1. Food Intake Adaptation to Dietary Fat Involves PSA-Dependent Rewiring of the Arcuate Melanocortin System in Mice
- Author
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Christophe Guissard, Cecile Hryhorczuk, Caroline Rigault, André Colom, Emmanuelle Nédélec, Luc Pénicaud, Anne Lorsignol, Claude Knauf, Philippe Valet, Alexandra Gouazé, Xavier Fioramonti, Alexandre Benani, Rita Gerardy-Schahn, Alice Krezymon, Thibaut Duparc, Aleth Lemoine, Xavier Brenachot, Jean Gascuel, Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Institut des Maladies Métaboliques et Cardiovasculaires ( I2MC ), Université Paul Sabatier - Toulouse 3 ( UPS ) -Hôpital de Rangueil-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recherches sur la Cognition Animale [Toulouse] ( CRCA ), Université Paul Sabatier - Toulouse 3 ( UPS ) -Centre National de la Recherche Scientifique ( CNRS ), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherches sur la Cognition Animale (CRCA), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), STROMALab, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Etablissement Français du Sang-Institut National de la Santé et de la Recherche Médicale (INSERM), CNRS, Institut National de la Recherche Agronomique, Agence Nationale de la Recherche [ANR-05-PNRA-004], Burgundy county [FABER-2009-9201-AAO036S00635], Association Francaise d'Etudes et de Recherches sur l'Obesite, and Institut B. Delessert
- Subjects
Male ,MESH: Signal Transduction ,Pro-Opiomelanocortin ,[ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition ,SYNAPTIC INPUT ORGANIZATION ,MESH: Energy Intake ,Weight Gain ,MESH: Mice, Knockout ,Mice ,0302 clinical medicine ,MESH : Sialic Acids ,NPY/AGRP NEURONS ,MESH: Pro-Opiomelanocortin ,MESH: Animals ,MESH : Neuronal Plasticity ,MESH: Neuronal Plasticity ,PLASTICITY ,MESH : Pro-Opiomelanocortin ,MESH : Adaptation, Physiological ,Mice, Knockout ,FEEDING CIRCUITS ,MESH : Organ Culture Techniques ,INSULIN-RESISTANCE ,0303 health sciences ,Neuronal Plasticity ,POLYSIALIC ACID ,General Neuroscience ,Leptin ,MESH: Energy Metabolism ,digestive, oral, and skin physiology ,INDUCED OBESITY ,MESH : Sialyltransferases ,MESH : Weight Gain ,Articles ,Adaptation, Physiological ,MESH : Mice, Transgenic ,BODY-WEIGHT ,MESH: Dietary Fats ,Hypothalamus ,CELL-ADHESION MOLECULE ,MESH: Weight Gain ,Ghrelin ,ENERGY-BALANCE ,Melanocortin ,hormones, hormone substitutes, and hormone antagonists ,Signal Transduction ,medicine.medical_specialty ,MESH: Mice, Transgenic ,MESH : Male ,MESH: Sialyltransferases ,MESH: Arcuate Nucleus ,Mice, Transgenic ,MESH : Mice, Inbred C57BL ,Biology ,MESH : Arcuate Nucleus ,MESH: Sialic Acids ,03 medical and health sciences ,Organ Culture Techniques ,Insulin resistance ,MESH: Mice, Inbred C57BL ,Arcuate nucleus ,Internal medicine ,MESH : Mice ,medicine ,Animals ,MESH: Mice ,030304 developmental biology ,MESH : Signal Transduction ,Arcuate Nucleus of Hypothalamus ,MESH : Energy Intake ,medicine.disease ,Dietary Fats ,MESH: Adaptation, Physiological ,Sialyltransferases ,MESH: Organ Culture Techniques ,MESH: Male ,Mice, Inbred C57BL ,MESH : Energy Metabolism ,Endocrinology ,MESH: Nerve Net ,Sialic Acids ,MESH : Nerve Net ,MESH : Mice, Knockout ,MESH : Animals ,Nerve Net ,Energy Intake ,Energy Metabolism ,[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition ,MESH : Dietary Fats ,030217 neurology & neurosurgery ,Homeostasis ,Hormone - Abstract
International audience; 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.
- Published
- 2012
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