Journal article

Loss of IL-15 receptor alpha alters the endurance, fatigability, and metabolic characteristics of mouse fast skeletal muscles

Emidio E Pistilli, Sasha Bogdanovich, Fleur Garton, Nan Yang, Jason P Gulbin, Jennifer D Conner, Barbara G Anderson, LeBris S Quinn, Kathryn North, Rexford S Ahima, Tejvir S Khurana

Journal of Clinical Investigation | AMER SOC CLINICAL INVESTIGATION INC | Published : 2011

Abstract

IL-15 receptor α (IL-15Rα) is a component of the heterotrimeric plasma membrane receptor for the pleiotropic cytokine IL-15. However, IL-15Rα is not merely an IL-15 receptor subunit, as mice lacking either IL-15 or IL-15Rα have unique phenotypes. IL-15 and IL-15Rα have been implicated in muscle phenotypes, but a role in muscle physiology has not been defined. Here, we have shown that loss of IL-15Rα induces a functional oxidative shift in fast muscles, substantially increasing fatigue resistance and exercise capacity. IL-15Rα-knockout (IL-15Rα-KO) mice ran greater distances and had greater ambulatory activity than controls. Fast muscles displayed fatigue resistance and a slower contractile p..

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Grants

Awarded by NIH under Ruth L. Kirschstein National Research Service from National Institute of Arthritis and Musculoskeletal and Skin Diseases



Awarded by NATIONAL EYE INSTITUTE


Awarded by NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES


Awarded by NATIONAL INSTITUTE ON AGING


Funding Acknowledgements

This research was supported by the NIH under Ruth L. Kirschstein National Research Service Award 5T32AR053461 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (to E.E. Pistilli), EY013862 and AR48871 to T.S. Khurana, and R01AG024136 to L.S. Quinn, with resources from the VA Puget Sound Health Care System. The authors acknowledge Ravindra Dhir for collection and analysis of body composition and ambulatory activity data.