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

The objective of this study was to determine the effect of pioglitazone on blood pressure (BP) and oxidative balance in obese, hypertensive, Sprague-Dawley rats and to identify some of the molecular mechanisms involved. After 12 weeks of a moderately high-fat diet, rats diverged into obesity-prone (OP) and obesity-resistant (OR) groups (n=6 per group). At the end of the diet, peroxisome proliferator activated receptor-gamma (PPARgamma) mRNA expression and activity in the renal cortex and medulla of OP rats were significantly lower compared with that in OR rats. Pioglitazone treatment increased PPARgamma expression and activity in OP rats, suggesting a possible direct ligand-related effect of pioglitazone. As opposed to the untreated OP group, which showed moderate hypertension (systolic BP=159+/-5.3 mm Hg) after 12 weeks, pioglitazone-treated rats were normotensive (systolic BP=123.9+/-2.7 mm Hg). Insulin production was reduced by 2-fold in the OP group treated with pioglitazone. Urinary isoprostanes and renal lipid peroxides were also reduced in OP rats treated with pioglitazone compared with untreated counterparts. Also, expression of p47phox and gp91phox, both increased in OP versus OR rats, was reduced in the former by pioglitazone treatment. In addition, pioglitazone treatment increased nitrate/nitrite excretion and expression of renal endothelial and neuronal nitric oxide synthase. Collectively, the results show that pioglitazone treatment prevented hypertension and renal oxidative stress both by reducing free-radical production and by increasing nitric oxide production/availability.
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PMID:Pioglitazone prevents hypertension and reduces oxidative stress in diet-induced obesity. 1463 18

Anorexia-associated malnutrition is a severe complication that increases mortality in peritoneal dialysis (PD) patients. Ghrelin is a recently-discovered orexigenic hormone with actions in brain and stomach. We analyzed, in 42 PD patients, the possible relationship between ghrelin and appetite regulation with regard to other orexigens [neuropeptide Y (NPY), NO3] and anorexigens [cholecystokinin (CCK), leptin, glucose-dependent insulinotropic peptide (GIP), tumor necrosis factor alpha (TNFalpha)]. All orexigens and anorexigens were determined in plasma. Eating motivation was evaluated using a visual analog scale (VAS). The patients were divided into three groups: those with anorexia (n = 12), those with obesity associated with high intake (n = 12), and those with no eating behavior disorders (n = 18). A control group of 10 healthy volunteers was also evaluated. Mean plasma levels of ghrelin were high (3618.6 +/- 1533 mg/mL), with 36 patients showing values above the normal range (< 2600 mg/mL). Patients with anorexia had lower ghrelin and NPY levels and higher peptide-C, CCK, interleukin-1 (IL-1), TNFalpha, and GIP levels than did the other patients. Patients with anorexia also had an early satiety score and low desire and pleasure in eating on the VAS and diet survey. We observed significant positive linear correlations between ghrelin and albumin (r = 0.43, p < 0.05), prealbumin (r = 0.51, p < 0.05), transferrin (r = 0.4, p < 0.05), growth hormone (r = 0.66, p < 0.01), NO3 (r = 0.36, p < 0.05), and eating motivation (VAS). At the same time, negative relationships were observed between blood ghrelin and GIP (r = -0.42, p < 0.05), insulin (r = -0.4, p < 0.05), leptin (r = -0.45, p < 0.05), and creatinine clearance [r = -0.33, p = 0.08 (nonsignificant)]. Ghrelin levels were not related to Kt/V or to levels of CCK and cytokines. Ghrelin plasma levels are elevated in PD patients. Uremic patients with anorexia show relatively lower ghrelin plasma levels than the levels seen in obese patients or in patients with normal appetite. The role of ghrelin in appetite modulation is altered in uremic PD patients, and that alteration is possibly associated with disorders in insulin and growth hormone metabolism.
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PMID:Ghrelin plasma levels and appetite in peritoneal dialysis patients. 1538 25

Currently, obesity is considered a systemic inflammation; however, the effects of obesity on the vulnerability of dopaminergic neurons to oxidative stress are not fully defined. We evaluated the effects of high-fat diet-induced obesity (HF DIO) on neurotoxicity in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Eight weeks after a HF or matched normal diet, a severe decrease in the levels of striatal dopamine and of nigral microtubule-associated protein 2, manganese superoxide dismutase, and tyrosine hydroxylase was observed in obese mice treated with subtoxic doses of MPTP (20 mg/kg) compared with the matched lean group. In addition, the levels of nitrate/nitrite and thiobarbituric acid-malondialdehyde adducts in the substantia nigra of obese mice were reciprocally elevated or suppressed by MPTP. Interestingly, striatal nNOS phosphorylation and dopamine turnover were elevated in obese mice after MPTP treatment, but were not observed in lean mice. The nitrotyrosine immunoreactivity for evaluation of nigral nitrogenous stress in obese mice with MPTP was higher than that in matched lean mice. At higher doses of MPTP (60 mg/kg), the mortality was higher in obese mice than in lean mice. These results suggest that DIO may increase the vulnerability of dopaminergic neurons to MPTP via increased levels of reactive oxygen and nitrogen species, and the role of nNOS phosphorylation in the MPTP toxicities and dopamine homeostasis should be further evaluated.
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PMID:Enhanced susceptibility to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity in high-fat diet-induced obesity. 1572 91

Hyperhomocysteinemia has been identified as independent risk factor for early atherosclerotic vascular disease. The purpose of our study was to investigate the plasma homocystein (Hcy) concentrations and its relationship with lipid peroxidation as thiobarbituric acid reactive substances (TBARS) and nitric oxide (NOx; nitrite plus nitrate) concentrations in age-matched non-obese (n=55) and obese (n=60) female subjects with type 2 diabetes mellitus. Non-obese diabetic patients have significantly higher plasma tHcy and TBARS (p<0.001 and p<0.001), and significantly lower NOx concentrations than the controls (n=25) (p<0.001). The plasma tHcy and TBARS concentrations were higher and nitric oxide concentrations were lower in obese diabetics than in non-obese diabetics (for each comparison; p<0.001). Correlation analysis demonstrated that there was a significant positive correlation between tHcy and TBARS (r=0.452, p<0.01) in diabetics groups. There was no significant correlation between tHcy and plasma NOx, insulin and blood pressure. We thought that Hcy might have a permissive role on the endothelium damage through free radical generating systems and the presence of obesity the free radical induced-damage has been elevated in diabetic patients.
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PMID:Plasma total homocysteine concentrations in obese and non-obese female patients with type 2 diabetes mellitus; its relations with plasma oxidative stress and nitric oxide levels. 1603 31

Metabolic syndrome is a cluster of metabolic abnormalities, including hypertension, hyperlipidemia, hyperinsulinemia, glucose intolerance and obesity. In such lifestyle-related diseases, impairment of nitric oxide (NO) production or bioactivity has been reported to lead to the development of atherogenic vascular diseases. Therefore, in the present study we investigated changes in the NO/cyclic guanosine monophosphate (cGMP) system in aortas of SHR/NDmcr-cp (cp/cp) rats (SHR-cp), a model of the metabolic syndrome. In aortas of SHR-cp, endothelium-dependent relaxations induced by acetylcholine and endothelium-independent relaxations induced by sodium nitroprusside were significantly impaired in comparison with Wistar-Kyoto rats. Furthermore, protein levels of soluble guanylyl cyclase and cGMP levels induced by sodium nitroprusside were significantly decreased. In contrast, protein levels of endothelium NO synthase and cGMP levels induced by acetylcholine were significantly increased, and plasma NO2 plus NO3 levels were also increased. The levels of lipid peroxide in plasma and the contents of 3-nitrotyrosine, a biomarker of peroxynitrite, in aortas were markedly increased. These findings indicate that in the aortas of SHR-cp, NO production from the endothelium is augmented, although the NO-induced relaxation response is impaired. Enhanced NO production may be a compensatory response to a variety of factors, including increases in oxidative stress.
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PMID:Disturbances in nitric oxide/cyclic guanosine monophosphate system in SHR/NDmcr-cp rats, a model of metabolic syndrome. 1618 78

The purpose of this study was to compare coronary collateral circulation and with other risk factors in patients with coronary artery disease and different body mass index. Between January 1999 and December 2001, of 867 patients who underwent angiography for the first time, 90 patients (24 women and 66 men), with occlusion in only 1 coronary artery participated in the study. Information regarding age, body mass index, sex, smoking, hypertension, diabetes mellitus, hyperlipidemia, preinfarction angina, and use of oral beta blockers and nitrates were recorded for all patients. The patients were separated into 2 groups in accordance with development of their coronary collateral circulation; those with insufficient (Rentrop 0, 1, and 2) and those with sufficient coronary collateral circulation. They were also divided into 3 groups on the basis of body mass index as follows: (I) 18.0-24.9 kg/m(2), (II) 25.0-29.9 kg/m(2), and (III) more than 30 kg/m(2). In the obesity and overweight groups, hyperlipidemia, diabetes mellitus, and nitrate use were identified more frequently than in the other groups (p < 0.05). Use of oral nitrates more than 6 months before the myocardial infarction and existence of preinfarction angina affected collateral coronary vessel development in the positive direction (p = 0.01, p = 0.03, respectively). There was no correlation between coronary artery disease and coronary collateral vessel development in the obese patients (p = 0.6). Although it has been shown that coronary collateral vessel development was affected negatively in obese patients with coronary artery disease, no statistical significance was identified.
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PMID:Effect of obesity on coronary collateral vessel development in patients with coronary artery disease. 1632 41

Obesity is associated with vascular endothelial cell dysfunction (ECD). Studies on nitric oxide (NO) production of vascular system in these subjects may help delineate the pathogenesis of obesity-associated ECD. In this study, we recruited 69 severely obese patients who were treated with gastric partition surgery for weight reduction and 69 matched healthy controls for comparison. The following parameters were obtained in the healthy control subjects and in the obese subjects both before and after gastric partition surgery: body mass index, blood pressure, serum lipids, high sensitivity C-reactive protein (hs-CRP), adiponectin, total nitrite and nitrate (NO(x)), and 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha), and insulin resistance index (as measured by homeostasis model assessment (HOMA-IR). At baseline, serum lipids, glucose, insulin, hs-CRP and 8-iso-PGF2alpha and HOMA-IR were all higher while adiponectin lower in the obese group than in the control group. The serum NO(x) levels were not different between the two groups. In the obese subjects, the adiponectin levels were significantly elevated but NO(x) markedly decreased after surgery. All other measurements, except for systolic blood pressure, were decreased after surgery. For healthy controls, the serum NO(x) levels were negatively associated with HOMA-IR and positively associated with serum adiponectin levels as analyzed by multiple linear regression analysis. In obese patients, the baseline serum NO(x) was positively associated with the serum TG levels. The changes of serum NO(x) levels after weight reduction surgery were positively associated with the changes of body mass index and serum TG levels. These observations suggested that, in the extremely obese patients, there might be excessive production and/or inactivation of NO and, after weight reduction surgery, the NO production was down-regulated. In conclusion, in the severely obese patients, the apparently normal NO production might be due to over-expression of iNOS. After gastric partition surgery, the NO production was significantly decreased which might be reflecting the usual status of NO production in obese subjects. The positive correlation between NO(x) and serum TG level might suggest that the metabolism of TG plays a role in the regulation of NO production.
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PMID:Nitric oxide production is paradoxically decreased after weight reduction surgery in morbid obesity patients. 1654 95

Several genes play a major role in obese phenotypes, and studies suggest that genetic variations among individuals, as well as their lifestyles, may bring about different body compositions. Among these genes, LEP, which codifies leptin, and the LEPR gene encoding its receptor were extensively studied for variants that could explain the obese phenotype. The LEPR p.Q223R gene polymorphism was analyzed in a sample of obese and nonobese individuals from Brazil to evaluate the role of this polymorphism in the obese phenotype in the population. Two hundred obese patients (60 males, 140 females, body mass index (BMI) >30 kg/m2) were screened, together with 150 lean or normal healthy individuals (63 males, 87 females, BMI <24 kg/m2). Genomic DNA was extracted and amplified by polymerase chain reaction (PCR). PCR products were digested with the restriction of endonuclease MspI, and separated by electrophoresis through an 8% polyacrilamide gel stained with silver nitrate. There was a significant difference in LEPR p.Q223R polymorphism frequency when comparing obese and lean subjects, with an odds ratio of 1.92 and a 95% confidence interval of 1.15-3.22 (P = 0.013). There is a strong association of the LEPR p.Q223R gene polymorphism with obesity in Brazil.
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PMID:p.Q223R leptin receptor polymorphism associated with obesity in Brazilian multiethnic subjects. 1678 91

Obesity continues to be an increasing health problem in worldwide and antiobesity drugs have commonly been used by obese patients. During the use of anorectic drugs, the antioxidant defense may be affected, especially by reactive oxygen species. It was decided to investigate the effects of dexfenfluramine on body weight, daily food intake, brain thiobarbituric acid-reactive substances (TBARS), glutathione (GSH) and nitric oxide (NO) levels, and 5-HT immunoreactivity. Mice were divided into two groups each containing 8 Swiss Albino adult (6 months) mice. Group 1, untreated, was used as a control; group 2 was treated with dexfenfluramine 0.4 mg/kg per day intraperitoneally for 7 days. Brain TBARS and GSH levels were assayed spectrophotometrically. The stable end-products of NO, nitrite and nitrate, were analyzed spectrophotometrically. Brain tissue 5-HT immunoreactivity was observed using an immunohistochemical method. There were significant decreases in body weight in the dexfenfluramine group (p < 0.05). Although brain GSH and NO(x) levels decreased significantly, brain TBARS levels increased in the dexfenfluramine group (p < 0.05). Brain 5-HT immunoreactivity also increased in the dexfenfluramine-treated group compared to control. In conclusion, our findings show that dexfenfluramine is effective in achieving weight loss and also increases lipid peroxidation in mouse brain.
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PMID:The effects of dexfenfluramine administration on brain serotonin immunoreactivity and lipid peroxidation in mice. 1700 98

Disruption of leptin signaling in the heart may contribute to obesity-related cardiac disease, as leptin deficient (oblob) mice display cardiac hypertrophy, increased cardiac apoptosis and reduced survival. Since leptin maintains a tonic level of neuronal nitric oxide synthase (NOS1) expression in the brain, we hypothesized that leptin deficiency would decrease NOS1 cardiac expression, in turn activating xanthine oxidoreductase (XOR) and creating nitroso-redox imbalance. We studied 2- to 6-month-old oblob (n=26) and C57Bl/6 controls (n=27). Cardiac NOS1 protein abundance (P<0.01) and mRNA expression (P=0.03) were reduced in oblob (n=10 and 6, respectively), while NOS3 protein abundance and mRNA expression were unaltered. Importantly, cardiac NOS1 protein abundance was restored towards normal in oblob mice after leptin treatment (n=3; P<0.05 vs leptin untreated oblob mice). NO metabolite (nitrite and nitrate) production within the myocardium was also reduced in oblob mice (n=5; P=0.02). Furthermore, oxidative stress was increased in oblob mice as GSH/GSSG ratio was decreased (n=4; P=0.02). Whereas XOR activity measured by Amplex Red fluorescence was increased (n=8; P=0.04), XOR and NADPH oxidase subunits protein abundance were not changed in oblob mice (n=6). Leptin deficiency did not disrupt NOS1 subcellular localization, as NOS1 co-localized with ryanodine receptor but not with caveolin-3. In conclusion, leptin deficiency is linked to decreased cardiac expression of NOS1 and NO production, with a concomitant increase in XOR activity and oxidative stress, resulting in nitroso-redox imbalance. These data offer novel insights into potential mechanisms of myocardial dysfunction in obesity.
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PMID:Reduced neuronal nitric oxide synthase expression contributes to cardiac oxidative stress and nitroso-redox imbalance in ob/ob mice. 1730 68


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