BCAA insufficiency leads to premature ovarian insufficiency via ceramide-induced elevation of ROS.
BCAA insufficiency leads to premature ovarian insufficiency via ceramide-induced elevation of ROS.
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DOI：
10.15252/emmm.202317450
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发表时间：
2023-04-11
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
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作者：
卵巢功能不全（POI）是一种以40岁前提前绝经为特征的疾病，伴有促卵泡激素升高。虽然POI影响妇女健康的许多方面，但其主要原因尚不清楚。许多临床研究表明，POI患者普遍体重过轻，这表明POI与代谢紊乱之间存在潜在的相关性。为了了解POI的发病机制，我们对来自两个诊所的两个独立队列进行了血清代谢组学分析，并鉴定了分支链氨基酸（BCAA）不足相关的代谢紊乱。低BCAA饮食在表型上再现了年轻C57BL/6J小鼠POI的代谢、内分泌、卵巢和生殖变化。一项机制研究表明，BCAA不足诱导的POI与神经酰胺活性氧（ROS）轴的异常激活以及随之而来的卵巢颗粒细胞功能损伤有关。值得注意的是，膳食补充BCAA可以阻止雌性小鼠ROS诱导的POI的发生。这项病原学研究的结果将导致POI特异性治疗的发展。卵巢功能不全（POI）是一种以40岁前提前绝经为特征的疾病。目前的研究发现POI与这些患者的代谢紊乱有关。
Premature ovarian insufficiency (POI) is a disease featured by early menopause before 40 years of age, accompanied by an elevation of follicle‐stimulating hormone. Though POI affects many aspects of women's health, its major causes remain unknown. Many clinical studies have shown that POI patients are generally underweight, indicating a potential correlation between POI and metabolic disorders. To understand the pathogenesis of POI, we performed metabolomics analysis on serum and identified branch‐chain amino acid (BCAA) insufficiency‐related metabolic disorders in two independent cohorts from two clinics. A low BCAA diet phenotypically reproduced the metabolic, endocrine, ovarian, and reproductive changes of POI in young C57BL/6J mice. A mechanism study revealed that the BCAA insufficiency‐induced POI is associated with abnormal activation of the ceramide‐reactive oxygen species (ROS) axis and consequent impairment of ovarian granulosa cell function. Significantly, the dietary supplement of BCAA prevented the development of ROS‐induced POI in female mice. The results of this pathogenic study will lead to the development of specific therapies for POI. Premature ovarian insufficiency (POI) is a disease featured by early menopause before 40 years. The current study identified that POI is related to metabolic disorders in these patients.
影响因子：
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作者：
He X;Zhang Y
通讯作者：
Zhang Y