biostudies-literaturePan HEuropean Research Council678-680https://www.ebi.ac.uk/biostudies/studies/S-EPMC11849933biostudies-literatureUnknown21(3)DBI/ACBP is a phylogenetically ancient hormone that stimulates appetite and lipo-anabolism. In response to starvation, DBI/ACBP is secreted through a noncanonical, macroautophagy/autophagy-dependent pathway. The physiological hunger reflex involves starvation-induced secretion of DBI/ACBP from multiple cell types. DBI/ACBP concentrations subsequently increase in extracellular fluids to stimulate food intake. Recently, we observed that glucocorticoids, which are endogenous stress hormones as well as anti-inflammatory drugs, upregulate DBI/ACBP expression at the transcriptional level and stimulate autophagy in hepatocytes, thereby causing a surge in circulating DBI/ACBP levels. Prolonged increase in glucocorticoid concentrations causes an extreme form of metabolic syndrome, dubbed "Cushing sAutophagyAutophagy-dependent hepatocyte secretion of DBI/ACBP induced by glucocorticoids determines the pathogenesis of Cushing syndrome.PMC11849933101052444Pan HKepp OTian ALMartins IKroemer GCastinetti FfalseAutophagy-dependent hepatocyte secretion of DBI/ACBP induced by glucocorticoids determines the pathogenesis of Cushing syndrome.DBI/ACBP is a phylogenetically ancient hormone that stimulates appetite and lipo-anabolism. In response to starvation, DBI/ACBP is secreted through a noncanonical, macroautophagy/autophagy-dependent pathway. The physiological hunger reflex involves starvation-induced secretion of DBI/ACBP from multiple cell types. DBI/ACBP concentrations subsequently increase in extracellular fluids to stimulate food intake. Recently, we observed that glucocorticoids, which are endogenous stress hormones as well as anti-inflammatory drugs, upregulate DBI/ACBP expression at the transcriptional level and stimulate autophagy in hepatocytes, thereby causing a surge in circulating DBI/ACBP levels. Prolonged increase in glucocorticoid concentrations causes an extreme form of metabolic syndrome, dubbed "Cushing s2025-01-01T00:00:00Z2025 Mar2026-06-06T00:18:22.062Z2026-05-23T03:14:06.297ZS-EPMC118499333966357210.1080/15548627.2024.2437649