Regulation of Body Weight by Malonyl-CoA in the CNS

Intermediary metabolites of fatty acid biosynthesis are used by the central nervous system to signal changes in body weight in response to alterations in dietary nutrients. This nutrient-sensing mechanism links cellular bioenergetics to complex animal behavior. The central molecule in this pathway, malonyl-coenzyme A (CoA), is the product of the rate-limiting and highly regulated step in fatty acid biosynthesis. Increased concentrations of hypothalamic malonyl-CoA, mediated by nutrient or endocrine cues, inhibit food intake and enhance peripheral energy expenditure resulting in a reduction in body weight. Conversely, the depletion of malonyl-CoA leads to an obese phenotype. Here, we describe the regulation and mechanism by which malonyl-CoA regulates body weight.