SIRT1 overexpression in skeletal muscle in vivo induces increased insulin sensitivity and enhanced complex I but not complex IIV functions in individual subsarcolemmal and intermyofibrillar mitochondria
J. physiol. biochem
; 71(2): 177-190, jun. 2015.
Article
in En
| IBECS
| ID: ibc-140527
Responsible library:
ES1.1
Localization: BNCS
ABSTRACT
SIRT1 is known to improve insulin resistance (IR), but whether this effect is direct or not is still unclear, and this question has not been addressed in vivo in the skeletal muscle. Therefore, we sought to test if acute overexpression of SIRT1 in skeletal muscle of high-fat diet (HFD) rats in vivo would affect subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondrial complexes IV activities and antioxidant enzymes thereby improving insulin action. In vivo electrotransfer was used to overexpress SIRT1 in the skeletal muscle of rats fed HFD for 12 weeks. Skeletal muscle insulin sensitivity and downstream effects of SIRT1 on AMPK, SIRT3, and mitochondrial biogenesis were studied. Citrate synthase (CS), complexes IV, oxidative stress, and antioxidant levels were assessed in SS and IMF mitochondria. HFD rats showed skeletal muscle IR as well as decreasedSIRT1 and SIRT3 expressions, mitochondrial DNA (mtDNA), and mitochondrial biogenesis (p < 0.05). SS and IMF mitochondria displayed lower CS, complexes IV, and antioxidant enzyme activities (p < 0.05). By contrast, moderate (~2.5 folds) SIRT1 overexpression attenuated HFD-induced skeletal muscle IR. This improvement was associated with increased AMPK, PGC-1alfa, SIRT3, and mtDNA expressions as well as SS and IMF mitochondrial CS and complexes IV activities. Importantly, SIRT1 overexpression largely restored antioxidant enzyme activities and enhanced complex I but not complexes IIV functions in individual SS and IMF mitochondria. This study suggests that SIRT1 overexpression improved IR at least partly by targeting complex I functions of SS and IMF mitochondria through the activation of SIRT1 and SIRT3
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Collection:
06-national
/
ES
Database:
IBECS
Main subject:
Insulin Resistance
/
Muscle, Skeletal
/
Sirtuin 1
Type of study:
Diagnostic_studies
Limits:
Animals
Language:
En
Journal:
J. physiol. biochem
Year:
2015
Document type:
Article