CEACAM1 in Liver Injury, Metabolic and Immune Regulation

Abstract

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a transmembrane glycoprotein that is expressed on epithelial, endothelial and immune cells. CEACAM1 is a differentiation antigen involved in the maintenance of epithelial polarity that is induced during hepatocyte differentiation and liver regeneration. CEACAM1 regulates insulin sensitivity by promoting hepatic insulin clearance, and controls liver tolerance and mucosal immunity. Obese insulin-resistant humans with non-alcoholic fatty liver disease manifest loss of hepatic CEACAM1. In mice, deletion or functional inactivation of CEACAM1 impairs insulin clearance and compromises metabolic homeostasis which initiates the development of obesity and hepatic steatosis and fibrosis with other features of non-alcoholic steatohepatitis, and adipogenesis in white adipose depot. This is followed by inflammation and endothelial and cardiovascular dysfunctions. In obstructive and inflammatory liver diseases, soluble CEACAM1 is shed into human bile where it can serve as an indicator of liver disease. On immune cells, CEACAM1 acts as an immune checkpoint regulator, and deletion of Ceacam1 gene in mice causes exacerbation of inflammation and hyperactivation of myeloid cells and lymphocytes. Hence, hepatic CEACAM1 resides at the central hub of immune and metabolic homeostasis in both humans and mice. This review focuses on the regulatory role of CEACAM1 in liver and biliary tract architecture in health and disease, and on its metabolic role and function as an immune checkpoint regulator of hepatic inflammation.

Hepatic CEACAM1 expression indicates donor liver quality and prevents early transplantation injury

“…Indeed, liver flush from cold-stored WT livers was found to increase mRNA levels coding for MCP1, CXCL2 and CXCL10, whereas liver flush from CC1-ly identified as a substrate of the insulin receptor tyrosine kinase in rat hepatocytes (12,13), and abundantly expressed by the bile capillary side of hepatocytes in rodents and humans, CEACAM1 is involved in hepatocyte differentiation/liver regeneration, and increasingly recognized as the master regulator of insulin clearance, while preventing metabolic disorders, such as diabetes and nonalcoholic steatohepatitis (NASH) (14,15). The emerging evidence of hepatic CEACAM1 residing at the central hub of immune liver injury and metabolic homeostasis (16) provides the rationale to study its relevance in IRI-OLT in the current study.…”

Association of Proteins Modulating Immune Response and Insulin Clearance during Gestation with Antenatal Complications in Patients with Gestational or Type 2 Diabetes Mellitus

“…Among 11 known CEACAM1 isoforms [66], only isoform-1 possesses the ability to interact with FASN through the insulin-dependent mechanism and exactly that isoform was detected in the samples of studied groups [50,53]. Turning to the obtained results of quantitative measurements, we assumed that the suppression of CEACAM1 has appeared as a consequence of GDM and T2DM manifestation ( Table 3 and Figure 4).…”

Association of circulating CEACAM1 levels and insulin sensitivity in gestational diabetes mellitus

“…In the past years, it had been studied as a tumor marker of different types of cancer. On the other hand, earlier studies indicated that CEACAM1 was also related to some metabolic diseases [17][18][19]. Previous articles reported that the hepatic CEACAM1 expression was markedly decreased in the severely obese subjects, high grade fatty livers and NASH, but not different between diabetic and non-diabetic persons [20].…”