While existing obesity therapeutics target energy intake, novel approaches that instead aim to increase energy expenditure hold significant therapeutic promise. Adipose tissue contains both energy storing white adipocytes, which contribute to the development of obesity, and thermogenic beige adipocyte, which can burn energy as heat. Activation of these thermogenic beige adipocytes has been shown to have beneficial metabolic effects in both mice and humans, including improved glucose tolerance, enhanced insulin sensitivity and leanness. Identifying endogenous mechanisms that drive beige adipocyte activation is critical to realising the therapeutic potential of this tissue in treating obesity.
Eosinophils residing in adipose tissue can promote beige adipocyte activation through the secretion of pro-beiging proteins, making these immune cells a promising therapeutic target for stimulating thermogenesis and increasing energy expenditure. However, progress in this area is limited by the lack of suitable in vitro models of adipose eosinophils. Primary adipose eosinophils are difficult to isolate, low in abundance and short lived in culture, while existing eosinophil cell lines such as EoL-1 cells are derived from human peripheral blood and may not recapitulate an adipose-specific phenotype.
To address this gap, we are developing immortalised eosinophil cell lines derived from mouse and human adipose tissue. Primary eosinophils will be isolated and transduced with viral vectors to deliver a range of immortalising transgenes. Detailed downstream characterisation will be performed to select lines that best model adipose eosinophils. These adipose-derived eosinophil cell lines will enable the identification of novel eosinophil secreted proteins that promote beige activation and energy expenditure. By uncovering new molecular drivers of adipose tissue thermogenesis, we aim to identify therapeutic targets with high translational potential for the treatment of obesity.