Differential effects of HFD and isolation on serum IGF-1 levels, despite both showing loss of brain IGF-1 activity, may be explained by the fact that while obesity is reported to elicit IGF-1 resistance in the whole body [2], isolation stress may affect only brain sensitivity to IGF-1, limiting its systemic impact. The gene discussed is IGF1; the disease is obesity due to melanocortin 4 receptor deficiency.