Loss of intestinal uroguanylin expression with chronic overnutrition mirrors loss of intestinal GUCY2C hormones in colorectal tumorigenesis.47 It is tempting to speculate that this represents one molecular basis for the established association between obesity and colon cancer,48, 49 and highlights the role of GUCY2C agonism underlying homeostatic physiology. Here, GUCY2C is linked to obesity due to melanocortin 4 receptor deficiency.