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

Katarzyna J. Siemienowicz, Flavien Coukan, Stephen Franks, Napier Rae, W. Colin Duncan

Research output: Contribution to journalArticlepeer-review

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 androgenised (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.
Original languageEnglish
Article number111042
JournalMolecular and Cellular Endocrinology
Volume519
Issue number1
Early online date1 Oct 2020
DOIs
Publication statusPublished - 1 Jan 2021

Keywords

  • Polycystic ovary syndrome
  • Adipose tissue
  • Adipogenesis
  • Prenatal programming
  • Metabolism
  • Androgens

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