Department of Integrative Medicine and Neurobiology, State Key Lab of Medical Neurobiology, Institute of Integrative Medicine of Fudan University, Institute of Brain Science, School of Basic Medical Sciences, Fudan University, 200032, Shanghai, China; Department of Obstetrics and Gynecology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 201203, Shanghai, China; Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, 40530, Gothenburg, Sweden.
Department of Integrative Medicine and Neurobiology, State Key Lab of Medical Neurobiology, Institute of Integrative Medicine of Fudan University, Institute of Brain Science, School of Basic Medical Sciences, Fudan University, 200032, Shanghai, China.
J Steroid Biochem Mol Biol. 2021 Apr;208:105829. doi: 10.1016/j.jsbmb.2021.105829. Epub 2021 Jan 26.
Women with polycystic ovary syndrome (PCOS) are at higher risk for metabolic disorders compared to healthy women, and about 51 % of women with PCOS suffer from non-alcoholic fatty liver disease (NAFLD). Investigation into the pathological mechanism behind this association will provide insights for the prevention and treatment of this complication.
Dihydrotestosterone (DHT), a nonaromatic androgen, was used to mimic the pathological conditions of hyperandrogenism and insulin resistance. Hematoxylin and eosin staining, Oil Red O staining, immunofluorescent staining, Western blots, and qRT-PCR were used to verify the hepatic steatosis and inflammation, and the latter two methods were also used for energy and mitochondrion-related assays. ELISA was used to measure the level of reactive oxygen species.
Twelve weeks of DHT exposure led to obesity and insulin resistance as well as hepatic steatosis, lipid deposition, and different degrees of inflammation. The expression of molecules involved in respiratory chain and aerobic respiration processes, such as electron transfer complex II, pyruvate dehydrogenase, and succinate dehydrogenase complex subunit A, was inhibited. In addition, molecules associated with apoptosis and autophagy were also abnormally expressed, such as increased Bak mRNA, an increased activated caspase-3 to caspase-3 ratio, and increased Atg12 protein expression. All of these changes are associated with the mitochondria and lead to lipid deposition and inflammation in the liver.
Long-term androgen excess contributes to insulin resistance and hepatic steatosis by affecting mitochondrial function and causing an imbalance in apoptosis and autophagy, thus suggesting the pathogenesis of NAFLD in women with PCOS.
与健康女性相比，患有多囊卵巢综合征（PCOS）的女性发生代谢紊乱的风险更高，约 51%的 PCOS 患者患有非酒精性脂肪性肝病（NAFLD）。研究这种关联的病理机制将为预防和治疗这种并发症提供思路。
二氢睾酮（DHT），一种非芳香族雄激素，用于模拟高雄激素和胰岛素抵抗的病理条件。苏木精和伊红染色、油红 O 染色、免疫荧光染色、Western blot 和 qRT-PCR 用于验证肝脂肪变性和炎症，后两种方法也用于能量和线粒体相关检测。ELISA 用于测量活性氧的水平。
12 周的 DHT 暴露导致肥胖和胰岛素抵抗，以及肝脂肪变性、脂质沉积和不同程度的炎症。涉及呼吸链和需氧呼吸过程的分子的表达受到抑制，如电子传递复合物 II、丙酮酸脱氢酶和琥珀酸脱氢酶复合物亚基 A。此外，与细胞凋亡和自噬相关的分子也异常表达，如 Bak mRNA 增加、激活的 caspase-3 与 caspase-3 的比值增加和 Atg12 蛋白表达增加。所有这些变化都与线粒体有关，导致肝脏的脂质沉积和炎症。
长期雄激素过多通过影响线粒体功能和导致细胞凋亡和自噬失衡，导致胰岛素抵抗和肝脂肪变性，从而提示 PCOS 女性的 NAFLD 发病机制。
