Several mechanisms acting at multiple steps, including decreased pituitary GH secretion due to decreased ghrelin secretion16 and suppressed IGF-1 production in the liver caused by obesity-related GH resistance7,29 may underlie the suppressed circulating IGF-1 levels associated with adiposity, although whether the alteration in hepatic IGF-BP production induced by hyperinsulinemia decreases or increases IGF-1 levels remains controversial15,18. The gene discussed is GHRL; the disease is obesity due to melanocortin 4 receptor deficiency.