High-fat diet enhances visceral advanced glycation end products, nuclear O-Glc-Nac modification, p38 mitogen-activated protein kinase activation and apoptosis

Diabetes Obes Metab. 2005 Jul;7(4):448-54. doi: 10.1111/j.1463-1326.2004.00387.x.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylglucosaminidase / metabolism*
  • Animals
  • Apoptosis / physiology*
  • Blood Pressure / physiology
  • Body Weight / physiology
  • Caspase 3
  • Caspases / metabolism
  • Cell Nucleus / physiology
  • Cytoplasm / metabolism
  • DNA Fragmentation / physiology
  • Dietary Fats / administration & dosage*
  • Glucose / metabolism*
  • Heart Rate / physiology
  • Histone Acetyltransferases / metabolism*
  • Kidney / metabolism
  • Liver / metabolism
  • Male
  • Multienzyme Complexes / metabolism*
  • Myocardium / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • beta-N-Acetylhexosaminidases
  • p38 Mitogen-Activated Protein Kinases / metabolism*


  • Dietary Fats
  • Multienzyme Complexes
  • Histone Acetyltransferases
  • p38 Mitogen-Activated Protein Kinases
  • hexosaminidase C
  • Acetylglucosaminidase
  • beta-N-Acetylhexosaminidases
  • Casp3 protein, rat
  • Caspase 3
  • Caspases
  • Glucose