Autophagy and apoptosis are powerful regulators of multiple facets of cellular metabolism and homeostasis. Here, we uncover that galanin, a pleiotropic peptide, regulates cardiac autophagy and deactivates apoptotic cell death through the Forkhead box protein O1 (FoxO1) pathway. In hypertrophied heart, galanin promotes autophagy and metabolic shift from fatty acid (FA) to glucose oxidation and preserves mitochondrial integrity. In cardiomyoblasts, galanin triggers autophagosome formation and alleviates hypertrophy, apoptotic cell death, and mitochondrial stress. Mechanistically, galanin dictates cell autophagic and anti-apoptotic phenotypes through FoxO1 pathway. Together, these findings uncover a previously unknown role for galanin in the regulation of cardiac autophagy and provide new insights into the molecular mechanisms supporting cell survival in the hypertrophic reprogramming of the heart.

自噬和细胞凋亡是细胞代谢和体内稳态的多个方面的有力调节器。在这里，我们发现多效肽甘丙肽通过叉头盒蛋白O1（FoxO1）途径调节心脏自噬并失活凋亡性细胞死亡。在肥大的心脏中，甘丙肽促进自噬和代谢从脂肪酸（FA）转变为葡萄糖氧化，并保持线粒体完整性。在心肌母细胞中，甘丙肽触发自噬体形成并减轻肥大，凋亡细胞死亡和线粒体应激。从机制上讲，甘丙肽通过FoxO1途径决定细胞的自噬和抗凋亡表型。一起，