Nervonic acid triggered ovarian inflammation by inducing mitochondrial oxidative stress to activate NLRP3/ IL-1β pathway

作者：Xiangzhou Zeng, Xiangzhou Zeng, Xinyin Fan, Haitao Yu, Shuang Cai, Liangrui Zhou, Huanwen Wu, Zhiwen Zhang, Quan Shuang, Siyu Li, Xinyu Wang, Bangxin Xue, Lu Liu, Shiyan Qiao, Xiangfang Zeng, Xiangfang Zeng · 发表于：Journal of Advanced Research · 年份：2024 · DOI：10.1016/j.jare.2024.08.028 · 被引用次数：17 · 研究领域：Fatty Acid Research and Health、Cholesterol and Lipid Metabolism、Inflammasome and immune disorders

INTRODUCTION: Metabolic syndrome is a serious public health concern across the globe. However, the typical metabolites and mechanisms underlying the decreased fertility related to metabolic syndrome is still elusive. OBJECTIVES: The aim of the present study was to explore the typical metabolites and mechanisms underlying the decreased fertility related with metabolic syndrome. METHODS: Utilizing metabolomics, a comparative analysis was conducted on fatty acid compositions in various tissues of sows with high and low reproductive performance. Additionally, serum fatty acid compositions in a metabolic syndrome model (obese mice) induced by a high-fat diet (HFD) were investigated to elucidate the lipid metabolites associated with metabolic syndrome. Furthermore, the impact of nervonic acid (NA) on ovarian function was examined using rodent animal models (rats and mice). Through biological techniques such as transcriptomics, CUT&Tag, and analysis of post-translational protein modifications, the molecular mechanisms underlying NA mediated ovarian inflammation were further elucidated based on models utilizing ovarian granulosa cells from pigs, humans, and mice. Finally, validation was performed on ovaries from patients diagnosed with polycystic ovary syndrome. RESULTS: In vitro, targeted serum lipidomic analysis revealed that sows with low embryo survival rates exhibited abnormal lipid metabolism characterized by abnormal accumulation of NA in the liver, ovary, and adipose tissue. ...