Tbx15 Controls Skeletal Muscle Fiber Type Determination and Muscle Metabolism

Skeletal muscle is composed of both slow-twich oxidative myofibers and fast-twitch glycolytic myofibers that differentially impact muscle metabolism, function, and eventually whole-body physiology. In the present study, we find that the mesodermal transcription factor T-box 15 (Tbx15) is highly and specifically expressed in glycolytic myofibers. Ablation of Tbx15 in vivo leads to a decrease in muscle size due to a decrease in the number of glycolytic fibers, associated with a small increase in the number of oxidative fibers. This shift in fiber composition results in muscles with slower myofiber contraction and relaxation, and also results in decreased whole-body oxygen consumption, decreased spontaneous activity, increased adiposity, and glucose intolerance. In order to identify genes regulated by Tbx15, we utilized C2C12 myoblasts with either a stable retroviral over-expression or stable lentiviral knockdown of Tbx15.

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Lee KY, Singh MK, Ussar S, Wetzel P, Hirshman MF, Goodyear LJ, Kispert A, Kahn CR