Dissociation between PGC-1α and GLUT-4 Expression in Skeletal Muscle of Rats Fed a High-Fat Diet

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概要

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• It has recently been reported that a 4-wk high-fat diet gradually increases skeletal muscle peroxisome proliferator activated receptor (PPAR) γ coactivator-1α (PGC-1α) protein content, which has been suggested to regulate GLUT-4 gene transcription. However, it has not been reported that a high-fat diet enhances GLUT-4 mRNA expression and protein content in skeletal muscle, suggesting that an increase in PGC-1α protein content is not sufficient to induce muscle GLUT-4 biogenesis in a high-fat fed animal. Therefore, we first evaluated the relationship between PGC-1α and GLUT-4 expression in skeletal muscle of rats fed a high-fat diet for 4 wk. The PGC-1α protein content in rat epitrochlearis muscle significantly increased by twofold after the 4-wk high-fat diet feeding. However, the high-fat diet had no effect on GLUT-4 protein content and induced a 30% decrease in GLUT-4 mRNA expression in rat skeletal muscle (p<0.05). To clarify the mechanism by which a high-fat diet downregulates GLUT-4 mRNA expression, we next examined the effect of PPARδ activation, which is known to occur in response to a high-fat diet, on GLUT-4 mRNA expression in L6 myotubes. Incubation with 500 nM GW501516 (PPARδ activator) for 24 h significantly decreased GLUT-4 mRNA in L6 myotubes. Taken together, these findings suggest that a high-fat diet downregulates GLUT-4 mRNA, possibly through the activation of PPARδ, despite an increase in PGC-1α protein content in rat skeletal muscle, and that a posttranscriptional regulatory mechanism maintains GLUT-4 protein content in skeletal muscle of rats fed a high-fat diet.

• 2009-12-01

著者

• HIGUCHI Mitsuru

  Faculty of Sport Sciences, Waseda University

• HIGASHIDA Kazuhiko

  Graduate School of Sport Sciences, Waseda University

• TERADA Shin

  Consolidated Research Institute for Advanced Science and Medical Care, Waseda University

• Higuchi Mitsuru

  Faculty Of Sport Sciences Waseda University

• Terada Shin

  Consolidated Research Institute For Advanced Science And Medical Care Waseda University

• Higashida Kazuhiko

  Graduate School Of Sport Sciences Waseda University

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