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

The effect of obesity on peroxisomal beta oxidation has been studied previously only in the liver of genetically obese animals. We measured activity of peroxisomal acyl CoA oxidase (ACO) in livers, hearts and rectus femoris muscles of gold-thioglucose treated obese mice (n = 17) and control mice (n = 8). Since production of H2O2 by ACO could contribute to oxidative stress, activities of H2O2-metabolizing enzymes, catalase and glutathione peroxidase, were also measured. ACO activity was assayed using dichlorofluorescein and peroxidase as detectors of H2O2. ACO activity was higher in the obese liver and skeletal muscles than in their respective controls, while the heart ACO activity was unaltered. The activities of H2O2-metabolizing enzymes were unchanged or tended to be decreased in the obese tissues. There was a close correlation between the body weight and ACO activity in both liver and rectus femoris muscles. The ACO activity in the liver also correlated with the liver triacylglycerol content. These results suggest that the activation of peroxisomal beta oxidation occurring in both hepatic and extrahepatic obese tissues is closely linked to weight gain (i.e. non-genetic in nature), but that this does not enhance oxidative stress detected as reactive change of the defense system against H2O2.
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PMID:Peroxisomal beta-oxidation in liver and muscles of gold-thioglucose-induced obese mice: correlation with body weight. 201 Feb 57

Adipose tissue slices were prepared from middle subcutaneous or perirenal adipose tissue excised from pigs of different ages (and obesity) and incubated with [U-14C]glucose. After incubation, the slices were fixed with osmium tetroxide and separated into diameter ranges of 20--63, 63--102, and 102--153 microgram, respectively. Following determination of cell size and number, the fixed adipocytes were decolorized with H2O2 prior to quantification of glucose conversion to total lipid, glyceride fatty acids, glycerideglycerol, and CO2. Glucose conversion to total lipid or CO2 was unaffected by the presence of purified porcine insulin (0, 10, 100, 1000, and 100,000 microM/ml). Within animals, adipocytes of different sizes were not different with regard to insulin sensitivity. Within a weight (age) group, conversion of glucose to total lipid (insulin present) or to glyceride fatty acids and glyceride-glycerol (insulin absent) per cell was significantly greater in large adipocytes compared to small adipocytes, regardless of the group examined. With increasing weight or age, there was a markedly decreased conversion of glucose to total lipid and glyceride fatty acids among adipocytes of similar size within a cell-size fraction. The diminution in glucose metabolism was greater (as a percentage) in 20--63 microgram adipocytes than for 63--102 or 102--153 microgram adipocytes. However, for all cell-size fractions there was a marked decrease in glucose conversion to fatty acids. Glyceride-glycerol synthesis was impaired in adipocytes from older pigs, but the decrease was less than observed for glyceride fatty acid synthesis.
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PMID:Effects of cell size and animal age on glucose metabolism in pig adipose tissue. 678 14

Several lines of evidence support an atherogenic role for oxidized low-density lipoprotein (LDL). Previous studies have suggested that although Mexican-Americans have an increased rate of diabetes, obesity, elevated triglyceride levels, and low high-density lipoprotein (HDL) cholesterol levels, their rates of coronary heart disease (CHD) are similar or possibly lower than in non-Hispanic whites. Mexican-Americans have smaller, denser LDL than non-Hispanic whites. On the basis of this latter observation, we postulated that lipid peroxide (LPO) levels would be increased in Mexican-Americans. We examined the oxidizability of plasma in 50 Mexican-Americans and 50 non-Hispanic whites from the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease, at baseline and after coincubation with a metal-independent system (2'2'-azobis-2-amidinopropane hydrochloride [AAPH]) and a metal-dependent system (Fe2+/H2O2) of oxidation. LPO levels were measured by a modified fluorimetric assay. Vitamin E and plasma fatty acid composition were also determined. We found significantly higher LPO levels at baseline and after AAPH coincubation in Mexican-Americans than in non-Hispanic whites (baseline, 2.75 +/- .09 v 2.07 +/- .09 micromol/L, P < .001; post-AAPH, 5.49 +/- .14 v 5.07 +/-. .04 micromol/L, P = .037). However, no significant ethnic differences were seen after coincubation with Fe2+/H2O2. Diabetes and cigarette-smoking were also associated with higher LPO levels. Mexican-Americans also had lower levels of vitamin E (the predominant lipid-soluble antioxidant in plasma) than non-Hispanic whites, although these differences only partially explained the differences in susceptibility to oxidation. Plasma fatty acids were similar in Mexican-Americans and non-Hispanic whites, suggesting only small differences in diet composition. We conclude that LPO levels are higher in Mexican-Americans than in non-Hispanic whites, and that these results are only partially related to differences in vitamin E levels.
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PMID:Plasma oxidizability in Mexican-Americans and non-Hispanic whites. 869 25

Obese hypertensive patients with cardiovascular risk factor clustering have increased plasma nonesterified fatty acid levels and are at high risk for atherosclerotic events. Our previous studies demonstrated that oleic acid induces a mitogenic response in rat aortic smooth muscle cells (RASMCs) through protein kinase C (PKC)- and extracellular signal-regulated kinase (ERK)-dependent pathways. In the present study we investigated the possibility that the generation of reactive oxygen species (ROS) constitutes a critical component of the oleic acid-induced mitogenic signaling pathway in RASMCs. We studied the effect(s) of oleic acid on the generation of ROS using the oxidant-sensitive fluoroprobe 2',7'-dichlorofluorescin diacetate. Relative fluorescence intensity and fluorescent images were obtained with laser confocal scanning microscopy from 1 to 5 minutes, since preliminary studies demonstrated that the peak fluorescence intensity occurred within 5 minutes. Oleic acid (100 micromol/L) induced a time-dependent increase of cell fluorescence that was >8-fold of that seen in control cells at 5 minutes. This was blocked by catalase, which suggests that H2O2 was the principal ROS. The oleic acid-induced increases in H2O2 were blocked when PKC was inhibited with the use of bisindolylmaleimide and when PKC activity was downregulated by exposing RASMCs to phorbol 12-myristate 13-acetate for 24 hours. Stearic and elaidic acids, which are weak PKC activators, did not significantly increase H2O2 production. The increase of H2O2 in response to oleic acid was inhibited by the antioxidant N-acetylcysteine. N-Acetylcysteine also completely blocked ERK activation and the increase of thymidine incorporation in response to oleic acid. The data suggest that generation of H2O2 in RASMCs exposed to oleic acid is PKC dependent. Moreover, H2O2 production emerges as a critical intermediary event in the oleic acid-mediated mitogenic signaling pathway between the activation of PKC and ERK. These observations raise the possibility that the elevated plasma nonesterified fatty acids, including oleic acid, in obese hypertensive patients contribute to vascular growth and remodeling by a PKC-dependent mechanism to generate ROS that subsequently activate ERK.
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PMID:Reactive oxygen species are critical in the oleic acid-mediated mitogenic signaling pathway in vascular smooth muscle cells. 985 64

1. Insulin resistance has been highlighted as a common causal factor for hypertension, hyperlipidaemia, diabetes mellitus and obesity, all of which are recognized to occur simultaneously, and a distinct clinical entity is defined as 'multiple risk factor syndrome'. 2. Recently, a new class of antidiabetic agents, thiazolidinediones (TZD) has been developed and has been shown to improve insulin resistance by binding and activating a nuclear receptor, peroxisome proliferator-activated receptor (PPAR) gamma. 3. cDNA of rat PPAR gamma 1 and gamma 2 were cloned and gene regulation of PPAR gamma in rat mature adipocytes was examined. Hydrogen peroxide, an oxygen radical, which is recognized to be the common intracellular signal for multiple risk factors, potently down-regulated PPAR gamma mRNA expression in rat mature adipocytes. 4. Tumour necrosis factor (TNF)-alpha, which is considered to play a role in obesity-induced non-insulin-dependent diabetes mellitus and to augment oxidative stress, also suppressed PPAR gamma expression. 5. Thiazolidinediones dose-dependently recovered TNF-alpha-induced down-regulation of PPAR gamma mRNA expression. 6. The modulation of PPAR gamma expression by TZD can be one mechanism for the improvement of insulin resistance by TZD. 7. Vascular tone and remodelling are controlled by several vasoactive autocrine/paracrine factors produced by endothelial cells in response to several vascular injury stimuli, including hypertension. The PPAR gamma gene transcript was detected in cultured endothelial cells. 8. The administration of TZD stimulated the endothelial secretion of type-C natriuretic peptide, which is one of the natriuretic peptide family and is demonstrated by us to act as a novel endothelium-derived relaxing peptide. 9. Concomitantly, TZD significantly suppressed the secretion of endothelin, a potent endothelium-derived vasoconstricting peptide. 10. Thiazolidinediones can affect vascular tone and growth by modulating the production of endothelium-derived vasoactive substances to influence occurrence and progression of hypertension and atherosclerosis.
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PMID:Hypertension and insulin resistance: role of peroxisome proliferator-activated receptor gamma. 1040 88

The clinical activities of the department of endocrinology encompass the care and treatment of diabetes, thyroid diseases, hypothalamo-pituitary, adrenal, gonadic and parathyroid diseases, obesity, hypercholesterolemia and paraneoplastic endocrine syndromes. These domains are briefly described. The research activities of the department have investigated the regulation of thyroid metabolism in vitro, the intrathyroid H2O2 generating system, the physiopathology of toxic thyroid nodules and the effects of ageing on the thyreotropic function of the normal ageing male. Studies of "jet lag" conditions have shed a new light on hormonal chronophysiology. Other investigations have considered the regulation of ketone body metabolism, the relationship between nutritional status and glucose metabolism, and some aspects of immunodiabetology.
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PMID:[The endocrinology department]. 1258 11

Increased oxidative stress is believed to be one of the mechanisms responsible for hyperglycemia-induced tissue damage and diabetic complications. In these studies, we undertook to characterize glucose uptake and oxidative stress in adipocytes of type 2 diabetic animals and to determine whether these promote the activation of PKC-delta. The adipocytes used were isolated either from C57Bl/6J mice that were raised on a high-fat diet (HF) and developed obesity and insulin resistance or from control animals. Basal glucose uptake significantly increased (8-fold) in HF adipocytes, and this was accompanied with upregulation of GLUT1 expression levels. Insulin-induced glucose uptake was inhibited in HF adipocytes and GLUT4 content reduced by 20% in these adipocytes. Reactive oxygen species (ROS) increased twofold in HF adipocytes compared with control adipocytes and were largely reduced with decreased glucose concentrations. At zero glucose, ROS levels were reduced to the normal levels seen in control adipocytes. The activity of PKC-delta increased twofold in HF adipocytes compared with control adipocytes and was further activated by H2O2. Moreover, PKC-delta activity was inhibited in HF adipocytes either by glucose deprivation or by treatment with the antioxidant N-acetyl-l-cysteine. In summary, we propose that increased glucose intake in HF adipocytes increases oxidative stress, which in turn promotes the activation of PKC-delta. These consequential events may be responsible, at least in part, for development of HF diet-induced insulin resistance in the fat tissue.
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PMID:Increased glucose uptake promotes oxidative stress and PKC-delta activation in adipocytes of obese, insulin-resistant mice. 1285 75

Adiponectin is emerging as an important molecule in obesity, the metabolic syndrome, and cardiovascular disease. On the other hand, smoking habit is well known to be related to cardiovascular disease and hypertension. To examine the association between adiponectin concentration and smoking habit, we performed an epidemiological survey and an acute exposure test in humans and an experiment in adipocytes to elucidate the mechanism underlying the association between adiponectin and smoking. In the epidemiological study, we enrolled a total of 331 male subjects to examine chronic smoking exposure. Plasma adiponectin was significantly lower (P=0.01) in current smokers (5.3+/-0.3 microg/mL) than in never-smokers (6.5+/-0.4 microg/mL). A significant association between smoking and low adiponectin level was also confirmed in multiple regression analysis including age, body mass index, hypertension, diabetes, hyperlipidemia, and creatinine clearance (never-smokers 6.5+/-0.4 microg/mL; past smokers 5.6+/-0.3 microg/mL; current smokers 5.2+/-0.4 microg/mL; F=4.52; P=0.01). To examine the acute effect of smoking on adiponectin concentration for 12 hours, we measured plasma adiponectin level in 5 male never-smokers before smoking and 3, 6, and 12 hours after smoking, with the result that adiponectin showed a significant decrease after smoking (12 hours; -14.5+/-0.6%; P<0.01). In cultured mouse 3T3-L1 adipocytes, H2O2 and nicotine reduced the mRNA expression and secretion of adiponectin in a dose-dependent manner. Smoking habit is associated with adiponectin concentration in men, and its suppressive effect is mediated in part through direct inhibition of smoking on adiponectin expression in adipocytes.
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PMID:Association of hypoadiponectinemia with smoking habit in men. 1589 61

Low plasma levels of adiponectin (hypoadiponectinemia) and elevated circulating concentrations of plasminogen activator inhibitor (PAI)-1 are causally associated with obesity-related insulin resistance and cardiovascular disease. However, the mechanism that mediates the aberrant production of these two adipokines in obesity remains poorly understood. In this study, we investigated the effects of hypoxia and reactive oxygen species (ROS) on production of adiponectin and PAI-1 in 3T3-L1 adipocytes. Quantitative PCR and immunoassays showed that ambient hypoxia markedly suppressed adiponectin mRNA expression and its protein secretion, and increased PAI-1 production in mature adipocytes. Dimethyloxallyl glycine, a stabilizer of hypoxia-inducible factor 1alpha (HIF-1alpha), mimicked the hypoxia-mediated modulations of these two adipokines. Hypoxia caused a modest elevation of ROS in adipocytes. However, ablation of intracellular ROS by antioxidants failed to alleviate hypoxia-induced aberrant production of adiponectin and PAI-1. On the other hand, the antioxidants could reverse hydrogen peroxide (H2O2)-induced dysregulation of adiponectin and PAI-1 production. H2O2 treatment decreased the expression levels of peroxisome proliferator-activated receptor gamma (PPARgamma) and CCAAT/enhancer binding protein (C/EBPalpha), but had no effect on HIF-1alpha, whereas hypoxia stabilized HIF-1alpha and decreased expression of C/EBPalpha, but not PPARgamma. Taken together, these data suggest that hypoxia and ROS decrease adiponectin production and augment PAI-1 expression in adipocytes via distinct signaling pathways. These effects may contribute to hypoadiponectinemia and elevated PAI-1 levels in obesity, type 2 diabetes, and cardiovascular diseases.
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PMID:Hypoxia dysregulates the production of adiponectin and plasminogen activator inhibitor-1 independent of reactive oxygen species in adipocytes. 1642 6

The release of fatty acids and glycerol from lipid droplets (LD) of mammalian adipose cells is tightly regulated by a number of counterregulatory signals and negative feedback mechanisms. In humans unrestrained lipolysis contributes to the pathogenesis of obesity and type II diabetes. In order to identify novel targets for the pharmacological interference with lipolysis, the molecular mechanisms of four antilipolytic agents were compared in isolated rat adipocytes. Incubation of the adipocytes with insulin, palmitate, glucose oxidase (for the generation of H2O2) and the antidiabetic sulfonylurea drug, glimepiride, reduced adenylyl cyclase-dependent, but not dibutyryl-cAMP-induced lipolysis as well as the translocation of hormone-sensitive lipase and the LD-associated protein, perilipin-A, to and from LD, respectively. The antilipolytic activity of palmitate, H2O2 and glimepiride rather than that of insulin was dependent on rolipram-sensitive but cilostamide-insensitive phosphodiesterase (PDE) but was not associated with detectable downregulation of total cytosolic cAMP and insulin signaling via phosphatidylinositol-3 kinase and protein kinase B. LD from adipocytes treated with palmitate, H2O2 and glimepiride were capable of converting cAMP to adenosine in vitro, which was hardly observed with those from basal cells. Conversion of cAMP to adenosine was blocked by rolipram and the 5'-nucleotidase inhibitor, AMPCP. Immunoblotting analysis revealed a limited salt-sensitive association with LD of some of the PDE isoforms currently known to be expressed in rat adipocytes. In contrast, the cAMP-to-adenosine converting activity was stripped off the LD by bacterial phosphatidylinositol-specific phospholipase C. These findings emphasize the importance of the compartmentalization of cAMP signaling for the regulation of lipolysis in adipocytes, in general, and of the involvement of LD-associated proteins for cAMP degradation, in particular.
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PMID:Inhibition of lipolysis by palmitate, H2O2 and the sulfonylurea drug, glimepiride, in rat adipocytes depends on cAMP degradation by lipid droplets. 1818 16


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