title: Central chronic apelin infusion decreases energy expenditure and thermogenesis in mice.
abstract: Apelin is a bioactive peptide involved in the control of energy metabolism. In the hypothalamus, chronic exposure to high levels of apelin is associated with an increase in hepatic glucose production, and then contributes to the onset of type 2 diabetes. However, the molecular mechanisms behind deleterious effects of chronic apelin in the brain and consequences on energy expenditure and thermogenesis are currently unknown. We aimed to evaluate the effects of chronic intracerebroventricular (icv) infusion of apelin in normal mice on hypothalamic inflammatory gene expression, energy expenditure, thermogenesis and brown adipose tissue functions. We have shown that chronic icv infusion of apelin increases the expression of pro-inflammatory factors in the hypothalamus associated with an increase in plasma interleukin-1 beta. In parallel, mice infused with icv apelin exhibit a significant lower energy expenditure coupled to a decrease in PGC1alpha, PRDM16 and UCP1 expression in brown adipose tissue which could explain the alteration of thermogenesis in these mice. These data provide compelling evidence that central apelin contributes to the development of type 2 diabetes by altering energy expenditure, thermogenesis and fat browning.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Université Paul Sabatier, UPS, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), CHU Rangueil, 1 Avenue Jean Poulhès, BP84225, 31432 Toulouse Cedex 4, France.|NeuroMicrobiota, European Associated Laboratory, (EAL) INSERM/UCL, INSERM U1220, Institut de Recherche en Santé Digestive (IRSD), CHU Purpan - Place du Docteur Baylac, CS 60039, 31024 Toulouse Cedex 3, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Drougard
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Université Paul Sabatier, UPS, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), CHU Rangueil, 1 Avenue Jean Poulhès, BP84225, 31432 Toulouse Cedex 4, France.|NeuroMicrobiota, European Associated Laboratory, (EAL) INSERM/UCL, INSERM U1220, Institut de Recherche en Santé Digestive (IRSD), CHU Purpan - Place du Docteur Baylac, CS 60039, 31024 Toulouse Cedex 3, France.
authors.forename: Audren
authors.initials: A
authors.lastname: Fournel
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Université Paul Sabatier, UPS, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), CHU Rangueil, 1 Avenue Jean Poulhès, BP84225, 31432 Toulouse Cedex 4, France.|NeuroMicrobiota, European Associated Laboratory, (EAL) INSERM/UCL, INSERM U1220, Institut de Recherche en Santé Digestive (IRSD), CHU Purpan - Place du Docteur Baylac, CS 60039, 31024 Toulouse Cedex 3, France.
authors.forename: Alysson
authors.initials: A
authors.lastname: Marlin
authors.affiliation: Focal Area Infection Biology, Biozentrum, University of Basel, Klingelbergstrasse 50/70 CH-4056 Basel, Switzerland.
authors.forename: Etienne
authors.initials: E
authors.lastname: Meunier
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Université Paul Sabatier, UPS, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), CHU Rangueil, 1 Avenue Jean Poulhès, BP84225, 31432 Toulouse Cedex 4, France.|NeuroMicrobiota, European Associated Laboratory, (EAL) INSERM/UCL, INSERM U1220, Institut de Recherche en Santé Digestive (IRSD), CHU Purpan - Place du Docteur Baylac, CS 60039, 31024 Toulouse Cedex 3, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Abot
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Université Paul Sabatier, UPS, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), CHU Rangueil, 1 Avenue Jean Poulhès, BP84225, 31432 Toulouse Cedex 4, France.|NeuroMicrobiota, European Associated Laboratory, (EAL) INSERM/UCL, INSERM U1220, Institut de Recherche en Santé Digestive (IRSD), CHU Purpan - Place du Docteur Baylac, CS 60039, 31024 Toulouse Cedex 3, France.
authors.forename: Tereza
authors.initials: T
authors.lastname: Bautzova
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Université Paul Sabatier, UPS, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), CHU Rangueil, 1 Avenue Jean Poulhès, BP84225, 31432 Toulouse Cedex 4, France.|NeuroMicrobiota, European Associated Laboratory, (EAL) INSERM/UCL, INSERM U1220, Institut de Recherche en Santé Digestive (IRSD), CHU Purpan - Place du Docteur Baylac, CS 60039, 31024 Toulouse Cedex 3, France.
authors.forename: Thibaut
authors.initials: T
authors.lastname: Duparc
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Université Paul Sabatier, UPS, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), CHU Rangueil, 1 Avenue Jean Poulhès, BP84225, 31432 Toulouse Cedex 4, France.
authors.forename: Katie
authors.initials: K
authors.lastname: Louche
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Université Paul Sabatier, UPS, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), CHU Rangueil, 1 Avenue Jean Poulhès, BP84225, 31432 Toulouse Cedex 4, France.
authors.forename: Aurelie
authors.initials: A
authors.lastname: Batut
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Université Paul Sabatier, UPS, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), CHU Rangueil, 1 Avenue Jean Poulhès, BP84225, 31432 Toulouse Cedex 4, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Lucas
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Université Paul Sabatier, UPS, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), CHU Rangueil, 1 Avenue Jean Poulhès, BP84225, 31432 Toulouse Cedex 4, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Le-Gonidec
authors.affiliation: Université de Lille, Unité environnement périnatal et santé, EA 4489, Équipe malnutrition maternelle et programmation des maladies métaboliques, Université de Lille1, Bâtiment SN4, 59655 Villeneuve d'Ascq, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Lesage
authors.affiliation: Centre des Sciences du Goût et de l'Alimentation, CNRS, INRA, Univ. Bourgogne Franche-Comté, F-21000 Dijon, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Fioramonti
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Université Paul Sabatier, UPS, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), CHU Rangueil, 1 Avenue Jean Poulhès, BP84225, 31432 Toulouse Cedex 4, France.
authors.forename: Cedric
authors.initials: C
authors.lastname: Moro
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Université Paul Sabatier, UPS, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), CHU Rangueil, 1 Avenue Jean Poulhès, BP84225, 31432 Toulouse Cedex 4, France.|NeuroMicrobiota, European Associated Laboratory, (EAL) INSERM/UCL, INSERM U1220, Institut de Recherche en Santé Digestive (IRSD), CHU Purpan - Place du Docteur Baylac, CS 60039, 31024 Toulouse Cedex 3, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Valet
authors.affiliation: NeuroMicrobiota, European Associated Laboratory, (EAL) INSERM/UCL, INSERM U1220, Institut de Recherche en Santé Digestive (IRSD), CHU Purpan - Place du Docteur Baylac, CS 60039, 31024 Toulouse Cedex 3, France.|Université catholique de Louvain (UCL), Louvain Drug Research Institute, LDRI, Metabolism and Nutrition research group, WELBIO, WELBIO (Walloon Excellence in Life sciences and BIOtechnology), Av. E. Mounier, 73 B1.73.11, B-1200, Brussels, Belgium.|NeuroMicrobiota, European Associated Laboratory, (EAL) INSERM/UCLAv. E. Mounier, 73 B1.73.11, B-1200, Brussels, Belgium.
authors.forename: Patrice D
authors.initials: PD
authors.lastname: Cani
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Université Paul Sabatier, UPS, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), CHU Rangueil, 1 Avenue Jean Poulhès, BP84225, 31432 Toulouse Cedex 4, France.|NeuroMicrobiota, European Associated Laboratory, (EAL) INSERM/UCL, INSERM U1220, Institut de Recherche en Santé Digestive (IRSD), CHU Purpan - Place du Docteur Baylac, CS 60039, 31024 Toulouse Cedex 3, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Knauf
mesh_terms: D002001:Adipose Tissue, Brown / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000073861:Apelin / Q000008:administration & dosage / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D057967:Infusions, Intraventricular; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics / Q000378:metabolism; D022722:Thermogenesis / Q000187:drug effects*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000071256:Uncoupling Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000073861:Apelin; D004268:DNA-Binding Proteins; D053583:Interleukin-1beta; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; C521133:Prdm16 protein, mouse; D014157:Transcription Factors; D000071256:Uncoupling Protein 1; D052247:Nitric Oxide Synthase Type II