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Research Paper|Volume 14, Issue 8|pp 3633—3651

Endothelin-1-mediated miR-let-7g-5p triggers interlukin-6 and TNF-α to cause myopathy and chronic adipose inflammation in elderly patients with diabetes mellitus

Chung-Huang Tsai1,2,3, Pei-Ju Huang4, IT Lee5,6,7, Chien-Min Chen8, Min Huan Wu3,9,10
  • 1Department of Family Medicine, Chung-Kang Branch, Cheng Ching Hospital, Taichung, Taiwan
  • 2Center for General Education, Tunghai University, Taiwan
  • 3Bachelor of Science in Senior Wellness and Sport Science, Tunghai University, Taiwan
  • 4Department of Family Medicine, Changhua Christian Hospital, Changhua, Taiwan
  • 5Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
  • 6School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
  • 7School of Medicine, Chung Shan Medical University, Taichung, Taiwan
  • 8Division of Traditional Chinese Medical, Sinying Hospital, Tainan, Taiwan
  • 9Senior Life and Innovation Technology Center, Tunghai University, Taiwan
  • 10Life Science Research Center, Tunghai University, Taiwan
* First author and co-first author
Received: February 10, 2022Accepted: April 13, 2022Published: April 25, 2022
https://doi.org/10.18632/aging.204034

Copyright: © 2022 Tsai 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

Background: Diabetes and sarcopenia are verified as mutual relationships, which seriously affect the quality of life of the elderly. Endothelin-1 is well investigated, is elevated in patients with diabetes, and is related to muscle cellular senescence and fibrosis. However, the mechanism of ET-1 between diabetes and myopathy is still unclear. The aim of this study was to evaluate the prevalence of sarcopenia in the elderly with diabetes and to clarify its relationship with ET-1 molecular biological mechanism, progress as well as changes in muscle and fat.

Methods: We recruited 157 type 2 diabetes patients over 55 years old and investigated the prevalence of sarcopenia in diabetes patients and examined the association of ET-1 alterations with HbA1c, creatinine, or AMS/ht2. Next, sought to determine how ET-1 regulates inflammation in muscle cells by western blot and qPCR assay. Using XF Seahorse Technology, we directly quantified mitochondrial bioenergetics in 3T3-L1 cells.

Results: ET-1 was positively correlated with HbA1c, creatinine levels, and duration of disease, and negatively correlated with AMS/ht2. We found that ET-1 dose-dependently induces tumor necrosis factor-α (TNF-α) and interleukin (IL)-6β expression through the PI3K/AKT, and NF-κB signaling pathways in C2C12 cells. Also identified that TNF-α, IL-6β, and visfatin releases were found in co-cultured with conditioned medium of ET-1/C2C12 in 3T3-L1 cells. ET-1 also reduces the energy metabolism of fat and induces micro-environment inflammation which causes myopathy. ET-1 also suppresses miR-let-7g-5p expression in myocytes and adipocytes.

Conclusion: We describe a new mechanism of ET-1 triggering chronic inflammation in patients with hyperglycemia.