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Carcinoembryonic Antigen\u2010related Cell Adhesion Molecule1 protein (CEACAM1) promotes insulin clearance to maintain insulin sensitivity and repress de novo lipogenesis, as bolstered by the development of insulin resistance and steatohepatitis in\n                      <jats:italic>AlbuminCre\u2009+\u2009Cc1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>fl\/fl<\/jats:italic>\n                      <\/jats:sup>\n                      mice with liver\u2010specific mouse gene encoding CEACAM1 protein\n                      <jats:italic>(Ceacam1)<\/jats:italic>\n                      deletion. We herein investigated whether these mice also developed hepatic fibrosis and whether hepatic CEACAM1 is reduced in patients with MASH at different fibrosis stages.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      <jats:italic>AlbuminCre\u2009+\u2009Cc1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>fl\/fl<\/jats:italic>\n                      <\/jats:sup>\n                      mice were fed a regular or a high\u2010fat diet before their insulin metabolism and action were assessed during IPGTT, and their livers excised for histochemical, immunohistochemical and Western blot analysis. Sirius red staining was used to assess fibrosis, and media transfer was employed to examine whether mutant hepatocytes activated hepatic stellate cells (HSCs). Hepatic CEACAM1 protein levels in patients with varying disease stages were assessed by ELISA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Hepatocytic deletion of\n                      <jats:italic>Ceacam1<\/jats:italic>\n                      caused hyperinsulinemia\u2010driven insulin resistance emanating from reduced hepatic insulin clearance.\n                      <jats:italic>AlbuminCre\u2009+\u2009Cc1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>fl\/fl<\/jats:italic>\n                      <\/jats:sup>\n                      livers showed inflammation, fibrosis and hepatic injury, with more advanced bridging and chicken\u2010wire hepatic fibrosis under high\u2010fat conditions. Media transferred from hepatocytes isolated from mutant mice activated control HSCs, likely owing to their elevated endothelin1 content. Interestingly, hepatic CEACAM1 levels were lower in the livers of patients with MASH and declined gradually with advanced fibrosis stage.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Hepatic CEACAM1 levels declined with progression of MASH in humans. The phenotype of\n                      <jats:italic>AlbuminCre\u2009+\u2009Cc1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>fl\/fl<\/jats:italic>\n                      <\/jats:sup>\n                      mice assigned a key role to CEACAM1 loss from hepatocytes in hepatic fibrosis independently of other liver cells.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/eci.14177","type":"journal-article","created":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T11:50:25Z","timestamp":1708516225000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Loss of\n                    <scp>CEACAM1<\/scp>\n                    in hepatocytes causes hepatic fibrosis"],"prefix":"10.1111","volume":"54","author":[{"given":"Sobia","family":"Zaidi","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Heritage College of Osteopathic 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