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http://hdl.handle.net/10662/19858
Title: | Acyl-CoA-Binding protein is a lipogenic factor that triggers food intake and obesity |
Authors: | Bravo San Pedro, José Manuel Sica, Valentina Martins, Isabelle Pol, Jonathan Loos, Friedemann Maiuri, Maria Chiara Durand, Sylvere Bossut, Noélie Anagnostopoulos, Gerasimos Niso Santano, Mireia Drake Aranda, Fernando Ramirez Pardo, Ignacio Denom, Justine Boedec, Erwan Gorwood, Philip Ramoz, Nicolas Clément, Karine Pelloux, Veronique Rohia, Alili Pattou, François Raverdy, Violeta Caiazzo, Robert Denis, Raphaël G.P. Boya, Patricia Galluzzi, Lorenzo Madeo, Frank Migrenne Li, Stéphanie Cruciani Guglielmacci, Céline Tavernarakis, Nektarios López Otín, Carlos Magnan, Christophe Kroemer, Guido |
Keywords: | Anorexia;Anorexy;Autofagia;Autophagy;Obesidad;Obesity;Lipid metabolism;Metabolismo de los lípidos |
Issue Date: | 2019 |
Publisher: | Sciendirect |
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. |
URI: | http://hdl.handle.net/10662/19858 |
DOI: | 10.1016/j.cmet.2019.07.010 |
Appears in Collections: | DBYBM - Artículos |
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