Gamma‐Tocotrienol Attenuates the Hepatic Inflammation and Fibrosis by Suppressing Endoplasmic Reticulum Stress in Mice. Issue 21 (9th September 2018)

• Record Type: Journal Article
• Authors: Kim, Yongeun; Natarajan, Sathish Kumar; Chung, Soonkyu
• Is Part Of: Molecular nutrition & food research. Volume 62:Issue 21(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-09-09
• Subjects: de novo lipogenesis -- ER stress -- gamma tocotrienol -- insulin resistance -- NAFLD; Food -- Biotechnology -- Periodicals; Food -- Microbiology -- Periodicals; Nutrition -- Periodicals; Food -- Toxicology -- Periodicals; Nutrition -- Periodicals; Food Microbiology -- Periodicals; Food Technology -- Periodicals; Molecular Biology -- Periodicals; 664.0705
• DOI: 10.1002/mnfr.201800519
• Languages: English
• ISSNs: 1613-4125

Abstract

Abstract : Scope: Gamma‐tocotrienol (γT3), an unsaturated isoform of vitamin E, is implicated in the hepatoprotective effects. The aim is to determine the effectiveness of γT3 on nonalcoholic fatty liver disease (NAFLD). Methods and Results: C57BL/6 male mice are fed a diet containing high fat (45%) and cholesterol (0.2%) along with sucrose drink (HFCS) or HFCS diet supplemented with 0.1% γT3 (HFCS + γT3). The inclusion of γT3 robustly decreases the HFCS diet‐induced de novo lipogenesis (DNL), ER stress, and inflammation leading to reduced hepatic steatosis and fibrosis. Next, mice are fed a methionine‐ and choline‐deficient (MCD) diet or MCD diet with γT3 (MCD + γT3). The γT3 supplementation significantly reduces the MCD diet‐induced hepatic ER stress and fibrosis despite the minimal impact on steatosis. To further investigate the role of ER stress, the mice with genetic ablation of CHOP are fed an MCD or MCD + γT3 diet. CHOP deletion abolishes the γT3‐mediated suppression of hepatic fibrosis, suggesting that modulation of ER stress is a prerequisite to inhibit hepatic inflammation and fibrosis. Conclusion: γT3 supplementation is effective in attenuating NAFLD and fibrosis through a synergistic mechanism of decreased DNL and hepatic ER stress. This work strongly supports the translational potential of γT3 supplementation against NAFLD. Abstract : Supplementation of gamma tocotrienol (γT3), an isoform of unsaturated vitamin E, attenuates the diet‐induced nonalcoholic fatty liver disease (NAFLD) and its progression to nonalcoholic steatohepatitis (NASH) by suppressing de novo lipogenesis (DNL) and ER stress‐mediated fibrosis. Also, γT3 mitigates the hepatic steatosis by reducing the influx of fatty acids (FA) from diets and adipose tissue inflammation.