Characterizing Effects of ADAM17 Deletion in Chronic Obesity
Abstract
Background
Immune cells such as macrophages and regulatory T cells (Tregs) play important roles in regulating metabolism and inflammation within adipose tissue. Obesity is characterized by dysregulation in these processes.
A Disintegrin And Metalloprotease 17 (ADAM17) is an enzyme responsible for cleaving tumor necrosis factor (TNF), which is an inflammatory protein mediator. The global inhibition of ADAM17 is associated with favorable effects in the context of obesity.
A previous study in the Martin lab investigated outcomes of ADAM17 deletion from macrophages in a 16-week model of diet-induced obesity. The present study is prolonged to 36 weeks as a chronic obesity model.
Methods
We used a mouse model to test the effects of macrophage-specific ADAM17 deletion achieved through the Cre-LoxP system. Wild-type and ADAM17 knockout mice were placed on either a normal chow diet or a high-fat diet (HFD) to induce obesity. Metabolic effects were assessed by body composition and glucose tolerance measurements. After euthanization, perigonadal adipose tissue was collected from each mouse to identify immune cells by their cellular markers using flow cytometry.
Results
Our data did not observe a significant difference in glucose tolerance in the ADAM17 knockout mice compared to their wild-type counterparts for mice fed a high-fat diet. Flow cytometry analysis revealed a lack of ST2+ Tregs in adipose tissue from ADAM17 knockout mice, which were increased in the previous study.
Conclusions
Our data suggest that prolonged diet-induced obesity may override the benefits of ADAM17 elimination on glucose tolerance and immune cell composition in adipose tissue.