Human skeletal muscle fibre type variations correlate with PPAR alpha, PPAR delta and PGC-1 alpha mRNA.
OBJECTIVE
Studies from genetically modified animals have been instrumental in highlighting genes and their products involved in the regulation of muscle fibre type and oxidative phenotypes; however, evidence in humans is limited. Our aim was therefore to investigate expression of those genes implicated in the regulation of oxidative fibre phenotypes in humans.


METHODS
Using quantitative polymerase chain reaction we determined mRNA expression of selected genes in skeletal muscle from three different groups, displaying physiological and pathological variations in muscle fibre type, activity and skeletal muscle metabolism respectively: (i) elite athletes (cyclists), with an increased proportion of type I slow twitch, oxidative fibres, (ii) normally active subjects with an average fibre type distribution, and (iii) spinal cord-injured subjects with a low proportion of type I fibres.


RESULTS
Skeletal muscle mRNA expression of calcineurin Aalpha and Abeta, peroxisome proliferator-activated receptor (PPAR)-alpha and -delta, and PPAR gamma coactivator (PGC)-1alpha and -1beta was determined. Calcineurin Aalpha and calcineurin Abeta mRNA expression was similar between groups. In contrast, mRNA expression of PPARalpha, PPARdelta, PGC-1alpha and -1beta was increased in athletes, when compared with normally active subjects. Furthermore, mRNA expression of PPARalpha, PPARdelta, PGC-1alpha and -1beta was reduced in spinal cord-injured subjects. Additionally, PPARalpha, PPARdelta and PGC-1alpha correlated with oxidative fibre content.


CONCLUSIONS
Skeletal muscle mRNA expression of PPARalpha, PPARdelta, PGC-1alpha and -1beta reflects differences in type I muscle fibres associated with pathologically and physiologically induced skeletal muscle fibre type differences.
Krämer
D K
DK
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Ahlsén
M
M
Norrbom
J
J
Jansson
E
E
Hjeltnes
N
N
Gustafsson
T
T
Krook
A
A
D000328:Adult; D001642:Bicycling / Q000502:physiology; D019703:Calcineurin / Q000032:analysis; D002352:Carrier Proteins / Q000235:genetics; D002574:Cervical Vertebrae; D005786:Gene Expression Regulation / Q000235:genetics; D006360:Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology*; D010084:Oxidation-Reduction; D047493:PPAR alpha / Q000235:genetics; D047494:PPAR delta / Q000235:genetics; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger / Q000032:analysis*; D016601:RNA-Binding Proteins; D013119:Spinal Cord Injuries / Q000235:genetics / Q000503:physiopathology; D014157:Transcription Factors / Q000235:genetics*
D002352:Carrier Proteins; D006360:Heat-Shock Proteins; D047493:PPAR alpha; D047494:PPAR delta; C486497:PPARGC1A protein, human; C455622:PPARGC1B protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D019703:Calcineurin