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

• Published in: Redox biology Vol. 45; p. 102048
• Main Authors: Chen, Ling-Li, Huang, Jia-Qiang, Wu, Yuan-Yuan, Chen, Liang-Bing, Li, Shu-Ping, Zhang, Xu, Wu, Sen, Ren, Fa-Zheng, Lei, Xin-Gen
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.09.2021; Elsevier
• Subjects: Body weight; Energy balance; High-fat diet; Lipid metabolism; O-GlcNAcylation; Research Paper; Selenoprotein; Energy balance; O-GlcNAcylation; Selenoprotein; Lipid metabolism; Body weight; High-fat diet
• ISSN: 2213-2317; 2213-2317
• DOI: 10.1016/j.redox.2021.102048

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) VO2 consumption (14–21%), VCO2 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. [Display omitted] •SELENOV knockout elevated body weight and fat mass accumulation in mice.•SELENOV knockout stimulated lipogenesis and inhibited lipolysis in adipose tissue.•SELENOV knockout attenuated thermogenesis, respiration, and body temperature.•SELENOV and O-GlcNAc transferase (OGT) depicted a protein-protein interaction.•SELENOV knockout lowered OGT protein, activity, and function in adipose tissue.