Endocrine Abstracts

Central obesity and increased visceral adipose tissue (VAT) are key factors contributing to metabolic dysfunction in PCOS. We therefore hypothesized that there would be alterations in the morphology and function of adipocytes from visceral fat depots. The female offspring of pregnant sheep treated biweekly with either 100 mg of testosterone propionate (TP) or vehicle control (C) from day 62–102 of gestation develop a clinically realistic PCOS-like condition. They develop hyperinsulinaemia and early fatty liver changes in adolescence followed by increases in body weight and adiposity in adulthood.

We examined adipose tissue development and function in PCOS-like sheep during fetal life (D112: C=9; TP=4), before puberty (11 weeks: C=8; TP=8), at adolescence (11 months: C=5; TP=9) and in adulthood (30 months: C=11; TP=4).

Impaired adipocyte differentiation was not observed in fetal or early life. There were no differences in the expression of the master adipogenic regulators (PPARG, CEBPA, CEBPB) or markers of fully differentiated adipocytes (LEP, ADIPOQ, PLIN1, LPL) in VAT of adolescent sheep, however all were downregulated in the subcutaneous adipose tissue (SAT) (P<0.05–0.01). This altered adipogenesis in SAT was accompanied by increased expression of TNF and HIF1A (P<0.05) and correlated with increased fasting Free Fatty Acids (FFA) (r=0.55; P<0.05). As adults PCOS-like sheep had decreased total adipocyte numbers (P<0.05) and increased mean adipocyte size in SAT (P<0.05) but not in VAT. SAT hypertrophy was associated with increased expression of CCL2, TNF and IL6 (P<0.05–0.01) and correlated with increased fasting FFA (r=0.61; P<0.05).

Altered adipogenesis in SAT, rather than VAT, of PCOS-like sheep correlates with onset of puberty and hyperinsulinaemia. Impaired preadipocyte differentiation in SAT in adolescents results in hypertrophy and inflammation of adult SAT. This consequently lowers capacity of SAT to safely store fat and potentially explains metabolic perturbations observed in PCOS-like female sheep.