MC4R and Hypercholesterolemia: Previous studies in mouse models have demonstrated that MC4R deficiency—particularly when combined with MC3R or LDL-receptor loss—exacerbates metabolic disturbances, resulting in marked hypercholesterolemia with elevated LDL and very low-density lipoprotein fractions, as well as triglycerides, thereby fostering a pro-atherogenic lipid profile [94, 95].