Abstract: Obesity has reached epidemic proportions globally. At least 2.8 million people die each year as a result of being overweight or obese, the biggest burden being obesity-related diseases. Glucagon like peptide 1 (GLP-1) targeted therapies show the greatest potential for intervention and are approved as weight loss agents. However not all patients respond to GLP-1 therapy. Understanding the mechanisms of bodyweight regulation and their role in GLP-1 responders vs. non-responders is essential to better serve our patients. We have previously shown that invariant natural killer T (iNKT) cells, which resides in adipose tissue, and acts as adipose tissue regulators are required for the full weight loss effect of GLP-1, a licensed weight loss therapy. In the absence of iNKT cells, GLP-1 therapy is 30% less effective at inducing weight loss, due to a loss of FGF-21 and thermogenic reprogramming. In the current project we have extended our findings from murine models into humans investigating the adipose tissue metabolic pathways induced by GLP-1 therapy in patients who display significant weight loss and a subset who fail to lose weight. We have also investigated if two immune cell derived proteins associated with obesity and insulin resistance (soluble CD163 and Galectin-3) could be used to predict responses to intervention (GLP-1 therapy or RYGB). We show that sCD163 but not Gal-3 is elevated in obesity from childhood through to adulthood, and within 1 week of RYGB and 8 weeks of GLP-1 therapy sCD163 levels are significantly reduced. Overall this project sheds light on novel mechanisms of bodyweight regulation and highlights the possible use of sCD163 in mapping the progression of obesity and predicting responders from non-responders to intervention.
20 May 2017 - 23 May 2017