PGC-1α plays a pivotal role in simvastatin-induced exercise impairment in mice.

ABSTRACT:

Aim

Statins decrease cardiovascular complications, but can induce myopathy. Here, we explored the implication of PGC-1α in statin-associated myotoxicity.

Methods

We treated PGC-1α knockout (KO), PGC-1α overexpression (OE) and wild-type (WT) mice orally with 5 mg simvastatin kg^-1  day^-1 for 3 weeks and assessed muscle function and metabolism.

Results

In WT and KO mice, but not in OE mice, simvastatin decreased grip strength, maximal running distance and vertical power assessed by ergometry. Post-exercise plasma lactate concentrations were higher in WT and KO compared to OE mice. In glycolytic gastrocnemius, simvastatin decreased mitochondrial respiration, increased mitochondrial ROS production and free radical leak in WT and KO, but not in OE mice

SUBMITTER: Panajatovic MV 

PROVIDER: S-EPMC7100017 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature