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Svensson 2017 Acta Physiol (Oxf)

From Bioblast
Publications in the MiPMap
Svensson K, LaBarge SA, Martins VF, Schenk S (2017) Temporal overexpression of SIRT1 in skeletal muscle of adult mice does not improve insulin sensitivity or markers of mitochondrial biogenesis. Acta Physiol (Oxf) 221:193-203.

Β» PMID: 28544355

Svensson K, LaBarge SA, Martins VF, Schenk S (2017) Acta Physiol (Oxf)

Abstract: 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.

Β© 2017 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd. β€’ Keywords: Glucose uptake, Insulin signaling, Respirometry, Tamoxifen β€’ Bioblast editor: Kandolf G β€’ O2k-Network Lab: US CA San Diego Schenk S

Labels: MiParea: Respiration, mt-Biogenesis;mt-density, mtDNA;mt-genetics, nDNA;cell genetics, Genetic knockout;overexpression, mt-Medicine  Pathology: Diabetes 

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

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