法国巴黎大学Guido Kroemer课题组近日取得一项新发现。他们的研究指出乙酰辅酶A结合蛋白是引起食物摄入和肥胖的因素。这一研究成果发表在2019年10月刊的国际学术期刊《细胞—代谢》上。

自噬能够促进对营养压力的适应。研究人员发现培养的细胞或小鼠的短期饥饿导致乙酰辅酶A结合蛋白（ACBP，也称为安定结合抑制蛋白，DBI）的自噬依赖性细胞释放，以及随之而来的ACBP介导的自噬反馈抑制。重要的是，肥胖患者的ACBP水平升高并且神经性厌食症降低。

在小鼠中，全身注射ACBP蛋白可抑制自噬、诱导脂肪生成、降低血糖、刺激食欲和增加体重。研究人员设计了三种中和ACBP的方法，即诱导性全身敲除、中和抗体的全身给药以及在小鼠中诱导抗ACBP自身抗体。ACBP中和作用增强自噬作用、刺激脂肪酸氧化、抑制食欲、在高脂饮食或瘦素缺乏的情况下体重增加减少，并因饮食变化而减轻体重。

总之，中和ACBP可能是治疗肥胖症及其并症的策略。

附：英文原文

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

Author: 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, Franois Pattou, Violeta Raverdy, Robert Caiazzo, Raphal G.P. Denis, Patricia Boya, Lorenzo Galluzzi, Frank Madeo, Stéphanie Migrenne-Li, Céline Cruciani-Guglielmacci, Nektarios Tavernarakis, Carlos López-Otín, Christophe Magnan, Guido Kroemer

Issue&Volume: VOLUME 30, ISSUE 4

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.

DOI: 10.1016/j.cmet.2019.07.010

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30383-3