ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Cellular Endocrinology
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1650805
This article is part of the Research TopicTissue Crosstalk in Obesity and Diabetes: A Focus on Skeletal MuscleView all 10 articles
Sex Differences in the Skeletal Muscle Response to Metformin Treatment and the Possible Association with Gut-muscle Axis in Rats
Provisionally accepted
- 1Xi'an Jiaotong University Health Science Center, Xi'an, China
- 2The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
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Metformin (MT) is widely used in treating type 2 diabetes, and muscle is one of the targets for MT action. Recent studies have shown that gut microbiota plays a key role in mediating the clinical effects of MT, as well as affects muscle function, through the gut-muscle axis. However, it is not clear whether the use of MT in non-diabetic population affects muscle metabolism via gutmuscle axis and whether there are sex differences. We investigated the effects of ten days MT administration (200 mg/kg/d) on metabolic phenotype, skeletal muscle morphology and functionrelated gene expression, gut microbiota composition, gut integrity and inflammation, and plasma short chain fatty acids (SCFAs) levels in adult male and female Sprauge-Dawley rats. We found MT treatment decreased body weight, blood glucose and muscle gene expression involved in myogenesis and mitochondrial biogenesis and dynamics more significant in females, while increased the colonic mRNA expression of more inflammatory markers in males. MT treatment also induced sex-specific alterations in the gut microbiota composition, plasma SCFAs contents and muscle SCFA receptors' mRNA expression in non-diabetic rats. Our research provides evidence that the use of MT in daily health maintenance may have sex-specific effects on gutmuscle axis and should be approached with caution.
Keywords: Metformin, Muscle, Gut Microbiota, Short chain fatty acid, sex differences
Received: 20 Jun 2025; Accepted: 11 Aug 2025.
Copyright: © 2025 Song, Wang, Cui, Hu, Wang, Xie, Miao and Sun. 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: Bo Sun, Xi'an Jiaotong University Health Science Center, Xi'an, China
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