RESUMEN
SCOPE: Peroxisome proliferator-activated receptor-α (PPARα) is a key regulator of circulating lipid level. Thus, various food-derived compounds that activate PPARα as agonists have been screened and characterized. METHODS AND RESULTS: We investigated the effects of auraptene, a citrus-derived compound serving as a PPARα 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 PPARα 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 HFD-induced hyperglycemia and abnormalities in glucose tolerance. CONCLUSIONS: These findings indicate that auraptene activates PPARα 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.
Asunto(s)
Cumarinas/farmacología , Regulación de la Expresión Génica , Metabolismo de los Lípidos/efectos de los fármacos , PPAR alfa/genética , Adipocitos/efectos de los fármacos , Animales , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/fisiopatología , Grasas de la Dieta/administración & dosificación , Hiperlipidemias/tratamiento farmacológico , Metabolismo de los Lípidos/genética , Hígado/metabolismo , Masculino , Enfermedades Metabólicas/tratamiento farmacológico , Ratones , Ratones Obesos , Oxidación-Reducción , PPAR alfa/metabolismo , Triglicéridos/sangreRESUMEN
Dehydroabietic acid (DAA) is a food-derived terpenoid with various bioactivities. Our previous study has revealed that DAA activates peroxisome proliferator-activated receptor-γ (PPARγ) in luciferase assay and suppresses chronic inflammation in obese adipose tissues. In this study, we examined the effects of DAA on adipocyte differentiation. DAA treatment stimulated the adipocyte differentiation of 3T3-L1 preadipocytes. The DAA treatment increased the mRNA expression levels of adipocyte differentiation marker genes such as aP2, lipoprotein lipase (LPL), and PPARγ. In particular, the expression level of adiponectin, which is an adipocytokine with stimulatory effects on insulin sensitivity, was increased at both the mRNA and protein levels by the DAA treatment. Moreover, the DAA treatment stimulated insulin-dependent glucose uptake into differentiated 3T3-L1 adipocytes. These findings indicate that DAA stimulates adipocyte differentiation and insulin sensitivity in 3T3-L1 cells, suggesting that DAA is a valuable food-derived compound for the management of metabolic syndrome.