Lycopene prevents lipid accumulation in hepatocytes by stimulating PPARα and improving mitochondrial function

Abstract

In the present study, we investigated the effects of lycopene (LYC) on nonalcoholic fatty liver disease (NAFLD)-induced hepatic lipid accumulation. Our results indicated that LYC alleviated palmitate-induced lipid accumulation in HepG2 hepatocytes cell line by stimulating PPARα expression and enhanced lipolysis. LYC also prevented mitochondrial dysfunction in palmitate-treated HepG2 cells through increasing mitochondrial complexes expressions and activating mitochondrial biogenesis pathway AMPK/SIRT1/PGC1α. Moreover, in line with in vitro study, LYC treatment suppressed lipid accumulation, enhanced PPARα expression and improved mitochondrial function in western diet-feeding mice liver. In conclusion, the mediating effects of LYC on mitochondrial function and PPARα signaling might play pivotal roles in its beneficial effects on NAFLD. • Lycopene promotes the expression of PPARα in palmitate-treated HepG2 cellsl. • LYC prevents palmitate-induced mitochondrial dysfunction in HepG2 cellsl. • LYC suppresses lipid accumulation in HFFD-feeding mice liver. The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased over the decades. Lycopene (LYC), a major carotenoid present in tomato, has been previously demonstrated to possess liver-protecting and lipid-lowering bioactivities. However, the underlying mechanism of how LYC impact on the lipid metabolism in the liver is elusive. Here, we found that LYC significantly suppressed lipid accumulation in palmitate- treated HepG2 hepatocytes cell line by stimulating PPARα expression and enhanced lipolysis consequently. It has also been revealed that LYC prevented palmitate-induced mitochondrial dysfunction by improving mitochondrial complex expression and activating mitochondrial biogenesis pathway AMPK/SIRT1/PGC1α. Moreover, in line with in vitro study, LYC treatment significantly suppressed lipid accumulation and enhanced PPARα expression in western diet-feeding mice liver. LYC also enhanced the expressions of mitochondrial complexes and antioxidant related enzymes HO-1/NQO1. In conclusion, the mediating effects of LYC on mitochondrial function and PPARα signaling might play pivotal roles in its beneficial effects on NAFLD.