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Publication : TFE3 regulates muscle metabolic gene expression, increases glycogen stores, and enhances insulin sensitivity in mice.

First Author  Iwasaki H Year  2012
Journal  Am J Physiol Endocrinol Metab Volume  302
Issue  7 Pages  E896-902
PubMed ID  22297304 Mgi Jnum  J:184629
Mgi Id  MGI:5425191 Doi  10.1152/ajpendo.00204.2011
Citation  Iwasaki H, et al. (2012) TFE3 regulates muscle metabolic gene expression, increases glycogen stores, and enhances insulin sensitivity in mice. Am J Physiol Endocrinol Metab 302(7):E896-902
abstractText  The role of transcription factor E3 (TFE3), a bHLH transcription factor, in immunology and cancer has been well characterized. Recently, we reported that TFE3 activates hepatic IRS-2 and hexokinase, participates in insulin signaling, and ameliorates diabetes. However, the effects of TFE3 in other organs are poorly understood. Herein, we examined the effects of TFE3 on skeletal muscle, an important organ involved in glucose metabolism. We generated transgenic mice that selectively express TFE3 in skeletal muscles. These mice exhibit a slight acceleration in growth prior to adulthood as well as a progressive increase in muscle mass. In TFE3 transgenic muscle, glycogen stores were more than twofold than in wild-type mice, and this was associated with an upregulation of genes involved in glucose metabolism, specifically glucose transporter 4, hexokinase II, and glycogen synthase. Consequently, exercise endurance capacity was enhanced in this transgenic model. Furthermore, insulin sensitivity was enhanced in transgenic mice and exhibited better improvement after 4 wk of exercise training, which was associated with increased IRS-2 expression. The effects of TFE3 on glucose metabolism in skeletal muscle were different from that in the liver, although they did, in part, overlap. The potential role of TFE3 in regulating metabolic genes and glucose metabolism within skeletal muscle suggests that it may be used for treating metabolic diseases as well as increasing endurance in sport.
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