Temporal overexpression of SIRT1 in skeletal muscle of adult mice does not improve insulin sensitivity or markers of mitochondrial biogenesis.

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, lifelong 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.

Svensson K ，LaBarge SA ，Martins VF ，Schenk S ... -  《-》

High-fat diet-induced impairment of skeletal muscle insulin sensitivity is not prevented by SIRT1 overexpression.

White AT ，Philp A ，Fridolfsson HN ，Schilling JM ，Murphy AN ，Hamilton DL ，McCurdy CE ，Patel HH ，Schenk S ... -  《-》

Skeletal muscle-specific overexpression of SIRT1 does not enhance whole-body energy expenditure or insulin sensitivity in young mice.

White AT ，McCurdy CE ，Philp A ，Hamilton DL ，Johnson CD ，Schenk S ... -  《-》

Vitamin K2 Alleviates Insulin Resistance in Skeletal Muscle by Improving Mitochondrial Function Via SIRT1 Signaling.

Su X ，Wang W ，Fang C ，Ni C ，Zhou J ，Wang X ，Zhang L ，Xu X ，Cao R ，Lang H ，Wang F ... -  《-》

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

Svensson K ，Tahvilian S ，Martins VF ，Dent JR ，Lemanek A ，Barooni N ，Greyslak K ，McCurdy CE ，Schenk S ... -  《-》