Green tea extract attenuates oxidative stress, inflammation, and lipogenesis through Nrf2‐dependent and ‐independent mechanisms in diet‐induced obese mice with nonalcoholic steatohepatitis

Abstract

Green tea extract (GTE) lowers oxidative stress and inflammation during nonalcoholic steatohepatitis (NASH). We hypothesized that GTE would attenuate these pathologic insults in a Nrf2-dependent manner. Wild-type (WT) and Nrf2-knockout (KO) mice were fed a high-fat diet containing 0 or 2% GTE for 8 wk prior to assessing NASH, lipid peroxidation, and mRNA expression of lipogenic and NFκB-dependent inflammatory genes. Nrf2 deficiency increased serum alanine aminotransferase (ALT), liver steatosis, malondialdehyde (MDA), and mRNA expression of genes involved in inflammation (TNFα, iNOS), lipid uptake (cluster of differentiation 36), and lipogenesis [sterol regulatory element-binding transcription factor-1c, fatty acid synthase, stearoyl-CoA desaturase-1, diglyceride acyltransferase (DGAT)]. GTE suppressed each of these regardless of Nrf2 status. In KO mice fed GTE, TNFα and DGAT were normalized to WT mice fed GTE whereas ALT, steatosis and other lipogenic genes were reduced only to WT controls. KO mice fed GTE had lower iNOS and MDA than KO controls, but remained elevated compared to WT controls. Collectively, Nrf2 deficiency exacerbates NASH, but GTE decreases TNFα and DGAT expression independent of Nrf2 whereas protective activities of GTE on liver injury, steatosis, lipid peroxidation, and expression of iNOS and most lipogenic genes are partly Nrf2-dependent. Supported by USDA-NIFA.