title: AMP-activated protein kinase stimulates Warburg-like glycolysis and activation of satellite cells during muscle regeneration.
abstract: Satellite cells are the major myogenic stem cells residing inside skeletal muscle and are indispensable for muscle regeneration. Satellite cells remain largely quiescent but are rapidly activated in response to muscle injury, and the derived myogenic cells then fuse to repair damaged muscle fibers or form new muscle fibers. However, mechanisms eliciting metabolic activation, an inseparable step for satellite cell activation following muscle injury, have not been defined. We found that a noncanonical Sonic Hedgehog (Shh) pathway is rapidly activated in response to muscle injury, which activates AMPK and induces a Warburg-like glycolysis in satellite cells. AMPKα1 is the dominant AMPKα isoform expressed in satellite cells, and AMPKα1 deficiency in satellite cells impairs their activation and myogenic differentiation during muscle regeneration. Drugs activating noncanonical Shh promote proliferation of satellite cells, which is abolished because of satellite cell-specific AMPKα1 knock-out. Taken together, AMPKα1 is a critical mediator linking noncanonical Shh pathway to Warburg-like glycolysis in satellite cells, which is required for satellite activation and muscle regeneration.
authors.affiliation: From the Department of Animal Sciences and Department of Pharmaceutical Sciences, Washington Center for Muscle Biology and.
authors.forename: Xing
authors.initials: X
authors.lastname: Fu
authors.affiliation: the School of Food Sciences, Washington State University, Pullman, Washington 99164.
authors.forename: Mei-Jun
authors.initials: MJ
authors.lastname: Zhu
authors.affiliation: From the Department of Animal Sciences and Department of Pharmaceutical Sciences, Washington Center for Muscle Biology and.
authors.forename: Mike V
authors.initials: MV
authors.lastname: Dodson
authors.affiliation: From the Department of Animal Sciences and Department of Pharmaceutical Sciences, Washington Center for Muscle Biology and min.du@wsu.edu.
authors.forename: Min
authors.initials: M
authors.lastname: Du
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D006019:Glycolysis / Q000502:physiology*; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D012038:Regeneration / Q000502:physiology*; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000201:enzymology*
chemical_list: D053823:Hedgehog Proteins; C465570:Shh protein, mouse; C548179:Prkaa1 protein, mouse; D055372:AMP-Activated Protein Kinases
keywords: AMP-activated kinase (AMPK); Sonic Hedgehog (SHH); myogenesis; regeneration; satellite cell; skeletal muscle