Metabolism Without Modification Obesity-associated metabolic disease has rapidly become a public health priority in the developed world and is being addressed through prevention strategies aimed at lifestyle changes and through pharmacological approaches. Barnett et al. (p. 1689 , published online 18 November) designed a drug that inhibits the action of ghrelin, a circulating peptide hormone that increases fat mass and food intake. The drug, a bisubstrate analog called GO-CoA-Tat, is a selective antagonist of ghrelin O-acyltransferase (GOAT), an enzyme that catalyzes a posttranslational modification that is essential for ghrelin activity. Injection of GO-CoA-Tat into wild-type mice on a high-fat diet improved glucose tolerance and reduced weight gain, probably through changes in metabolic activity. Because GO-CoA-Tat is a peptide-based drug that requires repeated injection, it is unsuitable for clinical use, but GOAT does represent a potentially valuable target for future drug development efforts in metabolic disease.