Weight gain and loss increase adipose dendritic cell proportions and antigen presentation 2257389

Abstract

Abstract Introduction Weight cycling is a growing health concern that has been shown to worsen risk of diabetes beyond that of obesity. Dendritic cells (DCs) play a causal role in obesity-associated inflammation and metabolic disease. However, their role in weight cycling-associated disease is not known. Previous data from single-cell sequencing showed some subsets of DCs and genes associated with antigen presentation increase with weight gain and weight loss. Our central hypothesis is that changes to DC antigen presentation may affect diabetes risk with weight regain. Here, we aimed to confirm our sequencing data and test the hypothesis that antigen presentation increases in DCs with weight cycling. Methods Mice were put on nutrient-matched low-fat or high-fat diets to elicit lean, obese, weight loss, and weight-cycled groups. Adipose tissue immune cells were isolated for flow cytometry. Results Adipose tissue conventional DC1, H2-Db, H2-IA/IE, and CD40 did not increase across groups. Monocyte-derived DC and type 2 conventional DC increased upon weight gain and weight loss. Similarly, protein expression of MHC Ib (Qa2 and CD1d) and CD86 molecules increased upon weight gain and weight loss. Conclusion The result points towards a potential role for non-classical antigen presentation and potential crosstalk to CD8, NKT, and NK cells. Interestingly, previous single-cell sequencing data also suggests that these populations increase similarly with weight gain and weight loss. Future studies will understand the functional role of DCs in weight cycling Funding Source Texas Chapter of the American College of Sports Medicine (TACSM) Topic Categories Classical and Non-Classical Antigen Presenting Cells (APC)