title: Acetoacetate Accelerates Muscle Regeneration and Ameliorates Muscular Dystrophy in Mice.
abstract: Acetoacetate (AA) is a ketone body and acts as a fuel to supply energy for cellular activity of various tissues. Here, we uncovered a novel function of AA in promoting muscle cell proliferation. Notably, the functional role of AA in regulating muscle cell function is further evidenced by its capability to accelerate muscle regeneration in normal mice, and it ameliorates muscular dystrophy in mdx mice. Mechanistically, our data from multiparameter analyses consistently support the notion that AA plays a non-metabolic role in regulating muscle cell function. Finally, we show that AA exerts its function through activation of the MEK1-ERK1/2-cyclin D1 pathway, revealing a novel mechanism in which AA serves as a signaling metabolite in mediating muscle cell function. Our findings highlight the profound functions of a small metabolite as signaling molecule in mammalian cells.
authors.affiliation: From the State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005 and.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Zou
authors.affiliation: From the State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005 and.
authors.forename: Jiao
authors.initials: J
authors.lastname: Meng
authors.affiliation: From the State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005 and.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: From the State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005 and.
authors.forename: Wanhong
authors.initials: W
authors.lastname: Han
authors.affiliation: From the State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005 and.
authors.forename: Changyin
authors.initials: C
authors.lastname: Li
authors.affiliation: From the State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005 and.
authors.forename: Ran
authors.initials: R
authors.lastname: Zhong
authors.affiliation: the Key Laboratory of Genomic and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xuexia
authors.initials: X
authors.lastname: Miao
authors.affiliation: the Key Laboratory of Genomic and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cai
authors.affiliation: From the State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005 and dr_zhangyong@126.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: From the State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005 and dhzhu@pumc.edu.cn.
authors.forename: Dahai
authors.initials: D
authors.lastname: Zhu
mesh_terms: D000090:Acetoacetates / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007657:Ketone Bodies / Q000737:chemistry; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D009137:Muscular Dystrophy, Animal / Q000188:drug therapy*; D012038:Regeneration / Q000187:drug effects*; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology; D015398:Signal Transduction
chemical_list: D000090:Acetoacetates; D007657:Ketone Bodies; D019938:Cyclin D1; C016635:acetoacetic acid; D048369:MAP Kinase Kinase 1; C482127:Map2k1 protein, mouse
keywords: acetoacetate; cyclin D1; extracellular-signal-regulated kinase (ERK); muscle regeneration; muscular dystrophy