The antidipsogenic action of nesfatin-1 requires activation of a GLP-1 receptor

Nesfatin-1 is a potent inhibitor of food and water ingestion, and it has been reported that the anorexigenic and antidipsogenic actions of glucagon-like peptide-1 (GLP-1) require recruitment of nesfatin-1-producing neurons in the brain. Multiple neuropeptides appear to interact in reciprocal fashion to control ingestive behaviors. We demonstrate now that the antidipsogenic action of nesfatin-1 can be significantly reversed by pretreatment with the GLP-1 antagonist, exendin-3. Our prior work indicated that the antidipsogenic and anorexigenic actions of nesfatin could also be abrogated by blockage of melanocortin, corticotropin-releasing factor, and oxytocin signaling. We now propose a novel neuronal circuit activated by nesfatin-1, including those other peptide-expressing neurons.NEW & NOTEWORTHY Nesfatin-1 is a potent inhibitor of food intake and water drinking in rodents. We demonstrate here that the action of nesfatin-1 on water drinking depends on the recruitment of GLP-1 receptor-expressing neurons. These original observations further detail the neural circuitry regulating fluid ingestion.