Acyl-CoA-Binding Protein Is a Lipogenic Factor that Triggers Food Intake and Obesity
José Bravo-San Pedro
(1, 2)
,
Valentina Sica
(1, 2)
,
Isabelle Martins
(1, 2)
,
Jonathan Pol
(1, 2)
,
Friedemann Loos
(1, 2)
,
Maria Chiara Maiuri
(1, 2)
,
Sylvère Durand
(1, 2)
,
Noélie Bossut
(1, 2)
,
Fanny Aprahamian
(2, 1)
,
Gerasimos Anagnostopoulos
(3, 1, 2)
,
Mireia Niso-Santano
(4)
,
Fernando Aranda
(5)
,
Ignacio Ramírez-Pardo
(6)
,
Justine Lallement
(7)
,
Jessica Denom
(7)
,
Erwan Boedec
(8)
,
Philip Gorwood
(9, 10)
,
Nicolas Ramoz
(10)
,
Karine Clement
(11)
,
Véronique Pelloux
(11)
,
Alili Rohia
(11)
,
François Pattou
(12)
,
Violeta Raverdy
(12)
,
Robert Caiazzo
(12)
,
Raphaël G.P. Denis
(7)
,
Patricia Boya
(6)
,
Lorenzo Galluzzi
(13, 14, 15, 16)
,
Frank Madeo
(17, 18)
,
Stéphanie Migrenne-Li
(7)
,
Céline Cruciani-Guglielmacci
(7)
,
Nektarios Tavernarakis
(19, 20)
,
Carlos López-Otín
(21, 1)
,
Christophe Magnan
(7)
,
Guido Kroemer
(13, 1, 2, 22, 23, 24)
1
CRC (UMR_S_1138 / U1138) -
Centre de Recherche des Cordeliers
2 IGR - Institut Gustave Roussy
3 Université Paris-Saclay
4 CIBERNED - Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas
5 Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
6 CSIC - Centro de Investigaciones Biológicas
7 BFA (UMR_8251 / U1133) - Unité de Biologie Fonctionnelle et Adaptative
8 CRI (UMR_S_1149 / ERL_8252 / U1149) - Centre de recherche sur l'Inflammation
9 CMME - Service de psychiatrie - Clinique des maladies mentales et de l'encéphale
10 U894 - Centre de Psychiatrie et Neurosciences
11 Nutriomics - Nutrition et obésités: approches systémiques (UMR-S 1269)
12 EGENODIA (GI3M) - Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283
13 U848 - Apoptose, cancer et immunité
14 Weill Medical College of Cornell University [New York]
15 Sandra and Edward Meyer Cancer Center [New-York]
16 YSM - Yale School of Medicine [New Haven, Connecticut]
17 BioTechMed-Graz
18 Institute of Molecular Biosciences
19 UOC - University of Crete [Heraklion]
20 IMBB-FORTH - Institute of Molecular Biology and Biotechnology
21 Universidad de Oviedo [Oviedo]
22 HEGP - Hôpital Européen Georges Pompidou [APHP]
23 University of Science & Technology of China [Suzhou]
24 Karolinska Institutet [Stockholm]
2 IGR - Institut Gustave Roussy
3 Université Paris-Saclay
4 CIBERNED - Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas
5 Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
6 CSIC - Centro de Investigaciones Biológicas
7 BFA (UMR_8251 / U1133) - Unité de Biologie Fonctionnelle et Adaptative
8 CRI (UMR_S_1149 / ERL_8252 / U1149) - Centre de recherche sur l'Inflammation
9 CMME - Service de psychiatrie - Clinique des maladies mentales et de l'encéphale
10 U894 - Centre de Psychiatrie et Neurosciences
11 Nutriomics - Nutrition et obésités: approches systémiques (UMR-S 1269)
12 EGENODIA (GI3M) - Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283
13 U848 - Apoptose, cancer et immunité
14 Weill Medical College of Cornell University [New York]
15 Sandra and Edward Meyer Cancer Center [New-York]
16 YSM - Yale School of Medicine [New Haven, Connecticut]
17 BioTechMed-Graz
18 Institute of Molecular Biosciences
19 UOC - University of Crete [Heraklion]
20 IMBB-FORTH - Institute of Molecular Biology and Biotechnology
21 Universidad de Oviedo [Oviedo]
22 HEGP - Hôpital Européen Georges Pompidou [APHP]
23 University of Science & Technology of China [Suzhou]
24 Karolinska Institutet [Stockholm]
Valentina Sica
- Fonction : Auteur
- PersonId : 780305
- ORCID : 0000-0003-2770-5847
Isabelle Martins
- Fonction : Auteur
- PersonId : 756407
- ORCID : 0000-0003-0885-613X
Jonathan Pol
- Fonction : Auteur
- PersonId : 181859
- IdHAL : jonathan-pol
- ORCID : 0000-0002-8355-7562
- IdRef : 136751822
Maria Chiara Maiuri
- Fonction : Auteur
- PersonId : 183931
- IdHAL : maria-chiara-maiuri
- ORCID : 0000-0001-9760-7674
- IdRef : 170681785
Nicolas Ramoz
- Fonction : Auteur
- PersonId : 758672
- ORCID : 0000-0002-8070-9938
- IdRef : 148867634
Véronique Pelloux
- Fonction : Auteur
- PersonId : 761583
- ORCID : 0000-0003-3630-4746
François Pattou
- Fonction : Auteur
- PersonId : 758667
- ORCID : 0000-0001-8388-3766
- IdRef : 074750364
Lorenzo Galluzzi
- Fonction : Auteur
- PersonId : 759719
- ORCID : 0000-0003-2257-8500
- IdRef : 134206029
Christophe Magnan
- Fonction : Auteur
- PersonId : 756914
- ORCID : 0000-0002-7044-2571
- IdRef : 089072200
Guido Kroemer
Connectez-vous pour contacter l'auteur
- Fonction : Auteur correspondant
- PersonId : 758378
- ORCID : 0000-0002-9334-4405
- IdRef : 071283250
Connectez-vous pour contacter l'auteur
Résumé
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.
Origine : Fichiers produits par l'(les) auteur(s)