FoxO6 and PGC-1 form a regulatory loop in myogenic cells

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 338-365-Metabolic & Stress Receptors in Energy Homeostasis
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-361
Shen Liang Chen*1, Shih Ying Chung1, Wei Chieh Huang1, Ching Wen Su1, Kuan Wei Lee1, Hsiang Cheng Chi1, Cheng Tao Lin1, Szu-Tah Chen2, Kai Min Huang1, Mu Shiun Tsai3 and Hui Peng Yu1
1National Central University, Jhongli, Taiwan, 2Chang Gung Memorial Hospital, Kweishan, Taiwan, 3Taiwan Landseed Hospital, Pingjen, Taiwan
Transcription factors of the FoxO family regulate a wide range of cellular physiological processes, including metabolic adaptation and myogenic differentiation.  The transcriptional activity of most FoxO members is inhibitory to myogenic differentiation and over-expression of FoxO1 inhibits the development of oxidative type I fibers in vivo.  In this study, we found that FoxO6, the last discovered FoxO family member, is expressed ubiquitously in various tissues but with higher expression levels in oxidative tissues, such as brain and oxidative muscles.  Both the expression level and promoter activity of FoxO6 were found to be enhanced by PGC-1α, thus explained its enriched expression in oxidative tissues.  We further demonstrated that FoxO6 represses the expression of PGC-1α via direct binding to an upstream A/T rich element (AAGATATCAAAACA, -2286~-2273) in the PGC-1α promoter.  Oxidative exercise induced PGC-1α but reduced FoxO6 expression levels in hind leg muscles, and the binding of FoxO6 to PGC-1α promoter was also prevented by exercise.    As FoxO6 promoter can be coactivated by PGC-1α and its promoter in turn can be repressed by FoxO6, it suggests that FoxO6 and PGC-1α form a regulatory loop for setting oxidative metabolism level in skeletal muscle, which can be entrained by exercise.

Nothing to Disclose: SLC, SYC, WCH, CWS, KWL, HCC, CTL, STC, KMH, MST, HPY

*Please take note of The Endocrine Society's News Embargo Policy at

Sources of Research Support: This study is supported by funding from the National Science Council of Taiwan, ROC to Shen Liang Chen [NSC-96-2311-B-008-006-MY3 and NSC-99-2314-B-008-001-MY3].  The authors have no conflict of interest to declare.