title: Green tea extract provides extensive Nrf2-independent protection against lipid accumulation and NFκB pro- inflammatory responses during nonalcoholic steatohepatitis in mice fed a high-fat diet.
abstract: METHODS
  Green tea extract (GTE) reduces liver steatosis and inflammation during nonalcoholic steatohepatitis (NASH). We hypothesized GTE would mitigate NASH in a nuclear factor erythroid-2-related-factor-2 (Nrf2)-dependent manner in a high fat (HF) induced model.
  
  
  RESULTS
  Nrf2-null and wild-type (WT) mice were fed an HF diet containing 0 or 2% GTE for eight weeks prior to assessing parameters of NASH. Compared to WT mice, Nrf2-null mice had increased serum alanine aminotransferase, hepatic triglyceride, expression of free fatty acid uptake and lipogenic genes, malondialdehyde and NFκB phosphorylation and expression of pro-inflammatory genes. In WT mice, GTE increased Nrf2 and NADPH:quinone oxidoreductase-1 mRNA, and lowered hepatic steatosis, lipid uptake and lipogenic gene expression, malondialdehyde, and NFκB-dependent inflammation. In Nrf2-null mice, GTE lowered NFκB phosphorylation and TNF-α and MCP1 mRNA to levels observed in WT mice fed GTE whereas hepatic triglyceride and lipogenic genes were lowered only to those of WT mice fed no GTE. Malondialdehyde was lowered in Nrf2-null mice fed GTE, but not to levels of WT mice, and without improving the hepatic antioxidants α-tocopherol, ascorbic acid and uric acid.
  
  
  CONCLUSIONS
  Nrf2 deficiency exacerbates NASH whereas anti-inflammatory and hypolipidemic activities of GTE likely occur largely independent of Nrf2 signaling.
authors.affiliation: Human Nutrition Program, The Ohio State University, Columbus, OH, USA.
authors.forename: Jinhui
authors.initials: J
authors.lastname: Li
authors.affiliation: Human Nutrition Program, The Ohio State University, Columbus, OH, USA.
authors.forename: Teryn N
authors.initials: TN
authors.lastname: Sapper
authors.affiliation: Human Nutrition Program, The Ohio State University, Columbus, OH, USA.|Biofortis, Inc, Addison, IL, USA.
authors.forename: Eunice
authors.initials: E
authors.lastname: Mah
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, USA.
authors.forename: Swetha
authors.initials: S
authors.lastname: Rudraiah
authors.affiliation: Human Nutrition Program, The Ohio State University, Columbus, OH, USA.
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Schill
authors.affiliation: Human Nutrition Program, The Ohio State University, Columbus, OH, USA.
authors.forename: Chureeporn
authors.initials: C
authors.lastname: Chitchumroonchokchai
authors.affiliation: Human Nutrition Program, The Ohio State University, Columbus, OH, USA.
authors.forename: Meredith V
authors.initials: MV
authors.lastname: Moller
authors.affiliation: Human Nutrition Program, The Ohio State University, Columbus, OH, USA.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: McDonald
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, USA.
authors.forename: Philip R
authors.initials: PR
authors.lastname: Rohrer
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, USA.
authors.forename: José E
authors.initials: JE
authors.lastname: Manautou
authors.affiliation: Human Nutrition Program, The Ohio State University, Columbus, OH, USA.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Bruno
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D028241:Camellia sinensis / Q000737:chemistry*; D059305:Diet, High-Fat / Q000009:adverse effects; D006801:Humans; D007249:Inflammation / Q000178:diet therapy / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects* / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D051267:NF-E2-Related Factor 2 / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000178:diet therapy / Q000209:etiology / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495636:Nfe2l2 protein, mouse; D010936:Plant Extracts; D020011:Protective Agents
keywords: Green tea; Inflammation; NASH; Nrf2; Oxidative stress