Temporal overexpression of SIRT1 in skeletal muscle of adult mice does not improve insulin sensitivity or markers of mitochondrial biogenesis.
Temporal overexpression of SIRT1 in skeletal muscle of adult mice does not improve insulin sensitivity or markers of mitochondrial biogenesis.
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DOI：
10.1111/apha.12897
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发表时间：
2017-11
期刊：
影响因子：
--
通讯作者：
Schenk S
中科院分区：
文献类型：
--
作者：
Svensson K;LaBarge SA;Martins VF;Schenk S
NAD+依赖性蛋白脱乙酰酶SIRT 1的激活已被提出作为治疗骨骼肌中线粒体功能障碍和胰岛素抵抗的治疗策略。然而，SIRT 1在骨骼肌中的终身过表达并不能改善线粒体功能和胰岛素敏感性的参数。在这项研究中，我们调查了SIRT 1在成年小鼠肌肉中的时间过表达是否会影响骨骼肌线粒体功能和胰岛素敏感性。为了避免生殖系SIRT 1过表达的潜在影响，我们利用了成年小鼠骨骼肌中SIRT 1过表达的诱导模型（i-mOX）。通过2-脱氧葡萄糖摄取评估胰岛素敏感性，通过高分辨率呼吸测定法评估肌肉最大呼吸功能，通过全身热量测定法评估全身能量消耗。虽然SIRT 1在i-mOX小鼠的骨骼肌中的表达高于WT小鼠，但基因型之间的葡萄糖耐量和骨骼肌胰岛素敏感性是相当的。此外，线粒体生物发生、肌肉最大呼吸功能和全身耗氧量的标志物也不受SIRT 1过表达的影响。这些结果支持了先前的工作，表明在出生或成年时骨骼肌中SIRT 1的诱导不会影响肌肉胰岛素作用或线粒体功能。
Activation of the NAD+ dependent protein deacetylase SIRT1 has been proposed as a therapeutic strategy to treat mitochondrial dysfunction and insulin resistance in skeletal muscle. However, life-long overexpression of SIRT1 in skeletal muscle does not improve parameters of mitochondrial function and insulin sensitivity. In this study we investigated whether temporal overexpression of SIRT1 in muscle of adult mice would affect skeletal muscle mitochondrial function and insulin sensitivity. To circumvent potential effects of germline SIRT1 overexpression, we utilized an inducible model of SIRT1 overexpression in skeletal muscle of adult mice (i-mOX). Insulin sensitivity was assessed by 2-deoxyglucose uptake, muscle maximal respiratory function by high-resolution respirometry and systemic energy expenditure was assessed by whole body calorimetry. Although SIRT1 was highly, and specifically, overexpressed in skeletal muscle of i-mOX compared to WT mice, glucose tolerance and skeletal muscle insulin sensitivity were comparable between genotypes. Additionally, markers of mitochondrial biogenesis, muscle maximal respiratory function and whole body oxygen consumption were also unaffected by SIRT1 overexpression. These results support previous work demonstrating that induction of SIRT1 in skeletal muscle, either at birth or in adulthood, does not impact muscle insulin action or mitochondrial function.
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影响因子：
29
作者：
Bai P;Canto C;Brunyánszki A;Huber A;Szántó M;Cen Y;Yamamoto H;Houten SM;Kiss B;Oudart H;Gergely P;Menissier-de Murcia J;Schreiber V;Sauve AA;Auwerx J
通讯作者：
Auwerx J
影响因子：
4.8
作者：
Lan, Fan;Cacicedo, Jose M.;Ido, Yasuo
通讯作者：
Ido, Yasuo
影响因子：
10.5
作者：
Chen, Danica;Bruno, Joanne;Guarente, Leonard
通讯作者：
Guarente, Leonard
DOI：
10.1073/pnas.0705070104
发表时间：
2007-07-17
影响因子：
11.1
作者：
Jaeger, Sibylle;Handschin, Christoph;Spiegelman, Bruce M.
通讯作者：
Spiegelman, Bruce M.
DOI：
10.1146/annurev.pathol.4.110807.092250
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Haigis MC;Sinclair DA
通讯作者：
Sinclair DA