Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aging / drug effects
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Aging / pathology
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Aging / physiology*
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Animals
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Calcineurin / metabolism
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Calcineurin Inhibitors
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Cell Division / drug effects
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Cell Fusion
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Cell Nucleus / physiology*
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Citrate (si)-Synthase / metabolism
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Cyclosporine / pharmacology
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Inbred Strains
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Mice, Transgenic
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Muscle Fibers, Fast-Twitch / cytology
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Muscle Fibers, Fast-Twitch / metabolism
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Muscle Fibers, Fast-Twitch / pathology
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Muscle Fibers, Skeletal / cytology
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Muscle Fibers, Skeletal / metabolism
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Muscle Fibers, Skeletal / pathology
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Muscle, Skeletal / cytology*
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Muscle, Skeletal / drug effects
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Muscle, Skeletal / metabolism
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Muscle, Skeletal / pathology
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NFATC Transcription Factors / metabolism
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PPAR-beta / agonists
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PPAR-beta / physiology*
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Proliferating Cell Nuclear Antigen / metabolism
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Satellite Cells, Skeletal Muscle / cytology
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Satellite Cells, Skeletal Muscle / drug effects
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Succinate Dehydrogenase / metabolism
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Thiazoles / pharmacology
Substances
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Calcineurin Inhibitors
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NFATC Transcription Factors
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Nfatc1 protein, mouse
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Nfatc3 protein, mouse
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PPAR-beta
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Proliferating Cell Nuclear Antigen
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Thiazoles
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(4-(((2-(3-fluoro-4-(trifluoromethyl)phenyl)-4-methyl-1,3-thiazol-5-yl)methyl)sulfanyl)-2-methylphenoxy)acetic acid
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Cyclosporine
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Succinate Dehydrogenase
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Citrate (si)-Synthase
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Calcineurin