The autophagy-repressive tissue hormone DBI/ACBP (diazepam binding inhibitor, acyl-CoA binding protein) suppresses anorexia
Year: 2024
Type: editorial
Abstract: DBI/ACBP (diazepam binding inhibitor, acyl-CoA binding protein) is produced by multiple cell types and detectable in blood plasma. DBI acts on GABRA (gamma-aminobutyric acid type A receptor) complexes containing GABRG2 (gamma-aminobutyric acid type A receptor, subunit gamma 2) to inhibit macroautophagy/autophagy and hence can be considered as an "autophagy checkpoint". In patients with poor-prognosis anorexia nervosa, as well as in mice developing stress-induced anorexia, circulating DBI levels are reduced. Using a chemical-genetic system that makes it possible to control DBI secretion by hepatocytes, we showed that increasing DBI levels suffices to prevent anorexia induced by chronic restraint stress or chemotherapy with cisplatin, doxorubicin or paclitaxel in mice. At the mechanistic level, DBI administration acts through GABRA outside of the central nervous system and reduces the plasma levels of anorexigenic factors such as GDF15 (growth differentiation factor 15) and LCN2 (lipocalin 2), as well as anorexigenic signaling via the LCN2 receptor MC4R (melanocortin 4 receptor) in the hypothalamus. Accordingly, DBI supplementation stimulates food intake and normalizes whole body weight, body composition and metabolism in mouse models of anorexia. This normalization extends to the liver transcriptome and metabolome. Altogether, it appears that enhancing DBI levels constitutes a promising strategy for combating anorexia.
Source: Autophagy
Authors: Hui Chen, Isabelle Martins, Guido Kroemer
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: bronze
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, Fondation pour la Recherche Médicale, Ligue Contre le Cancer, Institut Universitaire de France, Institut National Du Cancer, Cancéropôle Ile de France, Direction Générale de l’offre de Soins, Ministère des Solidarités et de la Santé, Université de Paris, Labex Immuno-Oncology, HORIZON EUROPE European Research Council
Awards: G1056382719, G1190173965, G1348591106, Development of “smart” amplifiers of reactive oxygen species specific to aberrant polymorphonuclear neutrophils for treatment of inflammatory and autoimmune diseases, cancer and myeloablation., G1540355574, Next-generation phenotypic screening for oncological applications, G1912211089, G1941370527, 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., G2669449745, G3231222199, Mitochondrial copper targeting to modulate inflammatory macrophages, G330243840, G434337789, G461710914, 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, Metabolic and Autophagic Control by Acyl CoA Binding Protein (ACBP/DBI), G6584169967, G7041469554, G7075379671, G7101784390, G7562053067, G82931992, G8471630636, Université de Paris, G8809306651, The RUSH (retention using selective hooks) system: a chemical-genetic system for the in vivo manipulation of intercellular communication, G915670629
OpenAlex ID: W4402467229