Nature metabolism · 2024
Pathogenic role of acyl coenzyme A binding protein (ACBP) in Cushing's syndrome.
СтатьяНазвание и аннотация: Перевод в очереди
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Pan Hui, Tian Ai-Ling, Chen Hui, Xia Yifan, Sauvat Allan, Moriceau Stephanie, Lambertucci Flavia, Motiño Omar, Zhao Liwei, Liu Peng, Mao Misha, Li Sijing, Zhang Shuai, Joseph Adrien, Durand Sylvère, Aprahamian Fanny, Luo Zeyu, Ou Yang, Shen Zhe, Xue Enfu, Pan Yuhong, Carbonnier Vincent, Stoll Gautier, Forveille Sabrina, Leduc Marion, Cerrato Giulia, Cerone Alexandra, Maiuri Maria Chiara, Castinetti Frederic, Brue Thierry, Wang Hongsheng, Ma Yuting, Martins Isabelle, Kepp Oliver, Kroemer Guido
Аннотация
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.