Peroxisome proliferator-activated receptor β activation promotes myonuclear accretion in skeletal muscle of adult and aged mice

Abstract

We reported recently that peroxisome proliferator-activated receptor β (PPARβ) 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 PPARβ activation alters myonuclear density. Transgenic muscle-specific PPARβ over-expression induced 14% increase of myonuclear density. Pharmacological PPARβ 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 PPARβ activation did not promote cell proliferation, suggesting that the PPARβ-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 PPARβ accompanied by decrease of both oxidative fibre number and myonuclear density. PPARβ pharmacological activation counteracts, at least in part, the ageing-driven muscle remodelling.