Pathogenic role of acyl coenzyme A binding protein (ACBP) in Cushing's syndrome

被引：3

作者：

Pan, Hui ^{[1
,2
,3
]}

Tian, Ai-Ling ^{[1
,2
,3
]}

Chen, Hui ^{[1
,2
,3
]}

Xia, Yifan ^{[4
]}

Sauvat, Allan ^{[1
,2
]}

Moriceau, Stephanie ^{[5
]}

Lambertucci, Flavia ^{[1
,2
]}

Motino, Omar ^{[1
,2
]}

Zhao, Liwei ^{[1
,2
]}

Liu, Peng ^{[1
,2
]}

Mao, Misha ^{[1
,2
,3
,6
]}

Li, Sijing ^{[1
,2
,3
]}

Zhang, Shuai ^{[1
,2
,3
,7
]}

Joseph, Adrien ^{[1
,2
,8
]}

Durand, Sylvere ^{[1
,2
]}

Aprahamian, Fanny ^{[1
,2
]}

Luo, Zeyu ^{[9
]}

Ou, Yang ^{[10
]}

Shen, Zhe ^{[1
,2
,3
]}

Xue, Enfu ^{[1
,2
,3
]}

Pan, Yuhong ^{[1
,2
,3
,11
]}

Carbonnier, Vincent ^{[1
,2
]}

Stoll, Gautier ^{[1
,2
]}

Forveille, Sabrina ^{[1
,2
]}

Leduc, Marion ^{[1
,2
]}

Cerrato, Giulia ^{[1
,2
]}

Cerone, Alexandra ^{[1
,2
]}

Maiuri, Maria Chiara ^{[1
,2
]}

Castinetti, Frederic ^{[12
]}

Brue, Thierry ^{[12
]}

Wang, Hongsheng ^{[13
,14
]}

Ma, Yuting ^{[4
]}

Martins, Isabelle ^{[1
,2
]}

Kepp, Oliver ^{[1
,2
]}

Kroemer, Guido ^{[1
,2
,15
]}

机构：

[1] Gustave Roussy Inst, Metabol & Cell Biol Platforms, UMS AMMICa, Villejuif, France

[2] Univ Paris Cite, Sorbonne Univ, Ctr Rech Cordeliers,INSERM U1138, Equipe labellisee Ligue Canc, Paris, France

[3] Univ Paris Saclay, Fac Med, Paris, France

[4] Chinese Acad Med Sci & Peking Union Med Coll, Suzhou Inst Syst Med, Natl Key Lab Immun & Inflammat, Suzhou, Peoples R China

[5] Inst Imagine Platform Neurobehav & Metab, Struct Federat Rech Necker, INSERM CNRS, UAR 26 US24, Paris, France

[6] Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Surg Oncol, Hangzhou, Peoples R China

[7] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Resp & Crit Care Med, Wuhan, Peoples R China

[8] Hop St Louis, Assistance Publ Hop Paris, Serv Reanimat Medicale, Paris, France

[9] Sichuan Univ, West China Hosp, West China Sch Med, Dept Orthoped, Chengdu, Peoples R China

[10] Fudan Univ, Jinshan Hosp, Ctr Tumor Diag & Therapy, Shanghai, Peoples R China

[11] Sichuan Agr Univ, Coll Vet Med, Res Ctr Avian Dis, Chengdu, Peoples R China

[12] Concept Hosp, Assistance Publ Hop Marseille, Dept Endocrinol, Marseille, France

[13] Chinese Acad Med Sci & Peking Union Med Coll, Hosp Skin Dis, Inst Dermatol,Dept Mycobacterium, Jiangsu Key Lab Mol Biol Skin Dis & STIs, Nanjing, Peoples R China

[14] Nanjing Med Univ, Ctr Global Hlth, Sch Publ Hlth, Nanjing, Peoples R China

[15] Hop Europeen Georges Pompidou, AP HP, Inst Canc Paris CARPEM, Dept Biol, Paris, France

来源：

NATURE METABOLISM | 2024年 / 6卷 / 12期

基金：

欧洲研究理事会; 国家重点研发计划;

关键词：

ANOREXIA-NERVOSA; SECRETION; QUANTIFICATION;

D O I：

10.1038/s42255-024-01170-0

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Cushing's syndrome is caused by an elevation of endogenous or pharmacologically administered glucocorticoids. Acyl coenzyme A binding protein (ACBP, encoded by the gene diazepam binding inhibitor, Dbi) stimulates food intake and lipo-anabolic reactions. Here we found that plasma ACBP/DBI concentrations were elevated in patients and mice with Cushing's syndrome. We used several methods for ACBP/DBI inhibition in mice, namely, (1) induction of ACBP/DBI autoantibodies, (2) injection of a neutralizing monoclonal antibody, (3) body-wide or hepatocyte-specific knockout of the Dbi gene, (4) mutation of the ACBP/DBI receptor Gabrg2 and (5) injections of triiodothyronine or (6) the thyroid hormone receptor-beta agonist resmetirom to block Dbi transcription. These six approaches abolished manifestations of Cushing's syndrome such as increased food intake, weight gain, excessive adiposity, liver damage, hypertriglyceridaemia and type 2 diabetes. In conclusion, it appears that ACBP/DBI constitutes an actionable target that is causally involved in the development of Cushing's syndrome. The authors highlight the role of acyl coenzyme A binding protein (encoded by DBI) in Cushing's syndrome by using six different inhibition methods and mapping the physiological effects.

引用

页数：34

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