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 & 1 others Andrea Ballabio

Research output: Contribution to journalArticle

60 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)182-196
Number of pages15
JournalCell Metabolism
Volume25
Issue number1
DOIs
StatePublished - Jan 10 2017

Fingerprint

Transcription Factors
Glucose
Food Deprivation
Muscles
Peroxisome Proliferator-Activated Receptors
Facilitative Glucose Transport Proteins
Oxidative Phosphorylation
Autophagy
Organelle Biogenesis
Glycogen
Skeletal Muscle
Homeostasis
Fatty Acids
Adenosine Triphosphate
Gene Expression
Enzymes

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

Cite this

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), 182-196. https://doi.org/10.1016/j.cmet.2016.11.003

Transcription Factor EB Controls Metabolic Flexibility during Exercise. / 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; Ballabio, Andrea.

In: Cell Metabolism, Vol. 25, No. 1, 10.01.2017, p. 182-196.

Research output: Contribution to journalArticle

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
Mansueto G, Armani A, Viscomi C, D'Orsi L, De Cegli R, Polishchuk EV et al. Transcription Factor EB Controls Metabolic Flexibility during Exercise. Cell Metabolism. 2017 Jan 10;25(1):182-196. https://doi.org/10.1016/j.cmet.2016.11.003
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 ; Ballabio, Andrea. / Transcription Factor EB Controls Metabolic Flexibility during Exercise. In: Cell Metabolism. 2017 ; Vol. 25, No. 1. pp. 182-196.
@article{28c645a356104a7bb51ed4fe1bca5b7d,
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 = "autophagy, diabetes, exercise, glucose, insulin, metabolic flexibility, mitochondria, mitochondrial fusion, PGC1alpha, TFEB",
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",
year = "2017",
month = "1",
day = "10",
doi = "10.1016/j.cmet.2016.11.003",
language = "English (US)",
volume = "25",
pages = "182--196",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "1",

}

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

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 - autophagy

KW - diabetes

KW - exercise

KW - glucose

KW - insulin

KW - metabolic flexibility

KW - mitochondria

KW - mitochondrial fusion

KW - PGC1alpha

KW - TFEB

UR - http://www.scopus.com/inward/record.url?scp=85008145754&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85008145754&partnerID=8YFLogxK

U2 - 10.1016/j.cmet.2016.11.003

DO - 10.1016/j.cmet.2016.11.003

M3 - Article

VL - 25

SP - 182

EP - 196

JO - Cell Metabolism

JF - Cell Metabolism

SN - 1550-4131

IS - 1

ER -