Auraptene regulates gene expression involved in lipid metabolism through PPARa activation in diabetic obese mice

Scope: Peroxisome proliferator-activated receptor-a (PPARa) is a key regulator of circulating lipid level. Thus, various food-derived compounds that activate PPARa as agonists have been screened and characterized. Methods and results: We investigated the effects of auraptene, a citrus-derived compound serving as a PPARa agonist in vitro, on abnormalities in lipid and glucose metabolisms. In high-fat-diet HFD)-fed KK-Ay diabetic obese mice, auraptene treatment suppressed hyperlipidemia and triglyceride accumulation in the liver and skeletal muscle, and increased the mRNA expression levels of the PPARa target genes involved in fatty acid oxidation in the liver and skeletal muscle. Moreover, the adipocyte size in the auraptene-treated mice was significantly smaller than that in the control HFD-fed mice resulting in the improvement of HFDinduced hyperglycemia and abnormalities in glucose tolerance. Conclusions: These findings indicate that auraptene activates PPARa also in vivo and its treatment may improve abnormalities in lipid and glucose metabolisms, suggesting that auraptene is a valuable food-derived compound for managing metabolic disorders.