Lycopene inhibits hepatic steatosis via microRNA‐21‐induced downregulation of fatty acid‐binding protein 7 in mice fed a high‐fat diet

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a chronic disorder characterized by hepatic fat accumulation and abnormal lipid metabolism. Here, we investigated the protective effect of lycopene on high-fat diet-induced hepatic steatosis and fatty acid-induced intracellular lipid accumulation by miRNA regulation. C57BL/6J mice were fed high-fat diet with or without 0.05% lycopene for 8 weeks. Hepa 1-6 cells were treated with stearic acid (SA) after 24 h pretreatment with lycopene. Treatment of lycopene improved hepatic steatosis in high-fat-fed mice and reduced intracellular lipid accumulation induced by SA in Hepa 1-6 cells. We demonstrated that miR-21 expression was decreased in livers from high-fat diet-fed mice and Hepa 1-6 cells treated with SA. Lycopene normalized the downregulation of miR-21, which led to the downregulation of fatty acid-binding protein 7 (FABP7), a direct target of miR-21, at both the transcriptional and translational levels. This specific negative regulation of miR-21 was achieved by targeting the FABP7 3'UTR. Upregulation of miR-21 markedly blocked SA-induced intracellular lipid accumulation by blocking FABP7 expression. Moreover, silencing of FABP7 reduced SA-evoked lipid accumulation in Hepa 1-6 cells. The results suggest that lycopene may be a useful functional compound for treating NAFLD by regulating hepatic lipid metabolism.