Reversal of obesity development in Ceacam1 ^−/− male mice by bone marrow transplantation or introduction of the human CEACAM1 gene

Abstract

Objective

Although Ceacam1 ^−/− male mice become obese on normal chow, the effect of bone marrow transplantation or introduction of the carcinoembryonic antigen‐related cell adhesion molecule 1 ( CEACAM1) gene has not been studied, to the knowledge of the authors.

Methods

This study analyzed Ceacam1 ^−/− mice on normal diet or high‐fat diet (HFD), including effects of bone marrow transplantation or introduction of the CEACAM1 gene.

Results

Male Ceacam1 ^−/− mice on normal diet versus HFD for 24 weeks gained significantly more weight than controls, and Ceacam1 ^−/− mice aged up to 2 years had a high frequency of liver cancer. Transplantation of wild‐type bone marrow into Ceacam1 ^−/− mice or introduction of the human CEACAM1 gene fully or partially reversed the obesity phenotype. Liver lipidomics on Ceacam1 ^−/− versus wild‐type controls on an HFD revealed a significant increase in diacyl glycerides. An increase in fatty acid transporter CD36 levels further suggests that loss of Ceacam1 leads to a major dysregulation of free fatty acid uptake.

Conclusions

CEACAM1 expression in both the liver and immune cells regulates obesity and lipid storage pathways in the liver. Bone marrow reconstitution of the immune system or introduction of the human CEACAM1 gene can fully or partially reverse the phenotype.