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Transcription Factor EB Controls Metabolic Flexibility during Exercise.
Cell Metab 2017; 25(1):182-196CM

Abstract

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.

Authors+Show Affiliations

Telethon Institute of Genetics and Medicine (TIGEM), Via Campi Flegrei 34, 80078 Pozzuoli, Naples, Italy.Department of Biomedical Science, University of Padova, Padova 35121, Italy.MRC Mitochondrial Biology Unit, Cambridge CB2 0XY, UK; Fondazione IRCCS Istituto Neurologico "C. Besta," 20133 Milan, Italy.Telethon Institute of Genetics and Medicine (TIGEM), Via Campi Flegrei 34, 80078 Pozzuoli, Naples, Italy.Telethon Institute of Genetics and Medicine (TIGEM), Via Campi Flegrei 34, 80078 Pozzuoli, Naples, Italy.Telethon Institute of Genetics and Medicine (TIGEM), Via Campi Flegrei 34, 80078 Pozzuoli, Naples, Italy.Fondazione IRCCS Istituto Neurologico "C. Besta," 20133 Milan, Italy.Fondazione IRCCS Istituto Neurologico "C. Besta," 20133 Milan, Italy.Department of Biomedical Science, University of Padova, Padova 35121, Italy; Venetian Institute of Molecular Medicine, Padova 35129, Italy.Fondazione IRCCS Istituto Neurologico "C. Besta," 20133 Milan, Italy.Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.Hepatobiliary, Pancreatic, and Intestinal Research Institute, North Sichuan Medical College, Nanchong, Sichuan 637000, China; Departments of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.Department of Biomedical Science, University of Padova, Padova 35121, Italy.Department of Biomedical Science, University of Padova, Padova 35121, Italy.Department of Biomedical Science, University of Padova, Padova 35121, Italy.Department of Molecular Medicine, University of Padova, Padova 35121, Italy.Department of Molecular Medicine, University of Padova, Padova 35121, Italy.Departments of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.MRC Mitochondrial Biology Unit, Cambridge CB2 0XY, UK; Fondazione IRCCS Istituto Neurologico "C. Besta," 20133 Milan, Italy.Telethon Institute of Genetics and Medicine (TIGEM), Via Campi Flegrei 34, 80078 Pozzuoli, Naples, Italy; Department of Biomedical Science, University of Padova, Padova 35121, Italy; Venetian Institute of Molecular Medicine, Padova 35129, Italy. Electronic address: marco.sandri@unipd.it.Telethon Institute of Genetics and Medicine (TIGEM), Via Campi Flegrei 34, 80078 Pozzuoli, Naples, Italy; Medical Genetics, Department of Pediatrics, Federico II University, Via Pansini 5, 80131 Naples, Italy; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA. Electronic address: ballabio@tigem.it.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28011087

Citation

Mansueto, Gelsomina, et al. "Transcription Factor EB Controls Metabolic Flexibility During Exercise." Cell Metabolism, vol. 25, no. 1, 2017, pp. 182-196.
Mansueto G, Armani A, Viscomi C, et al. Transcription Factor EB Controls Metabolic Flexibility during Exercise. Cell Metab. 2017;25(1):182-196.
Mansueto, G., Armani, A., Viscomi, C., D'Orsi, L., De Cegli, R., Polishchuk, E. V., ... Ballabio, A. (2017). Transcription Factor EB Controls Metabolic Flexibility during Exercise. Cell Metabolism, 25(1), pp. 182-196. doi:10.1016/j.cmet.2016.11.003.
Mansueto G, et al. Transcription Factor EB Controls Metabolic Flexibility During Exercise. Cell Metab. 2017 01 10;25(1):182-196. PubMed PMID: 28011087.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transcription Factor EB Controls Metabolic Flexibility during Exercise. AU - Mansueto,Gelsomina, AU - Armani,Andrea, AU - Viscomi,Carlo, AU - D'Orsi,Luca, AU - De Cegli,Rossella, AU - Polishchuk,Elena V, AU - Lamperti,Costanza, AU - Di Meo,Ivano, AU - Romanello,Vanina, AU - Marchet,Silvia, AU - Saha,Pradip K, AU - Zong,Haihong, AU - Blaauw,Bert, AU - Solagna,Francesca, AU - Tezze,Caterina, AU - Grumati,Paolo, AU - Bonaldo,Paolo, AU - Pessin,Jeffrey E, AU - Zeviani,Massimo, AU - Sandri,Marco, AU - Ballabio,Andrea, Y1 - 2016/12/20/ PY - 2016/01/19/received PY - 2016/06/24/revised PY - 2016/11/05/accepted PY - 2016/12/25/pubmed PY - 2017/7/14/medline PY - 2016/12/25/entrez KW - PGC1alpha KW - TFEB KW - autophagy KW - diabetes KW - exercise KW - glucose KW - insulin KW - metabolic flexibility KW - mitochondria KW - mitochondrial fusion SP - 182 EP - 196 JF - Cell metabolism JO - Cell Metab. VL - 25 IS - 1 N2 - 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. SN - 1932-7420 UR - https://www.unboundmedicine.com/medline/citation/28011087/Transcription_Factor_EB_Controls_Metabolic_Flexibility_during_Exercise_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1550-4131(16)30581-2 DB - PRIME DP - Unbound Medicine ER -