As FFAs have a role in downregulation of the AMPK-eNOS pathway, which is commonly observed in obesity, it can be suggested that Exendin-4 might regulate the activity of FFAs in obesity and thus improve obesity-related AMPK-eNOS pathway or endothelial function, which could be through the protective effects of Exendin-4 on FFA-induced apoptosis of the pancreatic β-cells [154, 155]. Here, NOS3 is linked to obesity due to melanocortin 4 receptor deficiency.