Loss of Selenov predisposes mice to extra fat accumulation and attenuated energy expenditure
Ling-Li Chen,
Jia-Qiang Huang,
Yuan-Yuan Wu,
Liang-Bing Chen,
Shu-Ping Li,
Xu Zhang,
Sen Wu,
Fa-Zheng Ren,
Xin-Gen Lei
Affiliations
Ling-Li Chen
Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Nutrition and Health, China Agricultural University, Beijing, 100083, China; Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, Department of Nutrition and Health, China Agricultural University, Beijing, 100083, China; College of Food Science and Engineering, Jiangxi Agricultural University, Nanchang, Jiangxi, 330045, China
Jia-Qiang Huang
Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Nutrition and Health, China Agricultural University, Beijing, 100083, China; Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, Department of Nutrition and Health, China Agricultural University, Beijing, 100083, China
Yuan-Yuan Wu
Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Nutrition and Health, China Agricultural University, Beijing, 100083, China
Liang-Bing Chen
Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Nutrition and Health, China Agricultural University, Beijing, 100083, China; Life Science and Agriculture Department, Zhoukou Normal University, Zhoukou, Henan, 466001, China
Shu-Ping Li
Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Nutrition and Health, China Agricultural University, Beijing, 100083, China
Xu Zhang
Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Nutrition and Health, China Agricultural University, Beijing, 100083, China
Sen Wu
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China
Fa-Zheng Ren
Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Nutrition and Health, China Agricultural University, Beijing, 100083, China; Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, Department of Nutrition and Health, China Agricultural University, Beijing, 100083, China; Corresponding author. Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Nutrition and Health, China Agricultural University, Beijing, 100083, China.
Xin-Gen Lei
Department of Animal Science, Cornell University, Ithaca, NY, 14853, USA; Corresponding author.
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.
