Hepatic proteomic analysis of selenoprotein T knockout mice by TMT: Implications for the role of selenoprotein T in glucose and lipid metabolism

Selenoprotein T (SELENOT, SelT), a thioredoxin-like enzyme, exerts an essential oxidoreductase activity in the endoplasmic reticulum. However, its precise function remains unknown. To gain more understanding of SELENOT function, a conventional SELENOT knockout (KO) mouse model was constructed for the first time by CRISPR/Cas9 technique. TMT proteomics analysis was conducted to explore the differentially expressed proteins (DEPs) in the liver, revealing 60 up-regulated and 94 down-regulated DEPs in KO mice. The results of proteomics were validated by western blot of 3 selected DEPs (Gys2, DIO1, Gsta2). Furthermore, the bioinformatics analysis showed that SELENOT KO-induced DEPs were mainly related to lipid metabolism, cancer and PPAR signaling pathway. Overall, these findings provide a holistic perspective into SELENOT KO-induced DEPs in the liver and novel insights into the role of SELENOT in glucose and lipid metabolism, and thus enhance our understanding of SELENOT function.