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

José M. Bravo-San Pedro; Valentina Sica; Isabelle Martins; Jonathan Pol; Friedemann Loos; Maria Chiara Maiuri; Sylvère Durand; Noélie Bossut; Fanny Aprahamian; Gerasimos Anagnostopoulos; Mireia Niso-Santano; Fernando Aranda; Ignacio Ramírez-Pardo; Justine Lallement; Jessica Denom; Erwan Boedec; Philip Gorwood; Nicolas Ramoz; Karine Clément; Veronique Pelloux; Alili Rohia; François Pattou; Violeta Raverdy; Robert Caiazzo; Raphaël G.P. Denis; Patricia Boya; Lorenzo Galluzzi; Frank Madeo; Stéphanie Migrenne-Li; Céline Cruciani-Guglielmacci; Nektarios Tavernarakis; Carlos López-Otín; Christophe Magnan; Guido Kroemer

doi:10.1016/j.cmet.2019.07.010

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

José M. Bravo-San Pedro, Valentina Sica, Isabelle Martins, Jonathan Pol, Friedemann Loos, Maria Chiara Maiuri, Sylvère Durand, Noélie Bossut, Fanny Aprahamian, Gerasimos Anagnostopoulos, Mireia Niso-Santano, Fernando Aranda, Ignacio Ramírez-Pardo, Justine Lallement, Jessica Denom, Erwan Boedec, Philip Gorwood, Nicolas Ramoz, Karine Clément, Veronique PellouxAlili Rohia, François Pattou, Violeta Raverdy, Robert Caiazzo, Raphaël G.P. Denis, Patricia Boya, Lorenzo Galluzzi, Frank Madeo, Stéphanie Migrenne-Li, Céline Cruciani-Guglielmacci, Nektarios Tavernarakis, Carlos López-Otín, Christophe Magnan, Guido Kroemer

Résultats de recherche: Contribution à un journal › Article › Revue par des pairs

70 Citations (Scopus)

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.

langue originale	Anglais
Pages (de - à)	754-767.e9
journal	Cell Metabolism
Volume	30
Numéro de publication	4
Les DOIs	https://doi.org/10.1016/j.cmet.2019.07.010
état	Publié - 1 oct. 2019

Accès au document

10.1016/j.cmet.2019.07.010

Autres fichiers et liens

Lien vers la publication dans Scopus

Contient cette citation

Bravo-San Pedro, J. M., Sica, V., Martins, I., Pol, J., Loos, F., Maiuri, M. C., Durand, S., Bossut, N., Aprahamian, F., Anagnostopoulos, G., Niso-Santano, M., Aranda, F., Ramírez-Pardo, I., Lallement, J., Denom, J., Boedec, E., Gorwood, P., Ramoz, N., Clément, K., ... Kroemer, G. (2019). Acyl-CoA-Binding Protein Is a Lipogenic Factor that Triggers Food Intake and Obesity. Cell Metabolism, 30(4), 754-767.e9. https://doi.org/10.1016/j.cmet.2019.07.010

@article{1673cc9f5a73434ba45e2127f496286c,

title = "Acyl-CoA-Binding Protein Is a Lipogenic Factor that Triggers Food Intake and Obesity",

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.",

keywords = "anorexia, autophagy, lipid metabolism, obesity",

author = "{Bravo-San Pedro}, {Jos{\'e} M.} and Valentina Sica and Isabelle Martins and Jonathan Pol and Friedemann Loos and Maiuri, {Maria Chiara} and Sylv{\`e}re Durand and No{\'e}lie Bossut and Fanny Aprahamian and Gerasimos Anagnostopoulos and Mireia Niso-Santano and Fernando Aranda and Ignacio Ram{\'i}rez-Pardo and Justine Lallement and Jessica Denom and Erwan Boedec and Philip Gorwood and Nicolas Ramoz and Karine Cl{\'e}ment and Veronique Pelloux and Alili Rohia and Fran{\c c}ois Pattou and Violeta Raverdy and Robert Caiazzo and Denis, {Rapha{\"e}l G.P.} and Patricia Boya and Lorenzo Galluzzi and Frank Madeo and St{\'e}phanie Migrenne-Li and C{\'e}line Cruciani-Guglielmacci and Nektarios Tavernarakis and Carlos L{\'o}pez-Ot{\'i}n and Christophe Magnan and Guido Kroemer",

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",

year = "2019",

month = oct,

day = "1",

doi = "10.1016/j.cmet.2019.07.010",

language = "English",

volume = "30",

pages = "754--767.e9",

journal = "Cell Metabolism",

issn = "1550-4131",

number = "4",

}

Bravo-San Pedro, JM, Sica, V, Martins, I, Pol, J, Loos, F, Maiuri, MC, Durand, S, Bossut, N, Aprahamian, F, Anagnostopoulos, G, Niso-Santano, M, Aranda, F, Ramírez-Pardo, I, Lallement, J, Denom, J, Boedec, E, Gorwood, P, Ramoz, N, Clément, K, Pelloux, V, Rohia, A, Pattou, F, Raverdy, V, Caiazzo, R, Denis, RGP, Boya, P, Galluzzi, L, Madeo, F, Migrenne-Li, S, Cruciani-Guglielmacci, C, Tavernarakis, N, López-Otín, C, Magnan, C & Kroemer, G 2019, 'Acyl-CoA-Binding Protein Is a Lipogenic Factor that Triggers Food Intake and Obesity', Cell Metabolism, VOL. 30, Numéro 4, p. 754-767.e9. https://doi.org/10.1016/j.cmet.2019.07.010

TY - JOUR

T1 - Acyl-CoA-Binding Protein Is a Lipogenic Factor that Triggers Food Intake and Obesity

AU - Bravo-San Pedro, José M.

AU - Sica, Valentina

AU - Martins, Isabelle

AU - Pol, Jonathan

AU - Loos, Friedemann

AU - Maiuri, Maria Chiara

AU - Durand, Sylvère

AU - Bossut, Noélie

AU - Aprahamian, Fanny

AU - Anagnostopoulos, Gerasimos

AU - Niso-Santano, Mireia

AU - Aranda, Fernando

AU - Ramírez-Pardo, Ignacio

AU - Lallement, Justine

AU - Denom, Jessica

AU - Boedec, Erwan

AU - Gorwood, Philip

AU - Ramoz, Nicolas

AU - Clément, Karine

AU - Pelloux, Veronique

AU - Rohia, Alili

AU - Pattou, François

AU - Raverdy, Violeta

AU - Caiazzo, Robert

AU - Denis, Raphaël G.P.

AU - Boya, Patricia

AU - Galluzzi, Lorenzo

AU - Madeo, Frank

AU - Migrenne-Li, Stéphanie

AU - Cruciani-Guglielmacci, Céline

AU - Tavernarakis, Nektarios

AU - López-Otín, Carlos

AU - Magnan, Christophe

AU - Kroemer, Guido

PY - 2019/10/1

Y1 - 2019/10/1

N2 - 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.

AB - 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.

KW - anorexia

KW - autophagy

KW - lipid metabolism

KW - obesity

UR - http://www.scopus.com/inward/record.url?scp=85072575903&partnerID=8YFLogxK

U2 - 10.1016/j.cmet.2019.07.010

DO - 10.1016/j.cmet.2019.07.010

M3 - Article

C2 - 31422903

AN - SCOPUS:85072575903

SN - 1550-4131

VL - 30

SP - 754-767.e9

JO - Cell Metabolism

JF - Cell Metabolism

IS - 4

ER -