One notable question concerns the so-called adiponectin paradox: despite being produced exclusively by adipose tissue, circulating adiponectin levels decrease in conditions of excess adiposity (i.e. obesity) but are elevated markedly in conditions of extreme leanness, such as during caloric restriction (CR) in animals and in human subjects with anorexia nervosa (AN). The gene discussed is ADIPOQ; the disease is obesity due to melanocortin 4 receptor deficiency.