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.