High-fat diet-induced changes in liver thioredoxin and thioredoxin reductase as a novel feature of insulin resistance

Huijun Qin; Xiaolin Zhang; Fei Ye; Liangwei Zhong

doi:10.1016/j.fob.2014.10.015

High-fat diet-induced changes in liver thioredoxin and thioredoxin reductase as a novel feature of insulin resistance

FEBS Open Bio. 2014 Oct 31:4:928-35. doi: 10.1016/j.fob.2014.10.015. eCollection 2014.

Authors

Huijun Qin¹, Xiaolin Zhang², Fei Ye², Liangwei Zhong¹

Affiliations

¹ College of Life Sciences, University of Chinese Academy of Sciences, 100049 Beijing, China.
² Institute of Materia Medica, Chinese Academy of Medical Sciences & Perking Union Medical College, 100050 Beijing, China.

Abstract

High-fat diet (HFD) can induce oxidative stress. Thioredoxin (Trx) and thioredoxin reductase (TrxR) are critical antioxidant proteins but how they are affected by HFD remains unclear. Using HFD-induced insulin-resistant mouse model, we show here that liver Trx and TrxR are significantly decreased, but, remarkably, the degree of their S-acylation is increased after consuming HFD. These HFD-induced changes in Trx/TrxR may reflect abnormalities of lipid metabolism and insulin signaling transduction. HFD-driven accumulation of 4-hydroxynonenal is another potential mechanism behind inactivation and decreased expression of Trx/TrxR. Thus, we propose HFD-induced impairment of liver Trx/TrxR as major contributor to oxidative stress and as a novel feature of insulin resistance.

Keywords: 4-HNE, 4-hydroxynonenal; ASK-1, apoptosis signal-regulating kinase-1; Gpx, glutathione peroxidase; HFD, high-fat diet; High-fat diet; IRS-1, insulin receptor substrate-1; ITT, insulin tolerance test; Insulin resistance; OGTT, oral glucose tolerance test; PTP-1B, protein-tyrosine phophatase-1B; S-acylation; Thioredoxin; Thioredoxin reductase; Trx, thioredoxin; TrxR, thioredoxin reductase.