Thioredoxin binding protein 2 (TBP2) plays a regulatory role in lipid metabolism and immune regulation. We previously reported the effect of TBP2 loss-of-function on lipid metabolism using TBP2 knockout (TBP2KO) mice. In this study, we employed TBP2 transgenic (TBP2TG) mice to analyze the in vivo effect of TBP2 gain-of-function. We revealed a decrease in the percentage of hepatic natural killer T (NKT) cells in TBP2KO mice and an increase in the percentage of hepatic NKT cells in TBP2TG mice. The TBP2KO mice were resistant to concanavalin A (ConA)-induced hepatitis, but they were highly susceptible to other types of hepatitis. TBP2 modulates lipid metabolism as well as NKT cell activity. Moreover, TBP2 expression was increased significantly in klotho-deficient mice, which exhibit a syndrome resembling aging human phenotypes. TBP2 may play multiple roles in lipid metabolism, innate immunity, and aging. Antioxid. Redox Signal. 11, 2585–2593.
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