Gao ShanHu, Long Fei, Jiang Zheng, Shi Jun, Ma DongXue, Yang Yang, Bai Jin, Han Ting-Li
State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, China.
Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Shatin, China.
Front Physiol. 2022 Sep 20;13:990987. doi: 10.3389/fphys.2022.990987. eCollection 2022.
Polycystic ovary syndrome (PCOS) is a common age-related endocrinopathy that promotes the metabolic disorder of the liver. Growing evidence suggests that the pathophysiology of this disorder is closely associated with the interaction between the liver and its exosome. However, the underlying mechanism of the interactions remains unclear. In this study, we aimed to investigate the metabolite profiles of liver tissues and hepatic exosomes between normal ( = 11) and PCOS ( = 13) mice of young- and middle-age using gas chromatograph-mass spectrometry (GC-MS) based metabolomics analysis. Within the 145 identified metabolites, 7 and 48 metabolites were statistically different ( < 0.05, < 0.05) in the liver tissue and exosomes, respectively, between PCOS and normal groups. The greater disparity in exosome indicated its potential to reflect the metabolic status of the liver. Based on hepatic exosome metabolome, the downregulations of glycolysis and TCA cycle were related to hepatic pathophysiology of PCOS independent of age. Fatty acids were the preferred substrates in young-age-PCOS liver while amino acids were the main substrates in middle-age-PCOS liver for the processes of gluconeogenesis. Overall, this study enables us to better understand the metabolic status of the PCOS liver at different ages, and exosome metabolomics shows its potential to gain the metabolic insights of parental cell or source organ.
多囊卵巢综合征（PCOS）是一种常见的与年龄相关的内分泌病，会引发肝脏的代谢紊乱。越来越多的证据表明，这种疾病的病理生理学与肝脏及其外泌体之间的相互作用密切相关。然而，这种相互作用的潜在机制仍不清楚。在本研究中，我们旨在使用基于气相色谱-质谱联用（GC-MS）的代谢组学分析，调查正常（n = 11）和PCOS（n = 13）的青年和中年小鼠肝脏组织和肝外泌体的代谢物谱。在145种已鉴定的代谢物中，PCOS组和正常组之间，肝脏组织和外泌体中分别有7种和48种代谢物存在统计学差异（P < 0.05，FDR < 0.05）。外泌体中更大的差异表明其有潜力反映肝脏的代谢状态。基于肝外泌体代谢组，糖酵解和三羧酸循环的下调与PCOS的肝脏病理生理学相关，且与年龄无关。脂肪酸是青年PCOS肝脏糖异生过程中的首选底物，而氨基酸是中年PCOS肝脏糖异生过程中的主要底物。总体而言，本研究使我们能够更好地了解不同年龄PCOS肝脏的代谢状态，外泌体代谢组学显示出其获取亲本细胞或源器官代谢见解的潜力。
