Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increased levels of endothelin (ET-1), a potent endothelium-derived vasoconstrictive peptide, have been found in plasma from non-insulin dependent diabetic (NIDDM) patients, suggesting that ET-1 might represent a new marker of diabetes-related vascular damage. To elucidate this topic, circulating ET-1 levels were evaluated in 16 NIDDM patients in good metabolic control without either cardiovascular risk factors (obesity, hypertension, smoking, hyperdislipidaemia, etc.) or diabetes-related damage of other districts and in 12 healthy subjects. Retinopathy was assessed by ophthalmological evaluation and its severity determined by Klein criteria. Resulting data showed higher levels of plasma ET-1 in NIDDM patients than in control subjects (0.80 +/- 0.13 vs 0.60 +/- 0.12 pg/mL, p < 0.001). Plasma ET-1 levels were directly correlated with retinopathy degrees in NIDDM patients affected by retinopathy (n = 10; r = 0.368; p = 0.02), and were significantly higher in these latter (n = 10) than in those without retinopathy (n = 6) (0.89 +/- 0.13 vs 0.71 +/- 0.19 pg/mL, p < 0.05). The increased levels of ET-1 could contribute to retinopathy development or, more probably, represent a marker of this diabetes-related complication.
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PMID:Increased levels of plasma endothelin-1 in non-insulin dependent diabetic patients with retinopathy but without other diabetes-related organ damage. 928 43

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

The aim of the study was to assess the plasma levels of endothelial injury markers in children from families with high risk of premature coronary heart disease (CHD) without other common CHD risk factors (hyperlipidaemia, obesity, hypertension, low physical activity). The study comprised 48 children, including 24 children from high-risk families (HR), according to the NCEP (National Cholesterol Education Programme) criteria: one or two parents had clinical manifestation of cardiovascular disease before the age of 65 years (mother) or 55 years (father). The control group included 24 healthy children with no familial history of cardiovascular disease. All the children were normolipidaemic according to the NCEP and the European Atherosclerosis Society criteria for children aged 2-19 years. In the HR group, the concentration of vWf was significantly elevated in comparison to that in the control group (p<0.0001). Plasma concentrations of ET-1 and TxB2 did not differ significantly between the HR group and the controls. Plasma concentrations of the 6-ketoPGF1alpha in the HR group and in the respective age and gender HR subgroups were significantly lower compared with those of the control group (p<0.00005). Concentration of vWf in the HR group was negatively correlated with the concentration of 6-ketoPGF1alpha (r = -0.47; p<0.05) and positively correlated with TxB2 (r=0.39; p<0.01). In a logistic regression analysis, we found that the 6-ketoPGF1alpha concentration in the lower quartile (< 16.1 pmol/L) was associated with a 3.4-fold odds of inclusion in the high-risk group versus the upper quartile (>23.0 pmol/L).
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PMID:Plasma levels of von willebrand factor, endothelin-1, prostacyclin and thromboxane in children from families with high risk of premature coronary artery disease. 1146 46

Endothelium-dependent vasodilation is impaired in clinical states of insulin resistance such as obesity and type 2 diabetes. Individuals who have hyperinsulinemic insulin resistance have relatively elevated circulating levels of endothelin (ET)-1, suggesting that ET-1 may be important in the endothelial dysfunction and alterations of vascular tone in these conditions. In 8 lean subjects, 12 nondiabetic obese subjects, and 8 subjects with type 2 diabetes, we measured basal and methacholine-stimulated rates of leg blood flow (LBF) and total serum nitrates (NOx) before and after the intrafemoral arterial administration of BQ123, a specific blocker of ET(A) receptors. BQ123 produced significant vasodilation in the obese and type 2 diabetic subjects (leg vascular resistance = mean arterial pressure/LBF fell by 34 and 36%; P < 0.005) but not in the lean subjects (13%; P = NS, P = 0.018 comparing all groups). ET(A) blockade did not change basal NOx flux (NOx*LBF). This suggests increased basal ET-1 constrictor tone among obese and type 2 diabetic subjects. BQ123 corrected the baseline defect in endothelium-dependent vasodilation seen in obese and type 2 diabetic subjects, suggesting an important contribution of ET-1 to endothelial dysfunction in these subjects. In contrast to basal conditions, stimulated NOx flux was augmented by BQ123 in obese and type 2 diabetic subjects but not in L subjects (P = 0.04), suggesting a combined effect of ET(A) blockade to reduce constrictor tone and augment dilator tone. Endothelin seems to contribute to endothelial dysfunction and the regulation of vascular tone in human obesity and type 2 diabetes.
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PMID:Endothelin contributes to basal vascular tone and endothelial dysfunction in human obesity and type 2 diabetes. 1245 9

The Lys198Asn polymorphism of the endothelin-1 gene has been associated with increased blood pressure levels in several studies involving European and Australian adults. The purpose of the present study was to examine the potential moderating influence of ethnicity, obesity, and socioeconomic status on associations between the ET-1/Lys198Asn polymorphism and hemodynamic function at rest and during two laboratory stressors (video game, forehead cold) in a sample of 161 black and 213 white American normotensive young adults (mean age, 18.5+/-2.7 years). Carrier status of the T allele was not associated with resting blood pressure or total peripheral resistance index. However, carriers of the T allele showed greater diastolic blood pressure increases to the video game (P<0.04), particularly among those who were obese (P<0.02). Carrier status also interacted with socioeconomic status such that T allele carriers who came from lower socioeconomic status backgrounds exhibited the greatest increases in systolic blood pressure to the video game challenge (P<0.05). In conclusion, the findings point out the importance of examining the impact of genetic polymorphisms on blood pressure control phenotypes within the context of potentiating environmental factors.
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PMID:Endothelin-1 gene Lys198Asn polymorphism and blood pressure reactivity. 1296 77

The diabetic heart shows increased fibrosis, which impairs cardiac function. Endothelin (ET)-1 and nuclear factor-kappaB (NF-kappaB) interactively regulate fibroblast growth. We have recently demonstrated that Punica granatum flower (PGF), a Unani anti-diabetic medicine, is a dual activator of peroxisome proliferator-activated receptor (PPAR)-alpha and -gamma, and improves hyperglycemia, hyperlipidemia, and fatty heart in Zucker diabetic fatty (ZDF) rat, a genetic animal model of type 2 diabetes and obesity. Here, we demonstrated that six-week treatment with PGF extract (500 mg/kg, p.o.) in Zucker diabetic fatty rats reduced the ratios of van Gieson-stained interstitial collagen deposit area to total left ventricular area and perivascular collagen deposit areas to coronary artery media area in the heart. This was accompanied by suppression of overexpressed cardiac fibronectin and collagen I and III mRNAs. Punica granatum flower extract reduced the up-regulated cardiac mRNA expression of ET-1, ETA, inhibitor-kappaBbeta and c-jun, and normalized the down-regulated mRNA expression of inhibitor-kappaBalpha in Zucker diabetic fatty rats. In vitro, Punica granatum flower extract and its components oleanolic acid, ursolic acid, and gallic acid inhibited lipopolysaccharide-induced NF-kappaB activation in macrophages. Our findings indicate that Punica granatum flower extract diminishes cardiac fibrosis in Zucker diabetic fatty rats, at least in part, by modulating cardiac ET-1 and NF-kappaB signaling.
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PMID:Pomegranate flower extract diminishes cardiac fibrosis in Zucker diabetic fatty rats: modulation of cardiac endothelin-1 and nuclear factor-kappaB pathways. 1630 13

Leptin is a 16 kDa product of the obesity gene secreted primarily by adipocytes. We recently identified cardiomyocytes as a target for the direct hypertrophic effects of leptin and suggested that leptin may be a biological link between obesity and cardiovascular pathologies. Activation of the renin-angiotensin and endothelin systems is associated with development of cardiovascular diseases and plasma renin levels are elevated in obese individuals. We therefore determined possible interaction between these factors in mediating hypertrophy in cultured neonatal rat ventricular myocytes. Treatment for 24 h with leptin (3.1 nM), angiotensin II (100 nM) or endothelin-1 (ET-1, 10 nM) significantly increased cell area by 37%, 36% and 35%, respectively and significantly increased gene expression of myosin light chain-2 and alpha-skeletal actin as well as leucine incorporation. The hypertrophic effects of all three agents were prevented by leptin and a leptin triple mutant receptor antagonist whereas the AT(1) receptor blocker (Sar1-lle(8))-Ang II or the ET(A) receptor blocker BQ123 was ineffective against leptin-induced hypertrophy. Both angiotensin II and ET-1 significantly increased leptin levels in the culture medium by fivefold. Moreover, both angiotensin II and ET-1 increased the gene expression of the short form (OBRa) by 180% and long form (OBRb) of leptin receptors by 200%, and this increase was abolished by both leptin receptor and leptin antibodies and leptin triple mutant. Although both angiotensin II and ET-1 increased phosphorylation of MAPK (p38, ERK1/2 and JNK) and NF-kappaB, the ability of leptin blockade to attenuate the hypertrophic responses was generally dissociated from these effects suggesting an alternate, yet to be identified cellular pathway mediating this role of leptin. Our studies therefore suggest a novel autocrine function for leptin in mediating the hypertrophic effects of both angiotensin II and ET-1 in cardiac myocytes.
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PMID:An autocrine role for leptin in mediating the cardiomyocyte hypertrophic effects of angiotensin II and endothelin-1. 1680 60

Obesity represents one of serious risk factors in chronic renal failure patients (CRF). In three years prospective double-blind randomised multicentre study we monitored 66 patients with advanced chronic renal insufficiency, GFR 24.4-37.3 ml/min (0.41 to 0.62 ml/s) and BMI > or = 30 kg/m2 on long term low-protein diet (0.6 P/kg BW/day) and ACEI + ARB. Thirty four randomly selected patients (group I) were treated with keto amino acids, 32 patients in control group (group II) with placebo. During the study period significant decrease of BMI, proteinuria and slowing in progression of renal failure (C(in)) were found. Significant changes were also noted in parameters of albumin and transferrin (p < 0.02), leucin and WQ (p < 0.01 - p < 0.02), glycaemia and HbA1c (p < 0.02), triglycerides (p < 0.01), leptin and ObRe (p < 0.01) and selected parameters of endothelial dysfunction (ET1, p < 0.02, TGFbeta1, p < 0.02). Significantly also decreased PTH value (p < 0.01). Successful treatment of obesity can significantly improve long term prognosis in CRF patients.
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PMID:[Obesity and progression of chronic renal insufficiency: a Czech long term prospective double-blind randomised multicentre study]. 1687 60

The discovery of leptin in 1994 led to research into the participation of that hormone in the development of many pathologic states. This article presents current knowledge on the role of leptin, in the pathogenesis of cardiovascular diseases. Leptin is a circulating peptide hormone produced by adipose cells which plays the main role in the regulation of metabolism in humans. Leptin, in the physiological range of plasma levels, is a regulator of cardiovascular function. In fact, higher plasma leptin levels as well as insulin resistance are directly correlated with adiposity. Hyperleptinemia accompanying obesity leads to many pathologic states: stimulation in platelets aggregation, tachycardia, hypertension, increases in plasma levels of pro-thrombotic factors and in levels of CRP and ET-1. In a multicenter study, hyperleptinemia turned out to be the main risk factor responsible for the ischemic disease, especially acute myocardial infarction. Elevated plasma leptin levels play a key role in increased incidence of cardiovascular mortality in obese.
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PMID:[Leptin--adipose tissue hormone and its role in cardiovascular diseases]. 1700 77

Endothelial dysfunction is one manifestation of the many changes induced in the arterial wall by the metabolic abnormalities accompanying diabetes and insulin resistance. In type 1 diabetes, endothelial dysfunction is most consistently found in advanced stages of the disease. In other patients, it is associated with nondiabetic insulin resistance and probably precedes type 2 diabetes. In obesity and insulin resistance, increased secretion of proinflammatory cytokines and decreased secretion of adiponectin from adipose tissue, increased circulating levels of free fatty acids, and postprandial hyperglycemia can all alter gene expression and cell signaling in vascular endothelium, cause vascular insulin resistance, and change the release of endothelium-derived factors. In diabetes, sustained hyperglycemia causes increased intracellular concentrations of glucose metabolites in endothelial cells. These changes cause mitochondrial dysfunction, increased oxidative stress, and activation of protein kinase C. Dysfunctional endothelium displays activation of vascular NADPH oxidase, uncoupling of endothelial nitric oxide synthase, increased expression of endothelin 1, a changed balance between the production of vasodilator and vasoconstrictor prostanoids, and induction of adhesion molecules. This review describes how these and other changes influence endothelium-dependent vasodilation in patients with insulin resistance and diabetes. The clinical utility of endothelial function testing and future therapeutic targets is also discussed.
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PMID:Mechanisms of Disease: endothelial dysfunction in insulin resistance and diabetes. 1717 29


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