Endocrine Abstracts

Obesity is linked to an increased risk of 13 different cancers in adulthood. The environment supporting this increased risk is multi-factorial but includes metabolic dysregulation, chronic inflammation and the loss of the anti-tumour activity of cells such natural killer (NK) cells. We present data which shows that this pro-cancer environment starts early in children with obesity, potentially increasing their risk of future disease. We investigated a cohort of 50 children with obesity and 50 healthy peers, and report significant metabolic dysregulation (e.g. insulin resistance), elevated inflammatory mediators (e.g. TNFa) and defective NK cell functionality (e.g. cytotoxicity). We provide evidence that altered nutrient availability in obesity underpins these alterations. Armed with this knowledge we set about investigating if GLP-1 analogue therapy could reverse the pro-cancer environment observed in obesity. We present data which shows that GLP-1 therapy significant reduces inflammation in cohorts of children with obesity (in vitro) and adults with obesity (in vivo). We show for the first time that GLP-1 analogue therapy rescues NK cell effector function in adults with obesity, independent of weight loss. We also provide evidence that GLP-1 can improve the functionality of NK cells from children with obesity in vitro. Collectively we present data which supports the presence of an obesity related pro-tumour environment in children with obesity, which we postulate may increase future risk of disease. We also show for the first time that GLP-1 therapy can attenuate this pro-tumour environment, supporting its use early in the life course of obesity.