Obesity is a global problem and represents a significant health and economic burden. Our research concentrates on understanding the hormones and molecular pathways that drive obesity.
Recently a new category of brown fat-like cells, so-called “beige” cells residing within subcutaneous white fat, has been identified. These cells burn fuels to generate heat and therefore may reduce obesity by burning off rather than storing excess fuels. Cells of the immune system – macrophages, innate lymphoid cells and recently eosinophils – appear to be essential to the “browning” of white fat cells.
While studying mice with a deletion in the gene encoding the transcription factor Kruppel-like Factor 3 (KLF3) we made a number of serendipitous discoveries. These mice are lean, even when fed a high fat diet and have higher numbers of eosinophils within their fat. Interestingly, these mice show evidence of an increased capacity for thermogenesis even when housed at room temperature.
We have performed genome-wide expression analyses on eosinophils isolated from white adipose tissue and saw expression of a number of genes that encode for known browning secreted proteins. Our data suggest that eosinophils may contribute to beige fat biogenesis by secreting these factors. The eosinophils from KLF3 knockout mice, where we see enhanced browning, expressed higher levels of these secreted proteins. Interestingly, we also detected expression of a number of novel secreted proteins in adipose tissue-derived eosinophils. We are now testing whether these novel secreted proteins are able to induce browning in cell culture and in vivo models.
Our data suggest that adipose tissue-resident eosinophils secrete a number of factors to drive the browning of adipocytes. This emphasises the importance of eosinophils in the browning process. Our study of these factors may provide a platform for the development of new therapeutic agents to drive browning and combat obesity.