Hepatocyte-specific Nrf2 deficiency mitigates high-fat diet-induced hepatic steatosis: Involvement of reduced PPARγ expression.

ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) is an emerging global disease with increasing prevalence. However, the mechanism of NAFLD development is not fully understood. To elucidate the cell-specific role of nuclear factor erythroid-derived 2-like 2 (NRF2) in the pathogenesis of NAFLD, we utilized hepatocyte- and macrophage-specific Nrf2-knockout [Nrf2(L)-KO and Nrf2(Mϕ)-KO] mice to examine the progress of NAFLD induced by high-fat diet (HFD). Compared to Nrf2-LoxP littermates, Nrf2(L)-KO mice showed less liver enlargement, milder inflammation and less hepatic steatosis after HFD feeding. In contrast, Nrf2(Mϕ)-KO mice displayed no significant difference in HFD-induced hepatic steatosis from Nrf2-LoxP control mice. Mechanistic investigations revealed that Nrf2 deficiency in hepatocytes damp

SUBMITTER: Li L 

PROVIDER: S-EPMC6940621 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature