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Publication : Transcription Factor EB Controls Metabolic Flexibility during Exercise.

First Author  Mansueto G Year  2017
Journal  Cell Metab Volume  25
Issue  1 Pages  182-196
PubMed ID  28011087 Mgi Jnum  J:251928
Mgi Id  MGI:6107104 Doi  10.1016/j.cmet.2016.11.003
Citation  Mansueto G, et al. (2017) Transcription Factor EB Controls Metabolic Flexibility during Exercise. Cell Metab 25(1):182-196
abstractText  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-gamma coactivator1alpha (PGC1alpha). 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.
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