biostudies-literatureMotino OEuropean Research Council434-446https://www.ebi.ac.uk/biostudies/studies/S-EPMC11894144biostudies-literatureUnknown32(3)Acyl-CoA binding protein (ACBP), also known as diazepam-binding inhibitor (DBI), is an extracellular checkpoint of autophagy. Here, we report that patients with histologically confirmed metabolic-associated steatohepatitis (MASH) or liver fibrosis exhibit elevated levels of circulating ACBP/DBI protein as compared to non-affected controls. Plasma ACBP/DBI strongly correlated with the NAFLD and FIB4 scores in patients, and these correlations were independent of age and body mass index. We studied the capacity of a monoclonal antibody (mAb) neutralizing mouse ACBP/DBI to combat active liver disease in several mouse models, in which steatohepatitis had been induced by four different protocols, namely, (i) methionine/choline-deficient diet, (ii) Western style diet (WD) alone, (iii) WD combinedCell death and differentiationACBP/DBI neutralization for the experimental treatment of fatty liver disease.PMC11894144101052444Lambertucci FCzernichow SVallet-Pichard AVan Beers BNogueira-Recalde UPoynard TMaiuri MCAnagnostopoulos GAprahamian FDurand Sde Preville NValla DLaouenan CBihan HQUID NASH InvestigatorsMotino OVidal-Trecan TManchon PBedossa PJunot CCastera LRiveline JPCarbonnier VDioguardi MBzrustowski ATerris BLarger EMontegut LGautier JFPietrocola FChen HKroemer GBoitard CCorreas JMZaleski IDLi SIbberson MParadis VVilgrain VNirmalathasan NGarteiser PMartins IJoseph AJulla JBPol SRautou PERoulot DfalseACBP/DBI neutralization for the experimental treatment of fatty liver disease.Acyl-CoA binding protein (ACBP), also known as diazepam-binding inhibitor (DBI), is an extracellular checkpoint of autophagy. Here, we report that patients with histologically confirmed metabolic-associated steatohepatitis (MASH) or liver fibrosis exhibit elevated levels of circulating ACBP/DBI protein as compared to non-affected controls. Plasma ACBP/DBI strongly correlated with the NAFLD and FIB4 scores in patients, and these correlations were independent of age and body mass index. We studied the capacity of a monoclonal antibody (mAb) neutralizing mouse ACBP/DBI to combat active liver disease in several mouse models, in which steatohepatitis had been induced by four different protocols, namely, (i) methionine/choline-deficient diet, (ii) Western style diet (WD) alone, (iii) WD combined2025-01-01T00:00:00Z2025 Mar2026-06-02T19:18:00.81Z2025-04-04T02:50:52.896ZS-EPMC118941443955051610.1038/s41418-024-01410-6