| First Author | Helal RA | Year | 2021 |
| Journal | Metabolism | Volume | 121 |
| Pages | 154801 | PubMed ID | 34058224 |
| Mgi Jnum | J:312529 | Mgi Id | MGI:6764680 |
| Doi | 10.1016/j.metabol.2021.154801 | Citation | Helal RA, et al. (2021) Regulation of hepatic fibrosis by carcinoembryonic antigen-related cell adhesion molecule 1. Metabolism 121:154801 |
| abstractText | 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 3-5months, 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. |
