Siemienowicz Katarzyna J, Furmanska Klaudia, Filis Panagiotis, Talia Chiara, Thomas Jennifer, Fowler Paul A, 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 Apr 5;525:111196. doi: 10.1016/j.mce.2021.111196. Epub 2021 Feb 6.
Polycystic ovary syndrome (PCOS), affecting over 10% of women, is associated with insulin resistance, obesity, dyslipidaemia, fatty liver and adipose tissue dysfunction. Its pathogenesis is poorly understood and consequently treatment remains suboptimal. Prenatally androgenized (PA) sheep, a clinically realistic model of PCOS, recapitulate the metabolic problems associated with PCOS. Fibroblast Growth Factor 21 (FGF21) is a metabolic hormone regulating lipid homeostasis, insulin sensitivity, energy balance and adipose tissue function. We therefore investigated the role of FGF21 in the metabolic phenotype of PA sheep. In adolescence PA sheep had decreased hepatic expression and circulating concentrations of FGF21. Adolescent PA sheep show decreased FGF21 signalling in subcutaneous adipose tissue, increased hepatic triglyceride content, trend towards reduced fatty acid oxidation capacity and increased hepatic expression of inflammatory markers. These data parallel studies on FGF21 deficiency, suggesting that FGF21 therapy during adolescence may represent a treatment strategy to mitigate metabolic problems associated with PCOS.
多囊卵巢综合征（PCOS）影响着超过10%的女性，与胰岛素抵抗、肥胖、血脂异常、脂肪肝和脂肪组织功能障碍有关。其发病机制尚不清楚，因此治疗效果仍不理想。产前雄激素化（PA）绵羊是一种临床现实的PCOS模型，概括了与PCOS相关的代谢问题。成纤维细胞生长因子21（FGF21）是一种调节脂质稳态、胰岛素敏感性、能量平衡和脂肪组织功能的代谢激素。因此，我们研究了FGF21在PA绵羊代谢表型中的作用。在青春期，PA绵羊肝脏中FGF21的表达和循环浓度降低。青春期PA绵羊皮下脂肪组织中FGF21信号减弱，肝脏甘油三酯含量增加，脂肪酸氧化能力有降低趋势，肝脏炎症标志物表达增加。这些数据与关于FGF21缺乏的研究结果相似，表明青春期进行FGF21治疗可能是减轻与PCOS相关代谢问题的一种治疗策略。
