PPARγ Controls Ectopic Adipogenesis and Cross-Talks with Myogenesis During Skeletal Muscle Regeneration.

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Version: Final published version
Serval ID
serval:BIB_DA3296240EF0
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
PPARγ Controls Ectopic Adipogenesis and Cross-Talks with Myogenesis During Skeletal Muscle Regeneration.
Journal
InternationalJjournal of Molecular Sciences
Author(s)
Dammone G., Karaz S., Lukjanenko L., Winkler C., Sizzano F., Jacot G., Migliavacca E., Palini A., Desvergne B., Gilardi F., Feige J.N.
ISSN
1422-0067 (Electronic)
ISSN-L
1422-0067
Publication state
Published
Issued date
2018
Peer-reviewed
Oui
Volume
19
Number
7
Pages
2044
Language
english
Abstract
Skeletal muscle is a regenerative tissue which can repair damaged myofibers through the activation of tissue-resident muscle stem cells (MuSCs). Many muscle diseases with impaired regeneration cause excessive adipose tissue accumulation in muscle, alter the myogenic fate of MuSCs, and deregulate the cross-talk between MuSCs and fibro/adipogenic progenitors (FAPs), a bi-potent cell population which supports myogenesis and controls intra-muscular fibrosis and adipocyte formation. In order to better characterize the interaction between adipogenesis and myogenesis, we studied muscle regeneration and MuSC function in whole body <i>Pparg</i> null mice generated by epiblast-specific Cre/lox deletion ( <i>Pparg <sup>Δ/Δ</sup></i> ). We demonstrate that deletion of PPARγ completely abolishes ectopic muscle adipogenesis during regeneration and impairs MuSC expansion and myogenesis after injury. Ex vivo assays revealed that perturbed myogenesis in <i>Pparg <sup>Δ/Δ</sup></i> mice does not primarily result from intrinsic defects of MuSCs or from perturbed myogenic support from FAPs. The immune transition from a pro- to anti-inflammatory MuSC niche during regeneration is perturbed in <i>Pparg <sup>Δ/Δ</sup></i> mice and suggests that PPARγ signaling in macrophages can interact with ectopic adipogenesis and influence muscle regeneration. Altogether, our study demonstrates that a PPARγ-dependent adipogenic response regulates muscle fat infiltration during regeneration and that PPARγ is required for MuSC function and efficient muscle repair.
Keywords
PPARg, Skeletal muscle, adipogenesis, inflammation, muscle stem cells, myogenesis, regeneration, satellite cells
Pubmed
Web of science
Open Access
Yes
Create date
13/09/2018 8:27
Last modification date
20/08/2019 16:59
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