Mendelian randomization and multi-omics approach analyses reveal impaired glucose metabolism and oxidative phosphorylation in visceral adipose tissue of women with polycystic ovary syndrome

doi:10.1093/humrep/deae244

科研成果详情

题名	Mendelian randomization and multi-omics approach analyses reveal impaired glucose metabolism and oxidative phosphorylation in visceral adipose tissue of women with polycystic ovary syndrome
作者	Yurong Zhang 1,2; Xintong Jiang 3; Xueling Song 1,2; Jiajia Zhang 1,2; Weian Mao4; Wei Chen 5; Shuai Yuan 6; Yijie Chen4; Liangshan Mu 5; Yue Zhao 1,2,7
发表日期	2024-10-24
发表期刊	Human reproduction (Oxford, England) 影响因子和分区
语种	英语
原始文献类型	Journal Article
关键词	Mendelian randomization glucose metabolism oxidative phosphorylation polycystic ovary syndrome visceral adipose tissue
摘要	What is the significance of visceral adipose tissue (VAT) in the pathogenesis of polycystic ovary syndrome (PCOS) and its impact on the regulation of metabolic disorders in women with PCOS?, We revealed a potentially causal relationship between increased genetically predicted VAT and PCOS-related traits, and found that VAT exhibited impaired glucose metabolism and mitochondrial oxidative phosphorylation (OXPHOS) in women with PCOS., PCOS is a common reproductive endocrine disorder accompanied by many metabolic abnormalities. Adipose tissue is a metabolically active endocrine organ that regulates multiple physiological processes, and VAT has a much stronger association with metabolism than subcutaneous adipose tissue does., Mendelian randomization (MR) analysis was used to investigate the potential causal association between genetically predicted VAT and the risk of PCOS. Data for MR analysis were extracted from European population cohorts. VAT samples from sixteen PCOS patients and eight control women who underwent laparoscopic surgery were collected for proteomics and targeted metabolomics analyses., PCOS was diagnosed according to the 2003 Rotterdam Criteria. The control subjects were women who underwent laparoscopic investigation for infertility or benign indications. Proteomics was performed by TMT labeling and liquid chromatography-tandem mass spectrometry analysis, and targeted metabolomics was performed by ultra-performance liquid chromatography-tandem mass spectrometry analysis. The key differentially expressed proteins (DEPs) were validated by immunoblotting., MR analysis revealed a potentially causal relationship between increased genetically predicted VAT and PCOS, as well as related traits, such as polycystic ovaries, total testosterone, bioavailable testosterone, and anti-Müllerian hormone, while a negative relationship was found with sex hormone-binding globulin. Enrichment pathway analysis of DEPs indicated the inhibition of glycolysis and activation of mitochondrial OXPHOS in the VAT of PCOS patients. MR analysis revealed that key DEPs involved in glycolysis and OXPHOS were significantly linked to PCOS and its related traits. Dot blot assay confirmed a significant decrease in glycolysis enzymes PKM2 and HK1, and an increase in mitochondrial Complex I and III subunits, NDUFS3 and UQCR10. Moreover, metabolomics analysis confirmed down-regulated metabolites of energy metabolic pathways, in particular glycolysis. Further analysis of PCOS and control subjects of normal weight revealed that dysregulation of glucose metabolism and OXPHOS in VAT of women with PCOS was independent of obesity., The mass spectrometry proteomics data have been deposited to the iProX database (http://www.iprox.org) with the iProX accession: IPX0005774001., There may be an overlap in some exposure and outcome data, which might affect the results in the MR analysis., The changes in protein expression of key enzymes affect their activities and disrupt the energy metabolic homeostasis in VAT, providing valuable insight for identifying potential intervention targets of PCOS., This work was supported by the National Key Research and Development Project of China (2021YFC2700402), the National Natural Science Foundation of China (82071608, 82271665), the Key Clinical Projects of Peking University Third Hospital (BYSY2022043), and the CAMS Innovation Fund for Medical Sciences (2019-I2M-5-001). All authors report no conflict of interest., N/A.
资助项目	National Key Research and Development Project of China[2021YFC2700402];National Natural Science Foundation of China[82071608];Key Clinical Projects of Peking University Third Hospital[BYSY2022043];CAMS Innovation Fund for Medical Sciences[2019-I2M-5-001]
ISSN	0268-1161
EISSN	1460-2350
DOI	10.1093/humrep/deae244
收录类别	PUBMED
URL	查看原文
PubMed ID	39448886
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/221003
专题	药学院（分析测试中心）附属第二医院第二临床医学院、附属第二医院、育英儿童医院附属第二医院_妇产科
作者单位	1.State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.; 2.National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), National Clinical Key Specialty Construction Program, Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China.; 3.The First School of Medicine, Wenzhou Medical University, Wenzhou, China.; 4.Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.; 5.Reproductive Medicine Center, Zhongshan Hospital, Fudan University, Shanghai, China.; 6.Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.; 7.Research Units of Comprehensive Diagnosis and Treatment of Oocyte Maturation Arrest, Chinese Academy of Medical Sciences, Beijing, China.
推荐引用方式 GB/T 7714	Yurong Zhang,Xintong Jiang,Xueling Song,et al. Mendelian randomization and multi-omics approach analyses reveal impaired glucose metabolism and oxidative phosphorylation in visceral adipose tissue of women with polycystic ovary syndrome[J]. Human reproduction (Oxford, England),2024.
APA	Yurong Zhang., Xintong Jiang., Xueling Song., Jiajia Zhang., Weian Mao., ... & Yue Zhao. (2024). Mendelian randomization and multi-omics approach analyses reveal impaired glucose metabolism and oxidative phosphorylation in visceral adipose tissue of women with polycystic ovary syndrome. Human reproduction (Oxford, England).
MLA	Yurong Zhang,et al."Mendelian randomization and multi-omics approach analyses reveal impaired glucose metabolism and oxidative phosphorylation in visceral adipose tissue of women with polycystic ovary syndrome".Human reproduction (Oxford, England) (2024).