Obesity is a global epidemic that is causing significant socioeconomic and health problems. An excess of white fat typifies obesity, but newly described beige fat can burn calories through its thermogenic activity, leading to weight loss and metabolic improvements. There is a network of anti-inflammatory type 2 immune cells residing in healthy adipose tissue, including macrophages, eosinophils, innate lymphoid cells, and T lymphocyte subsets, which drives adipose beiging and thermogenesis. Thus, studying these cells may enable identification of new molecular targets for treating obesity. We have recently shown that the lean, obesity-resistant KLF3-knockout mouse model has increased adipose tissue beiging, as well as elevated numbers of adipose eosinophils. We found that the transcriptional repressor KLF3 is an important regulator of adipose eosinophil gene expression and function.
Here, we aim to further investigate gene regulation by KLF3 in other adipose-resident immune cells that contribute to adipose tissue beiging. Regulatory T cells, invariant natural killer T cells and type 2 innate lymphoid cells were simultaneously isolated from subcutaneous adipose tissue of WT and KLF3 knockout mice for RNA-seq. Using in silico prediction coupled with experimental validation, we are identifying novel secreted molecules produced by these immune cells that act on beige adipocytes to stimulate thermogenesis. We hypothesise that in the absence of KLF3, genes encoding secreted factors that regulate beiging are differentially expressed, in line with the enhanced beige fat phenotype in mice lacking KLF3. This work will contribute to a growing understanding of the immune regulation of adipose metabolism, supporting the development of targeted therapeutics for activating energy expenditure via beiging.