FNDC5 and obesity due to melanocortin 4 receptor deficiency: Similar to irisin, FGF21 levels increase with acute or short durations of exercise [35], [36], decrease with regular exercise and caloric restriction in animals and humans [37], [38], decrease in extreme states of malnutrition (as in anorexia nervosa) related to BMI [24], and increase in obesity and the metabolic syndrome related to fat mass [39], [40], [41].