Irisin Signaling Resistance in Myalgic Encephalomyelitis: A Proposed Mechanistic Framework for Post-Exertional Malaise Involving the TSP-1–HSP90α–αvβ5 Axis
Dr. Alain Moreau, Director of OMF’s Collaborative Center at Montreal, and his team recently published a paper on their work investigating the dysregulation of irisin signaling and its potential role in post-exertional malaise (PEM) for people with ME/CFS.
Irisin is an exercise-induced myokine—a protein/peptide produced by skeletal muscle fibers when a muscle contracts—that interacts with thrombospondin-1 (TSP-1), which is a regulator of immune response, wound healing, and more. This study included 92 people with ME/CFS and 44 sedentary healthy controls and found lower baseline irisin levels and blunted exertional response in people with ME/CFS. After more detailed probing, the team showed that in people with ME/CFS, elevated circulating TSP-1 correlates to symptom severity and there was a lower ability to counteract TSP-1. Together, these findings indicate dysregulation of the irisin-TSP-1 axis contributes to metabolic dysfunction in ME/CFS.
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LIVE EVENT | OMF JOURNAL CLUB
If you want to dive deeper into this paper, join Dr. Danielle Meadows, OMF’s VP of Research Programs, for the next session of OMF Journal Club on July 9 at 1pm ET.
During the session, Dr. Meadows will talk through the main ideas of the paper, the figures, and the implications for people with ME/CFS and Long COVID. If you’re not able to join the session live, a recording will be sent to all registrants.
The Bigger Picture
Overall, the findings in this paper are consistent with other evidence of energy production dysfunction in ME/CFS. The study provides a possible explanation for the impaired response to exertion that people with ME/CFS exhibit, and the proposed mechanism aligns with other observations made in the field related to exertion intolerance. Ultimately, the project has implications for metabolic subsets of ME/CFS and subsequently tailoring treatment strategies to those subsets.
This manuscript is part of the Precision Medicine for Myalgic EncephalomyelitisDrug Discovery and Clinical Trials (REMEDIAL) project. Read the full paper in the International Journal of Molecular Sciences.
