Eosinophils in thermogenic beige fat

About the talk: Beige adipocytes within white adipose tissue burn fuels to generate heat and therefore may reduce obesity by burning rather than storing excess fuels. Cells of the immune system – including eosinophils – appear to be essential in the beiging of white adipocytes.Knockout mice for the transcriptional repressor Kruppel-like Factor 3 (KLF3) are lean and are protected from diet-induced obesity. Interestingly, these mice show evidence of an increased capacity for thermogenesis. We performed a bone marrow transplantation study and were able to confer the lean beige phenotype on wild type mice. This suggested that KLF3 deficiency in cells of the haematopoietic lineage may drive leanness in this mouse model.  We interrogated different types of adipose-resident immune cells and discovered that there are three times as many eosinophils in KLF3-deficient adipose tissue.We performed genome-wide expression analyses on eosinophils isolated from white adipose tissue and uncovered widespread gene expression differences within these primary cells in the absence of KLF3. Interestingly, we saw expression of a number of genes that encode secreted proteins known for their role in beiging. The eosinophils from KLF3 knockout mice, where we saw enhanced beiging, expressed higher levels of these secreted proteins. Our data suggest that KLF3 is a master regulator of gene expression programs in adipose tissue-resident eosinophils and that adipose tissue-resident eosinophils secrete important factors that drive beiging of adipose tissue. We are now testing whether novel secreted proteins we have identified are able to induce beiging and energy expenditure and may present novel targets for obesity. We are also exploring how the gene expression programs in adipose tissue-resident eosinophils differ from eosinophils residing in other tissues and the transcription factors that drive this niche specification.