Insights into manipulating postprandial energy expenditure to manage weight gain in polycystic ovary syndrome (PCOS)

Siemienowicz, Katarzyna; Rae, Michael T.; Howells, Fiona; Anderson, Chloe; Nicol, Linda M.; Franks, Stephen; Duncan, William C.

Abstract

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.

Citation

Siemienowicz, K., Rae, M. T., Howells, F., Anderson, C., Nicol, L. M., Franks, S., & Duncan, W. C. (2020). Insights into manipulating postprandial energy expenditure to manage weight gain in polycystic ovary syndrome (PCOS). iScience, 23(6), Article 101164. https://doi.org/10.1016/j.isci.2020.101164

• Journal Article Type: Article
• Acceptance Date: May 11, 2020
• Online Publication Date: May 15, 2020
• Publication Date: Jun 26, 2020
• Deposit Date: May 21, 2020
• Journal: iScience
• Electronic ISSN: 2589-0042
• Publisher: Cell Press
• Peer Reviewed: Peer Reviewed
• Volume: 23
• Issue: 6
• Article Number: 101164
• DOI: https://doi.org/10.1016/j.isci.2020.101164
• Public URL: http://researchrepository.napier.ac.uk/Output/2664351