Sirtuin 3 deficiency accelerates Angiotensin II-induced skeletal muscle atrophy

Connect Tissue Res. 2020 Nov;61(6):586-593. doi: 10.1080/03008207.2019.1648443. Epub 2019 Aug 1.


Background: It has been reported that Angiotensin II (Ang II) induced skeletal muscle atrophy. However, the precise mechanisms remain elusive. Sirtuin 3 (SIRT3), an NAD-dependent deacetylase, plays a central role in maintaining cellular metabolic homeostasis. This work aims to determine the role of SIRT3-mediated cellular metabolism in skeletal muscle wasting. Methods and Results: Eight-week-old male wild-type (WT) and SIRT3 knockout (SIRT3 KO) mice were infused with Ang II or saline for 4 weeks. Ang II induces skeletal muscle atrophy by inducing expression of the muscle-enriched E3 ubiquitin ligase muscle RING-finger-1 (MuRF1) and atrogin-1, accompanied by a reduction in SIRT3 in skeletal muscle. SIRT3 deficiency accelerated Ang II-induced loss of lean mass and protein hyper-acetylation, while the activities of mitochondrial oxidative enzymes, such as complex I and complex V, were significantly decreased. Furthermore, SIRT3 deficiency accelerated the Ang II-induced shift from slow-twitch towards fast-twitch fibres. Similarly, the three major rate-limiting enzymes in the glycolytic pathway, hexokinase 2 (HK2), phosphofructokinase-1(PFK) and pyruvate kinase (PK), were upregulated in Ang II-treated SIRT3 KO mice. Conclusion: These studies indicate that SIRT3 deficiency augmented Ang II-induced fibre-type shifting and metabolic reprogramming.

Keywords: Atrophy; SIRT3; glycolysis; hypertension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II
  • Animals
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondria, Muscle / pathology
  • Muscle Fibers, Skeletal / pathology
  • Muscle, Skeletal / pathology*
  • Muscular Atrophy / pathology*
  • Sirtuin 3 / deficiency*
  • Sirtuin 3 / metabolism


  • Angiotensin II
  • Sirtuin 3