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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, * 
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.
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José Bravo-San Pedro, Valentina Sica, Isabelle Martins, Jonathan Pol, Friedemann Loos, et al.. Acyl-CoA-Binding Protein Is a Lipogenic Factor that Triggers Food Intake and Obesity. Cell Metabolism, Elsevier, 2019, 30 (4), pp.754-767.e9. ⟨10.1016/j.cmet.2019.07.010⟩. ⟨hal-02494254⟩

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