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Acyl coenzyme A binding protein (ACBP, encoded by the gene diazepam binding inhibitor, <jats:italic>Dbi<\/jats:italic>) stimulates food intake and lipo-anabolic reactions. Here we found that plasma ACBP\/DBI concentrations were elevated in patients and mice with Cushing\u2019s 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 <jats:italic>Dbi<\/jats:italic> gene, (4) mutation of the ACBP\/DBI receptor <jats:italic>Gabrg2<\/jats:italic> and (5) injections of triiodothyronine or (6) the thyroid hormone receptor-\u03b2 agonist resmetirom to block <jats:italic>Dbi<\/jats:italic> transcription. These six approaches abolished manifestations of Cushing\u2019s 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\u2019s syndrome.<\/jats:p>","DOI":"10.1038\/s42255-024-01170-0","type":"journal-article","created":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T10:06:59Z","timestamp":1732270019000},"page":"2281-2299","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Pathogenic role of acyl coenzyme A binding protein (ACBP) in Cushing\u2019s 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I.M. consults for Osasuna Therapeutics. G.K. has been holding research contracts with Daiichi Sankyo, Eleor, Kaleido, Lytix Pharma, PharmaMar, Osasuna Therapeutics, Samsara Therapeutics, Sanofi, Sutro, Tollys and Vascage. G.K. is on the Board of Directors of the Bristol Myers Squibb Foundation France. G.K. is a scientific co-founder of everImmune, Osasuna Therapeutics, Samsara Therapeutics and Therafast Bio; is in the scientific advisory boards of Hevolution, Institut Servier, Longevity Vision Funds and Rejuveron Life Sciences; and is the inventor of patents covering therapeutic targeting of ageing, cancer, cystic fibrosis and metabolic disorders. Among these patents, one, \u2018Methods for weight reduction\u2019 (US11905330B1), is relevant to this study. G.K.\u2019s brother, Romano Kroemer, was an employee of Sanofi and now consults for Boehringer-Ingelheim. G.K.\u2019s wife, Laurence Zitvogel, has held research contracts with GSK, Incyte, Lytix, Kaleido, Innovate Pharma, Daiichi Sankyo, Pilege, Merus, Transgene, 9m, Tusk and Roche, was on the on the Board of Directors of Transgene, is a co-founder of everImmune and holds patents covering the treatment of cancer and the therapeutic manipulation of the microbiota. The funders had no role in the design of the study, in the writing of the manuscript or in the decision to publish the results. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}