Acyl-CoA binding protein for the experimental treatment of anorexia-Reference-Cited by-同舟云学术

Acyl-CoA binding protein for the experimental treatment of anorexia

Published:2024-08-14 Issue:760 Volume:16 Page:
ISSN:1946-6234
Container-title:Science Translational Medicine
language:en
Short-container-title:Sci. Transl. Med.

Author:

Chen Hui¹²³^ORCID,Moriceau Stéphanie⁴,Joseph Adrien¹⁵^ORCID,Mailliet Francois⁶^ORCID,Li Sijing¹²³^ORCID,Tolle Virginie⁷^ORCID,Duriez Philibert⁷⁸^ORCID,Dardennes Roland⁸^ORCID,Durand Sylvère¹²,Carbonnier Vincent¹²^ORCID,Stoll Gautier¹²^ORCID,Sauvat Allan¹²^ORCID,Lachkar Sylvie¹²^ORCID,Aprahamian Fanny¹²^ORCID,Alves Costa Silva Carolina⁹¹⁰¹¹^ORCID,Pan Hui¹²³,Montégut Léa¹²³^ORCID,Anagnostopoulos Gerasimos¹²^ORCID,Lambertucci Flavia¹²^ORCID,Motiño Omar¹²^ORCID,Nogueira-Recalde Uxía¹²¹²^ORCID,Bourgin Mélanie¹²^ORCID,Mao Misha¹²³¹³,Pan Yuhong¹²³,Cerone Alexandra¹²,Boedec Erwan¹⁴^ORCID,Gouveia Zelia L.¹⁵^ORCID,Marmorino Federica¹⁶¹⁷^ORCID,Cremolini Chiara¹⁶¹⁷,Derosa Lisa⁹¹⁰¹¹^ORCID,Zitvogel Laurence⁹¹⁰¹¹^ORCID,Kepp Oliver¹²^ORCID,López-Otín Carlos¹¹⁸¹⁹,Maiuri Maria Chiara¹²²⁰,Perez Franck¹⁵^ORCID,Gorwood Philip⁷⁸^ORCID,Ramoz Nicolas⁷⁸^ORCID,Oury Franck⁶,Martins Isabelle¹²^ORCID,Kroemer Guido¹²²¹^ORCID

Affiliation:

1. Centre de Recherche des Cordeliers, Equipe labellisée par la Ligue contre le cancer, Inserm U1138, Université Paris Cité, Sorbonne Université, 75006 Paris, France.

2. Metabolomics and Cell Biology Platforms, Gustave Roussy Institut, 94805 Villejuif, France.

3. Faculté de Médecine, Université de Paris Saclay, Kremlin Bicêtre, 91400 Paris, France.

4. Institut Imagine, Platform for Neurobehavioral and Metabolism, Structure Fédérative de Recherche Necker, 26 INSERM US24/CNRS UAR, 3633, 75015 Paris, France.

5. Service de Réanimation Médicale, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, 75010 Paris, France.

6. Université Paris Cité, INSERM UMR-S1151, CNRS UMR-S8253, Institut Necker Enfants Malades, Team 8, F-75015 Paris, France.

7. Université de Paris Cité, Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266, Genetic Vulnerability to Addictive and Psychiatric Disorders Team, 75015 Paris, France.

8. Université Paris Cité and GHU Paris Psychiatrie et Neurosciences, CMME, Hôpital Sainte-Anne, 75014 Paris, France.

9. Gustave Roussy Cancer Campus, 94805 Villejuif Cedex, France.

10. Université Paris-Saclay, Faculté de Médecine, 94800 Le Kremlin-Bicêtre, France.

11. Institut National de la Santé Et de la Recherche Médicale (INSERM) U1015, Équipe Labellisée–Ligue Nationale contre le Cancer, 94805 Villejuif, France.

12. Rheumatology Research Group (GIR), Biomedical Research Institute of A Coruña (INIBIC), Professor Novoa Santos Foundation, 15006 A Coruña, Spain.

13. Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, 310016 Hangzhou, Zhejiang, China.

14. Université Paris Cité, Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266, Biochemistry and Biophysics (B&B) Core Facility, 75014 Paris, France.

15. Cell Biology and Cancer Unit, Institut Curie, PSL Research University, CNRS, 75005 Paris, France.

16. Unit of Medical Oncology 2, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy.

17. Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy.

18. Facultad de Ciencias de la Vida y la Naturaleza, Universidad Nebrija, 28248 Madrid, Spain.

19. Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Oncología (IUOPA), Universidad de Oviedo, 33006 Oviedo, Spain.

20. Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, 80131 Naples, Italy.

21. Institut du Cancer Paris CARPEM, Department of Biology, Hôpital Européen Georges Pompidou, AP-HP, 75015 Paris, France.

Abstract

Extracellular acyl-coenzyme A binding protein [ACBP encoded by diazepam binding inhibitor (DBI)] is a phylogenetically ancient appetite stimulator that is secreted in a nonconventional, autophagy-dependent fashion. Here, we show that low ACBP/DBI plasma concentrations are associated with poor prognosis in patients with anorexia nervosa, a frequent and often intractable eating disorder. In mice, anorexia induced by chronic restraint stress (CRS) is accompanied by a reduction in circulating ACBP/DBI concentrations. We engineered a chemical-genetic system for the secretion of ACBP/DBI through a biotin-activatable, autophagy-independent pathway. In transgenic mice expressing this system in hepatocytes, biotin-induced elevations in plasma ACBP/DBI concentrations prevented anorexia induced by CRS or chemotherapeutic agents including cisplatin, doxorubicin, and paclitaxel. ACBP/DBI reversed the CRS or cisplatin-induced increase in plasma lipocalin-2 concentrations and the hypothalamic activation of anorexigenic melanocortin 4 receptors, for which lipocalin-2 is an agonist. Daily intravenous injections of recombinant ACBP/DBI protein or subcutaneous implantation of osmotic pumps releasing recombinant ACBP/DBI mimicked the orexigenic effects of the chemical-genetic system. In conclusion, the supplementation of extracellular and peripheral ACBP/DBI might constitute a viable strategy for treating anorexia.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/scitranslmed.adl0715

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