Edinburgh Napier University

  Women with polycystic ovary syndrome (PCOS) are more likely to be obese and have difficulty in losing weight. They demonstrate an obesity-independent deficit in adaptive energy expenditure. We used a clinically-realistic preclinical model to investigate the molecular basis for the reduced post-prandial thermogenesis (PPT) and develop a therapeutic strategy to normalise this deficit. Sheep exposed to increased androgens before birth develop the clinical features of PCOS. In adulthood they develop obesity and demonstrate an obesity-independent reduction in PPT. This is associated with reduced
adipose tissue uncoupling protein expression and adipose tissue noradrenaline concentrations. These sheep are insulin-resistant with reduced insulin signalling in the brain. Increasing brain insulin concentrations using intranasal insulin administration increased PPT in PCOS-sheep without any effects on blood glucose concentrations. Intranasal insulin administration with food is a potential novel strategy to improve adaptive energy expenditure and normalise the responses to weight loss strategies in women with PCOS.