Reversal of Cushing syndrome by antibody-mediated neutralization of ACBP/DBI
Year: 2026
Type: article
Abstract: Cushing syndrome (CS) is caused by an increase in endogenous or exogenous glucocorticoids, leading to major alterations in body composition, including visceral obesity, sarcopenia, osteoporosis, type 2 diabetes, and dyslipidemia. Cardiovascular complications resulting from CS are often lethal. We previously demonstrated that CS induced by oral corticosterone (CORT) supplementation in mice can be prevented by inhibition of the peptide hormone acyl-CoA binding protein (ACBP), encoded by the gene diazepam binding inhibitor (DBI). Here, we investigated whether ACBP/DBI inhibition could be used to treat, rather than prevent, CS. To this end, we initiated treatment with anti-ACBP/DBI monoclonal antibodies (mAbs) in mice three weeks after the start of CORT supplementation, when hyperphagia and body weight gain were already established. Two anti-ACBP/DBI mAbs, 7G4a (specific for mouse ACBP/DBI only) and 82 (which recognizes both mouse and human ACBP/DBI), were able to normalize food intake and halt weight gain in mice under continuous CORT treatment. In addition, both mAbs attenuated CORT-induced sarcopenia, adiposity in inguinal, perigonadal, and visceral fat depots, and fully restored metabolic parameters, including type-2 diabetes, insulinemia, free fatty acids, triglycerides, and liver transaminases. In conclusion, neutralization of ACBP/DBI may serve as an effective therapeutic strategy for the treatment of established CS.
Source: Cell Stress
Institutions: Inserm, Université Paris Cité, Université Paris-Saclay, Institut Gustave Roussy, Sorbonne Université, Centre de Recherche des Cordeliers, Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse, Sichuan University, West China Hospital of Sichuan University, Assistance Publique – Hôpitaux de Paris, Hôpital Européen Georges-Pompidou
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,283
Funders: Association pour la Recherche sur le Cancer, Seerave Foundation, Equipex, European Commission, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, National Natural Science Foundation of China, Fondation pour la Recherche Médicale, Ligue Contre le Cancer, China Scholarship Council, Institut Universitaire de France, Institut National Du Cancer, Direction Générale de l’offre de Soins, Ministère des Solidarités et de la Santé, Université de Paris, HORIZON EUROPE European Innovation Council, HORIZON EUROPE European Research Council
Awards: G1190173965, Development of “smart” amplifiers of reactive oxygen species specific to aberrant polymorphonuclear neutrophils for treatment of inflammatory and autoimmune diseases, cancer and myeloablation., Next-generation phenotypic screening for oncological applications, G1963894250, Lung cancer prevention and interception, Biomarkers affecting the transition from cardiovascular disease to lung cancer: towards stratified interception., Gut OncoMicrobiome Signatures (GOMS) associated with cancer incidence, prognosis and prediction of treatment response., Mitochondrial copper targeting to modulate inflammatory macrophages, G434337789, G4656594441, G4707887143, Microbiota-centered interventions to solve antibiotics-induced primary resistance to immune checkpoint inhibitors, Immunogenic cell death (ICD) in the cancer-immune dialogue, Energizing the failing heart, G7041469554, G7562053067, G82931992, G8471630636, Université de Paris, The RUSH (retention using selective hooks) system: a chemical-genetic system for the in vivo manipulation of intercellular communication
OpenAlex ID: W7125832334