FoxO1 inhibits skeletal muscle hypertrophy through mTOR-independent mechanisms

Rachael A. Potter, Alissa D. DeLong, Sierra M. Smith, Benjamin M. Erb, Bryon Renwand, Yasutomi Kamei, Yoshihiro Ogawa, Thomas J. McLoughlin

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The canonical Akt/mTOR signaling pathway plays a strong role in promoting skeletal muscle hypertrophy through regulating anabolic and catabolic signaling cascades. The transcription factor, FoxO1, a downstream molecular target of Akt signaling, may play a negative role in skeletal muscle hypertrophy through suppression of growth signaling and/or upregulation of atrophy gene expression. Using a transgenic mouse model in which FoxO1 is specifically expressed within skeletal muscle, we tested the hypotheses: (a) that FoxO1 inhibits skeletal muscle hypertrophy in vivo; and (b) that inhibition of skeletal muscle hypertrophy conferred through FoxO1 expression is associated with suppression of Akt/mTOR signaling and upregulation of muscle atrophy F-box (MAFbx/atrogin-1) gene expression. The findings confirm that FoxO1 inhibits skeletal muscle hypertrophy associated with 2 wks of mechanical overload (synergist ablation), evidenced through dampened increases in muscle mass, protein content, and muscle cross sectional area. We conclude that FoxO1 overexpression hampers the ability of skeletal muscle to hypertrophy, and that this suppression involves mechanisms independent of mTOR signaling.

Original languageEnglish
Pages (from-to)32-50
Number of pages19
JournalJournal of Exercise Physiology Online
Volume16
Issue number4
Publication statusPublished - Sep 11 2013
Externally publishedYes

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Hypertrophy
Skeletal Muscle
Up-Regulation
Gene Expression
Muscular Atrophy
Muscle Proteins
Transgenic Mice
Atrophy
Transcription Factors
Muscles
Growth

All Science Journal Classification (ASJC) codes

  • Physiology (medical)

Cite this

Potter, R. A., DeLong, A. D., Smith, S. M., Erb, B. M., Renwand, B., Kamei, Y., ... McLoughlin, T. J. (2013). FoxO1 inhibits skeletal muscle hypertrophy through mTOR-independent mechanisms. Journal of Exercise Physiology Online, 16(4), 32-50.

FoxO1 inhibits skeletal muscle hypertrophy through mTOR-independent mechanisms. / Potter, Rachael A.; DeLong, Alissa D.; Smith, Sierra M.; Erb, Benjamin M.; Renwand, Bryon; Kamei, Yasutomi; Ogawa, Yoshihiro; McLoughlin, Thomas J.

In: Journal of Exercise Physiology Online, Vol. 16, No. 4, 11.09.2013, p. 32-50.

Research output: Contribution to journalArticle

Potter, RA, DeLong, AD, Smith, SM, Erb, BM, Renwand, B, Kamei, Y, Ogawa, Y & McLoughlin, TJ 2013, 'FoxO1 inhibits skeletal muscle hypertrophy through mTOR-independent mechanisms', Journal of Exercise Physiology Online, vol. 16, no. 4, pp. 32-50.
Potter RA, DeLong AD, Smith SM, Erb BM, Renwand B, Kamei Y et al. FoxO1 inhibits skeletal muscle hypertrophy through mTOR-independent mechanisms. Journal of Exercise Physiology Online. 2013 Sep 11;16(4):32-50.
Potter, Rachael A. ; DeLong, Alissa D. ; Smith, Sierra M. ; Erb, Benjamin M. ; Renwand, Bryon ; Kamei, Yasutomi ; Ogawa, Yoshihiro ; McLoughlin, Thomas J. / FoxO1 inhibits skeletal muscle hypertrophy through mTOR-independent mechanisms. In: Journal of Exercise Physiology Online. 2013 ; Vol. 16, No. 4. pp. 32-50.
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