{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T02:04:51Z","timestamp":1790215491234,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Obesity"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      High\u2010fat diet represses\n                      <jats:italic>Ceacam1<\/jats:italic>\n                      transcription via a PPAR\u03b1\u2010mediated mechanism to cause insulin resistance before inflammation develops. The current study investigated whether mutating PPRE\u2010RXR\u03b1 in\n                      <jats:italic>Ceacam1<\/jats:italic>\n                      promoter prevents diet\u2010induced metabolic abnormalities and hepatic fibrosis in male C57BL6\/J mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A knock\u2010in mouse line (KI) bearing mutation on PPRE\u2010RXR\u03b1 in\n                      <jats:italic>Ceacam1<\/jats:italic>\n                      promoter was generated. Male mice were fed with regular chow, high\u2010fat diet, or GAN diet for 1\u20134\u2009months before insulin action was assessed in\u00a0vivo by hyperinsulinemia\u2010euglycemia clamp analysis and energy balance was analyzed by indirect calorimetry. H&amp;E and Sirius Red staining were carried out to detect steatohepatitis and hepatic fibrosis, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Feeding with high\u2010fat or GAN diet for 1\u20134\u2009months repressed hepatic CEACAM1 expression in wild\u2010type but not KI mice. Mutating PPRE\u2010RXR\u03b1 prevented diet\u2010induced impairment of insulin clearance to maintain normoinsulinemia and insulin sensitivity. High\u2010fat diet failed to reduce energy expenditure and spontaneous locomotor activity in KI, as it did in wild\u2010type mice. GAN feeding for 4\u2009months caused mounting of a Th1\u2010inflammatory response and hepatic fibrosis in wild\u2010type but not KI mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Blocking CEACAM1 repression while maintaining endogenous regulatory mechanisms and normal physiologic conditions sufficed to curb diet\u2010induced metabolic dysregulation, steatosis, energy imbalance, and MASH progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/oby.70302","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T01:21:58Z","timestamp":1790212918000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Protecting\n                    <scp>CEACAM1<\/scp>\n                    Expression Prevents Diet\u2010Induced Metabolic Dysfunction and Hepatic Fibrosis in Male Mice"],"prefix":"10.1002","author":[{"given":"Raziyeh","family":"Abdolahipour","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Heritage College of Osteopathic Medicine Ohio University  Athens Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9101-3744","authenticated-orcid":false,"given":"Saja S.","family":"Khuder","sequence":"additional","affiliation":[{"name":"Center for Diabetes and Endocrine Research, College of Medicine and Life Sciences University of Toledo  Toledo Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9219-8322","authenticated-orcid":false,"given":"William M.","family":"Philbrick","sequence":"additional","affiliation":[{"name":"Section of Endocrinology and Metabolism and Yale Genome Editing Center, Department of Internal Medicine Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9007-7741","authenticated-orcid":false,"given":"Agnes O.","family":"Portuphy","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Heritage College of Osteopathic Medicine Ohio University  Athens Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Getachew D.","family":"Belew","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Heritage College of Osteopathic Medicine Ohio University  Athens Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hatem G.","family":"Fallouh","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Heritage College of Osteopathic Medicine Ohio University  Athens Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harrison T.","family":"Muturi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Heritage College of Osteopathic Medicine Ohio University  Athens Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boyeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine University of Massachusetts Medical School  Worcester Massachusetts USA"},{"name":"Division of Endocrinology, Metabolism and Diabetes University of Massachusetts Medical School  Worcester Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason K.","family":"Kim","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine University of Massachusetts Medical School  Worcester Massachusetts USA"},{"name":"Division of Endocrinology, Metabolism and Diabetes University of Massachusetts Medical School  Worcester Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6209-8902","authenticated-orcid":false,"given":"Sonia M.","family":"Najjar","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Heritage College of Osteopathic Medicine Ohio University  Athens Ohio USA"},{"name":"Center for Diabetes and Endocrine Research, College of Medicine and Life Sciences University of Toledo  Toledo Ohio USA"},{"name":"Diabetes Institute, Heritage College of Osteopathic Medicine Ohio University  Athens Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"e_1_2_11_2_1","first-page":"198","article-title":"Hepatic Insulin Clearance: Mechanism and Physiology","volume":"34","author":"Najjar S. 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