dFNDC5 Regulates Exercise Performance and Adaptations in Drosophila
Authors: Tyler Cobb 1; Jun Hee Lee 2; Myungjin Kim 2; Robert Wessells 1
Affiliations: 1) Wayne State University; 2) University of Michigan
Keywords: t. other (Exercise); j. physiology of adult organs
Endurance exercise has profound benefits on health and mobility, but the mechanisms underlying these benefits are not fully understood. Identification of targets that mediate the benefits of exercise can be useful for the development of therapies to improve health in populations that cannot exercise or display exercise intolerance. We have developed a model to exercise train Drosophila and have shown that many adaptations in mobility, metabolism, and gene expression are conserved. Using this model, we have identified dFNDC5 as a key mediator of endurance exercise performance and adaptations. dFNDC5 is a homolog of mammalian FNDC5, which encodes a transmembrane protein expressed in muscle that is cleaved during exercise to give rise to a peptide called Irisin that regulates systemic adaptations in mammals. However, its role in exercise performance and endurance adaptation has not been studied in depth. We show that dFNDC5 mutants have impaired baseline endurance and do not adapt to chronic exercise training. Tissue-specific experiments reveal that dFNDC5 is required in muscle for normal baseline running endurance and for the ability to adapt to exercise. We also show muscle-specific dFNDC5 overexpression extends baseline endurance and is sufficient to promote mobility adaptations in unexercised flies. These findings suggest a conserved role of dFNDC5 in the exercise response.