Dissimilar Effects of Selenite and Selenium Nanoparticles on Skeletal Muscle Development Unrelated to GPx1 Activity During Adolescence in Rats

<b>Background/Objectives</b>: During adolescence, the critical growth period, the antioxidant selenium (Se), either as sodium selenite or selenium nanoparticles (SeNPs), has shown contrasting effects on adipose tissue (AT) in rats, due to its role in insulin signaling. Since skeletal muscle (SKM) is also a key insulin-target tissue, this study aimed to assess whether a similar effect occurs in this tissue. <b>Methods</b>: Three groups of male adolescent rats (<i>n</i> = 18) were used: control (C), selenite supplemented (S), and SeNPs supplemented (NS). Low doses of Se were administered via drinking water in both supplemented groups. AT was utilized for transcriptomic analyses, while SKM was analyzed for oxidative balance, insulin-induced anabolic effects, and proteolysis. Myokine levels in serum were also determined. <b>Results</b>: SeNPs administration decreased SKM mass and protein content, increased serum creatinine, and decreased insulin levels, indicating impaired SKM development. Both supplemented groups upregulated genes related to creatine metabolism and muscle contraction. However, only the NS group showed upregulation of genes associated with glycogenolysis and glycolysis. Despite unchanged GPx1 expression, NS rats presented lower oxidation and insulin-pmTOR activation, and higher expression of proteins related to proteolysis (pAMPK, SIRT1, ULK1, FOXO3a, and MaFbx) and a myokine profile compatible to muscle atrophy, fatty acid oxidation, and impaired myoblast proliferation. Ultimately, the selenite group impaired SKM catabolism mainly by increasing insulin-pmTOR activation. <b>Conclusions</b>: Once again, the form of Se administration exerts opposing effects on metabolism tissues, suggests a potential therapeutic role for selenite in disorders that compromise muscle growth, such as muscular dystrophies, cachexia, or sarcopenia.