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Research Paper|Volume 13, Issue 4|pp 4881—4894

MiR-141-3p promotes mitochondrial dysfunction in ovariectomy-induced sarcopenia via targeting Fkbp5 and Fibin

Hyunjung Lee1, Young In Kim1,2, Farida S. Nirmala1,3, Ji-Sun Kim4, Hyo-Deok Seo1, Tae Youl Ha1,3, Young-Jin Jang1, Chang Hwa Jung1,3, Jiyun Ahn1,3
  • 1Research Group of Natural Material and Metabolism, Korea Food Research Institute, Wanju, South Korea
  • 2Department of Food Science and Technology, Jeonbuk National University, Jeonju-Si, South Korea
  • 3Department of Food Biotechnology, University of Science and Technology, Daejeon, South Korea
  • 4Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, South Korea
Received: February 28, 2020Accepted: December 9, 2020Published: February 3, 2021
https://doi.org/10.18632/aging.202617

Copyright: © 2021 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Post-menopausal conditions exacerbate the biological aging process and this is often accompanied by visceral adiposity with sarcopenia. Mitochondrial impairment is a hallmark of frailty and sarcopenia in the elderly. However, the exact mechanism underlying the development of obesogenic sarcopenia and the involvement of mitochondria remains unclear. This study confirmed that there is a decline in muscle mass and function as well as mitochondrial dysfunction in the quadriceps of ovariectomized (OVX) mice. To investigate the role of microRNA (miRNA) in this process, we performed miRNA and mRNA arrays and found that miR-141-3p directly targets and downregulates FK506 binding protein 5 (Fkbp5) and Fibin. Overexpression of miR-141-3p decreased mitochondrial function and inhibited myogenic differentiation in C2C12 cells. These effects were mediated by Fkbp5 and Fibin inhibition. Conversely, knockdown of miR-141-3p increased mitochondrial respiration and enhanced myogenesis. Treatment with β-estradiol effectively reversed the palmitic acid-induced upregulation of miR-141-3p and subsequent downregulation of Fkbp5 and Fibin. In conclusion, miR-141-3p is upregulated in OVX mice, and this is associated with mitochondrial dysfunction through inhibition of Fkbp5 and Fibin. These findings suggest that inhibiting miR-141-3p could be a therapeutic target for alleviating obesogenic sarcopenia.