Fat, or adipose tissue, comes in two main forms – white, where energy is stored, and brown, where energy is burned in a process called thermogenesis to produce heat. In the last decade it has been discovered that white fat, where energy is stored in the form of lipid droplets, can be naturally converted to become like brown fat, where energy is burned. This phenomenon is called ‘browning’ and results in the development of ‘beige’ fat. This is a key area of current research into treating metabolic diseases because the induction of beige fat results in weight loss and improved metabolic parameters. Our research is focused on how this transition is regulated at the transcriptional level, with a particular interest in the contribution of resident immune cells.
While studying a mouse model lacking the transcriptional repressor Krüppel-like factor 3 (KLF3), we noticed that these mice remain lean and glucose tolerant on a Western diet, with greatly reduced fat mass. Upon closer examination, we determined that the white fat of KLF3 knockout mice appeared ‘browner’ due to increased mitochondria, had more resident eosinophils and showed high levels of thermogenic gene expression – all distinct hallmarks of beige fat. We isolated eosinophils, where KLF3 is highly expressed, from the fat of wildtype and KLF3 knockout mice and found that cells lacking KLF3 expressed important secreted factors implicated in beige fat development. These results point towards a role for KLF3 in the regulation of important eosinophil-derived factors that drive the ‘browning’ of fat, which we have termed ‘eosinokines’.
Initial studies have shown that the administration of certain eosinokines can improve whole body energy expenditure and metabolism, alleviating metabolic disorders. Further understanding of how these eosinokines are regulated will help us to better tailor for them therapeutic delivery.