Dissociation between PGC-1α and GLUT-4 expression in skeletal muscle of rats fed a high-fat diet

Kazuhiko Higashida, Mitsuru Higuchi, Shin Terada

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

It has recently been reported that a 4-wk high-fat diet gradually increases skeletal muscle peroxisome proliferator activated receptor (PPAR) γ coactivator-1 α (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-lα 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-1 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.

Original languageEnglish
Pages (from-to)486-491
Number of pages6
JournalJournal of Nutritional Science and Vitaminology
Volume55
Issue number6
DOIs
Publication statusPublished - 2009

Keywords

  • GLUT-4
  • High-fat diet
  • PGC-1α
  • PPARδ
  • Skeletal muscle

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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