To the editor—Energy homeostasis in mammals, including humans, is a robust process that matches caloric intake to caloric expenditure. Individuals detect and respond to sources of energy in their environment, and they ingest more or fewer food calories as appropriate for their needs. At a different level, individual cells have intricate and regulated pathways that monitor their metabolic needs and actively change their uptake and use of different energy sources (particularly fats and carbohydrates). Studies using compounds that alter metabolism, such as 2-deoxyglucose or the fatty-acid synthase (FAS) inhibitor C75 (refs. 1–6), show that cells of the central nervous system (CNS) have the ability to detect changes in available energy in the local environment and initiate appropriate behavioral and physiological responses. Considerable interest has been focused on the precise mechanism (s) enabling the cellular detection of metabolic status and its translation into neuronal signals. Recent reports that C75 decreases food intake and body weight imply that the FAS pathway is a key component of the connection between neuronal CNS metabolism and neuronal signaling1–6. Rats and mice respond to central (third-cerebral ventricular (icv)) or peripheral (intraperitoneal (ip)) C75 administration