title: Tbx15 controls skeletal muscle fibre-type determination and muscle metabolism.
abstract: Skeletal muscle is composed of both slow-twitch oxidative myofibers and fast-twitch glycolytic myofibers that differentially impact muscle metabolism, function and eventually whole-body physiology. Here we show 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 fibres, associated with a small increase in the number of oxidative fibres. This shift in fibre composition results in muscles with slower myofiber contraction and relaxation, and also decreases whole-body oxygen consumption, reduces spontaneous activity, increases adiposity and glucose intolerance. Mechanistically, ablation of Tbx15 leads to activation of AMPK signalling and a decrease in Igf2 expression. Thus, Tbx15 is one of a limited number of transcription factors to be identified with a critical role in regulating glycolytic fibre identity and muscle metabolism.
authors: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, 1 Joslin Plaza, Boston, Massachusetts 02215, USA.
authors: Kevin Y
authors: KY
authors: Lee
authors: Institut für Molekularbiologie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany.|Signature Research Program in Cardiovascular and Metabolic Disorders, Duke-NUS Graduate Medical School Singapore, National Heart Centre Singapore, 8 College Road, Singapore 169857, Singapore.
authors: Manvendra K
authors: MK
authors: Singh
authors: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, 1 Joslin Plaza, Boston, Massachusetts 02215, USA.|Institute for Diabetes and Obesity, Helmholtz Center, Parkring, 1385748 Munich/Garching, Germany.
authors: Siegfried
authors: S
authors: Ussar
authors: Zentrum Physiologie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany.
authors: Petra
authors: P
authors: Wetzel
authors: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, 1 Joslin Plaza, Boston, Massachusetts 02215, USA.
authors: Michael F
authors: MF
authors: Hirshman
authors: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, 1 Joslin Plaza, Boston, Massachusetts 02215, USA.
authors: Laurie J
authors: LJ
authors: Goodyear
authors: Institut für Molekularbiologie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany.
authors: Andreas
authors: A
authors: Kispert
authors: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, 1 Joslin Plaza, Boston, Massachusetts 02215, USA.
authors: C Ronald
authors: CR
authors: Kahn
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects; D005786:Gene Expression Regulation / Q000502:physiology; D018149:Glucose Intolerance / Q000235:genetics / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000145:classification* / Q000378:metabolism*; D009765:Obesity / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D004041:Dietary Fats; C513121:IGF2 protein, mouse; D020825:T-Box Domain Proteins; C114093:TBX15 protein, mouse; D007335:Insulin-Like Growth Factor II; D055372:AMP-Activated Protein Kinases