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Curr Pharm Des. 2013;19(39):6955-9.

Role of brain NUCB2/nesfatin-1 in the regulation of food intake.

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CURE: Digestive Diseases Research Center, Building 115, Room 117, VA Greater Los Angeles Healthcare System, 11301 Wilshire Boulevard, Los Angeles, CA 90073, USA.


Nesfatin-1 was recently identified in the rat brain as a potential post-translational processing product derived from nucleobindin2 (NUCB2). The first biological action identified for nesfatin-1 was the reduction of nocturnal food intake in rats. The anorexigenic effect of nesfatin-1 was corroborated by several independent laboratories and is now established as a physiological action of this peptide based on the regulation of brain NUCB2/nesfatin-1 under different metabolic conditions and the stimulation of food intake and body weight when endogenous brain NUCB2/nesfatin-1 is blocked. Nesfatin-1 shows extensive co-localization with various other, predominantly food intake inhibitory, hypothalamic peptides including corticotropin-releasing factor (CRF), oxytocin, cholecystokinin, proopiomelanocortin, -αmelanocyte stimulating hormone (α-MSH), thyrotropin-releasing hormone (TRH), the orexigenic neuropeptide Y and brain biogenic amines, histamine, serotonin, and catecholamines. The food intake suppressing effect of centrally injected nesfatin-1 has been established so far to involve several downstream mechanisms including H1, CRF2, TRH, oxytocin as well as melanocortin-3/4 receptor signaling pathways. This intricate embedding of NUCB2/nesfatin-1 in central food intake regulatory pathways recruited during the dark phase corresponding to the eating period in rodents, unlike the orexigenic response to a fast, points towards a role for nesfatin-1 in modulating the nocturnal food intake. Although our knowledge on the regulation and effects of NUCB2/nesfatin-1 as a new anorexic peptide markedly increased during the past five years, several important gaps of knowledge remain to be filled in the near future such as the regulation of NUCB2 processing and nesfatin-1 release as well as the identification, localization and regulation of the nesfatin-1 receptor.

[Indexed for MEDLINE]

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