Protecting CEACAM1 Expression Prevents Diet‐Induced Metabolic Dysfunction and Hepatic Fibrosis in Male Mice
6 affiliations
- 1Department of Biomedical Sciences, Heritage College of Osteopathic Medicine Ohio University Athens Ohio USA
- 2Center for Diabetes and Endocrine Research, College of Medicine and Life Sciences University of Toledo Toledo Ohio USA
- 3Section of Endocrinology and Metabolism and Yale Genome Editing Center, Department of Internal Medicine Yale University School of Medicine New Haven Connecticut USA
- 4Program in Molecular Medicine University of Massachusetts Medical School Worcester Massachusetts USA
- 5Division of Endocrinology, Metabolism and Diabetes University of Massachusetts Medical School Worcester Massachusetts USA
- 6Diabetes Institute, Heritage College of Osteopathic Medicine Ohio University Athens Ohio USA
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.
Methods: 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.
Results: 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.
Conclusions: 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.
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BibTeX
@article{abdolahipour2026protecting,
title = {{Protecting CEACAM1 Expression Prevents Diet‐Induced Metabolic Dysfunction and Hepatic Fibrosis in Male Mice}},
author = {Raziyeh Abdolahipour and Saja S. Khuder and William M. Philbrick and Agnes O. Portuphy and Getachew D. Belew and Hatem G. Fallouh and Harrison T. Muturi and Boyeon Kim and Jason K. Kim and Sonia M. Najjar},
journal = {Obesity (Silver Spring, Md.)},
year = {2026},
month = sep,
doi = {10.1002/oby.70302},
url = {https://doi.org/10.1002/oby.70302},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Protecting CEACAM1 Expression Prevents Diet‐Induced Metabolic Dysfunction and Hepatic Fibrosis in Male Mice
AU - Raziyeh Abdolahipour
AU - Saja S. Khuder
AU - William M. Philbrick
AU - Agnes O. Portuphy
AU - Getachew D. Belew
AU - Hatem G. Fallouh
AU - Harrison T. Muturi
AU - Boyeon Kim
AU - Jason K. Kim
AU - Sonia M. Najjar
PY - 2026
DA - 2026/09/23
JO - Obesity (Silver Spring, Md.)
DO - 10.1002/oby.70302
UR - https://doi.org/10.1002/oby.70302
AB - 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. Methods: 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. Results: 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. Conclusions: 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.
SN - 1930-7381
SN - 1930-739X
ER -