Article Dans Une Revue Cell Death and Disease Année : 2020

Metabolic and psychiatric effects of acyl coenzyme A binding protein (ACBP)/diazepam binding inhibitor (DBI)

1 CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers
2 IGR - Institut Gustave Roussy
3 Service de Réanimation Médicale, Hôpital Saint Louis, Paris, France
4 Université Paris-Saclay
5 INEM - UM 111 (UMR 8253 / U1151) - Institut Necker Enfants-Malades
6 UPF - Universitat Pompeu Fabra [Barcelona]
7 Plateforme de métabolomique
8 INSERM - Institut National de la Santé et de la Recherche Médicale
9 UPD5 - Université Paris Descartes - Paris 5
10 ESPE Paris - Sorbonne Université - École supérieure du professorat et de l'éducation - Académie de Paris
11 Equipe labellisée Ligue contre le cancer - CRC - Inserm U1138 - Apoptose, cancer et immunité
12 UPCité - Université Paris Cité
13 IMRB - Institut Mondor de Recherche Biomédicale
14 U955 Inserm - UPEC - IMRB - "Neuropsychiatrie translationnelle" [Créteil]
15 Centre Hospitalier Princesse Grace
16 OPTeN (UMR_S 1144 / U1144) - Optimisation thérapeutique en Neuropsychopharmacologie
17 Service de Psychiatrie et de Médecine Addictologique [AP-HP, GH Saint-Louis-Lariboisière-F.Widal]
18 INT - Institut de Neurosciences de la Timone
19 Hôpitaux Sud - Hôpital Sainte-Marguerite [CHU - APHM]
20 NCPS - Neuropsychologie Cognitive et Physiopathologie de la Schizophrénie
21 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
22 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
23 PSNREC - Neuropsychiatrie : recherche épidémiologique et clinique
24 Hôpital Louis Mourier - AP-HP [Colombes]
25 IPNP - U1266 Inserm - Institut de psychiatrie et neurosciences de Paris
26 Fondation FondaMental [Créteil]
27 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
28 CEReSS - Centre d'études et de recherche sur les services de santé et la qualité de vie
29 Centre hospitalier Charles Perrens [Bordeaux]
30 CHU Clermont-Ferrand
31 IP - Institut Pascal
32 INCIA - Institut de Neurosciences cognitives et intégratives d'Aquitaine
33 CESP - Centre de recherche en épidémiologie et santé des populations
34 GIN - [GIN] Grenoble Institut des Neurosciences
35 HANDIReSP - Laboratoire de recherches cliniques et en santé publique sur les handicaps psychique, cognitif et moteur
36 CHV - Centre Hospitalier de Versailles André Mignot
37 Pôle Psychiatrie Enfant-Adulte [CHU Clermont-Ferrand]
38 Pôle de Psychiatrie [Hôpital Henri Mondor]
39 UPEC Médecine - Université Paris-Est Créteil Val-de-Marne - Faculté de médecine
40 CPN - Centre Psychothérapique de Nancy [Laxou]
41 IADI - Imagerie Adaptative Diagnostique et Interventionnelle
42 BFA (UMR_8251 / U1133) - Unité de Biologie Fonctionnelle et Adaptative
43 Equipe labellisée Ligue contre le Cancer
44 SIRIC CARPEM - Cancer Research and Personalized Medicine - CARPEM [Paris]
D’. Amato Thierry
  • Fonction : Auteur

Résumé

Acyl coenzyme A binding protein (ACBP), also known as diazepam binding inhibitor (DBI) is a multifunctional protein with an intracellular action (as ACBP), as well as with an extracellular role (as DBI). The plasma levels of soluble ACBP/DBI are elevated in human obesity and reduced in anorexia nervosa. Accumulating evidence indicates that genetic or antibody-mediated neutralization of ACBP/DBI has anorexigenic effects, thus inhibiting food intake and inducing lipo-catabolic reactions in mice. A number of anorexiants have been withdrawn from clinical development because of their side effects including an increase in depression and suicide. For this reason, we investigated the psychiatric impact of ACBP/DBI in mouse models and patient cohorts. Intravenously (i.v.) injected ACBP/DBI protein conserved its orexigenic function when the protein was mutated to abolish acyl coenzyme A binding, but lost its appetite-stimulatory effect in mice bearing a mutation in the γ2 subunit of the γ-aminobutyric acid (GABA) A receptor (GABA A R). ACBP/DBI neutralization by intraperitoneal (i.p.) injection of a specific mAb blunted excessive food intake in starved and leptin-deficient mice, but not in ghrelin-treated animals. Neither i.v. nor i.p. injected anti-ACBP/DBI antibody affected the behavior of mice in the dark–light box and open-field test. In contrast, ACBP/DBI increased immobility in the forced swim test, while anti-ACBP/DBI antibody counteracted this sign of depression. In patients diagnosed with therapy-resistant bipolar disorder or schizophrenia, ACBP/DBI similarly correlated with body mass index (BMI), not with the psychiatric diagnosis. Patients with high levels of ACBP/DBI were at risk of dyslipidemia and this effect was independent from BMI, as indicated by multivariate analysis. In summary, it appears that ACBP/DBI neutralization has no negative impact on mood and that human depression is not associated with alterations in ACBP/DBI concentrations.
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hal-04905832 , version 1 (22-01-2025)

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Adrien Joseph, Stéphanie Moriceau, Valentina Sica, Gerasimos Anagnostopoulos, Jonathan Pol, et al.. Metabolic and psychiatric effects of acyl coenzyme A binding protein (ACBP)/diazepam binding inhibitor (DBI). Cell Death and Disease, 2020, 11 (7), pp.502. ⟨10.1038/s41419-020-2716-5⟩. ⟨hal-04905832⟩
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