Effect of statin treatment in obese selenium-supplemented mice lacking selenocysteine lyase

Abstract

People with obesity are often dyslipidemic and prescribed statins to prevent cardiovascular events. A common side effect of statin use is myopathy. This could potentially be caused by the reduction of selenoproteins that curb oxidative stress, in turn, affecting creatine metabolism. We determined if statins regulate hepatic and muscular selenoprotein expression, oxidative stress and creatine metabolism. Mice lacking selenocysteine lyase (Scly KO), a selenium-provider enzyme for selenoprotein synthesis, were fed a high-fat, Se-supplemented diet and treated with simvastatin. Statin improved creatine metabolism in females and oxidative responses in both sexes. Male Scly KO mice were heavier than females after statin treatment. Hepatic selenoproteins were unaffected by statin and genotype in females. Statin upregulated muscular Gpx1 in females but not males, while Scly loss downregulated muscular Gpx1 in males and Selenon in females. Osgin1 was reduced in statin-treated Scly KO males after AmpliSeq analysis. These results refine our understanding of the sex-dependent role of selenium in statin responses.