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

Abstract

ObjectiveAlthough 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.MethodsThis study analyzed Ceacam1−/− mice on normal diet or high‐fat diet (HFD), including effects of bone marrow transplantation or introduction of the CEACAM1 gene.ResultsMale 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.ConclusionsCEACAM1 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.

A Multifunctional Therapeutic Strategy Using P7C3 as A Countermeasure Against Bone Loss and Fragility in An Ovariectomized Rat Model of Postmenopausal Osteoporosis

“…[ 196 ] The expression of FGF21 in this group, along with a ≈5‐fold increase in CEACAM1 expression, is likely significantly associated with the increase in bone marrow adiposity and whole‐body weight gain measured in this group. [ 197 ] Estrogen has been shown to reduce adipogenesis through the direct inhibition of PPARγ, [ 198–201 ] however, our in vitro investigations reveal no P7C3‐induced reduction in this major adipogenic regulatory gene, suggesting the induction of an alternative adipogenic route. Insulin receptor was also upregulated by P7C3.…”

Heart Uptake of [18F]Fluoro-4-Thia-Oleate in a Non-Alcoholic Fatty Liver Disease Mouse Model

“…In this respect, we have recently shown that human CEACAM1 directly associates with the fatty acid uptake receptor CD36 in human HepG2 hepatocytes [21] and is phosphorylated by a combination of protein kinase A (PKA) and glycogen synthase kinase 3b (GSK3b) [22]-key kinases that regulate glucagon [23] and insulin signaling [24,25]. In addition, the deletion of CEACAM1 in mice leads to an elevation of CD36 and pAMPK expression [26]-proteins that are co-regulated in skeletal and heart muscle [27]. In terms of CVD, endocardiography revealed increased septal wall thickness in male Ceacam1 −/− mice but not in CEACAM1 liver-reconstituted male Ceacam1 −/− mice [19].…”