Pubertal FGF21 deficit is central in the metabolic pathophysiology of an ovine model of polycystic ovary syndrome

Siemienowicz, Katarzyna J.; Furmanska, Klaudia; Filis, Panagiotis; Talia, Chiara; Thomas, Jennifer; Fowler, Paul A.; Rae, Mick T.; Colin Duncan, W.

Abstract

Polycystic ovary syndrome (PCOS), affecting over 10% of women, is associated with insulin resistance, obesity, dyslipidaemia, fatty liver and adipose tissue dysfunction. Its pathogenesis is poorly understood and consequently treatment remains suboptimal. Prenatally androgenized (PA) sheep, a clinically realistic model of PCOS, recapitulate the metabolic problems associated with PCOS. Fibroblast Growth Factor 21 (FGF21) is a metabolic hormone regulating lipid homeostasis, insulin sensitivity, energy balance and adipose tissue function. We therefore investigated the role of FGF21 in the metabolic phenotype of PA sheep. In adolescence PA sheep had decreased hepatic expression and circulating concentrations of FGF21. Adolescent PA sheep show decreased FGF21 signalling in subcutaneous adipose tissue, increased hepatic triglyceride content, trend towards reduced fatty acid oxidation capacity and increased hepatic expression of inflammatory markers. These data parallel studies on FGF21 deficiency, suggesting that FGF21 therapy during adolescence may represent a treatment strategy to mitigate metabolic problems associated with PCOS.

Citation

Siemienowicz, K. J., Furmanska, K., Filis, P., Talia, C., Thomas, J., Fowler, P. A., Rae, M. T., & Colin Duncan, W. (2021). Pubertal FGF21 deficit is central in the metabolic pathophysiology of an ovine model of polycystic ovary syndrome. Molecular and Cellular Endocrinology, 525, Article 111196. https://doi.org/10.1016/j.mce.2021.111196

• Journal Article Type: Article
• Acceptance Date: Feb 1, 2021
• Online Publication Date: Feb 6, 2021
• Publication Date: 2021-04
• Deposit Date: Feb 4, 2021
• Publicly Available Date: Feb 7, 2022
• Journal: Molecular and Cellular Endocrinology
• Print ISSN: 0303-7207
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 525
• Article Number: 111196
• DOI: https://doi.org/10.1016/j.mce.2021.111196
• Keywords: polycystic ovary syndrome, Fibroblast Growth Factor 21 (FGF21), metabolism, prenatal programming, androgens
• Public URL: http://researchrepository.napier.ac.uk/Output/2725588