title: Food intake adaptation to dietary fat involves PSA-dependent rewiring of the arcuate melanocortin system in mice.
abstract: Hormones such as leptin and ghrelin can rapidly rewire hypothalamic feeding circuits when injected into rodent brains. These experimental manipulations suggest that the hypothalamus might reorganize continually in adulthood to integrate the metabolic status of the whole body. In this study, we examined whether hypothalamic plasticity occurs in naive animals according to their nutritional conditions. For this purpose, we fed mice with a short-term high-fat diet (HFD) and assessed brain remodeling through its molecular and functional signature. We found that HFD for 3 d rewired the hypothalamic arcuate nucleus, increasing the anorexigenic tone due to activated pro-opiomelanocortin (POMC) neurons. We identified the polysialic acid molecule (PSA) as a mediator of the diet-induced rewiring of arcuate POMC. Moreover, local pharmacological inhibition and genetic disruption of the PSA signaling limits the behavioral and metabolic adaptation to HFD, as treated mice failed to normalize energy intake and showed increased body weight gain after the HFD challenge. Altogether, these findings reveal the existence of physiological hypothalamic rewiring involved in the homeostatic response to dietary fat. Furthermore, defects in the hypothalamic plasticity-driven adaptive response to HFD are obesogenic and could be involved in the development of metabolic diseases.
authors.affiliation: Centre des Sciences du Goût et de l'Alimentation, Unité Mixte de Recherche 6265-CNRS, 1324-INRA, Université de Bourgogne, 21000 Dijon, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Benani
authors.forename: Cécile
authors.initials: C
authors.lastname: Hryhorczuk
authors.forename: Alexandra
authors.initials: A
authors.lastname: Gouazé
authors.forename: Xavier
authors.initials: X
authors.lastname: Fioramonti
authors.forename: Xavier
authors.initials: X
authors.lastname: Brenachot
authors.forename: Christophe
authors.initials: C
authors.lastname: Guissard
authors.forename: Alice
authors.initials: A
authors.lastname: Krezymon
authors.forename: Thibaut
authors.initials: T
authors.lastname: Duparc
authors.forename: André
authors.initials: A
authors.lastname: Colom
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Nédélec
authors.forename: Caroline
authors.initials: C
authors.lastname: Rigault
authors.forename: Aleth
authors.initials: A
authors.lastname: Lemoine
authors.forename: Jean
authors.initials: J
authors.lastname: Gascuel
authors.forename: Rita
authors.initials: R
authors.lastname: Gerardy-Schahn
authors.forename: Philippe
authors.initials: P
authors.lastname: Valet
authors.forename: Claude
authors.initials: C
authors.lastname: Knauf
authors.forename: Anne
authors.initials: A
authors.lastname: Lorsignol
authors.forename: Luc
authors.initials: L
authors.lastname: Pénicaud
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000502:physiology*; D004041:Dietary Fats / Q000008:administration & dosage*; D002149:Energy Intake / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009415:Nerve Net / Q000502:physiology; D009473:Neuronal Plasticity / Q000235:genetics; D009924:Organ Culture Techniques; D011333:Pro-Opiomelanocortin / Q000378:metabolism / Q000502:physiology*; D012794:Sialic Acids / Q000502:physiology*; D012799:Sialyltransferases / Q000172:deficiency / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D015430:Weight Gain / Q000235:genetics
chemical_list: D004041:Dietary Fats; D012794:Sialic Acids; C021319:polysialic acid; D011333:Pro-Opiomelanocortin; D012799:Sialyltransferases; C551345:polysialyltransferase-1, human