## 4 Discussion
Cardiac TG homeostasis is mainly determined by the balance between de novo synthesis, endogenous TG catabolism, and probably the re-esterification of DAGs originating from TG breakdown. The heart has an extremely high turnover rate of TGs and contributes to mitochondrial FA supply [43]. The de novo pathway of TG formation is initiatedby glycerol-3-phosphate acyltransferases (GPATs)-catalyzed FA esterification at the \(sn\)-1 position of glycerol-3-phosphate (G3P), resulting in the formation of lysophosphatidic acid (LPA) [12]. Fatty acyl moieties can be incorporated into phospholipids (e.g., PC) by lysophospholipid acyltransferases or released from them by PLA2 [44]. Two pathways involved in PC metabolism, the Kennedy pathway and Lands cycle, act coordinately to regulate triacylglycerglycerol content. The metabolomic results show that the 7 KCh-treated cardiac cells have reduced TG content. The transcriptomic results reveal the downregulation of the expression of TG biosynthesis-related genes. As cardiac TG formation and lipolysis determine the amount of FAs that can be used for energy metabolism, defective cardiac TG homeostasis may result in metabolic aberration, lipotoxicity, and cardiac dysfunction. Apart from the increases in PLA2 activity and lipolysis, FAs can be made available for cholesteryl ester formation by reducing de novo TG biosynthesis. Decreases in both TGs and phospholipids may adversely affect the physiology of cardiomyocytes. The proposed scheme is shown in Figure 6. The present study gives an insight into the 7 KCh-induced reprogramming of lipid metabolism in cardiac cells. The following are available online at [[https://www.mdpi.com/article/10.3390/cells10123597/s1](https://www.mdpi.com/article/10.3390/cells10123597/s1)]([https://www.mdpi.com/article/10.3390/cells10123597/s1](https://www.mdpi.com/article/10.3390/cells10123597/s1)), Table S1: gene list in Figures 4 and 6. Conceptualization, M.-L.C. and H.-Y.H. ; methodology, H.-Y.T., C.-J.L. and J.-F.L. ; software, P.-T.W. and C.-H.Y. ; validation, H.-Y.T. and C.-H.Y. ; formal analysis, P.-T.W. and [PERSON]-F.L. ; investigation, P.-T.W. and C.-J.L. ; writing and editing, H.-Y.H., [PERSON]-[PERSON] and [PERSON]-[PERSON]. All authors have read and agreed to the published version of the manuscript. This research was funded by Chang Gung Memorial Hospital (grant number: BMRP819, BMRP564, CMRPD1L0161, CMRPD1H0201, CMRPD1H0202, CMRPD1H0203, CMRPD1J0341, CMRPD1J0342, CMRPD1H0511, CMRPD1H0512, CMRPD1J0261, CMRPD1J0262, and CMRPD1J0263); Ministry of Science and Technology in Taiwan (MOST) (grant number: MOST 107-2320-B-182-011-MY3, 110-2320-B-182-017-MY3, 110-2320-B-182-007); and Ministry of Education in Taiwan (MOE) (EMRPD1K0441, EMRPD1K0481, and EMRPD1D4421). This work was also supported by the Research Center for Emerging Viral Infections from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan and the Ministry of Science and Technology (MOST) in Taiwan (MOST 110-2634-F-182-001). Not applicable. The data presented in this study are available on request from the corresponding author. The data are not publicly available due to patent application request. We thank the staff of the Metabolomics Core Laboratory of Chang Gung University Healthy Aging Research Center for technical support. The authors declare no conflict of interest.