{
  "abstract": "Objective: High‐fat diet represses Ceacam1 transcription via a PPARα‐mediated mechanism to cause insulin resistance before inflammation develops. The current study investigated whether mutating PPRE‐RXRα in Ceacam1 promoter prevents diet‐induced metabolic abnormalities and hepatic fibrosis in male C57BL6/J mice.\n\nMethods: A knock‐in mouse line (KI) bearing mutation on PPRE‐RXRα in Ceacam1 promoter was generated. Male mice were fed with regular chow, high‐fat diet, or GAN diet for 1–4 months before insulin action was assessed in vivo by hyperinsulinemia‐euglycemia clamp analysis and energy balance was analyzed by indirect calorimetry. H&E and Sirius Red staining were carried out to detect steatohepatitis and hepatic fibrosis, respectively.\n\nResults: Feeding with high‐fat or GAN diet for 1–4 months repressed hepatic CEACAM1 expression in wild‐type but not KI mice. Mutating PPRE‐RXRα prevented diet‐induced impairment of insulin clearance to maintain normoinsulinemia and insulin sensitivity. High‐fat diet failed to reduce energy expenditure and spontaneous locomotor activity in KI, as it did in wild‐type mice. GAN feeding for 4 months caused mounting of a Th1‐inflammatory response and hepatic fibrosis in wild‐type but not KI mice.\n\nConclusions: Blocking CEACAM1 repression while maintaining endogenous regulatory mechanisms and normal physiologic conditions sufficed to curb diet‐induced metabolic dysregulation, steatosis, energy imbalance, and MASH progression.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biomedical Sciences, Heritage College of Osteopathic Medicine Ohio University Athens Ohio USA",
    "Center for Diabetes and Endocrine Research, College of Medicine and Life Sciences University of Toledo Toledo Ohio USA",
    "Section of Endocrinology and Metabolism and Yale Genome Editing Center, Department of Internal Medicine Yale University School of Medicine New Haven Connecticut USA",
    "Program in Molecular Medicine University of Massachusetts Medical School Worcester Massachusetts USA",
    "Division of Endocrinology, Metabolism and Diabetes University of Massachusetts Medical School Worcester Massachusetts USA",
    "Diabetes Institute, Heritage College of Osteopathic Medicine Ohio University Athens Ohio USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Raziyeh Abdolahipour"
    },
    {
      "affs": [
        1
      ],
      "name": "Saja S. Khuder",
      "orcid": "0000-0001-9101-3744"
    },
    {
      "affs": [
        2
      ],
      "name": "William M. Philbrick",
      "orcid": "0000-0001-9219-8322"
    },
    {
      "affs": [
        0
      ],
      "name": "Agnes O. Portuphy",
      "orcid": "0009-0009-9007-7741"
    },
    {
      "affs": [
        0
      ],
      "name": "Getachew D. Belew"
    },
    {
      "affs": [
        0
      ],
      "name": "Hatem G. Fallouh"
    },
    {
      "affs": [
        0
      ],
      "name": "Harrison T. Muturi"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Boyeon Kim"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Jason K. Kim"
    },
    {
      "affs": [
        0,
        1,
        5
      ],
      "name": "Sonia M. Najjar",
      "orcid": "0000-0001-6209-8902"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/c1ngm343hz0ts.bib",
  "cited_by": 0,
  "doi": "10.1002/oby.70302",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13716184/",
  "id": "c1ngm343hz0ts",
  "issns": [
    "1930-7381",
    "1930-739X"
  ],
  "landing_url": "https://doi.org/10.1002/oby.70302",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "ORIGINAL ARTICLE"
    ],
    [
      "heading",
      "Obesity Biology and Integrated Physiology"
    ],
    [
      "heading",
      "Original Article"
    ],
    [
      "openalex",
      "2713|Liver Disease Diagnosis and Treatment"
    ]
  ],
  "openalex": "W7214096343",
  "pdf_url": "https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/oby.70302",
  "pmcid": "PMC13716184",
  "pmid": "42778341",
  "published": "2026-09-23",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/c1ngm343hz0ts.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T12:23:14Z",
      "native_id": "PMC13716184",
      "source": "pmc",
      "url": "https://doi.org/10.1002/oby.70302"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Liver Disease Diagnosis and Treatment",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Protecting CEACAM1 Expression Prevents Diet‐Induced Metabolic Dysfunction and Hepatic Fibrosis in Male Mice",
  "title_text": "Protecting CEACAM1 Expression Prevents Diet‐Induced Metabolic Dysfunction and Hepatic Fibrosis in Male Mice",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:23:14Z",
  "url": "https://research.draconitic.com/paper/c1ngm343hz0ts",
  "venue": "Obesity (Silver Spring, Md.)",
  "versions": []
}