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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 Université Paris-Saclay
4 INEM - UM 111 (UMR 8253 / U1151) - Institut Necker Enfants-Malades
5 Fondation FondaMental [Créteil]
6 IMRB - Institut Mondor de Recherche Biomédicale
7 CHU Henri Mondor [Créteil]
8 CHPG - Centre Hospitalier Princesse Grace de Monaco
9 Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]
10 APHM - Assistance Publique - Hôpitaux de Marseille
11 INT - Institut de Neurosciences de la Timone
12 NCPS - Neuropsychologie Cognitive et Physiopathologie de la Schizophrénie
13 PSNREC - Neuropsychiatrie : recherche épidémiologique et clinique
14 CHU - Hôpital Lapeyronie [Montpellier]
15 IPNP - U1266 Inserm - Institut de psychiatrie et neurosciences de Paris
16 CRNL - Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center
17 TIMONE - Hôpital de la Timone [CHU - APHM]
18 CEReSS - Centre d'études et de recherche sur les services de santé et la qualité de vie
19 Centre hospitalier Charles Perrens [Bordeaux]
20 CESP - Centre de recherche en épidémiologie et santé des populations
21 GIN - [GIN] Grenoble Institut des Neurosciences
22 CPN - Centre Psychothérapique de Nancy [Laxou]
23 IADI - Imagerie Adaptative Diagnostique et Interventionnelle
24 BFA (UMR_8251 / U1133) - Unité de Biologie Fonctionnelle et Adaptative
25 UCM - Universidad Complutense de Madrid = Complutense University of Madrid [Madrid]
26 Service de Biologie [Hôpital Européen Georges Pompidou, APHP]
27 Karolinska University Hospital [Stockholm]
Julien Dubreucq
Franck Oury

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 A number of anorexiants have been withdrawn from clinical development because of their side effects including an increase in depression and suicide.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 (GABAAR). 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-02927426 , version 1 (26-05-2021)

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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-02927426⟩
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