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

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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.