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)

Aim of this study was to evaluate whether the age of onset of obesity might affect the prevalence of CV risk factors in severely obese patients. Five hundred forty-five (385 F aged 42.3 +/- 7.1 yrs, BMI 47.3 +/- 5.1 w/h2 and 160 M of 39.0 +/- 1.1 yrs and BMI of 41.8 +/- 5.3 w/h2) severely obese patients hospitalized in the Metabolic Unit between 1972 and 1985 were subdivided in four classes according to the age of onset of obesity. Severely obese women with maturity onset obesity (i.e. onset greater than or equal to 20 yrs) (MOO) had higher (p less than or equal to .01) serum glucose (118 vs 103 mg/dl) and triglyceride (167 vs 126 mg/dl) than those with early onset obesity (EOO) (i.e. onset less than or equal to 3 yrs) with the same age, BMI and smoking habits. Similar trend was also found in men. In males arterial blood pressure was found to be higher (p less than or equal to .01) in EOO than in MOO (SBP = 152 vs 133 mmHg and DBP = 92 vs 83 mmHg). Similar trend was found in females. In conclusion age of onset of obesity may, at least in part, affect the prevalence of cardiovascular risk factors in severe obesity.
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PMID:Cardiovascular risk factors and age of onset of obesity in severely obese patients. 317 99

Renal depletion of myo-inositol (MI) is associated with the pathogenesis of diabetic nephropathy in animal models, but the underlying mechanisms involved are unclear. We hypothesized that MI depletion was due to changes in inositol metabolism and therefore examined the expression of genes regulating de novo biosynthesis, reabsorption, and catabolism of MI. We also extended the analyses from diabetes mellitus to animal models of dietary-induced obesity and hypertension. We found that renal MI depletion was pervasive across these three distinct disease states in the relative order: hypertension (-51%)>diabetes mellitus (-35%)>dietary-induced obesity (-19%). In 4-wk diabetic kidneys and in kidneys derived from insulin-resistant and hypertensive rats, MI depletion was correlated with activity of the MI-degrading enzyme myo-inositol oxygenase (MIOX). By contrast, there was decreased MIOX expression in 8-wk diabetic kidneys. Immunohistochemistry localized the MI-degrading pathway comprising MIOX and the glucuronate-xylulose (GX) pathway to the proximal tubules within the renal cortex. These findings indicate that MI depletion could reflect increased catabolism through MIOX and the GX pathway and implicate a common pathological mechanism contributing to renal oxidative stress in metabolic disease.
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PMID:Renal depletion of myo-inositol is associated with its increased degradation in animal models of metabolic disease. 2631 Nov 12

The kidney is one of the target organs for various metabolic diseases, including diabetes, metabolic syndrome, and obesity. Most of the metabolic studies underscore glomerular pathobiology, although the tubulo-interstitial compartment has been underemphasized. This study highlights mechanisms concerning the pathobiology of tubular injury in the context of myo-inositol oxygenase (Miox), a tubular enzyme. The kidneys of mice fed a high fat diet (HFD) had increased Miox expression and activity, and the latter was related to phosphorylation of serine/threonine residues. Also, expression of sterol regulatory element-binding protein1 (Srebp1) and markers of cellular/nuclear damage was increased along with accentuated apoptosis and loss of tubular brush border. Similar results were observed in cells treated with palmitate/BSA. Multiple sterol-response elements and E-box motifs were found in the miox promoter, and its activity was modulated by palmitate/BSA. Electrophoretic mobility and ChIP assays confirmed binding of Srebp to consensus sequences of the miox promoter. Exposure of palmitate/BSA-treated cells to rapamycin normalized Miox expression and prevented Srebp1 nuclear translocation. In addition, rapamycin treatment reduced p53 expression and apoptosis. Like rapamycin, srebp siRNA reduced Miox expression. Increased expression of Miox was associated with the generation of reactive oxygen species (ROS) in kidney tubules of mice fed an HFD and cell exposed to palmitate/BSA. Both miox and srebp1 siRNAs reduced generation of ROS. Collectively, these findings suggest that HFD or fatty acids modulate transcriptional, translational, and post-translational regulation of Miox expression/activity and underscore Miox being a novel target of the transcription factor Srebp1. Conceivably, activation of the mTORC1/Srebp1/Miox pathway leads to the generation of ROS culminating into tubulo-interstitial injury in states of obesity.
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PMID:Transcriptional and Translational Modulation of myo-Inositol Oxygenase (Miox) by Fatty Acids: IMPLICATIONS IN RENAL TUBULAR INJURY INDUCED IN OBESITY AND DIABETES. 2657 17