2. Academic Validation
  3. Metformin Mitigates Adipogenesis of Fibro-adipogenic Progenitors After Rotator Cuff Tears Via Activating mTOR/ULK1 Mediated Autophagy

Metformin Mitigates Adipogenesis of Fibro-adipogenic Progenitors After Rotator Cuff Tears Via Activating mTOR/ULK1 Mediated Autophagy

  • Am J Physiol Cell Physiol. 2024 Apr 8. doi: 10.1152/ajpcell.00034.2024.
Hao Zhou 1,  Xingzuan Lin 2,  Shujing Feng 3,  Siyuan Zhu 4,  Han Zhou 2,  Huifang Chen 3,  He Youwu 5,  Zekai Wang 6,  Ru Wang 7,  Xiexiang Shao 2,  Jianhua Wang 8
Affiliations

Affiliations

  • 1 XinHua Hospital, Shanghai, --None--, China.
  • 2 XinHua Hospital, China.
  • 3 Shanghai University of Sport, China.
  • 4 Huashan Hospital, China.
  • 5 Department of Hand Plastic Surgery, The First People's Hospital of Linping District, Hangzhou, China, China.
  • 6 University of Toronto, Canada.
  • 7 Shanghai University of Sport, shanghai, - Shanghai Shi, China.
  • 8 XinHua Hospital, Shanghai, China.
PMID: 38586878 DOI: 10.1152/ajpcell.00034.2024
Abstract

Muscular fatty infiltration is a common issue after rotator cuff tears (RCT) which impairs shoulder function. Females suffer higher prevalence and more severe degree of muscular fatty infiltration after RCT when compared to males, with the underlying mechanisms remaining unclear. Fibro/adipogenic progenitors (FAPs) are the primary source of muscular fatty infiltration following RCT. Our findings disclose that gender-specific disparities in muscular fatty infiltration are linked to mTOR/ULK1-mediated Autophagy of FAPs. Decreased autophagic activity contributes to adipogenic differentiation in female FAPs after RCT. Furthermore, metformin could enhance mTOR/ULK1 mediated autophagic processes of FAPs, thereby alleviating fatty infiltration and improving shoulder functionality after RCT. Together, our study reveals that gender differences in muscular fatty infiltration arise from distinct autophagic activities. Metformin could be a promising non-invasive intervention to ameliorate muscular fatty infiltration of RCT.

Keywords

Autophagy; Muscular fatty infiltration; Rotator cuff tear; fibro-adipogenic progenitors; mTOR/ULK1 signaling pathway.

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