Endocrine Abstracts

Women with Polycystic Ovary Syndrome (PCOS) are at increased risk of developing insulin resistance, obesity and dyslipidemia, however obesity per se does not explain the higher incidence of insulin resistance in PCOS women when compared to the general population. Altered adipose tissue morphology and function may be a central factor contributing to metabolic disturbances in PCOS. Using a clinically realistic ovine model of PCOS we reported hyperinsulinaemia and early fatty liver changes, with no difference in body weight and adiposity, in adolescence.

Here we aimed to examine adipose tissue development during transition from adolescence to adulthood. Pregnant Scottish Greyface ewes were treated biweekly with either 100 mg of testosterone propionate (TP) or vehicle control (C) from day 62–102 of gestation. Two cohorts of animals, adolescent 11 months old (C=5; TP=9) and adult 30 months old (C=11; TP=4), were investigated.

PPARG expression, the master regulator of adipogenesis, was downregulated (P<0.01) in subcutaneous adipose tissue (SAT) but not visceral adipose tissue (VAT) of adolescent TP-treated animals. This suggests decreased differentiation of preadipocytes into mature adipocytes. As adults, TP-exposed animals had increased body weight (P<0.05), increased fasting insulin concentration (P<0.05), decreased fasting glucose to insulin ratio (P<0.05) and increased fasting non-esterified fatty acid concentration (P<0.05). Histological analysis revealed that TP-exposed animals have decreased total number of adipocytes (P<0.05) and increased mean adipocyte size in SAT (P<0.05) but not in VAT.

In summary, impaired preadipocyte differentiation into adipocytes in SAT in adolescent prenatally androgenized female sheep results in decreased numbers of adipocytes and increased mean size of adipocytes in adult SAT. This consequently lowers capacity of SAT to safely store fat and potentially explains presence of fatty liver and hyperinsulinaemia in TP-treated animals, due to increased release of FFA into circulation, subsequent lipotoxicity and decreased insulin sensitivity in peripheral tissue.