Muscle-specific knockout of general control of amino acid synthesis 5 (GCN5) does not enhance basal or endurance exercise-induced mitochondrial adaptation

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Muscle-specific knockout of general control of amino acid synthesis 5 (GCN5) does not enhance basal or endurance exercise-induced mitochondrial adaptation. / Dent, Jessica R.; Martins, Vitor F.; Svensson, Kristoffer; Labarge, Samuel A.; Schlenk, Noah C.; Esparza, Mary C.; Buckner, Elisa H.; Meyer, Gretchen A.; Hamilton, D. Lee.; Schenk, Simon; Philp, Andrew.

In: Molecular metabolism, Vol. 6, No. 12, 01.12.2017, p. 1574-1584.

Research output: Contribution to journalArticlepeer-review

Harvard

Dent, JR, Martins, VF, Svensson, K, Labarge, SA, Schlenk, NC, Esparza, MC, Buckner, EH, Meyer, GA, Hamilton, DL, Schenk, S & Philp, A 2017, 'Muscle-specific knockout of general control of amino acid synthesis 5 (GCN5) does not enhance basal or endurance exercise-induced mitochondrial adaptation', Molecular metabolism, vol. 6, no. 12, pp. 1574-1584. https://doi.org/10.1016/j.molmet.2017.10.004

APA

Dent, J. R., Martins, V. F., Svensson, K., Labarge, S. A., Schlenk, N. C., Esparza, M. C., Buckner, E. H., Meyer, G. A., Hamilton, D. L., Schenk, S., & Philp, A. (2017). Muscle-specific knockout of general control of amino acid synthesis 5 (GCN5) does not enhance basal or endurance exercise-induced mitochondrial adaptation. Molecular metabolism, 6(12), 1574-1584. https://doi.org/10.1016/j.molmet.2017.10.004

Vancouver

Author

Dent, Jessica R. ; Martins, Vitor F. ; Svensson, Kristoffer ; Labarge, Samuel A. ; Schlenk, Noah C. ; Esparza, Mary C. ; Buckner, Elisa H. ; Meyer, Gretchen A. ; Hamilton, D. Lee. ; Schenk, Simon ; Philp, Andrew. / Muscle-specific knockout of general control of amino acid synthesis 5 (GCN5) does not enhance basal or endurance exercise-induced mitochondrial adaptation. In: Molecular metabolism. 2017 ; Vol. 6, No. 12. pp. 1574-1584.

Bibtex

@article{1b401472612b4d97a699b29e224f3039,
title = "Muscle-specific knockout of general control of amino acid synthesis 5 (GCN5) does not enhance basal or endurance exercise-induced mitochondrial adaptation",
abstract = "Objective: Lysine acetylation is an important post-translational modification that regulates metabolic function in skeletal muscle. The acetyltransferase, general control of amino acid synthesis 5 (GCN5), has been proposed as a regulator of mitochondrial biogenesis via its inhibitory action on peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α). However, the specific contribution of GCN5 to skeletal muscle metabolism and mitochondrial adaptations to endurance exercise in vivo remain to be defined. We aimed to determine whether loss of GCN5 in skeletal muscle enhances mitochondrial density and function, and the adaptive response to endurance exercise training.Methods: We used Cre-LoxP methodology to generate mice with muscle-specific knockout of GCN5 (mKO) and floxed, wildtype (WT) littermates. We measured whole-body energy expenditure, as well as markers of mitochondrial density, biogenesis, and function in skeletal muscle from sedentary mice, and mice that performed 20 days of voluntary endurance exercise training.Results: Despite successful knockdown of GCN5 activity in skeletal muscle of mKO mice, whole-body energy expenditure as well as skeletal muscle mitochondrial abundance and maximal respiratory capacity were comparable between mKO and WT mice. Further, there were no genotype differences in endurance exercise-mediated mitochondrial biogenesis or increases in PGC-1α protein content.Conclusion: These results demonstrate that loss of GCN5 in vivo does not promote metabolic remodeling in mouse skeletal muscle.",
keywords = "acetylation , GCN5 , mitochondria , SIRT1 , deacetylase , PGC-1α",
author = "Dent, {Jessica R.} and Martins, {Vitor F.} and Kristoffer Svensson and Labarge, {Samuel A.} and Schlenk, {Noah C.} and Esparza, {Mary C.} and Buckner, {Elisa H.} and Meyer, {Gretchen A.} and Hamilton, {D. Lee.} and Simon Schenk and Andrew Philp",
year = "2017",
month = dec,
day = "1",
doi = "10.1016/j.molmet.2017.10.004",
language = "English",
volume = "6",
pages = "1574--1584",
journal = "Molecular metabolism",
issn = "2212-8778",
publisher = "Elsevier",
number = "12",

}

RIS

TY - JOUR

T1 - Muscle-specific knockout of general control of amino acid synthesis 5 (GCN5) does not enhance basal or endurance exercise-induced mitochondrial adaptation

AU - Dent, Jessica R.

AU - Martins, Vitor F.

AU - Svensson, Kristoffer

AU - Labarge, Samuel A.

AU - Schlenk, Noah C.

AU - Esparza, Mary C.

AU - Buckner, Elisa H.

AU - Meyer, Gretchen A.

AU - Hamilton, D. Lee.

AU - Schenk, Simon

AU - Philp, Andrew

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Objective: Lysine acetylation is an important post-translational modification that regulates metabolic function in skeletal muscle. The acetyltransferase, general control of amino acid synthesis 5 (GCN5), has been proposed as a regulator of mitochondrial biogenesis via its inhibitory action on peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α). However, the specific contribution of GCN5 to skeletal muscle metabolism and mitochondrial adaptations to endurance exercise in vivo remain to be defined. We aimed to determine whether loss of GCN5 in skeletal muscle enhances mitochondrial density and function, and the adaptive response to endurance exercise training.Methods: We used Cre-LoxP methodology to generate mice with muscle-specific knockout of GCN5 (mKO) and floxed, wildtype (WT) littermates. We measured whole-body energy expenditure, as well as markers of mitochondrial density, biogenesis, and function in skeletal muscle from sedentary mice, and mice that performed 20 days of voluntary endurance exercise training.Results: Despite successful knockdown of GCN5 activity in skeletal muscle of mKO mice, whole-body energy expenditure as well as skeletal muscle mitochondrial abundance and maximal respiratory capacity were comparable between mKO and WT mice. Further, there were no genotype differences in endurance exercise-mediated mitochondrial biogenesis or increases in PGC-1α protein content.Conclusion: These results demonstrate that loss of GCN5 in vivo does not promote metabolic remodeling in mouse skeletal muscle.

AB - Objective: Lysine acetylation is an important post-translational modification that regulates metabolic function in skeletal muscle. The acetyltransferase, general control of amino acid synthesis 5 (GCN5), has been proposed as a regulator of mitochondrial biogenesis via its inhibitory action on peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α). However, the specific contribution of GCN5 to skeletal muscle metabolism and mitochondrial adaptations to endurance exercise in vivo remain to be defined. We aimed to determine whether loss of GCN5 in skeletal muscle enhances mitochondrial density and function, and the adaptive response to endurance exercise training.Methods: We used Cre-LoxP methodology to generate mice with muscle-specific knockout of GCN5 (mKO) and floxed, wildtype (WT) littermates. We measured whole-body energy expenditure, as well as markers of mitochondrial density, biogenesis, and function in skeletal muscle from sedentary mice, and mice that performed 20 days of voluntary endurance exercise training.Results: Despite successful knockdown of GCN5 activity in skeletal muscle of mKO mice, whole-body energy expenditure as well as skeletal muscle mitochondrial abundance and maximal respiratory capacity were comparable between mKO and WT mice. Further, there were no genotype differences in endurance exercise-mediated mitochondrial biogenesis or increases in PGC-1α protein content.Conclusion: These results demonstrate that loss of GCN5 in vivo does not promote metabolic remodeling in mouse skeletal muscle.

KW - acetylation

KW - GCN5

KW - mitochondria

KW - SIRT1

KW - deacetylase

KW - PGC-1α

U2 - 10.1016/j.molmet.2017.10.004

DO - 10.1016/j.molmet.2017.10.004

M3 - Article

C2 - 29111103

VL - 6

SP - 1574

EP - 1584

JO - Molecular metabolism

JF - Molecular metabolism

SN - 2212-8778

IS - 12

ER -