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Acyl-CoA-Binding Protein Is a Lipogenic Factor that Triggers Food Intake and Obesity.

Authors
  • Bravo-San Pedro, José M1
  • Sica, Valentina1
  • Martins, Isabelle1
  • Pol, Jonathan1
  • Loos, Friedemann1
  • Maiuri, Maria Chiara1
  • Durand, Sylvère1
  • Bossut, Noélie1
  • Aprahamian, Fanny1
  • Anagnostopoulos, Gerasimos2
  • Niso-Santano, Mireia3
  • Aranda, Fernando4
  • Ramírez-Pardo, Ignacio5
  • Lallement, Justine6
  • Denom, Jessica6
  • Boedec, Erwan7
  • Gorwood, Philip8
  • Ramoz, Nicolas9
  • Clément, Karine10
  • Pelloux, Veronique10
  • And 14 more
  • 1 INSERM U1138, Centre de Recherche des Cordeliers, Sorbonne Université, Université de Paris, Paris, France; Team "Metabolism, Cancer & Immunity", Équipe 11 labellisée par la Ligue contre le Cancer, Paris, France; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France. , (France)
  • 2 INSERM U1138, Centre de Recherche des Cordeliers, Sorbonne Université, Université de Paris, Paris, France; Team "Metabolism, Cancer & Immunity", Équipe 11 labellisée par la Ligue contre le Cancer, Paris, France; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France; Faculté de Médecine, Université de Paris Saclay, Kremlin Bicêtre, France. , (France)
  • 3 Biomedical Research Networking Center on Neurodegenerative Diseases (CIBERNED), Department of Biochemistry and Molecular Biology and Genetics, University of Extremadura, Faculty of Nursing and Occupational Therapy, Cáceres, Spain. , (Spain)
  • 4 Group of Immune receptors of the Innate and Adaptive System, Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. , (Spain)
  • 5 Department of Cellular and Molecular Biology, Centro de Investigaciones Biológicas, CSIC, Madrid, Spain. , (Spain)
  • 6 Université of Paris, Unité de Biologie Fonctionnelle et Adaptative, CNRS UMR 8251, Paris, France. , (France)
  • 7 INSERM U1149, Center of Research on Inflammation, Paris, France; Paris Diderot University, Sorbonne Paris Cité, Paris, France; National French Center of Scientific Research (CNRS), ERL 8252, Paris, France. , (France)
  • 8 Clinique des Maladies Mentales et de l'Encéphale (CMME), Hôpital Sainte-Anne, Université of Paris, Paris, France; INSERM U894, Centre de Psychiatrie et Neurosciences (CPN), Université of Paris, Paris, France. , (France)
  • 9 INSERM U894, Centre de Psychiatrie et Neurosciences (CPN), Université of Paris, Paris, France. , (France)
  • 10 Sorbonne Université, Inserm, NutriOMics team, Pitié-Salpêtrière Hospital, Paris, France. , (France)
  • 11 University of Lille, CHU Lille, Inserm UMR 1190, European Genomic Institute for Diabetes, Lille, France. , (France)
  • 12 Team "Metabolism, Cancer & Immunity", Équipe 11 labellisée par la Ligue contre le Cancer, Paris, France; Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA; Sandra and Edward Meyer Cancer Center, New York, NY, USA; Department of Dermatology, Yale School of Medicine, New Haven, CT, USA. , (France)
  • 13 BioTechMed, Graz, Austria; Institute of Molecular Biosciences, NAWI Graz, University of Graz, Humboldtstrasse, Graz, Austria. , (Austria)
  • 14 Department of Basic Sciences, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece; Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, Hellas, Nikolaou Plastira 100, Heraklion, Crete, Greece. , (Greece)
  • 15 INSERM U1138, Centre de Recherche des Cordeliers, Sorbonne Université, Université de Paris, Paris, France; Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Oncología (IUOPA), Universidad de Oviedo, Oviedo, Spain. , (Spain)
  • 16 INSERM U1138, Centre de Recherche des Cordeliers, Sorbonne Université, Université de Paris, Paris, France; Team "Metabolism, Cancer & Immunity", Équipe 11 labellisée par la Ligue contre le Cancer, Paris, France; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France; Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France; Suzhou Institute for Systems Medicine, Chinese Academy of Sciences, Suzhou, China; Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden. Electronic address: [email protected] , (China)
Type
Published Article
Journal
Cell metabolism
Publication Date
Oct 01, 2019
Volume
30
Issue
4
Identifiers
DOI: 10.1016/j.cmet.2019.07.010
PMID: 31422903
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Autophagy facilitates the adaptation to nutritional stress. Here, we show that short-term starvation of cultured cells or mice caused the autophagy-dependent cellular release of acyl-CoA-binding protein (ACBP, also known as diazepam-binding inhibitor, DBI) and consequent ACBP-mediated feedback inhibition of autophagy. Importantly, ACBP levels were elevated in obese patients and reduced in anorexia nervosa. In mice, systemic injection of ACBP protein inhibited autophagy, induced lipogenesis, reduced glycemia, and stimulated appetite as well as weight gain. We designed three approaches to neutralize ACBP, namely, inducible whole-body knockout, systemic administration of neutralizing antibodies, and induction of antiACBP autoantibodies in mice. ACBP neutralization enhanced autophagy, stimulated fatty acid oxidation, inhibited appetite, reduced weight gain in the context of a high-fat diet or leptin deficiency, and accelerated weight loss in response to dietary changes. In conclusion, neutralization of ACBP might constitute a strategy for treating obesity and its co-morbidities. Copyright © 2019 Elsevier Inc. All rights reserved.

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