FOXO1 and Other metabolic disease: However, excessive or dysregulated FoxO1 activation can lead to energy metabolism disorders and contribute to increased ketone body production through several mechanisms: first, by depleting oxaloacetate through its diversion to gluconeogenesis, FoxO1 activation reduces oxaloacetate availability for citric acid cycle function, thereby shunting excess acetyl-CoA toward ketogenesis; second, FoxO1 may directly or indirectly influence the expression of ketogenic enzymes.