PGC‐1α promotes exercise‐induced autophagy in mouse skeletal muscle

Recent evidence suggests that exercise stimulates the degradation of cellular components in skeletal muscle through activation of autophagy, but the time course of the autophagy response during recovery from exercise has not been determined. Furthermore, the regulatory mechanisms behind exercise‐ind...

Full description

Bibliographic Details
Main Authors:	Halling, Jens F., Ringholm, Stine, Nielsen, Maja M., Overby, Peter, Pilegaard, Henriette
Format:	Online
Language:	English
Published:	John Wiley and Sons Inc. 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4758928/

id	pubmed-4758928
recordtype	oai_dc
spelling	pubmed-47589282016-02-29 PGC‐1α promotes exercise‐induced autophagy in mouse skeletal muscle Halling, Jens F. Ringholm, Stine Nielsen, Maja M. Overby, Peter Pilegaard, Henriette Original Research Recent evidence suggests that exercise stimulates the degradation of cellular components in skeletal muscle through activation of autophagy, but the time course of the autophagy response during recovery from exercise has not been determined. Furthermore, the regulatory mechanisms behind exercise‐induced autophagy remain unclear, although the muscle oxidative phenotype has been linked with basal autophagy levels. Therefore, the aim of this study was to investigate the role of the key regulator of muscle oxidative capacity, PGC‐1α, in exercise‐induced autophagy at several time points during recovery. Mice with transgenic muscle‐specific overexpression (TG) or knockout (MKO) of PGC‐1α and their respective littermate controls were subjected to a single 1 h bout of treadmill running and euthanized immediately (0 h), 2, 6, and 10 h after exercise. In the PGC‐1α MKO strain, quadriceps protein content of the autophagy marker LC3II was increased from 2 h into recovery in lox/lox control, but not in MKO mice. In the PGC‐1α TG strain, quadriceps protein content of LC3II was increased from 2 h after exercise in TG, but not in WT. Although AMPK and ACC phosphorylation was increased immediately following exercise, the observed exercise‐induced autophagy response was not associated with phosphorylation of the AMPK‐target ULK1. However, lower protein carbonyl content was observed in lox/lox and TG mice after exercise coinciding with the increased LC3 lipidation. In conclusion, the present results suggest a role of skeletal muscle PGC‐1α in coordinating several exercise‐induced adaptive responses including autophagic removal of damaged cellular components. John Wiley and Sons Inc. 2016-02-11 /pmc/articles/PMC4758928/ /pubmed/26869683 http://dx.doi.org/10.14814/phy2.12698 Text en © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Halling, Jens F. Ringholm, Stine Nielsen, Maja M. Overby, Peter Pilegaard, Henriette
spellingShingle	Halling, Jens F. Ringholm, Stine Nielsen, Maja M. Overby, Peter Pilegaard, Henriette PGC‐1α promotes exercise‐induced autophagy in mouse skeletal muscle
author_facet	Halling, Jens F. Ringholm, Stine Nielsen, Maja M. Overby, Peter Pilegaard, Henriette
author_sort	Halling, Jens F.
title	PGC‐1α promotes exercise‐induced autophagy in mouse skeletal muscle
title_short	PGC‐1α promotes exercise‐induced autophagy in mouse skeletal muscle
title_full	PGC‐1α promotes exercise‐induced autophagy in mouse skeletal muscle
title_fullStr	PGC‐1α promotes exercise‐induced autophagy in mouse skeletal muscle
title_full_unstemmed	PGC‐1α promotes exercise‐induced autophagy in mouse skeletal muscle
title_sort	pgc‐1α promotes exercise‐induced autophagy in mouse skeletal muscle
description	Recent evidence suggests that exercise stimulates the degradation of cellular components in skeletal muscle through activation of autophagy, but the time course of the autophagy response during recovery from exercise has not been determined. Furthermore, the regulatory mechanisms behind exercise‐induced autophagy remain unclear, although the muscle oxidative phenotype has been linked with basal autophagy levels. Therefore, the aim of this study was to investigate the role of the key regulator of muscle oxidative capacity, PGC‐1α, in exercise‐induced autophagy at several time points during recovery. Mice with transgenic muscle‐specific overexpression (TG) or knockout (MKO) of PGC‐1α and their respective littermate controls were subjected to a single 1 h bout of treadmill running and euthanized immediately (0 h), 2, 6, and 10 h after exercise. In the PGC‐1α MKO strain, quadriceps protein content of the autophagy marker LC3II was increased from 2 h into recovery in lox/lox control, but not in MKO mice. In the PGC‐1α TG strain, quadriceps protein content of LC3II was increased from 2 h after exercise in TG, but not in WT. Although AMPK and ACC phosphorylation was increased immediately following exercise, the observed exercise‐induced autophagy response was not associated with phosphorylation of the AMPK‐target ULK1. However, lower protein carbonyl content was observed in lox/lox and TG mice after exercise coinciding with the increased LC3 lipidation. In conclusion, the present results suggest a role of skeletal muscle PGC‐1α in coordinating several exercise‐induced adaptive responses including autophagic removal of damaged cellular components.
publisher	John Wiley and Sons Inc.
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4758928/
_version_	1613540477202595840

PGC‐1α promotes exercise‐induced autophagy in mouse skeletal muscle

Similar Items