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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Gastrointestinal and Hepatic Pharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1477212

Metformin's Effect on Metabolic Dysfunction-associated Steatotic Liver Disease through the miR-200a-5p and AMPK/SERCA2b Pathway

Provisionally accepted
Hang Chen Hang Chen 1Minshan Huang Minshan Huang 1*Dan Zhang Dan Zhang 1Hui Wang Hui Wang 1*Da Wang Da Wang 1*Mengwei Li Mengwei Li 1*Xianmei Wang Xianmei Wang 1*Rui Zhu Rui Zhu 2*Jianjun Liu Jianjun Liu 1*Lan-Qing Ma Lan-Qing Ma 1*
  • 1 Kunming Medical University, Kunming, China
  • 2 State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan Agricultural University, Kunming, Yunnan Province, China

The final, formatted version of the article will be published soon.

    Metformin has shown benefits in treating metabolic dysfunction-associated steatotic liver disease (MASLD), but its mechanisms remain unclear. This study investigates miR-200a-5p's role in the AMPK/SERCA2b pathway to reduce liver fat accumulation and ER stress in MASLD. A PA cell model induced by palmitic and oleic acids (2:1) was used to assess lipid accumulation via Oil Red O and Nile Red staining. mRNA levels of miR-200a-5p and lipid metabolism genes were measured with RT-PCR, and AMPK, p-AMPK, and SERCA2b protein levels were analyzed by Western blotting. The interaction between miR-200a-5p and AMPK was studied using a luciferase reporter assay. A high-fat diet-induced MASLD mouse model was used to evaluate metformin's effects on liver steatosis and lipid profiles. Serum miR-200a-5p levels were also analyzed in MASLD patients.In the PA cell model, elevated miR-200a-5p and lipid metabolism gene mRNA levels were observed, with decreased AMPK and SERCA2b protein levels. miR-200a-5p mimic reduced AMPK and SERCA2b expression. Metformin treatment reduced liver steatosis and lipid deposition in mice, normalizing miR-200a-5p, lipid metabolism gene mRNA, and AMPK/SERCA2b protein levels. Elevated serum miR-200a-5p was detected in MASLD patients. These findings suggest that metformin alleviates lipid deposition and ER stress in MASLD through the modulation of the AMPK/SERCA2b pathway via miR-200a-5p.

    Keywords: MASLD, Metformin, miR-200a-5p, AMPK, SERCA2b

    Received: 07 Aug 2024; Accepted: 02 Dec 2024.

    Copyright: © 2024 Chen, Huang, Zhang, Wang, Wang, Li, Wang, Zhu, Liu 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) or licensor 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.

    * Correspondence:
    Minshan Huang, Kunming Medical University, Kunming, China
    Hui Wang, Kunming Medical University, Kunming, China
    Da Wang, Kunming Medical University, Kunming, China
    Mengwei Li, Kunming Medical University, Kunming, China
    Xianmei Wang, Kunming Medical University, Kunming, China
    Rui Zhu, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan Agricultural University, Kunming, Yunnan Province, China
    Jianjun Liu, Kunming Medical University, Kunming, China
    Lan-Qing Ma, Kunming Medical University, Kunming, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.