Combined overexpression of SIRT1 and knockout of GCN5 in adult skeletal muscle does not affect glucose homeostasis or exercise performance in mice

被引:13
作者
Svensson, Kristoffer [1 ]
Tahvilian, Shahriar [1 ]
Martins, Vitor F. [1 ,2 ]
Dent, Jessica R. [1 ]
Lemanek, Adrianna [1 ]
Barooni, Neeka [1 ]
Greyslak, Keenan [3 ]
McCurdy, Carrie E. [3 ]
Schenk, Simon [1 ,2 ]
机构
[1] Univ Calif San Diego, Dept Orthopaed Surg, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Biomed Sci Grad Program, La Jolla, CA 92093 USA
[3] Univ Oregon, Dept Human Physiol, Eugene, OR 97403 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM | 2020年 / 318卷 / 02期
基金
瑞士国家科学基金会; 美国国家卫生研究院;
关键词
acetyltransferase; deacetylase; mitochondria; peroxisome proliferator-activated receptor-gamma coactivator 1 alpha; INSULIN SENSITIVITY; MITOCHONDRIAL BIOGENESIS; ENERGY-EXPENDITURE; PGC-1-ALPHA; METABOLISM; COMPLEX;
D O I
10.1152/ajpendo.00370.2019
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Sirtuin 1 (SIRT1) and general control of amino acid synthesis 5 (GCN5) regulate mitochondrial biogenesis via opposing modulation of peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha) 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 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 left perpendicularwild type (WT)right perpendicular littermates using a Cre-LoxP approach. All mice were treated with tamoxifen at 5-6 wk of age, and 4-7 wk later 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 were assessed. 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.
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页码:E145 / E151
页数:7
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