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.

库欣综合征是由内源性或药物性糖皮质激素升高引起的。酰基辅酶 A 结合蛋白 （ACBP，由基因地西泮结合抑制剂 Dbi 编码） 刺激食物摄入和脂肪合成代谢反应。在这里，我们发现库欣综合征患者和小鼠的血浆 ACBP/DBI 浓度升高。我们使用了几种方法在小鼠中抑制 ACBP/DBI，即 （1） 诱导 ACBP/DBI 自身抗体，（2） 注射中和单克隆抗体，（3） Dbi 基因的全体或肝细胞特异性敲除，（4） ACBP/DBI 受体 Gabrg2 突变和 （5） 注射三碘甲状腺原氨酸或 （6） 甲状腺激素受体β激动剂 resmetirom 以阻断 Dbi转录。这六种方法消除了库欣综合征的表现，例如食物摄入量增加、体重增加、过度肥胖、肝损伤、高甘油三酯血症和 2 型糖尿病。总之，ACBP/DBI 似乎构成了一个可操作的目标，它与库欣综合征的发展有因果关系。