BRS3 and obesity due to melanocortin 4 receptor deficiency: Single doses of a BRS3 agonist increased blood pressure in humans (Reitman et al., 2012), likely via increased sympathetic tone (Lateef et al., 2016), reducing interest in central agonism as a human therapeutic for obesity and stimulating interest in studying BRS3 agonists that do not enter the brain (Kiyotsuka et al., 2016).