Resveratrol prevents the impairment of advanced glycosylation end products (AGE) on macrophage lipid homeostasis by suppressing the receptor for AGE via peroxisome proliferator-activated receptor γ activation

Abstract

Abstract. Advanced glycosylation end products (AGE) and its receptor (RAGE) axis is involved in the regulation of lipid homeostasis and is critical in the pathogenesis of diabetic atherosclerosis. We investigated the protective role of resveratrol against the AGE-induced impairment on macrophage lipid homeostasis. In THP-1-derived macrophages, RAGE was dose-dependently induced by AGE and played a key role in the AGE-induced cholesterol accumulation. Resveratrol markedly reduced RAGE expression via peroxisome proliferator-activated receptor (PPAR) Á but not PPAR· or AMP-activated protein kinase. Importantly, pretreatment with resveratrol significantly ameliorated AGE-induced upregulation of scavenger receptor-A (SR-A) and down-regulation of ATP-binding cassette (ABC) A1 and ABCG1 and thus effectively prevented the cholesterol accumulation in macrophages as shown by cellular cholesterol analysis and oil red O staining. Moreover, blockade of PPARÁ abolished all these effects of resveratrol. Collectively, our results indicate that resveratrol prevents the impairment of AGE on macrophage lipid homeostasis partially by suppressing RAGE via PPARÁ activation, which might provide new insight into the protective role of resveratrol against diabetic atherosclerosis.

Soluble Receptor for Advanced Glycation End Products: A Protective Molecule against Intramyocardial Lipid Accumulation in Obese Zucker Rats?

“…Which is the role of RAGE in promoting fat accumulation? Previous studies demonstrated a link between increased RAGE expression and activation of pathways that can promote lipid accumulation in many cell types/tissues and suggested that therapies preventing RAGE activation are able to reduce these effects [21, 30, 33, 34, 42]. Results obtained in this study emphasized the potential association between RAGE, lipid accumulation, and genes involved in lipid metabolism in the heart; however, they did not prove a direct cause-effect relationship.…”