Metformin’s effect on metabolic dysfunction-associated steatotic liver disease through the miR-200a-5p and AMPK/SERCA2b pathway

Metformin’s effect on metabolic dysfunction-associated steatotic liver disease through the miR-200a-5p and AMPK/SERCA2b pathway

IntroductionMetformin 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.MethodsA PA cell mo...

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Main Authors: Hang Chen, Minshan Huang, Dan Zhang, Hui Wang, Da Wang, Mengwei Li, Xianmei Wang, Rui Zhu, Jianjun Liu, Lanqing Ma
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-12-01
Series:Frontiers in Pharmacology
Subjects:
MASLD
metformin
miR-200a-5p
AMPK
SERCA2b
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2024.1477212/full
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Summary:IntroductionMetformin 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.MethodsA 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.ResultsIn 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.DiscussionThese findings suggest that metformin alleviates lipid deposition and ER stress in MASLD through the modulation of the AMPK/SERCA2b pathway via miR-200a-5p.
ISSN:1663-9812

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