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Nesfatin-1, derived from the nucleobindin-2 gene product, is expressed in neurons located in brain centers known to be important in the central regulation of both cardiovascular function and fluid and electrolyte homeostasis. In fact the peptide colocalizes in those neurons with an impressive list of neuropeptides and neurotransmitters known to be important in the regulation of thirst, appetite and central autonomic control. We and others have demonstrated potent sympatho-stimulatory actions of nesfatin-1 in brain and the potential physiologic relevance of those effects. In addition, although nesfatin-1 was originally described as a peptide with potent anorexigenic actions in brain, effects corroborated by several groups, it is possible that the anorexigenic actions of nesfatin-1 are secondary to a primary action to reduce thirst. Progress in unraveling the importance of endogenous nesfatin-1 in cardiovascular function, or fluid and electrolyte homeostasis, has been limited due to the to date unavailability of nesfatin-1 antagonists and the fact that the receptor for nesfatin-1 remains unidentified.