Loss of Selenov predisposes mice to extra fat accumulation and attenuated energy expenditure

Selenoprotein V (SELENOV) is a new and the least conserved member of the selenoprotein family. Herein we generated Selenov knockout (KO) mice to determine its in vivo function. The KO led to 16–19% increases (P < 0.05) in body weight that were largely due to 54% higher (P < 0.05) fat mass accumulation, compared with the wild-type (WT) controls. The extra fat accumulation in the KO mice was mediated by up-regulations of genes and proteins involved in lipogenesis (Acc, Fas, Dgat, and Lpl; up by 40%–1.1-fold) and down-regulations of lipolysis (Atgl, Hsl, Ces1d, and Cpt1a; down by 36–89%) in the adipose tissues. The KO also decreased (P < 0.05) VO(2) consumption (14–21%), VCO(2) production (14–16%), and energy expenditure (14–23%), compared with the WT controls. SELENOV and O-GlcNAc transferase (OGT) exhibited a novel protein-protein interaction that explained the KO-induced decreases (P < 0.05) of OGT protein (15–29%), activity (33%), and function (O-GlcNAcylation, 10–21%) in the adipose tissues. A potential cascade of SELENOV-OGT-AMP-activated protein kinase might serve as a central mechanism to link the biochemical and molecular responses to the KO. Overall, our data revealed a novel in vivo function and mechanism of SELENOV as a new inhibitor of body fat accumulation, activator of energy expenditure, regulator of O-GlcNAcylation, and therapeutic target of such related disorders.