Oleic acid-induced perilipin 5 expression and lipid droplets formation are regulated by the PI3K/PPARα pathway in HepG2 cells

Perilipin 5 (Plin5), a member of the PAT (Perilipin, ADRP, and Tip47) protein family, has been implicated in the regulation of cellular neutral lipid accumulation in nonalcoholic fatty liver diseases. However, the underlying regulatory mechanisms of Plin5 are not clear. The goal of the present study was to explore the mechanism of oleic acid (OA)-induced Plin5 expression in HepG2 cells. We found that the expression of Plin5 was increased during OA-induced lipid droplets formation in a dose- and time-dependent manner. During this process of OA-stimulated lipid droplets formation, peroxisome proliferator-activated receptor alpha (PPAR alpha) was also upregulated. When PPAR alpha activation was blocked by GW6471, OA-induced Plin5 expression and lipid droplets formation were effectively ablated. We further found that the phosphoinositide 3-kinase (PI3K) inhibitor LY294002 was able to downregulate both PPAR alpha and Plin5 expression and lipid droplets formation. Thus, we concluded that PI3K may, at least in part, act upstream of PPAR alpha to regulate Plin5 expression and lipid droplets formation in HepG2 cells.