Critically, we demonstrate that pharmacological inhibition of zDHHC activity directly, or indirectly via FoxO1 inhibition and decreased zDHHC4 (zinc finger DHHC-type palmitoyltransferase 4) expression, normalizes CD36 S-acylation and localization, FA metabolism, and cardiac function in T2D. The gene discussed is FOXO1; the disease is type 2 diabetes mellitus.