Svensson 2019 Am J Physiol Endocrinol Metab

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Svensson K, Tahvilian S, Martins VF, Dent JR, Lemanek A, Barooni N, Greyslak K, McCurdy CE, Schenk S (2019) Combined overexpression of SIRT1 and knockout of GCN5 in adult skeletal muscle does not affect glucose homeostasis or exercise performance in mice. Am J Physiol Endocrinol Metab 318:E145-51.

» PMID: 31794263

Svensson K, Tahvilian S, Martins VF, Dent JR, Lemanek A, Barooni N, Greyslak K, McCurdy CE, Schenk S (2019) Am J Physiol Endocrinol Metab

Abstract: Sirtuin 1 (SIRT1) and general control of amino acid synthesis 5 (GCN5) regulate mitochondrial biogenesis via opposing modulation of peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α) acetylation status and activity. However, the combined contribution of SIRT1 and GCN5 to skeletal muscle metabolism and endurance performance in vivo is unknown. In this study, we investigated the impact of combined skeletal muscle-specific overexpression of SIRT1 and deletion of GCN5 on glucose homeostasis, skeletal muscle mitochondrial biogenesis and function, and the metabolic adaptation to endurance exercise training in mice. We generated mice with combined and tamoxifen-inducible skeletal muscle-specific overexpression of SIRT1 and knockout of GCN5 (dTG) and floxed (wildtype [WT]) littermates using a Cre-LoxP approach. All mice were treated with tamoxifen at 5-6 weeks of age and 4-7 weeks later we assessed glucose homeostasis, skeletal muscle contractile function, mitochondrial function, and the effects of 14 days of voluntary wheel running on expression of metabolic proteins and exercise capacity. There was no difference in oral glucose tolerance, skeletal muscle contractile function, mitochondrial abundance or maximal respiratory capacity between dTG and WT mice. Additionally, there were no genotype differences in exercise performance and markers of mitochondrial biogenesis after 14 days of voluntary wheel running. These results demonstrate that combined overexpression of SIRT1 and loss of GCN5 in vivo does not promote metabolic remodeling in skeletal muscle of sedentary or exercise-trained mice.

Keywords: PGC-1α, Acetyltransferase, Deacetylase, Mitochondria Bioblast editor: Plangger M O2k-Network Lab: US CA San Diego Schenk S, US OR Eugene McCurdy CE


Labels: MiParea: Respiration, mt-Biogenesis;mt-density, Genetic knockout;overexpression, Exercise physiology;nutrition;life style 


Organism: Mouse  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue 


Coupling state: LEAK, OXPHOS, ET  Pathway: F, N, S, NS, ROX  HRR: Oxygraph-2k 

Labels, 2019-12