机构：[1]Department of Pharmacology, Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, United States,[2]Department of Pathology, Shanghai University of Traditional Chinese Medicine, Shanghai, China,[3]Department of Physiology, Cardiovascular Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, United States,[4]Division of Geriatrics and Nutritional Sciences, Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO, United States[5]Tongtong Cao, Beijing Children’s Hospital, Beijing, China首都医科大学附属北京儿童医院
Cardiomyocyte proliferation accounts for the increase of cardiac muscle during fetal mammalian heart development. Shortly after birth, cardiomyocyte transits from hyperplasia to hypertrophic growth. Here, we have investigated the role of fatty acid beta-oxidation in cardiomyocyte proliferation and hypertrophic growth during early postnatal life in mice. A transient wave of increased cell cycle activity of cardiomyocyte was observed between postnatal day 3 and 5, that proceeded as cardiomyocyte hypertrophic growth and maturation. Assessment of cardiomyocyte metabolism in neonatal mouse heart revealed a myocardial metabolic shift from glycolysis to fatty acid beta-oxidation that coincided with the burst of cardiomyocyte cell cycle reactivation and hypertrophic growth. Inhibition of fatty acid beta-oxidation metabolism in infant mouse heart delayed cardiomyocyte cell cycle exit, hypertrophic growth and maturation. By contrast, pharmacologic and genetic activation of PPAR alpha, a major regulator of cardiac fatty acid metabolism, induced fatty acid beta-oxidation and initially promoted cardiomyocyte proliferation rate in infant mice. As the cell cycle proceeded, activation of PPAR alpha-mediated fatty acid beta-oxidation promoted cardiomyocytes hypertrophic growth and maturation, which led to cell cycle exit. As a consequence, activation of PPAR alpha-mediated fatty acid beta-oxidation did not alter the total number of cardiomyocytes in infant mice. These findings indicate a unique role of fatty acid beta-oxidation in regulating cardiomyocyte proliferation and hypertrophic growth in infant mice.
基金：
This work was supported by grants from the National
Institutes for Health to YT (R00-HL111348, RO1-HL132115
and W.W. Smith Charitable Trust H1606), to KD (R00-
HL112853, RO1-HL130218).
第一作者机构：[1]Department of Pharmacology, Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, United States,[2]Department of Pathology, Shanghai University of Traditional Chinese Medicine, Shanghai, China,[5]Tongtong Cao, Beijing Children’s Hospital, Beijing, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Pharmacology, Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, United States,
推荐引用方式(GB/T 7714)：
Cao Tongtong,Liccardo Daniela,LaCanna Ryan,et al.Fatty Acid Oxidation Promotes Cardiomyocyte Proliferation Rate but Does Not Change Cardiomyocyte Number in Infant Mice[J].FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY.2019,7(MAR):-.doi:10.3389/fcell.2019.00042.
APA：
Cao, Tongtong,Liccardo, Daniela,LaCanna, Ryan,Zhang, Xiaoying,Luz, Rong...&Tian, Ying.(2019).Fatty Acid Oxidation Promotes Cardiomyocyte Proliferation Rate but Does Not Change Cardiomyocyte Number in Infant Mice.FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY,7,(MAR)
MLA：
Cao, Tongtong,et al."Fatty Acid Oxidation Promotes Cardiomyocyte Proliferation Rate but Does Not Change Cardiomyocyte Number in Infant Mice".FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY 7..MAR(2019):-
