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. 2022 Jan 19;12:770652. doi: 10.3389/fphar.2021.770652

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Copyright © 2022 Zhang, Niu, Ma, Chen, Wen, Li, Zhou, Deng, Shi, Pu, Yang, Wang, Zou, Chen and Ma.

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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The mechanism of fenofibrate that leads to improved hepatic lipid accumulation and insulin resistance. The levels of let-7 are upregulated in HFD-induced obese (DIO) mice. Fenofibrate reduced the levels of the let-7 family members and upregulated the levels of SERCA2b, which is a target of let-7. Fenofibrate treatment also attenuated insulin resistance and suppressed excessive lipid accumulation in HFD-fed mice. Thus, the protective effect of fenofibrate could be reasonably related to alteration of the let-7/SERCA2b axis and alleviation of ER stress.