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

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. (C) 2021 Elsevier Inc. All rights reserved.

Automated summary

The study revealed that reconstituting CEACAM1 in the liver of Cc1(-/-) mice can reverse diet-induced liver dysfunction and NASH, including hepatic fibrosis. Treatment with nicotinic acid failed to eliminate hepatic fibrosis in HF-fed Cc1(-/-) mice.