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

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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
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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.

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大类 | 1 区 医学
小类 | 1 区 内分泌学与代谢
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Q1 ENDOCRINOLOGY & METABOLISM

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第一作者机构: [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
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通讯机构: [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 [15]Hop Europeen Georges Pompidou, AP HP, Inst Canc Paris CARPEM, Dept Biol, Paris, France
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