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Immunol."],"abstract":"<jats:p>Metformin is not only the first-line medication for the treatment of type 2 diabetes, but it is also effective as an anti-inflammatory, anti-oxidative and anti-tumor agent. However, the effect of metformin during viral hepatitis remains elusive. Using an adenovirus (Ad)-induced viral hepatitis mouse model, we found that metformin treatment significantly attenuated liver injury, with reduced serum aspartate transaminase (AST) and alanine transaminase (ALT) levels and liver histological changes, presumably <jats:italic>via<\/jats:italic> decreased effector T cell responses. We then demonstrated that metformin reduced mTORC1 activity in T cells from infected mice, as evidenced by decreased phosphorylation of ribosome protein S6 (p-S6). The inhibitory effects on the mTORC1 signaling by metformin was dependent on the tuberous sclerosis complex 1 (TSC1). Mechanistically, metformin treatment modulated the phosphorylation of dynamin-related protein 1 (Drp-1) and mitochondrial fission 1 protein (FIS1), resulting in increased mass in effector T cells. Moreover, metformin treatment promoted mitochondrial superoxide production, which can inhibit excessive T cell activation in viral hepatitis. Together, our results revealed a protective role and therapeutic potential of metformin against liver injury in acute viral hepatitis <jats:italic>via<\/jats:italic> modulating effector T cell activation <jats:italic>via<\/jats:italic> regulating the mTORC1 pathway and mitochondrial functions.<\/jats:p>","DOI":"10.3389\/fimmu.2021.638575","type":"journal-article","created":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T18:55:43Z","timestamp":1619031343000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Metformin Modulates T Cell Function and Alleviates Liver Injury Through Bioenergetic Regulation in Viral 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