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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 combined with the hepatotoxic agent CCl<jats:sub>4<\/jats:sub>, and (iv) a combination of CCl<jats:sub>4<\/jats:sub> injections and oral ethanol challenge. Injections of anti-ACBP\/DBI mAb attenuated histological, enzymological, metabolomic and transcriptomic signs of liver damage in these four models, hence halting or reducing the progression of non-alcoholic and alcoholic liver disease. Steatosis, inflammation, ballooning and fibrosis responded to ACBP\/DBI inhibition at the preclinical level. Altogether, these findings support a causal role of ACBP\/DBI in MASH and liver fibrosis, as well as the possibility to therapeutically target ACBP\/DBI.<\/jats:p>","DOI":"10.1038\/s41418-024-01410-6","type":"journal-article","created":{"date-parts":[[2024,11,16]],"date-time":"2024-11-16T18:16:54Z","timestamp":1731781014000},"page":"434-446","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["ACBP\/DBI neutralization for the experimental treatment of fatty liver 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LC reports consulting fees from Boston Pharmaceutical, Echosens, Gilead, GSK, Madrigal, MSD, Novo Nordisk, Pfizer, Sagimet and Siemens Healthineers, lecture fees from Echosens, Gilead, Inventiva, Madrigal, and Novo Nordisk. IM reports consulting feed from Osasuna Therapeutics. GK has been holding research contracts with Daiichi Sankyo, Eleor, Kaleido, Lytix Pharma, PharmaMar, Osasuna Therapeutics, Samsara Therapeutics, Sanofi, Sutro, Tollys, and Vascage. GK is on the Board of Directors of the Bristol Myers Squibb Foundation France. GK is a scientific co-founder of everImmune, Osasuna Therapeutics, Samsara Therapeutics and Therafast Bio. GK is in the scientific advisory boards of Hevolution, Institut Servier, Longevity Vision Funds and Rejuveron Life Sciences. GK is the inventor of patents covering therapeutic targeting of aging, cancer, cystic fibrosis and metabolic disorders. GK\u2019s wife, Laurence Zitvogel, has held research contracts with Glaxo Smyth Kline, Incyte, Lytix, Kaleido, Innovate Pharma, Daiichi Sankyo, Pilege, Merus, Transgene, 9\u2009m, Tusk and Roche, was on the on the Board of Directors of Transgene, is a cofounder of everImmune, and holds patents covering the treatment of cancer and the therapeutic manipulation of the microbiota. GK\u2019s brother, Romano Kroemer, was an employee of Sanofi and now consults for Boehringer-Ingelheim. The funders had no role in the design of the study; in the writing of the manuscript, or in the decision to publish the results.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}