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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Physiol. | doi: 10.3389/fphys.2019.01439

Effect of Interleukin-15 receptor alpha ablation on the metabolic responses to moderate exercise simulated by in vivo isometric muscle contractions.

 Emanuele Loro1*, Cholsoon Jang2, William J. Quinn1, Joseph A. Baur1,  Zoltan P. Arany1 and Tejvir S. Khurana1*
  • 1University of Pennsylvania, United States
  • 2Princeton University, United States

Lack of interleukin 15 receptor alpha (IL15RA) increases spontaneous activity, exercise capacity and protects from diet-induced obesity by enhancing muscle energy metabolism, suggesting a role as exercise mimetic for IL15RA antagonists. Using controlled in vivo muscle stimulation mimicking moderate exercise in normal and Il15ra-/- mice, we mapped and contrasted the metabolic pathways activated upon stimulation or deletion of IL15RA. Stimulation caused the differential regulation of 123 out of the 321 detected metabolites (FDR<=0.05 and fold change>=±1.5). The main energy pathways activated were fatty acid oxidation, nucleotide metabolism, and anaplerotic reactions. Notably, resting Il15ra-/- muscles were primed in a semi-exercised state, characterized by higher pool sizes of fatty acids oxidized to support muscle activity. These studies identify the role of IL15RA in the system-wide metabolic response to exercise and should enable translational studies to harness the potential of IL15RA blockade as a novel exercise mimetic strategy.

Keywords: Muscle, Exercise, Interleukin-15 receptor alpha, Metabolomics, in vivo stimulation, Exercise mimetics, Metabolism, Fatty acid oxidation (FAO), Endurance

Received: 19 Jul 2019; Accepted: 07 Nov 2019.

Copyright: © 2019 Loro, Jang, Quinn, Baur, Arany and Khurana. 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) and the copyright owner(s) 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:
Dr. Emanuele Loro, University of Pennsylvania, Philadelphia, United States, eloro@pennmedicine.upenn.edu
Prof. Tejvir S. Khurana, University of Pennsylvania, Philadelphia, United States, tsk@pennmedicine.upenn.edu