PGC-1α in the Myofibers Regulates the Balance Between Myogenic and Adipogenic Progenitors Affecting Muscle Regeneration

Overview

Journal iScience

Publisher Cell Press

Date 2022 Nov 17

PMID 36388980

Authors

Marc Beltra

Fabrizio Pin

Domiziana Costamagna

Robin Duelen

Alessandra Renzini

Riccardo Ballaro

Lorena Garcia-Castillo

Ambra Iannuzzi

Viviana Moresi

Dario Coletti

Maurilio Sampaolesi

Fabio Penna

Paola Costelli

Affiliations

Soon will be listed here.

Abstract

Skeletal muscle repair is accomplished by satellite cells (MuSCs) in cooperation with interstitial stromal cells (ISCs), but the relationship between the function of these cells and the metabolic state of myofibers remains unclear. This study reports an altered proportion of MuSCs and ISCs (including adipogenesis-regulatory cells; Aregs) induced by the transgenic overexpression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in the myofibers (MCK-PGC-1α mice). Although PGC-1α-driven increase of MuSCs does not accelerate muscle regeneration, myogenic progenitors isolated from MCK-PGC-1α mice and transplanted into intact and regenerating muscles are more prone to fuse with recipient myofibers than those derived from wild-type donors. Moreover, both young and aged MCK-PGC-1α animals exhibit reduced perilipin-positive areas when challenged with an adipogenic stimulus, demonstrating low propensity to accumulate adipocytes within the muscle. Overall, these results unveil that increased PGC-1α expression in the myofibers favors pro-myogenic and anti-adipogenic cell populations in the skeletal muscle.

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References

Zhang H, Ryu D, Wu Y, Gariani K, Wang X, Luan P . NAD⁺ repletion improves mitochondrial and stem cell function and enhances life span in mice. Science. 2016; 352(6292):1436-43. DOI: 10.1126/science.aaf2693. View

Sandri M, Lin J, Handschin C, Yang W, Arany Z, Lecker S . PGC-1alpha protects skeletal muscle from atrophy by suppressing FoxO3 action and atrophy-specific gene transcription. Proc Natl Acad Sci U S A. 2006; 103(44):16260-5. PMC: 1637570. DOI: 10.1073/pnas.0607795103. View

Da Cruz S, Parone P, Lopes V, Lillo C, McAlonis-Downes M, Lee S . Elevated PGC-1α activity sustains mitochondrial biogenesis and muscle function without extending survival in a mouse model of inherited ALS. Cell Metab. 2012; 15(5):778-86. PMC: 3565468. DOI: 10.1016/j.cmet.2012.03.019. View

Sacco A, Doyonnas R, Kraft P, Vitorovic S, Blau H . Self-renewal and expansion of single transplanted muscle stem cells. Nature. 2008; 456(7221):502-6. PMC: 2919355. DOI: 10.1038/nature07384. View

Li W, Zheng Y, Zhang W, Wang Z, Xiao J, Yuan Y . Progression and variation of fatty infiltration of the thigh muscles in Duchenne muscular dystrophy, a muscle magnetic resonance imaging study. Neuromuscul Disord. 2015; 25(5):375-80. DOI: 10.1016/j.nmd.2015.01.003. View

Brett J, Arjona M, Ikeda M, Quarta M, de Morree A, Egner I . Exercise rejuvenates quiescent skeletal muscle stem cells in old mice through restoration of Cyclin D1. Nat Metab. 2020; 2(4):307-317. PMC: 7323974. DOI: 10.1038/s42255-020-0190-0. View

Fu X, Zhu M, Zhang S, Foretz M, Viollet B, Du M . Obesity Impairs Skeletal Muscle Regeneration Through Inhibition of AMPK. Diabetes. 2015; 65(1):188-200. PMC: 4686944. DOI: 10.2337/db15-0647. View

Li X, Egervari G, Wang Y, Berger S, Lu Z . Regulation of chromatin and gene expression by metabolic enzymes and metabolites. Nat Rev Mol Cell Biol. 2018; 19(9):563-578. PMC: 6907087. DOI: 10.1038/s41580-018-0029-7. View

Addison O, Drummond M, LaStayo P, Dibble L, Wende A, McClain D . Intramuscular fat and inflammation differ in older adults: the impact of frailty and inactivity. J Nutr Health Aging. 2014; 18(5):532-8. PMC: 6639009. DOI: 10.1007/s12603-014-0019-1. View

10.

Dinulovic I, Furrer R, Beer M, Ferry A, Cardel B, Handschin C . Muscle PGC-1α modulates satellite cell number and proliferation by remodeling the stem cell niche. Skelet Muscle. 2016; 6(1):39. PMC: 5134094. DOI: 10.1186/s13395-016-0111-9. View

11.

Hood D, Memme J, Oliveira A, Triolo M . Maintenance of Skeletal Muscle Mitochondria in Health, Exercise, and Aging. Annu Rev Physiol. 2018; 81:19-41. DOI: 10.1146/annurev-physiol-020518-114310. View

12.

Shapira S, Christofk H . Metabolic Regulation of Tissue Stem Cells. Trends Cell Biol. 2020; 30(7):566-576. PMC: 8059102. DOI: 10.1016/j.tcb.2020.04.004. View

13.

Schnyder S, Handschin C . Skeletal muscle as an endocrine organ: PGC-1α, myokines and exercise. Bone. 2015; 80:115-125. PMC: 4657151. DOI: 10.1016/j.bone.2015.02.008. View

14.

Filadi R, Pendin D, Pizzo P . Mitofusin 2: from functions to disease. Cell Death Dis. 2018; 9(3):330. PMC: 5832425. DOI: 10.1038/s41419-017-0023-6. View

15.

Bostrom P, Wu J, Jedrychowski M, Korde A, Ye L, Lo J . A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012; 481(7382):463-8. PMC: 3522098. DOI: 10.1038/nature10777. View

16.

Costamagna D, Duelen R, Penna F, Neumann D, Costelli P, Sampaolesi M . Interleukin-4 administration improves muscle function, adult myogenesis, and lifespan of colon carcinoma-bearing mice. J Cachexia Sarcopenia Muscle. 2020; 11(3):783-801. PMC: 7296260. DOI: 10.1002/jcsm.12539. View

17.

Pisani D, Bottema C, Butori C, Dani C, Dechesne C . Mouse model of skeletal muscle adiposity: a glycerol treatment approach. Biochem Biophys Res Commun. 2010; 396(3):767-73. DOI: 10.1016/j.bbrc.2010.05.021. View

18.

Furrer R, Eisele P, Schmidt A, Beer M, Handschin C . Paracrine cross-talk between skeletal muscle and macrophages in exercise by PGC-1α-controlled BNP. Sci Rep. 2017; 7:40789. PMC: 5238507. DOI: 10.1038/srep40789. View

19.

Lukjanenko L, Karaz S, Stuelsatz P, Gurriaran-Rodriguez U, Michaud J, Dammone G . Aging Disrupts Muscle Stem Cell Function by Impairing Matricellular WISP1 Secretion from Fibro-Adipogenic Progenitors. Cell Stem Cell. 2019; 24(3):433-446.e7. PMC: 6408230. DOI: 10.1016/j.stem.2018.12.014. View

20.

Liu L, Charville G, Cheung T, Yoo B, Santos P, Schroeder M . Impaired Notch Signaling Leads to a Decrease in p53 Activity and Mitotic Catastrophe in Aged Muscle Stem Cells. Cell Stem Cell. 2018; 23(4):544-556.e4. PMC: 6173623. DOI: 10.1016/j.stem.2018.08.019. View