Regulation of hepatic fibrosis by carcinoembryonic antigen-related cell adhesion molecule 1

Metabolism. 2021 Aug:121:154801. doi: 10.1016/j.metabol.2021.154801. Epub 2021 May 28.


Objective: NAFLD is a complex disease marked by cellular abnormalities leading to NASH. NAFLD patients manifest low hepatic levels of CEACAM1, a promoter of insulin clearance. Consistently, Cc1-/- null mice displayed spontaneous hyperinsulinemia/insulin resistance and steatohepatitis. Liver-specific reconstitution of Ceacam1 reversed these metabolic anomalies in 8-month-old Cc1-/-xliver+ mice fed a regular chow diet. The current study examined whether it would also reverse progressive hepatic fibrosis in mice fed a high-fat (HF) diet.

Methods: 3-Month-old mice were fed a high-fat diet for 3-5 months, and metabolic and histopathological analysis were conducted to evaluate their NASH phenotype.

Results: Reconstituting CEACAM1 to Cc1-/- livers curbed diet-induced liver dysfunction and NASH, including macrovesicular steatosis, lobular inflammation, apoptosis, oxidative stress, and chicken-wire bridging fibrosis. Persistence of hepatic fibrosis in HF-fed Cc1-/- treated with nicotinic acid demonstrated a limited role for lipolysis and adipokine release in hepatic fibrosis caused by Ceacam1 deletion.

Conclusions: Restored metabolic and histopathological phenotype of HF-fed Cc1-/-xliver+xliver+ assigned a critical role for hepatic CEACAM1 in preventing NAFLD/NASH including progressive hepatic fibrosis.

Keywords: Hyperinsulinemia; hepatic fibrosis; insulin clearance; insulin resistance; nonalcoholic fatty liver disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoembryonic Antigen / genetics
  • Carcinoembryonic Antigen / physiology*
  • Diet, High-Fat
  • Insulin / metabolism
  • Insulin Resistance / genetics
  • Lipid Metabolism / genetics
  • Liver Cirrhosis / genetics*
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout


  • Carcinoembryonic Antigen
  • Ceacam1 protein, mouse
  • Insulin