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 (PPARα) was also upregulated. When PPARα 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 PPARα and Plin5 expression and lipid droplets formation. Thus, we concluded that PI3K may, at least in part, act upstream of PPARα to regulate Plin5 expression and lipid droplets formation in HepG2 cells.

Beige adipocytes in white adipose tissue (WAT) have received considerable recognition because of their potential protective effect against obesity. Pycnogenol (PYC), extracted from French maritime pine bark, has anti-inflammatory and antioxidant properties and can improve lipid profiles. However, the effect of PYC on obesity has never been explored. In this study, we investigated the effects of PYC on obesity and WAT browning in apolipoprotein E- (ApoE-) deficient mice. The results showed that PYC treatment clearly reversed body weight and the mass of eWAT gain resulting from a high-cholesterol and high-fat diet (HCD), but no difference in food intake. The morphology results showed that the size of the adipocytes in the PYC-treated mice was obviously smaller than that in the HCD-fed mice. Next, we found that PYC upregulated the expression of genes related to lipolysis (ATGL and HSL), while it decreased the mRNA level of PLIN1. PYC significantly increased the expression of UCP1 and other genes related to beige adipogenesis. Additionally, PYC increased the expression of proteins related to the protein kinase A (PKA) signaling pathway. The findings suggested that PYC decreased obesity by promoting lipolysis and WAT browning. Thus, PYC may be a novel therapeutic target for obesity.