In addition to generalizing the metabolic significance of UCP1 and BAT, this investigation also demonstrates that all diet-induced UCP1-dependent facultative thermogenesis originates from classical BAT (rather than brite/beige adipose tissue) and that no UCP1-independent mechanism for recruitable adrenergic thermogenesis exists, not even in obesity-resistant animals. The gene discussed is UCP1; the disease is obesity due to melanocortin 4 receptor deficiency.