Poster Topical Area: Dietary Bioactive Components

Location: Hall D

Poster Board Number: 310

P08-052 - Gamma tocotrienol attenuates hepatic steatosis and ER stress against high-fat and high-sucrose diet

Monday, Jun 11
8:00 AM – 3:00 PM

Objectives: Gamma-tocotrienol (gT3), an unsaturated isomer of vitamin E, has been reported to exhibit anti-obesity and anti-inflammatory properties against high fat (HF) diet. This study aims to define the role of gT3 in the pathogenic progression of hepatic steatosis and fibrosis to a combined dietary stimulus of HF and chronic sucrose consumption (HFHS).

Methods: To promote hepatic stress, obesity-prone C57BL/6 male mice (n=8 per group) were challenged with an HFHS dietary regimen composed of 20% sucrose drink and HF (45% calories from fat) alone (HFHS) or HF-diet containing 0.1 % of gT3 (HFHS-gT3). Low fat diet (LF, 10% calories from fat) fed mice without sugar intake were used as the control. After 16 weeks, hepatic steatosis was quantified by triglyceride (TG) contents and lipogenic gene expression by qPCR. The markers of hepatic toxicity, plasma lipid profiles were quantified by a chemistry analyzer. The ER stress markers and signaling were determined by Western blot analysis. The impact of gT3 in energy expenditure and insulin sensitivity were measured by metabolic cage and by glucose and insulin tolerance test, respectively.

Results: Chronic HFHS challenge induced massive weight gain and enlargement of liver compared to LF, which was significantly reduced in mice fed a HFHS-gT3 diet without altering food intake. Compared with mice fed HFHS alone, HFHS-gT3 fed mice featured substantial reductions of 1) hepatic steatosis evidenced by ~50% decrease of hepatic TG content and lipogenic gene expressions including Srebp1c, Dgat2, Fas, Scd1 and Lpl., 2) hepatic ER stress by lowering the signaling of p-JNK, CHOP, BiP and p-eIF2a, and 3) hepatic toxicity by decreasing ALT and AST levels, inflammatory gene expression, and expression of fibrosis-related gene, Timp1. In addition, the presence of gT3 in HSHS was associated with increased whole-body energy expenditure, improved insulin sensitivity, and reduced adipose and pancreatic inflammation compared to the dietary stimulus of HFHS only.

Conclusions: Our results demonstrated that gT3 supplementation was effective in attenuating HFHS diet-mediated hepatic steatosis and ER stress. This work suggests that inclusion of gT3 in a diet may help mitigate or prevent non-alcoholic fatty liver diseases and fibrosis progression.

Funding Source: This study was supported by American Heart Association SDG grant to S.C. (13SDG14410043), the USDA-Hatch grant at the University of Nebraska-Lincoln.

CoAuthors: Soonkyu Chung – University of Nebraska-Lincoln

Yongeun Kim

Nutrition and health sciences
Lincoln, Nebraska