Aberrant subcutaneous adipogenesis precedes adult metabolic dysfunction in an ovine model of polycystic ovary syndrome (PCOS)

Siemienowicz, Katarzyna J.; Coukan, Flavien; Franks, Stephen; Rae, Mick T.; Colin Duncan, W.

Abstract

Polycystic ovary syndrome (PCOS) affects over 10% of women. Insulin resistance, elevated free fatty acids (FFAs) and increased adiposity are key factors contributing to metabolic dysfunction in PCOS. We hypothesised that aberrant adipogenesis during adolescence, and downstream metabolic perturbations, contributes to the metabolic phenotype of adult PCOS. We used prenatally androgenized (PA) sheep as a clinically realistic model of PCOS. During adolescence, but not during fetal or early life of PA sheep, adipogenesis was decreased in subcutaneous adipose tissue (SAT) accompanied by decreased leptin, adiponectin, and increased FFAs. In adulthood, PA sheep developed adipocyte hypertrophy in SAT paralleled by increased expression of inflammatory markers, elevated FFAs and increased expression of genes linked to fat accumulation in visceral adipose tissue. This study provides better understanding into the pathophysiology of PCOS from puberty to adulthood and identifies opportunity for early clinical intervention to normalise adipogenesis and ameliorate the metabolic phenotype.

Citation

Siemienowicz, K. J., Coukan, F., Franks, S., Rae, M. T., & Colin Duncan, W. (2021). Aberrant subcutaneous adipogenesis precedes adult metabolic dysfunction in an ovine model of polycystic ovary syndrome (PCOS). Molecular and Cellular Endocrinology, 519, Article 111042. https://doi.org/10.1016/j.mce.2020.111042

• Journal Article Type: Article
• Acceptance Date: Sep 28, 2020
• Online Publication Date: Oct 1, 2020
• Publication Date: 2021-01
• Deposit Date: Oct 1, 2020
• Publicly Available Date: Oct 2, 2021
• Print ISSN: 0303-7207
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 519
• Article Number: 111042
• DOI: https://doi.org/10.1016/j.mce.2020.111042
• Keywords: Polycystic ovary syndrome, Adipose tissue, Adipogenesis, Prenatal programming, Metabolism, Androgens
• Public URL: http://researchrepository.napier.ac.uk/Output/2689976