title: High-fat diet enhances visceral advanced glycation end products, nuclear O-Glc-Nac modification, p38 mitogen-activated protein kinase activation and apoptosis.
abstract: High-fat diet intake often leads to obesity, insulin resistance and hypertension, which present a common and detrimental health problem. However, precise mechanism underlying tissue damage due to high-fat diet-induced obesity has not been carefully elucidated. The present study was designed to examine the effect of high-fat diet intake on visceral advanced glycation end products (AGEs) formation, nuclear O-Glc-NAc modification and apoptosis in heart, liver and kidney. Adult male Sprague-Dawley weight-matched rats were fed for 12 weeks with a high-fat diet (45% kcal from fat) or an isocaloric low-fat diet (10% kcal from fat). High-fat diet feeding significantly elevated body weight. Blood pressure and heart rate were comparable between the two rat groups. Competitive enzyme-linked immunosorbent assay showed significantly elevated serum AGE levels, visceral AGE formation, caspase-3 activation and cytoplasmic DNA fragmentation in heart and liver but not kidney samples of high-fat diet fed rats compared with those from low-fat diet fed group. Western blot analysis further revealed that high-fat diet feeding induced overt nuclear O-Glc-NAc modification and p38 mitogen-activated protein kinase activation in heart and liver although not in kidney samples of the high-fat diet-fed rats. Collectively, our results indicated that high-fat diet intake is associated with obesity accompanied by elevated serum and visceral AGEs, visceral post-translational nuclear O-Glc-NAcylated modification and apoptosis, which may contribute to high-fat diet-induced tissue damage.
authors.affiliation: Division of Pharmaceutical Sciences and Graduate Neuroscience Program, University of Wyoming College of Health Sciences, Laramie, WY 82071-3375, USA.
authors.forename: S-Y
authors.initials: SY
authors.lastname: Li
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: V K
authors.initials: VK
authors.lastname: Sigmon
authors.forename: A
authors.initials: A
authors.lastname: McCort
authors.forename: J
authors.initials: J
authors.lastname: Ren
mesh_terms: D000118:Acetylglucosaminidase / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001794:Blood Pressure / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002467:Cell Nucleus / Q000502:physiology; D003593:Cytoplasm / Q000378:metabolism; D053938:DNA Fragmentation / Q000502:physiology; D004041:Dietary Fats / Q000008:administration & dosage*; D005947:Glucose / Q000378:metabolism*; D006339:Heart Rate / Q000502:physiology; D051548:Histone Acetyltransferases / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D001619:beta-N-Acetylhexosaminidases; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D004041:Dietary Fats; D009097:Multienzyme Complexes; D051548:Histone Acetyltransferases; D048051:p38 Mitogen-Activated Protein Kinases; C110628:hexosaminidase C; D000118:Acetylglucosaminidase; D001619:beta-N-Acetylhexosaminidases; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D005947:Glucose