Whether brain-sparing agonists phenocopy the anti-obesity and cardioprotective effects of PEGyAMPH will have to be experimentally tested—the loss of function of ADRB2 in this study is limited to demonstrating necessity and does not predict the outcome of a gain of function of ADRB2 based on peripherally restricted agonists. The gene discussed is ADRB2; the disease is obesity due to melanocortin 4 receptor deficiency.