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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 and Philp, Andrew 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, doi: 10.1016/j.molmet.2017.10.004.

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Title Muscle-specific knockout of general control of amino acid synthesis 5 (GCN5) does not enhance basal or endurance exercise-induced mitochondrial adaptation
Author(s) 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
Journal name Molecular metabolism
Volume number 6
Issue number 12
Start page 1574
End page 1584
Total pages 11
Publisher Elsevier
Place of publication Berlin, Germany
Publication date 2017-12
ISSN 2212-8778
Keyword(s) Acetylation
Deacetylase
GCN5
Mitochondria
PGC-1α
SIRT1
Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
PGC-1 alpha
HUMAN SKELETAL-MUSCLE
ACETYLTRANSFERASE ACTIVITY
METABOLIC ADAPTATION
TRANSCRIPTION FACTOR
GLUCOSE-HOMEOSTASIS
INSULIN SENSITIVITY
SIRT1 ACTIVITY
PGC-1-ALPHA
MOUSE
Summary 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.
Language eng
DOI 10.1016/j.molmet.2017.10.004
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2017, The Authors
Free to Read? Yes
Use Rights Creative Commons Attribution Non-Commercial No-Derivatives licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30112697

Document type: Journal Article
Collections: School of Life and Environmental Sciences
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.