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.

多囊卵巢综合征 (PCOS) 影响超过 10% 的女性。胰岛素抵抗、游离脂肪酸 (FFA) 升高和肥胖增加是导致 PCOS 代谢功能障碍的关键因素。我们假设青春期异常的脂肪生成和下游代谢扰动导致成人 PCOS 的代谢表型。我们使用产前雄激素化 (PA) 绵羊作为 PCOS 的临床现实模型。在青春期，而不是在 PA 绵羊的胎儿或生命早期，皮下脂肪组织 (SAT) 的脂肪生成减少，伴随着瘦素、脂联素减少和游离脂肪酸增加。在成年期，PA 绵羊在 SAT 中出现脂肪细胞肥大，同时炎症标志物的表达增加，升高的游离脂肪酸和增加与内脏脂肪组织中脂肪积累相关的基因表达。这项研究提供了对 PCOS 从青春期到成年期的病理生理学的更好理解，并确定了早期临床干预以使脂肪生成正常化和改善代谢表型的机会。