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

Abstract

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.

• Authors: Raghd Abu Helal, Lucia Russo, Hilda E Ghadieh, Harrison T Muturi, Suman Asalla, Abraham D Lee, Cara Gatto-Weis, Sonia M Najjar
• Journal: Metabolism: clinical and experimental (Metabolism) Vol. 121 Pg. 154801 (08 2021) ISSN: 1532-8600 [Electronic] United States
• PMID: 34058224 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• Carcinoembryonic Antigen
• Ceacam1 protein, mouse
• Insulin

Topics

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