Obesity, affecting more than one in four Danish adults, roughly doubles the risk of heart failure in people with cardiomyopathy. In these patients, the heart burns through energy too quickly, but current treatments rarely target this fundamental energetic problem. This project focuses on myosin, a major motor protein in heart muscle that uses large amounts of energy and can switch into a ‘resting’ state to save fuel. Using unique human heart tissue, advanced imaging, multi‑omics and AI‑guided discovery of myosin‑targeting compounds, the project will define how obesity alters myosin regulation and identify candidate molecules that restore efficient energy use without weakening contraction. This will deliver mechanistic biomarkers, human cardiac platforms, and first-in-class myosin modulators, seeding clinical translation and cementing Danish leadership in cardiometabolic biophysics.