Nesfatin-1: a novel inhibitory regulator of food intake and body weight.
The protein nucleobindin 2 (NUCB2) or NEFA (DNA binding/EF-hand/acidic amino acid rich region) was identified over a decade ago and implicated in intracellular processes. New developments came with the report that post-translational processing of hypothalamic NUCB2 may result in nesfatin-1, nesfatin-2 and nesfatin-3 and convergent studies showing that nesfatin-1 and full length NUCB2 injected in the brain potently inhibit the dark phase food intake in rodents including leptin receptor deficient Zucker rats. Nesfatin-1 also reduces body weight gain, suggesting a role as a new anorexigenic factor and modulator of energy balance. In light of the obesity epidemic and its associated diseases, underlying new mechanisms regulating food intake may be promising targets in the drug treatment of obese patients particularly as the vast majority of them display reduced leptin sensitivity or leptin resistance while nesfatin-1's mechanism of action is leptin independent. Although much progress on the localization of NUCB2/nesfatin-1 in the brain and periphery as well as on the understanding of nesfatin-1's anorexic effect have been achieved during the past three years, several important mechanisms have yet to be unraveled such as the identification of the nesfatin-1 receptor and the regulation of NUCB2 processing and nesfatin-1 release.
Stengel
A
A
Department of Medicine, CURE Digestive Diseases Research Center and Center for Neurobiology of Stress, Digestive Diseases Division UCLA, and VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA.
Goebel
M
M
Taché
Y
Y
D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects* / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D004435:Eating; D002149:Energy Intake / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D020738:Leptin / Q000378:metabolism; D009419:Nerve Tissue Proteins; D000080866:Nucleobindins; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism; D036361:Peptide Hormones / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D012528:Satiety Response / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction
D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D020738:Leptin; C000630650:NUCB2 protein, human; D009419:Nerve Tissue Proteins; C000630652:Nucb1 protein, rat; D000080866:Nucleobindins; D036361:Peptide Hormones