Pathogenic role of acyl coenzyme A binding protein (ACBP) in Cushing’s syndrome
Résumé
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 d am age, hyp ertr ig lyce-
ridaemia 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.
Domaines
Sciences du Vivant [q-bio]Origine | Publication financée par une institution |
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licence |