Metformin induces a shift from glycolysis to fatty acid oxidation in cardiac hypertrophy via PHB1

• Identifying therapies that arrest the metabolic shift from FAO to glycolysis in cardiac hypertrophy (CH) may prevent heart failure. • It is unknown whether metformin can be used as a therapy to arrest metabolic shift in CH. • Prohibitin 1 (PHB1), a mitochondrial resident improves mitochondrial health and functioning in CH. • We asked whether metformin induces a shift from glycolysis to FAO in ISO-induced hypertrophy in cardiomyoblasts, H9C2 cells via PHB1. • We observed that metformin induces a shift from glycolysis to FAO and reduces hypertrophy in ISO-treated H9C2 cells. • Metformin induces and stabilizes PHB1 increasing FAO. • Metformin may be considered a therapy to ameliorate CH. • Metformin induces a shift from glycolysis to FAO in ISO-induced hypertrophy in H9C2 cells. • Metformin requires PHB1 to activate FAO in ISO-induced hypertrophy in H9C2 cells. • Depleting PHB1 blocks metformin-mediated increase in FAO marker and metabolic enzyme levels. • Metformin may be considered as therapy to ameliorate CH.