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

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-β 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.

Authors

Institutions

Publication Details

Journal
Nature Metabolism
Published
2024-11-22
DOI
https://doi.org/10.1038/s42255-024-01170-0
Citations
9
Primary Topic
Pituitary Gland Disorders and Treatments
Type
article
Field-Weighted Citation Impact
3.22

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

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

Fanny Aprahamian, Yang Ou, Frédéric Castinetti, Giulia Cerrato et al.
9 citations
Nature Metabolism
Pituitary Gland Disorders and Treatments
3.22
article

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

Fanny Aprahamian, Yang Ou, Frédéric Castinetti, Giulia Cerrato, Flavia Lambertucci, Allan Sauvat, Sabrina Forveille, Misha Mao, Yuhong Pan, Omar Motiño, Marion Leduc, Hui Chen, Ai-Ling Tian, Yuting Ma, Oliver Kepp, Vincent Carbonnier, Gautier Stoll, Adrien Joseph, Thierry Christian Brue, Guido Kroemer, Isabelle Martins, Maria Chiara Maiuri, Sylvère Durand, Shuai Zhang, Hui Pan, Liwei Zhao, Peng Liu, Stéphanie Moriceau, Hongsheng Wang, Zeyu Luo, Yi-Fan Xia, Zhe Shen, Alexandra Cerone, Enfu Xue, S N Li
article en
9 citations

Abstract

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-β 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.

Nature MetabolismVol. 6(12)
Centre National de la Recherche Scientifique (FR), Union Hospital (HK), Inserm (FR), Chinese Academy of Medical Sciences & Peking Union Medical College (CN), Université Paris Cité (FR), Sichuan University (CN), Université Paris-Saclay (FR), Institut Gustave Roussy (FR), Sir Run Run Shaw Hospital (CN), Sichuan Agricultural University (CN), Sorbonne Université (FR), Assistance Publique Hôpitaux de Marseille (FR), Sorbonne Paris Cité (FR), Centre de Recherche des Cordeliers (FR), Hôpital de la Conception (FR), Assistance Publique – Hôpitaux de Paris (FR), Jinshan Hospital of Fudan University (CN), Hôpital Européen Georges-Pompidou (FR), Hôpital Européen (FR), Chinese Academy of Medical Sciences Dermatology Hospital (CN), Suzhou Institute of Systems Medicine (CN), Hôpital Saint-Louis (FR), Structure fédérative de recherche Necker (FR), Huazhong University of Science and Technology (CN), Zhejiang University (CN), Nanjing Medical University (CN)
Association pour la Recherche sur le Cancer, Seerave Foundation, Equipex, European Commission, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, National Natural Science Foundation of China, Fondation pour la Recherche Médicale, Ligue Contre le Cancer, China Scholarship Council, Centre National de la Recherche Scientifique, Institut Universitaire de France, Chinese Academy of Medical Sciences, Institut National Du Cancer, Institut Gustave-Roussy, Peking Union Medical College, Labex Immuno-Oncology
Zero hunger
Openalex Percentile: Top 7%
Pituitary Gland Disorders and Treatments
3.22
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.