Reduction of glucose intolerance with high fat feeding is associated with anti-inflammatory effects of thioredoxin 1 overexpression in mice

Abstract

Aging is associated with reduced ability to maintain normal glucose homeostasis. It has been suggested that an age-associated increase in chronic pro-inflammatory state could drive this reduction in glucoregulatory function. Thioredoxins (Trx) are oxido-reductase enzymes that play an important role in the regulation of oxidative stress and inflammation. In this study, we tested whether overexpression of Trx1 in mice [Tg(TRX1)^+/0] could protect from glucose metabolism dysfunction caused by high fat diet feeding. Body weight and fat mass gains with high fat feeding were similar in Tg(TRX1)^+/0 and wild-type mice; however, high fat diet induced glucose intolerance was reduced in Tg(TRX1)^+/0 mice relative to wild-type mice. In addition, expression of the pro-inflammatory cytokine TNF-α was reduced in adipose tissue of Tg(TRX1)^+/0 mice compared to wild-type mice. These findings suggest that activation of thioredoxins may be a potential therapeutic target for maintenance of glucose metabolism with obesity or aging.

• oxidative stress
• diabetes
• obesity
• glucose homeostasis
• aging

Acknowledgements

This work was supported by NIA training grant T32 AG021890-05 for the study of the basic biology of aging (to A.B.S.) and Award Number 1 I01BX001023 from the Biomedical Laboratory Research & Development Service of the Veteran's Affairs Office of Research and Development (to Y.I.). Measurement of cytokine RT-PCR was performed by the Nathan Shock Center Oxidative stress and mitochondrial function core facility at UTHSCSA.