Cell子刊:靶向ACBP或能降低食欲助减肥
  • 人体细胞和小鼠中,短期饥饿引发的自噬可诱导细胞释放乙酰辅酶A结合蛋白(ACBP),ACBP反过来可抑制自噬;
  • ACBP水平在肥胖患者中升高、在神经性食欲缺乏患者中降低;
  • 给小鼠注射ACBP蛋白可抑制自噬,诱导脂肪生成,减少血糖过多,刺激食欲,促进增重;
  • 小鼠中,敲除ACBP、施用ACBP抗体、诱导抗ACBP的自身抗体表达等方法降低ACBP水平,可增强自噬,刺激脂肪酸氧化,抑制食欲,减少高脂饮食或瘦素缺陷下的体重增加、促进饮食干预减重。
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mildbreeze
发表在Cell Metabolism的一项最新研究表明,可调控自噬的乙酰辅酶A结合蛋白(ACBP)在肥胖患者中水平升高,可在小鼠模型中促进脂肪生成和进食,而用抗体等方法中和/抑制ACBP可抵抗肥胖,提示ACBP或是治疗肥胖及其相关疾病的有效靶点。
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Cell Metabolism [IF:21.567]

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

乙酰辅酶A结合蛋白是一种可触发食物摄入和肥胖的脂肪生成因子

10.1016/j.cmet.2019.07.010

2019-08-09, Article

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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.

First Authors:
José M Bravo-San Pedro,Valentina Sica

Correspondence Authors:
Guido Kroemer

All Authors:
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,Véronique Pelloux,Alili Rohia,François Pattou,Violeta Raverdy,Robert Caiazzo,Raphaël GP Denis,Patricia Boya,Lorenzo Galluzzi,Frank Madeo,Stéphanie Migrenne-Li,Céline Cruciani-Guglielmacci,Nektarios Tavernarakis,Carlos López-Otín,Christophe Magnan,Guido Kroemer

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