1. Transcription Factor EB Controls Metabolic Flexibility during Exercise
- Author
-
Jeffrey E. Pessin, Pradip K. Saha, Gelsomina Mansueto, Francesca Solagna, Haihong Zong, Andrea Ballabio, Ivano Di Meo, Andrea Armani, Massimo Zeviani, Luca D’Orsi, Vanina Romanello, Marco Sandri, Paolo Grumati, Costanza Lamperti, Rossella De Cegli, Caterina Tezze, Silvia Marchet, Bert Blaauw, Carlo Viscomi, Paolo Bonaldo, Elena V. Polishchuk, Mansueto, Gelsomina, Armani, Andrea, Viscomi, Carlo, D'Orsi, Luca, DE CEGLI, Rossella, Polishchuk, Elena V., Lamperti, Costanza, Di Meo, Ivano, Romanello, Vanina, Marchet, Silvia, Saha, Pradip K., Zong, Haihong, Blaauw, Bert, Solagna, Francesca, Tezze, Caterina, Grumati, Paolo, Bonaldo, Paolo, Pessin, Jeffrey E., Zeviani, Massimo, Sandri, Marco, and Ballabio, Andrea
- Subjects
0301 basic medicine ,medicine.medical_specialty ,autophagy ,insulin ,Physiology ,Glucose uptake ,Mitochondrion ,Biology ,Article ,03 medical and health sciences ,metabolic flexibility ,Internal medicine ,medicine ,Glucose homeostasis ,glucose ,Molecular Biology ,TFEB ,PGC1alpha ,exercise ,diabetes ,Autophagy ,Glucose transporter ,mitochondria ,mitochondrial fusion ,Cell Biology ,Cell biology ,030104 developmental biology ,Endocrinology ,Mitochondrial biogenesis ,diabete - Abstract
Summary The transcription factor EB (TFEB) is an essential component of lysosomal biogenesis and autophagy for the adaptive response to food deprivation. To address the physiological function of TFEB in skeletal muscle, we have used muscle-specific gain- and loss-of-function approaches. Here, we show that TFEB controls metabolic flexibility in muscle during exercise and that this action is independent of peroxisome proliferator-activated receptor-γ coactivator1α (PGC1α). Indeed, TFEB translocates into the myonuclei during physical activity and regulates glucose uptake and glycogen content by controlling expression of glucose transporters, glycolytic enzymes, and pathways related to glucose homeostasis. In addition, TFEB induces the expression of genes involved in mitochondrial biogenesis, fatty acid oxidation, and oxidative phosphorylation. This coordinated action optimizes mitochondrial substrate utilization, thus enhancing ATP production and exercise capacity. These findings identify TFEB as a critical mediator of the beneficial effects of exercise on metabolism., Graphical Abstract, Highlights • TFEB regulates mitochondrial biogenesis and function in muscle • Glucose homeostasis in skeletal muscle requires TFEB • The effects of TFEB on muscle metabolism are independent from PGC1α • TFEB coordinates metabolic flexibility during physical exercise, Mansueto et al. show that TFEB acts as a central coordinator of skeletal muscle insulin sensitivity, glucose homeostasis, lipid oxidation, and mitochondrial function in the adaptive metabolic response to physical exercise in a PGC1α-independent manner.
- Published
- 2016
- Full Text
- View/download PDF