Journal
MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 533, Issue -, Pages -Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2021.111335
Keywords
Selenium; Selenocysteine lyase; Obesity; Statin
Categories
Funding
- National Institutes of Health (NIH) - Centers of Biomedical Research Excellence (COBRE) in Diabetes [P20GM113134]
- Hawaii Community Foundation [20ADVC-102166]
- NIH [R01DK047320, U54MD007601, 5544, R01DK128390, F32DK124963, R01DK047320-22S2]
- NIH Office of Dietary Supplements (ODS) [R01DK047320-22S1]
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2018/09478-4]
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This study investigated the effects of statins on hepatic and muscular selenoprotein expression, oxidative stress, and creatine metabolism, revealing a sex-dependent role of selenium in statin responses.
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.
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