Pinolenic acid ameliorates oleic acid-induced lipogenesis and oxidative stress via AMPK/SIRT1 signaling pathway in HepG2 cells.

Pinolenic acid (PLA), a natural compound isolated from pine nut oil, has been reported to exert bioactivity against lipid anabolism. Nonetheless, the underlying mechanisms still poorly elucidated. The aim of this study is to comprehensively demonstrate the effects of PLA on oleic acid (OA)-induced non-alcoholic fatty liver disease (NAFLD) and their relationship with the lipid metabolic regulation. The results demonstrated that treatment with PLA dramatically inhibited lipid accumulation, oxidative stress as well as inflammatory responses induced by oleic acid in HepG2 cells. PLA also obviously decreased the levels of cellular triglyceride (TG), total cholesterol (TC), malondialdehyde (MDA), reactive oxygen species (ROS) and nitric oxide (NO). As well as PLA stilled promoted the antioxidant enzymes activity including superoxide dismutase (SOD) and glutathione peroxidase (GPX). Furthermore, PLA could increase the expressions of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase1 (HO-1) to alleviate oxidative damage. It also could reduce lipogenesis-related transcription factors expression, such as sterol regulatory element-binding protein 1 (SREBP1c), fatty acid synthase (FASN) and stearoyl-CoA desaturase 1 (SCD1). PLA treatment resulted in increasing phosphorylation of AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-α (PPARα) expression. However, pretreatment with compound C (inhibitor of AMPK) inhibited the effect of PLA on promoting the expression of p-AMPK, SIRT1 and PPARα for lipolysis. Taken together, these results demonstrated that PLA possessed the potential to prevent lipid accumulation in OA-induced HepG2 cells via upregulating the AMPK/SIRT1 signaling pathway, which supported the development of new drug candidate against non-alcoholic steatohepatitis.