title: PPARδ preserves a high resistance to fatigue in the mouse medial gastrocnemius after spinal cord transection.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles, 610 Charles E. Young Drive East, Los Angeles, California, 90095-7239, USA.
authors.forename: Jung A
authors.initials: JA
authors.lastname: Kim
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles, 610 Charles E. Young Drive East, Los Angeles, California, 90095-7239, USA.|Department of Neurosurgery, University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: Roland R
authors.initials: RR
authors.lastname: Roy
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles, 610 Charles E. Young Drive East, Los Angeles, California, 90095-7239, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhong
authors.affiliation: Gene Expression Laboratory, Salk Institute, La Jolla, California, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Alaynick
authors.affiliation: Gene Expression Laboratory, Salk Institute, La Jolla, California, USA.
authors.forename: Emi
authors.initials: E
authors.lastname: Embler
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles, 610 Charles E. Young Drive East, Los Angeles, California, 90095-7239, USA.
authors.forename: Claire
authors.initials: C
authors.lastname: Jang
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles, 610 Charles E. Young Drive East, Los Angeles, California, 90095-7239, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Gomez
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles, 610 Charles E. Young Drive East, Los Angeles, California, 90095-7239, USA.
authors.forename: Takuma
authors.initials: T
authors.lastname: Sonoda
authors.affiliation: Gene Expression Laboratory, Salk Institute, La Jolla, California, USA.|Howard Hughes Medical Institute, La Jolla, California, USA.
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Evans
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles, 610 Charles E. Young Drive East, Los Angeles, California, 90095-7239, USA.|Department of Neurosurgery, University of California, Los Angeles, Los Angeles, California, USA.|Department of Neurobiology, University of California, Los Angeles, Los Angeles, California, USA.|Brain Research Institute, University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: V Reggie
authors.initials: VR
authors.lastname: Edgerton
mesh_terms: D000818:Animals; D001835:Body Weight / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018763:Muscle Fatigue / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D018995:Myosin Heavy Chains / Q000378:metabolism; D009929:Organ Size / Q000235:genetics; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000503:physiopathology*; D018709:Statistics, Nonparametric; D013385:Succinate Dehydrogenase / Q000378:metabolism
chemical_list: D047493:PPAR alpha; D012333:RNA, Messenger; D013385:Succinate Dehydrogenase; D018995:Myosin Heavy Chains
keywords: fatigability; isometric contractile properties; myosin heavy chain; oxidative metabolism; spinal cord injury