Peroxisome proliferator-activated receptor beta activation promotes myonuclear accretion in skeletal muscle of adult and aged mice.
We reported recently that peroxisome proliferator-activated receptor beta (PPARbeta) activation promotes a calcineurin-dependent exercise-like remodelling characterised by increased numbers of oxidative fibres and capillaries. As physical exercise also induces myonuclear accretion, we investigated whether PPARbeta activation alters myonuclear density. Transgenic muscle-specific PPARbeta over-expression induced 14% increase of myonuclear density. Pharmacological PPARbeta activation promoted rapid and massive myonuclear accretion (20% increase after 48 h), which is dependent upon calcineurin/nuclear factor of activated T cells signalling pathway. In vivo bromodeoxyuridine labelling and proliferating cell nuclear antigen immunodetection revealed that PPARbeta activation did not promote cell proliferation, suggesting that the PPARbeta-promoted myonuclear accretion involves fusion of pre-existing muscle precursor cells to myofibres rather than cell division. Finally, we showed that in skeletal muscle, ageing led to a down-regulation of PPARbeta accompanied by decrease of both oxidative fibre number and myonuclear density. PPARbeta pharmacological activation counteracts, at least in part, the ageing-driven muscle remodelling.
INSERM U907, Université de Nice-Sophia Antipolis, Faculté de Médecine, 28 avenue de Valombrose, 06107, Nice, France.
C
C
Giordano
A S
AS
Rousseau
N
N
Wagner
C
C
Gaudel
J
J
Murdaca
C
C
Jehl-Piétri
B
B
Sibille
P A
PA
Grimaldi
P
P
Lopez
D000375:Aging / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D065095:Calcineurin Inhibitors; D002455:Cell Division / Q000187:drug effects; D002459:Cell Fusion; D002467:Cell Nucleus / Q000502:physiology*; D002950:Citrate (si)-Synthase / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D018656:Muscle Fibers, Fast-Twitch / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D050778:NFATC Transcription Factors / Q000378:metabolism; D048068:PPAR-beta / Q000819:agonists / Q000502:physiology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000187:drug effects; D013385:Succinate Dehydrogenase / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology; D010636:Phenols; D013438:Sulfhydryl Compounds
D019703:Calcineurin; D065095:Calcineurin Inhibitors; D002950:Citrate (si)-Synthase; D016572:Cyclosporine; D050778:NFATC Transcription Factors; D048068:PPAR-beta; D018809:Proliferating Cell Nuclear Antigen; D013385:Succinate Dehydrogenase; D013844:Thiazoles; C494005:Nfatc1 protein, mouse; C494009:Nfatc3 protein, mouse; C479979:(4-(((2-(3-fluoro-4-(trifluoromethyl)phenyl)-4-methyl-1,3-thiazol-5-yl)methyl)sulfanyl)-2-methylphenoxy)acetic acid; D010636:Phenols; D013438:Sulfhydryl Compounds