PPARδ preserves a high resistance to fatigue in the mouse medial gastrocnemius after spinal cord transection

• Published in: Muscle & nerve Vol. 53; no. 2; pp. 287 - 296
• Main Authors: Kim, Jung A., Roy, Roland R., Zhong, Hui, Alaynick, William A., Embler, Emi, Jang, Claire, Gomez, Gabriel, Sonoda, Takuma, Evans, Ronald M., Edgerton, V. Reggie
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.02.2016
• Subjects: Animals; Body Weight - genetics; Disease Models, Animal; fatigability; Female; isometric contractile properties; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Muscle Fatigue - genetics; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Muscle, Skeletal - physiopathology; myosin heavy chain; Myosin Heavy Chains - metabolism; Organ Size - genetics; oxidative metabolism; PPAR alpha - genetics; PPAR alpha - metabolism; RNA, Messenger - metabolism; Spinal Cord Injuries - pathology; Spinal Cord Injuries - physiopathology; spinal cord injury; Statistics, Nonparametric; Succinate Dehydrogenase - metabolism; fatigability; oxidative metabolism; spinal cord injury; isometric contractile properties; myosin heavy chain
• ISSN: 0148-639X; 1097-4598
• DOI: 10.1002/mus.24723

ABSTRACT Introduction: Skeletal muscle oxidative capacity decreases and fatigability increases after spinal cord injury. Transcription factor peroxisome proliferator‐activated receptor δ (PPARδ) promotes a more oxidative phenotype. Methods: We asked whether PPARδ overexpression could ameliorate these deficits in the medial gastrocnemius of spinal cord transected (ST) adult mice. Results: Time‐to‐peak tension and half‐relaxation times were longer in PPARδ‐Con and PPARδ‐ST compared with littermate wild‐type (WT) controls. Fatigue index was 50% higher in PPARδ‐Con than WT‐Con and 70% higher in the PPARδ‐ST than WT‐ST. There was an overall higher percent of darkly stained fibers for succinate dehydrogenase in both PPARδ groups. Conclusions: The results indicate a conversion toward slower, more oxidative, and less fatigable muscle properties with overexpression of PPARδ. Importantly, the elevated fatigue resistance was maintained after ST, suggesting that enhanced PPARδ expression, and possibly small molecule agonists, could ameliorate the increased fatigability routinely observed in chronically paralyzed muscles. Muscle Nerve 53: 287–296, 2016