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Autoantibodies against apolipoprotein A-1 (AAA-1) are a possible novel CVD risk factor promoting inflammation and disrupting cellular lipid homeostasis, two prominent pathogenic features of NAFLD. We explored the role of AAA-1 in NAFLD and their association with CVD risk.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>HepaRG cells and liver sections from ApoE\u2212\/\u2212 mice exposed to AAA-1 were used for lipid quantification and conditional protein expression. Randomly selected sera from 312 subjects of the Prevention of Renal and Vascular End-stage Disease (PREVEND) general population cohort were used to measure AAA-1. A Fatty Liver Index (FLI)\u2009\u2265\u200960 and a 10-year Framingham Risk Score (FRS)\u2009\u2265\u200920% were used as proxy of NAFLD and high CVD risk, respectively.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In-vitro and mouse models showed that AAA-1 increased triglyceride synthesis leading to steatosis, and promoted inflammation and hepatocyte injury. In the 112 PREVEND participants with FLI\u2009\u2265\u200960, AAA-1 were associated with higher FRS, alkaline phosphatase levels, lower HDL cholesterol and tended to display higher FLI values. Univariate linear and logistic regression analyses (LRA) confirmed significant associations between AAA-1, FLI and FRS\u2009\u2265\u200920%, while in adjusted LRA, FLI was the sole independent predictor of FRS\u2009\u2265\u200920% (OR: 1.05, 95%CI 1.01\u20131.09, P\u2009=\u20090.003). AAA-1 was not an independent FLI predictor.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>AAA-1 induce a NAFLD-compatible phenotype in vitro and in mice. Intricate associations exist between AAA-1, CVD risk and FLI in the general population. Further work is required to refine the role of AAA-1 in NAFLD and to determine if the AAA-1 association with CVD is affected by hepatic steatosis.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12967-023-04569-7","type":"journal-article","created":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T07:01:50Z","timestamp":1696489310000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Antibody against apolipoprotein-A1, non-alcoholic fatty liver disease and cardiovascular risk: a translational study"],"prefix":"10.1186","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7075-1182","authenticated-orcid":false,"given":"Sabrina","family":"Pagano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan J. 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