Knockout of Selenoprotein V Affects Regulation of Selenoprotein Expression by Dietary Selenium and Fat Intakes in Mice

Abstract

Background:The metabolic function of selenoprotein V (SELENOV) remains unknown. Objectives:Two experiments were conducted to determine effects of the Selenov knockout (KO) on selenium concentration and mRNA, protein, and/or activity of 4 major selenoproteins [glutathione peroxidase (GPX) 1, GPX4, thioredoxin reductase-1 (TXNRD1), and selenoprotein P (SELENOP)] in the serum, liver, testis, and/or white adipose tissue (WAT) of mice fed different dietary selenium and fat concentrations. Methods:In Experiment (Expt) 1, 40 KO and 40 wild-type (WT) mice (males, 8 wk old) were fed (n= 10/genotype) a casein-sucrose basal diet plus 0, 0.3, 1, or 3 mg Se/kg (as sodium selenite) for 32 wk . In Expt 2, 20 KO and 20 WT mice (males, 8 wk old) were fed (n = 10/genotype) a normal-fat diet (NF; 10% calories from fat) or a high-fat diet (HF; 60% calories from fat) for 19 wk. Results:In Expt 1, the KO caused consistent or substantial decreases (P < 0.05) of mRNA amounts of Gpx1, Txnrd1,and Selenop in the testis (≤52%), but selenium concentrations (19–29%) and GPX activities (≤ 50%) were decreasedin the liver across different dietary selenium concentrations . Hepatic and testis GPX1 protein was elevated (≤31%) anddecreased (≤45%) by the KO, respectively. In Expt 2, the genotype and dietary fat intake exerted interaction effects (P < 0.05) on Gpx1 mRNA amounts in the WAT; Gpx1, Txnrd1, and Selenop mRNA amounts and TXNRD activities in thetestis; and selenium concentrations in the serum and liver. However, these 2 treatments produced largely independentor additive effects (P < 0.05) on the GPX1 and SELENOP protein amounts in the liver and testis (up to } 50% changes) Conclusions:The KO-mediated changes in the tissue selenium concentrations and functional expression of 3 major selenoproteins implied potential for SELENOV in regulating body selenium metabolism in the mouse.