Transcription Factor EB Controls Metabolic Flexibility during Exercise

Gelsomina Mansueto; Andrea Armani; Carlo Viscomi; Luca D'Orsi; Rossella De Cegli; Elena V. Polishchuk; Costanza Lamperti; Ivano Di Meo; Vanina Romanello; Silvia Marchet; Pradip K. Saha; Haihong Zong; Bert Blaauw; Francesca Solagna; Caterina Tezze; Paolo Grumati; Paolo Bonaldo; Jeffrey E. Pessin; Massimo Zeviani; Marco Sandri; Andrea Ballabio

doi:10.1016/j.cmet.2016.11.003

Transcription Factor EB Controls Metabolic Flexibility during Exercise

Gelsomina Mansueto, Andrea Armani, Carlo Viscomi, Luca D'Orsi, Rossella De Cegli, Elena V. Polishchuk, Costanza Lamperti, Ivano Di Meo, Vanina Romanello, Silvia Marchet, Pradip K. Saha, Haihong Zong, Bert Blaauw, Francesca Solagna, Caterina Tezze, Paolo Grumati, Paolo Bonaldo, Jeffrey E. Pessin, Massimo Zeviani, Marco SandriAndrea Ballabio

Medicine

Research output: Contribution to journal › Article › peer-review

223 Scopus citations

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.

Original language	English (US)
Pages (from-to)	182-196
Number of pages	15
Journal	Cell metabolism
Volume	25
Issue number	1
DOIs	https://doi.org/10.1016/j.cmet.2016.11.003
State	Published - Jan 10 2017

Keywords

PGC1alpha
TFEB
autophagy
diabetes
exercise
glucose
insulin
metabolic flexibility
mitochondria
mitochondrial fusion

ASJC Scopus subject areas

Physiology
Molecular Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.cmet.2016.11.003

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Mansueto, G., Armani, A., Viscomi, C., D'Orsi, L., De Cegli, R., Polishchuk, E. V., Lamperti, C., Di Meo, I., Romanello, V., Marchet, S., Saha, P. K., Zong, H., Blaauw, B., Solagna, F., Tezze, C., Grumati, P., Bonaldo, P., Pessin, J. E., Zeviani, M., ... Ballabio, A. (2017). Transcription Factor EB Controls Metabolic Flexibility during Exercise. Cell metabolism, 25(1), 182-196. https://doi.org/10.1016/j.cmet.2016.11.003

Mansueto, G, Armani, A, Viscomi, C, D'Orsi, L, De Cegli, R, Polishchuk, EV, Lamperti, C, Di Meo, I, Romanello, V, Marchet, S, Saha, PK, Zong, H, Blaauw, B, Solagna, F, Tezze, C, Grumati, P, Bonaldo, P, Pessin, JE, Zeviani, M, Sandri, M & Ballabio, A 2017, 'Transcription Factor EB Controls Metabolic Flexibility during Exercise', Cell metabolism, vol. 25, no. 1, pp. 182-196. https://doi.org/10.1016/j.cmet.2016.11.003

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title = "Transcription Factor EB Controls Metabolic Flexibility during Exercise",

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.",

keywords = "PGC1alpha, TFEB, autophagy, diabetes, exercise, glucose, insulin, metabolic flexibility, mitochondria, mitochondrial fusion",

author = "Gelsomina Mansueto and Andrea Armani and Carlo Viscomi and Luca D'Orsi and {De Cegli}, Rossella and Polishchuk, {Elena V.} and Costanza Lamperti and {Di Meo}, Ivano and Vanina Romanello and Silvia Marchet and Saha, {Pradip K.} and Haihong Zong and Bert Blaauw and Francesca Solagna and Caterina Tezze and Paolo Grumati and Paolo Bonaldo and Pessin, {Jeffrey E.} and Massimo Zeviani and Marco Sandri and Andrea Ballabio",

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doi = "10.1016/j.cmet.2016.11.003",

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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

PY - 2017/1/10

Y1 - 2017/1/10

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.

AB - 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.

KW - PGC1alpha

KW - TFEB

KW - autophagy

KW - diabetes

KW - exercise

KW - glucose

KW - insulin

KW - metabolic flexibility

KW - mitochondria

KW - mitochondrial fusion

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ER -

Transcription Factor EB Controls Metabolic Flexibility during Exercise

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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