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

SCOPE:

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.

METHODS AND 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.

CONCLUSION:

Nrf2 deficiency exacerbates NASH whereas anti-inflammatory and hypolipidemic activities of GTE likely occur largely independent of Nrf2 signaling.

• Authors: Jinhui Li, Teryn N Sapper, Eunice Mah, Swetha Rudraiah, Kevin E Schill, Chureeporn Chitchumroonchokchai, Meredith V Moller, Joshua D McDonald, Philip R Rohrer, José E Manautou, Richard S Bruno
• Journal: Molecular nutrition & food research (Mol Nutr Food Res) Vol. 60 Issue 4 Pg. 858-70 (Apr 2016) ISSN: 1613-4133 [Electronic] Germany
• PMID: 26679056 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• NF-E2-Related Factor 2
• NF-kappa B
• Nfe2l2 protein, mouse
• Plant Extracts
• Protective Agents

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Camellia sinensis (chemistry)
• Diet, High-Fat (adverse effects)
• Humans
• Inflammation (diet therapy, metabolism)
• Lipid Metabolism (drug effects, genetics)
• Liver (drug effects, metabolism)
• Male
• Mice, Inbred C57BL
• Mice, Mutant Strains
• NF-E2-Related Factor 2 (genetics, metabolism)
• NF-kappa B (metabolism)
• Non-alcoholic Fatty Liver Disease (diet therapy, etiology, metabolism)
• Plant Extracts (pharmacology)
• Protective Agents (pharmacology)