title: Apelin and the proopiomelanocortin system: a new regulatory pathway of hypothalamic α-MSH release.
abstract: Neuronal networks originating in the hypothalamic arcuate nucleus (Arc) play a fundamental role in controlling energy balance. In the Arc, neuropeptide Y (NPY)-producing neurons stimulate food intake, whereas neurons releasing the proopiomelanocortin (POMC)-derived peptide α-melanocyte-stimulating hormone (α-MSH) strongly decrease food intake. There is growing evidence to suggest that apelin and its receptor may play a role in the central control of food intake, and both are concentrated in the Arc. We investigated the presence of apelin and its receptor in Arc NPY- and POMC-containing neurons and the effects of apelin on α-MSH release in the hypothalamus. We showed, by immunofluorescence and confocal microscopy, that apelin-immunoreactive (IR) neuronal cell bodies were distributed throughout the rostrocaudal extent of the Arc and that apelin was strongly colocalized with POMC, but weakly colocalized with NPY. However, there were numerous NPY-IR nerve fibers close to the apelin-IR neuronal cell bodies. By combining in situ hybridization with immunohistochemistry, we demonstrated the presence of apelin receptor mRNA in Arc POMC neurons. Moreover, using a perifusion technique for hypothalamic explants, we demonstrated that apelin-17 (K17F) increased α-MSH release, suggesting that apelin released somato-dendritically or axonally from POMC neurons may stimulate α-MSH release in an autocrine manner. Consistent with these data, hypothalamic apelin levels were found to be higher in obese db/db mice and fa/fa Zucker rats than in wild-type animals. These findings support the hypothesis that central apelin is involved in regulating body weight and feeding behavior through the direct stimulation of α-MSH release.
authors.affiliation: Institut National de Santé et de Recherche Médicale, Unité Mixte de Recherche S 691, Centre for Interdisciplinary Research in Biology, Collège de France, and Université Pierre et Marie Curie-Paris 6, Paris, France.
authors.forename: Annabelle
authors.initials: A
authors.lastname: Reaux-Le Goazigo
authors.forename: Laurence
authors.initials: L
authors.lastname: Bodineau
authors.forename: Nadia
authors.initials: N
authors.lastname: De Mota
authors.forename: Lydie
authors.initials: L
authors.lastname: Jeandel
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chartrel
authors.forename: Claude
authors.initials: C
authors.lastname: Knauf
authors.forename: Carine
authors.initials: C
authors.lastname: Raad
authors.forename: Philippe
authors.initials: P
authors.lastname: Valet
authors.forename: Catherine
authors.initials: C
authors.lastname: Llorens-Cortes
mesh_terms: D054392:Adipokines; D000818:Animals; D000073861:Apelin; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008954:Models, Biological; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D011333:Pro-Opiomelanocortin / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011924:Rats, Zucker; D015398:Signal Transduction / Q000187:drug effects; D000521:alpha-MSH / Q000378:metabolism*
chemical_list: D054392:Adipokines; D000073861:Apelin; C402826:Apln protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin