Journal de biochimie et de biologie cellulaire

Abstrait

A protein replacement Reduces Dysregulation of Lipid Metabolism in Liver and Adipose Tissue in Ceruloplasmin-Deficient Mice

Kashaf K

Ceruloplasmin is a ferroxidase associated with iron homeostasis; The liver stores iron, which is necessary for the production of the soluble protein secreted into the bloodstream, as one consequence of its absence. Adipose tissue also secretes ceruloplasmin, but little is known about how it works in adipocytes. We hypothesized that the interaction between iron and lipids might be mediated by ceruloplasmin. To determine whether ceruloplasmin replacement was successful, we examined iron/lipid dysmetabolism in the liver and adipose tissue of the CpKO mouse model of aceruloplasminemia. Steatosis, iron deposition in the liver, and fat accumulation in the adipose tissue were observed in CpKO mice. Iron homeostasis was unaffected in CpKO mice's adipose tissue. On the other hand, the behavior of adiponectin and leptin was distinct from that of the wild-type. CpKO mice's liver and adipose tissue showed an increase in macrophage infiltration, indicating tissue inflammation. Ceruloplasmin reduced liver iron accumulation and steatosis in CpKO mice without normalizing the expression of iron homeostasis-related proteins. Protein replacement reduced serum triglycerides, partially restored adipokines, and limited macrophage infiltration in both the adipose and hepatic tissues of CpKO mice. A correlation between iron and lipid dysmetabolism in mice lacking ceruloplasmin suggests that the anti-inflammatory function of ceruloplasmin in adipose tissue may be more important to iron homeostasis than iron homeostasis. Additionally, these findings suggest that ceruloplasmin replacement therapy might be useful throughout the body.