GCG and obesity due to melanocortin 4 receptor deficiency: Preclinically, the robustness of glucagon’s thermogenic activity is exemplified by its ability to increase energy expenditure across multiple species, including mice, rats, penguins, pigs, and dogs [see Figure 1 (59–62)], and by findings showing that the administration of glucagon reduces body weight in already obese animals and protects from diet-induced obesity in mice and rats (17, 20, 54, 63).