Siemienowicz Katarzyna J, Coukan Flavien, Franks Stephen, Rae Mick T, Duncan W Colin
MRC Centre for Reproductive Health, The University of Edinburgh, Edinburgh, EH16 4TJ, UK; School of Applied Sciences, Edinburgh Napier University, Edinburgh, EH11 4BN, UK.
School of Applied Sciences, Edinburgh Napier University, Edinburgh, EH11 4BN, UK.
Mol Cell Endocrinol. 2021 Jan 1;519:111042. doi: 10.1016/j.mce.2020.111042. Epub 2020 Oct 1.
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。我们推测青春期异常的脂肪生成以及下游代谢紊乱促成了成年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，而非PA绵羊的胎儿期或生命早期，皮下脂肪组织（SAT）中的脂肪生成减少，同时瘦素、脂联素减少，FFA增加。成年后，PA绵羊的SAT中出现脂肪细胞肥大，同时炎症标志物表达增加、FFA升高以及与内脏脂肪组织中脂肪积累相关的基因表达增加。本研究为从青春期到成年期的PCOS病理生理学提供了更好的理解，并确定了早期临床干预以使脂肪生成正常化并改善代谢表型的机会。
