Drugs targets in sympathetic neurons controlling adiposity.
Obesity is a metabolic disorder with unmet medical need for which a pharmacotherapy is urgently needed. The Domingos lab has recently discovered that sympathetic (SNS) neuro-adipose junctions mediate lipolysis and fat mass reduction (Pirzgalska, R.M., Cell, 2015).Thus direct and targeted activation of sympathetic inputs to adipose tissues could represent a new strategy for the induction of fat loss. Our main objective is to identify drug targets in SNS neurons innervating fat, which are suitable for an anti-obesity therapy. To achieve this, we will use technologies such as Translational Ribosome Affinity Purification (TRAP) for translational profiling of neurons innervating fat. We will differentially screen for molecular targets that are enriched in SNS neurons in fat. We will validate target expression in human SNS tissues. This project will identify neuro-excitatory drug targets in sympathetic inputs to adipose tissues, and may lead the development of pharmacotherapies which would circumvent side effects.