biostudies-literatureUnknown16(1)Wang JRegular exercise enhances heart function and metabolism. The N6-methyladenosine (m⁶A) RNA modification is related to myocardial homeostasis, with the demethylase fat mass and obesity-associated protein (FTO) crucial for myocardial remodeling. However, its role in exercise-induced heart protection is unclear. We analyzed m⁶A levels and methylation enzymes to evaluate FTO changes in transverse aortic constriction (TAC) mice hearts after six weeks of treadmill exercise. Further in vivo experiments explored the effect of FTO. High-throughput sequencing identified the target gene enoyl-CoA delta isomerase 1 (Eci1). Cardiac-specific <i>Eci1</i> knockout mice were used to assess the role of Eci1. The influence of FTO on Eci1 expression was explored by eliminating demethylaseBiomolecules98https://www.ebi.ac.uk/biostudies/studies/S-EPMC12839096biostudies-literatureFTO-Eci1 Axis Mediates Exercise-Induced Cardioprotection in Pressure Overload Mice.PMC12839096Sha GXia JLin SWang SDeng QHu MChang ZHuang QWang JZeng WfalseFTO-Eci1 Axis Mediates Exercise-Induced Cardioprotection in Pressure Overload Mice.Regular exercise enhances heart function and metabolism. The N6-methyladenosine (m⁶A) RNA modification is related to myocardial homeostasis, with the demethylase fat mass and obesity-associated protein (FTO) crucial for myocardial remodeling. However, its role in exercise-induced heart protection is unclear. We analyzed m⁶A levels and methylation enzymes to evaluate FTO changes in transverse aortic constriction (TAC) mice hearts after six weeks of treadmill exercise. Further in vivo experiments explored the effect of FTO. High-throughput sequencing identified the target gene enoyl-CoA delta isomerase 1 (Eci1). Cardiac-specific <i>Eci1</i> knockout mice were used to assess the role of Eci1. The influence of FTO on Eci1 expression was explored by eliminating demethylase2026-01-01T00:00:00Z2026 Jan2026-06-18T03:09:51.78Z2026-06-18T03:07:34.276ZS-EPMC128390964159463810.3390/biom16010098