental data obtained in the last few years have modified the concept of adipose tissue as one solely directed at energy storage and release. The adipose tissue is a target organ for glucocorticoids and several studies have been carried out on the function of hypothalamic-pituitary-adrenal axis in obese subjects without conclusive results. A recent and innovative finding is that adipose tissue can produce cortisol from its inactive precursor, cortisone. The identification of leptin, a hormone synthesised by fat tissue, has ushered in the modern view of this tissue as a true endocrine organ. Leptin is produced primarily by subcutaneous and to a lesser extent by visceral adipose tissue, and has a central role in controlling body weight and, especially in regulating fat stores. Leptin is also involved in several complex functions, including physiological processes associated with puberty. Another hormone of fat tissue is angiotensinogen, which is produced in larger amounts by visceral than subcutaneous fat. Human and animals adipose tissue express a whole renin-angiotensin system (RAS). Angiotensin II, the final effector of this system is probably produced locally by adipose tissue. The function of adipose RAS is not well known. RAS can participate together with other hormones and substances, in adipocyte differentiation and fat tissue growth, but could be also involved in the pathogenesis of complications of obesity including arterial hypertension.
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PMID:Adipose tissue as an endocrine organ? A review of recent data related to cardiovascular complications of endocrine dysfunctions. 1519 92

Nitric oxide (NO) is involved in adipose tissue biology by influencing adipogenesis, insulin-stimulated glucose uptake, and lipolysis. The enzymes responsible for NO formation in adipose cells are endothelial NO synthase (eNOS) and inducible NO synthase (iNOS), whereas neuronal NO synthase (bNOS) is not expressed in adipocytes. We characterized the expression pattern and the influence of adipogenesis, obesity, and weight loss on genes belonging to the NO system in human subcutaneous adipose cells by combining in vivo and in vitro studies. Expression of most of the genes known to belong to the NO system (eNOS, iNOS, subunits of the soluble guanylate cyclase, and both genes encoding cGMP-dependent protein kinases) in human adipose tissue and isolated human adipocytes was detected. In vitro adipogenic differentiation increased the expression level of iNOS significantly, whereas eNOS expression levels were not influenced. The genes encoding eNOS, iNOS, and cGMP-dependent protein kinase 1 were expressed at higher levels in obese women. Expression of these genes, however, was not influenced by 5% weight loss. Insulin and angiotensin II (Ang II) increased NO production by human preadipocytes in vitro. Increased eNOS and iNOS expression in adipocytes and local effects of insulin and Ang II may increase adipose tissue production of NO in obesity.
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PMID:Regulation of the nitric oxide system in human adipose tissue. 1523 49

Obesity and insulin resistance confer increased risk for accelerated coronary disease and cardiomyopathic phenomena. We have previously shown that inhibition of angiotensin-converting enzyme (ACE) prevents coronary perimicrovascular fibrosis in genetically obese mice that develop insulin resistance. This study was performed to elucidate mechanism(s) implicated and to determine the effects of attenuation of angiotensin II (Ang) II. Genetically obese ob/ob mice were given ACE inhibitor (temocapril) or Ang II type 1 (AT(1)) receptor blocker (olmesartan) from 10 to 20 weeks. Cardiac expressions of plasminogen activator inhibitor (PAI)-1, the major physiologic inhibitor of fibrinolysis, and transforming growth factor (TGF)-beta(1), a prototypic profibrotic molecule, were determined and extent of perivascular coronary fibrosis was measured. Twenty-week-old obese mice exhibited increased plasma levels of PAI-1 and TGF-beta(1) compared with the values in lean counterpart. Perivascular coronary fibrosis in arterioles and small arteries was evident in obese mice that also showed increased left ventricular collagen as measured by hydroxyproline assay. Immunohistochemistry confirmed the deposition of perivascular type 1 collagen. Markedly increased PAI-1 and TGF-beta were seen immunohistochemically in coronary vascular wall and confirmed by western blotting. When obese mice were treated with temocapril or olmesartan from 10 to 20 weeks, both were equally effective and prevented increases in perivascular fibrosis, plasma PAI-1 and TGF-beta(1), left ventricular collagen and mural immunoreactivity for PAI-1, TGF-beta and collagen type 1. The c-Jun NH(2)-terminal kinase (JNK) activity was elevated in the left ventricle of obese mice (western) and blocked by temocapril and olmesartan. Ang II-mediated upregulation of PAI-1 and TGF-beta(1) with collagen deposition may explain the mechanism of perivascular fibrosis in obese mice. ACE inhibition and blockade of AT(1) receptor may prevent coronary perivascular fibrosis and collagen deposition even before development of overt diabetes. JNK activation may be a mediator of obesity-related cardiac dysfunction and a potential therapeutic target.
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PMID:Salutary effects of attenuation of angiotensin II on coronary perivascular fibrosis associated with insulin resistance and obesity. 1527 22

Upper body obesity is associated with insulin resistance, hypertension, and endothelial dysfunction. We examined forearm vascular function in response to vasodilator (endothelium-dependent and endothelium-independent) and vasoconstrictor stimuli in 8 normotensive, upper body/viscerally obese men with a positive family history of hypertension and 8 age-matched nonobese men. We also measured body composition and insulin regulation of free fatty acid (FFA) and glucose metabolism. Forearm blood flow was measured before and during brachial artery infusions of acetylcholine (Ach), sodium nitroprusside (NTP), and angiotensin II (+/-nitric oxide synthase [NO]) synthase blockade with N(G)-monomethyl L-arginine [L-NMMA]). On a separate day, baseline and insulin-regulated glucose ([3-3H]glucose) and FFA ([9,10-3H]palmitate) turnover were measured. The vasoconstrictor response to angiotensin II was greater (P<0.05) in obese men than in nonobese men, whereas endothelium-dependent vasodilation was similar. The slope of the angiotensin II dose-response curve correlated significantly with the basal plasma palmitate concentration. Basal and insulin-mediated glucose disposal was significantly reduced and FFA turnover significantly increased in viscerally obese men. No differences in endothelium-independent vasodilation or relationships between vascular responsivity and palmitate and glucose kinetics or body composition were found. Angiotensin II-stimulated forearm vasoconstriction is increased in viscerally obese normotensive men.
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PMID:Vascular response to angiotensin II in upper body obesity. 1533 33

The major cause of morbidity and mortality in persons with diabetes is cardiovascular disease (CVD), the risk of which is increased three- to four-fold versus persons without diabetes. The biology of diabetes is characterized not only by hyperglycemia but also by hypertension, dyslipidemia, microalbuminuria, inflammation, and abnormal thrombolysis. Hypertension is a common feature of diabetes and is the primary contributor to CVD. Recent investigations have revealed a relationship between vascular derangements, insulin resistance, and visceral obesity and have implicated the renin-angiotensin-aldosterone system (RAAS) as a key mediator of cardiovascular dysfunction in diabetes. Angiotensin II has been shown to have direct effects on endothelial dysfunction, oxidative stress, inflammation, skeletal muscle, and adipocyte function. These pathophysiologic considerations have formed the basis for CVD prevention strategies in diabetes. Clinical trials have demonstrated a reduction in cardiovascular events with aspirin, lipid-lowering agents, and antihypertensive agents. Blood pressure (BP) control (<130/80 mm Hg) is a crucial component of risk reduction, and several studies have demonstrated the need for multiple agents to reach therapeutic goals. Clinical trials also demonstrated the benefit of RAAS blocking agents in reducing BP and cardiovascular and renal risk, and suggest clinical benefits beyond BP reduction.
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PMID:Insights into the biology of diabetic vascular disease: what's new? 1553 7

The renin-angiotensin system with its active metabolite angiotensin (Ang) II has been related not only to hypertension but also to obesity and insulin resistance. Recent evidence obtained in vitro suggests that the type 2 Ang II receptor (AT2R) mediates the trophic action of Ang II on adipocyte differentiation and lipogenesis. We used AT2R(y/-) mice to delineate a potential role of AT2R in adipose tissue development and metabolism. AT2R(y/-) mice had a normal adiposity but displayed a striking adipose tissue phenotype characterized by small adipocytes and an increase in cell number. In muscle, the expression of several genes involved in lipid metabolism, including fatty acid translocase, uncoupling protein-3, peroxisome proliferator-activated receptors (alpha, delta), and carnitine palmitoyl transferase-1, was increased in AT2R-deficient mice. In response to high-fat feeding, these mice were protected against obesity and obesity-related glucose intolerance, as assessed by glucose tolerance tests. Moreover, lipid oxidation assessed by indirect calorimetry was higher in AT2R-deficient mice than in wild-type mice, irrespective of the diet. This suggests that AT2R-dependent signaling exerts a direct or indirect negative control on lipid utilization in muscles. These data support the idea that AT2R-dependent Ang II signaling increases adipose cell mass and glucose intolerance and thus could participate to the deleterious effects of a high-fat diet.
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PMID:Deletion of the angiotensin type 2 receptor (AT2R) reduces adipose cell size and protects from diet-induced obesity and insulin resistance. 1579 37

Diabetes (particularly type 2 diabetes) represents a global health problem of epidemic proportions. Individuals with diabetes are not only more likely to develop hypertension, dyslipidemia, and obesity, but are also at a significantly higher risk for coronary heart disease, peripheral vascular disease, and stroke. Angiotensin II plays a key pathophysiological role in the progression of diabetic renal disease, and blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II antagonists has therefore become an important therapeutic strategy to reduce renal and cardiovascular events in patients with diabetes. Several studies have demonstrated the effects of angiotensin II antagonists on the reduction of albuminuria and the progression of renal disease from microalbuminuria to macroalbuminuria. More importantly, several endpoint trials have shown that the antiproteinuric effects of losartan and irbesartan translate into cardiovascular and renoprotective benefits beyond blood pressure lowering, thereby delaying the need for dialysis or kidney transplantation by several years. These and other studies indicate that angiotensin II antagonists not only improve survival and quality of life of patients with diabetic nephropathy, but also have the potential to reduce the substantial healthcare burden associated with managing these patients. ACEi also appear to exert similar beneficial effects in diabetic patients, but whether clinically significant differences in renoprotection or mortality exist between angiotensin II antagonists and ACEi in patients with type 2 diabetes remains to be fully investigated in appropriate head-to-head studies.
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PMID:Blockade of the renin-angiotensin-aldosterone system: a key therapeutic strategy to reduce renal and cardiovascular events in patients with diabetes. 1633 Oct 93

The level of proteinuria is one of the most important risk factors for progressive renal function loss in renal diseases. Any therapeutic measure that reduces proteinuria will slow or halt the progression of proteinuric nephropathies. Blockade of the renin-angiotensin-aldosterone system (RAAS) with angiotensin-converting enzyme (ACE) inhibitors or AT1-receptor antagonists (ARA) is currently the most powerful available antiproteinuric treatment. Recent investigations point out that blockade of RAAS at other levels (e.g., aldosterone or renin antagonists) could also induce a significant decrease in proteinuria. Because angiotensin II is also generated from angiotensin I by enzymes other than ACE, ARA would provide a more effective blockade of angiotensin II; however, ACE inhibition increases plasma levels of substances such as bradykinin and N-acetyl-seryl-aspartyl-lysyl-proline, which have strong antifibrotic properties. These differential effects of ACE inhibitors and ARA are the rationale for combined administration of both agents, which in clinical studies has demonstrated a significantly higher antiproteinuric and renoprotective effect than by either drug alone. Salt and protein restriction, as well as cautious use of diuretics, can also increase the antiproteinuric effect of RAAS blockade. Treatment with statins or other lipid-lowering agents leads to reduction in proteinuria levels, as some meta-analyses have demonstrated. Smoking is associated with an increased risk for the appearance of proteinuria, so cessation of smoking should be mandatory in proteinuric renal diseases. Recent studies have highlighted an epidemic increase of obesity-related proteinuric glomerulopathies; weight loss is effective not only in this condition, but also in overweight patients with proteinuric nephropathies of other etiologies.
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PMID:Therapeutic measures in proteinuric nephropathy. 1633 67

The altered vascular responses to various vasopressors and relaxants have been well reported in various animal models of hypertension, insulin resistance and diabetes. Though the role of oxidative stress (increased superoxide levels) associated with these altered vascular responses in hyperglycemic/diabetic state is well documented, the role of the same remains to be largely unknown in vascular dysfunction coupled with prediabetic insulin resistant state. The objective of the present study was therefore to elucidate the role of free radicals particularly superoxides if any associated with vascular dysfunction in diet-induced insulin resistance of rats. In this regard, the effect of tempol (a membrane permeable superoxide dismutase mimetic/free radical scavenger) on the enhanced Ang II-induced contraction and impaired-ACh mediated relaxation in thoracic aorta of rats with insulin resistance was studied. Ang II-induced contraction and ACh-mediated relaxation responses were recorded isometrically in endothelium intact and denuded thoracic aortic ring preparations isolated from male Sprague-Dawley rats which were fed with either normal pellet diet (NPD) (control group) or high fat diet (HFD) (insulin resistant group) for 4 weeks. The HFD-fed rats exhibited characteristic features of insulin resistance syndrome viz., obesity, hyperinsulinaemia, mild hyperglycemia, hypertriglyceridemia, hypercholesterolemia, glucose intolerance and hypertension. Maximal contractile response (E(max)) to Ang II was increased in endothelium intact aortic ring preparations obtained from HFD-fed rats as compared to NPD-fed control rats. Denudation of endothelium significantly increased Ang II-mediated E(max) responses in thoracic aortic rings of NPD-fed rats, whereas it produced only minimal alteration to the E(max) in the HFD-fed rats. In addition, ACh-mediated relaxation response was impaired in endothelium intact aortic rings isolated from HFD-fed rats. Tempol (30-300 microM) significantly and dose dependently inhibited enhanced vascular responses (E(max)) of Ang II in endothelium intact, but not in endothelium denuded aortic ring preparations. Tempol (30 microM) reversed the impaired acetylcholine (ACh)-mediated relaxations in endothelium intact aortic ring preparations of HFD-fed rats. Endothelium independent vasorelaxations (EIV) to sodium nitroprusside (SNP) were similar for both NPD and HFD. In conclusion, our results indicate that superoxide radicals play crucial role in enhanced contractile and impaired vasodilatory responses to Ang II and ACh, respectively, in thoracic aortic rings isolated from diet-induced insulin resistant rats.
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PMID:Effect of tempol on altered angiotensin II and acetylcholine-mediated vascular responses in thoracic aorta isolated from rats with insulin resistance. 1641 60

Renal angiotensin II (AII) is suggested to play a role in the enhanced sodium reabsorption that causes a shift in pressure natriuresis in obesity related hypertension; however, the mechanism is not known. Therefore, to assess the influence of AII on tubular sodium transport, we determined the effect of AII on the Na+, K+-ATPase activity (NKA), an active transporter regulated by the AT1 receptor activity, in the isolated proximal tubules of lean and obese Zucker rats. Also, we determined the levels of the tubular AT1 receptor and associated signal transducing G proteins, as the initial signaling components that mediate the effects of AII on Na+, K+-ATPase activity. In the isolated proximal tubules, AII produced greater stimulation of the NKA activity in obese compared with lean rats. Determination of the AT1 receptors by Scatchard analysis of the [125I] Sar-Ang II binding and Western blot analysis in the basolateral (BLM) and brush border membrane (BBM) revealed a modest but significant increase (23%) in the AT1 receptor number mainly in the BLM of obese compared with lean rats. The AII affinity for AT1 receptors, as determined by IC50 values of AII to displace [125I] Sar-Ang II binding in BLM and BBM were similar in lean and obese rats. Western blot analysis revealed significant increases in Gialpha1, Gialpha2, Gialpha3, and Gq/11alpha in BLM and Gialpha1, Gialpha3, and Gq/11alpha in BBM of obese as compared with lean rats. The increase in the levels of the AT1 receptor and G proteins, mainly in the BLM, may be contributing to the enhanced AII-induced activation of NKA in the proximal tubules of obese rats. This phenomenon, in part, may be responsible for the increased sodium reabsorption and the development of hypertension in obese Zucker rats.
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PMID:Enhanced angiotensin II-induced activation of Na+, K+-ATPase in the proximal tubules of obese Zucker rats. 1644 62

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