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. 2021 Aug 18;12:704112. doi: 10.3389/fphar.2021.704112

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Copyright © 2021 Guo, Liu, Cheng, Liu, Zheng, Liang and Xu.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Proposed mechanism for metformin-alleviated steatohepatitis. A SIRT1-dependent cholesterol catabolism and M1 macrophages polarization are involved in metformin-induced alleviation of steatohepatitis in DIO mice. Metformin upregulates CH25H and may result in increased level of 25-HC, which has been reported to inhibit IL-1β-driven inflammation, thus ameliorates hepatic inflammation. On the other hand, metformin also downregulates the M1 macrophage markers, which suggests that metformin may inhibit the M1 macrophages polarization to alleviate steatohepatitis. Importantly, SIRT1 deficiency impairs the beneficial effects of metformin on steatohepatitis.