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.
基金:
National Key Laboratory of Immunity and Inflammation, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Suzhou, Jiangsu, China; ARARD; Imaging and Cytometry platform of the Gustave Roussy Institute [INSERM U1266]; Association pour la recherche sur le cancer (ARC); Institut National du Cancer (INCa); Ligue contre le Cancer [quipe labellise]; Agence National de la Recherche (ANR) [AMMICa US23/CNRS UMS3655]; ARC; Fondation pour la Recherche Mdicale (FRM) [ANR 21-ESRE-0028]; European Joint Programme on Rare Diseases; European Research Council Advanced Investigator Award; ICD-Cancer [101052444]; European Union [101095604, 101016923]; Fondation Carrefour; INCa; Institut Universitaire de France; LabEx Immuno-Oncology [ANR-18-IDEX-0001]; Mark Foundation; Seerave Foundation; SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); SIRIC Cancer Research and Personalized Medicine (CARPEM); China Scholarship Council (CSC) [201908500100, 201803250050, 201908070134, 201907060011, 202106320287, 2021069100, 202308330135, 202306270045]; ANR [ANR-10-/AHU-01, 2022ZD0205700]; Natural Science Foundation of China (NSFC) [81972701]; CAMS Innovation Fund for Medical Sciences (CIFMS) [2021-I2M-1-074, 2022-I2M-2-004]; National special support plan for high-level talents; Suzhou Municipal Key Laboratory [SZS2023005]; NCTIB Fund for R&D Platform for Cell and Gene Therapy; National Key R&D Program of China [2019YFE0113300]
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
共同第一作者:
通讯作者:
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
推荐引用方式(GB/T 7714):
Pan Hui,Tian Ai-Ling,Chen Hui,et al.Pathogenic role of acyl coenzyme A binding protein (ACBP) in Cushing's syndrome[J].NATURE METABOLISM.2024,6(12):doi:10.1038/s42255-024-01170-0.
APA:
Pan, Hui,Tian, Ai-Ling,Chen, Hui,Xia, Yifan,Sauvat, Allan...&Kroemer, Guido.(2024).Pathogenic role of acyl coenzyme A binding protein (ACBP) in Cushing's syndrome.NATURE METABOLISM,6,(12)
MLA:
Pan, Hui,et al."Pathogenic role of acyl coenzyme A binding protein (ACBP) in Cushing's syndrome".NATURE METABOLISM 6..12(2024)