Characterised by a chronic imbalance between energy intake and energy expenditure, obesity is a global health issue. Currently available therapies mainly target one side of the scale – energy intake – and are often limited in efficacy, are invasive, or trigger adverse side effects. The other side of the scale, energy expenditure, is equally critical to the induction of weight loss, yet the pharmacotherapeutic potential of increasing energy expenditure remains relatively unexplored.
Fat-storing white adipocytes contribute to the development of obesity, whereas thermogenic beige adipocytes can be stimulated to expend energy in the form of fat by converting it into heat. Increased thermogenic fat is associated with leanness, improved glucose tolerance, and enhanced insulin sensitivity in both mice and humans. Of interest, adipose tissue-resident eosinophils have been shown to promote metabolic homeostasis and secrete proteins that stimulate energy expenditure in multiple murine studies. Additionally, a recent human study reported that adipose eosinophil numbers decline in people with obesity, which also correlated with decreased HOMA-IR. However, little is understood about whether human adipose eosinophils confer the same metabolic benefits as their murine counterparts.
Therefore, we aim to characterise the functions of human adipose eosinophils in leanness and obesity. To do so, we will obtain subcutaneous adipose tissue samples from consenting participants across a range of BMIs. We will then isolate eosinophils via FACS to examine their transcriptome, via RNA-seq, and their secreted proteome, by performing mass spectrometry on conditioned media obtained from culturing the isolated eosinophils. From these two datasets, we will identify secreted proteins that are highly expressed in lean compared to obese adipose tissue and test their thermogenic potential in vitro and in vivo. These candidate proteins may elucidate novel energy expenditure pathways that lead to the development of new pharmacotherapies for obesity.