AUTHOR=Yang Jingxin , Zhang Yalin , Pan Yiming , Sun Can , Liu Zuwang , Liu Ning , Fu Yu , Li Xiaofeng , Li Ye , Kong Juan TITLE=The Protective Effect of 1,25(OH)2D3 on Myocardial Function is Mediated via Sirtuin 3-Regulated Fatty Acid Metabolism JOURNAL=Frontiers in Cell and Developmental Biology VOLUME=Volume 9 - 2021 YEAR=2021 URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.627135 DOI=10.3389/fcell.2021.627135 ISSN=2296-634X ABSTRACT=Imbalance of energy substrate is a major cause of cardiac dysfunction. Vitamin D/vitamin D receptor (VD/VDR) deficiency is involved in the pathogenesis of various cardiac diseases,however, the mechanism remains unclear. The aim of this study was to investigate whether vitamin D modulated fatty acid oxidase in mitochondria via Sirtuin3 signal pathway to protect myocardium. The 1 alpha-hydroxylase-/- mice with high metabolic rate had lower myocardial contractility compared to wild type mice. Up-regulated sirtuin3 was detected in the mice treated by vitamin D3-high fat diet compared with the high fat diet mice. Sirtuin3 blocker and Sirtuin3 knockout inhibited the effect of VD/VDR on down-regulation of fatty acid oxidase in myocardial mitochondria. VD/VDR moderated fatty acid metabolism by up-regulating Sirtuin3 and lowering mitochondrial fat uptake, thereby improving myocardial function and balancing energy substance, rather than altering endocytosis and exocytosis.