Citrus peel flavonoids modulate miRNA-PPAR-mediated signalling pathway, a novel mechanism for improving hepatic lipid metabolism in obesity

Citrus flavonoids have demonstrated anti-obesity effects. However, the molecular mechanisms behind citrus flavonoid-induced lipid-lowering regulation have not been well elucidated. The refined citrus peel flavonoids (CPFs) contain hesperidin, nobiletin and tangeretin. CPFs ameliorated high-fat diet (HFD)-induced obesity in KM mice by reducing triglyceride and total cholesterol levels both in serum and liver. The RT-qPCR analysis demonstrated that CPFs have a regulatory effect on the genes associated with lipid metabolism. CPFs significantly up-regulated the gene expression levels of carnitine palmitoyltransferase 1a (CPT1a), ATP-binding cassette transporter A1 (ABCA1) and peroxisome proliferator-activated receptor α (PPARα). However, the mRNA expression level of fatty acid synthase (FAS) was down-regulated by CPFs approximately 39.68%. Supplementation of CPFs resulted in a sharp decrease in the expression levels of miR-33 and miR-122, both of which modulated the mRNA expression levels of CPT1a, ABCA1 and FAS. The preventative effects of CPFs against dyslipidemia in mice are likely due to modulation of the miRNA and PPARα signaling pathway.