Login / Signup

Acyl-CoA binding protein for the experimental treatment of anorexia.

Hui ChenStéphanie MoriceauAdrien JosephFrancois MaillietSijing LiVirginie TollePhilibert DuriezRoland DardennesSylvère DurandVincent CarbonnierGautier StollAllan SauvatSylvie LachkarFanny AprahamianCarolina Alves Costa SilvaHui PanLéa MontégutGerasimos AnagnostopoulosFlavia LambertucciOmar MotiñoUxía Nogueira-RecaldeMélanie BourginMisha MaoYuhong PanAlexandra CeroneErwan BoedecZelia L GouveiaFederica MarmorinoChiara CremoliniLisa DerosaLaurence ZitvogelOliver KeppCarlos López-OtínMaria Chiara MaiuriFranck PerezPhilip GorwoodNicolas RamozFranck OuryIsabelle MartinsGuido Kroemer
Published in: Science translational medicine (2024)
Extracellular acyl-coenzyme A binding protein [ACBP encoded by diazepam binding inhibitor (DBI)] is a phylogenetically ancient appetite stimulator that is secreted in a nonconventional, autophagy-dependent fashion. Here, we show that low ACBP/DBI plasma concentrations are associated with poor prognosis in patients with anorexia nervosa, a frequent and often intractable eating disorder. In mice, anorexia induced by chronic restraint stress (CRS) is accompanied by a reduction in circulating ACBP/DBI concentrations. We engineered a chemical-genetic system for the secretion of ACBP/DBI through a biotin-activatable, autophagy-independent pathway. In transgenic mice expressing this system in hepatocytes, biotin-induced elevations in plasma ACBP/DBI concentrations prevented anorexia induced by CRS or chemotherapeutic agents including cisplatin, doxorubicin, and paclitaxel. ACBP/DBI reversed the CRS or cisplatin-induced increase in plasma lipocalin-2 concentrations and the hypothalamic activation of anorexigenic melanocortin 4 receptors, for which lipocalin-2 is an agonist. Daily intravenous injections of recombinant ACBP/DBI protein or subcutaneous implantation of osmotic pumps releasing recombinant ACBP/DBI mimicked the orexigenic effects of the chemical-genetic system. In conclusion, the supplementation of extracellular and peripheral ACBP/DBI might constitute a viable strategy for treating anorexia.
Keyphrases