FTO and obesity due to melanocortin 4 receptor deficiency: Whatever the explanation for the effects of intronic polymorphism on human adiposity, studies of humans and mice carrying genetic variants that functionally perturb FTO indicate that FTO itself is an important regulator of body size and composition, with loss of function mutations being associated with low body weight in humans [9] and mice [10,11,12] and transgenic overexpression resulting in obesity in mice [13].