PDF(Pubmed)
Abstract：
After surgical or natural menopause, women face a high risk of nonalcoholic fatty liver disease (NAFLD), which can be diminished by hormone replacement therapy (HRT). The gut microbiota is subject to modulation by various physiological changes and the progression of diseases. This microbial ecosystem coexists symbiotically with the host, playing pivotal roles in immune maturation, microbial defense mechanisms, and metabolic functions essential for nutritional and hormone homeostasis. E2 supplementation effectively prevented the development of NAFLD after bilateral oophorectomy (OVX) in female rats. The changes in the gut microbiota such as abnormal biosynthetic metabolism of fatty acids caused by OVX were partially restored by E2 supplementation. The combination of liver transcriptomics and metabolomics analysis revealed that linoleic acid (LA) metabolism, a pivotal pathway in fatty acids metabolism was mainly manipulated during the induction and treatment of NAFLD. Further correlation analysis indicated that the gut microbes were associated with abnormal serum indicators and different LA metabolites. These metabolites are also closely related to serum indicators of NAFLD. An in vitro study verified that LA is an inducer of hepatic steatosis. The changes in transcription in the LA metabolism pathway could be normalized by E2 treatment. The metabolic perturbations of LA may directly and secondhand impact the development of NAFLD in postmenopausal individuals. This research focused on the sex-specific pathophysiology and treatment of NAFLD, providing more evidence for HRT and calling for the multitiered management of NAFLD.
摘要：
手术或自然绝经后，女性面临非酒精性脂肪性肝病（NAFLD）的高风险，激素替代疗法（HRT）可以减少。肠道微生物群受到各种生理变化和疾病进展的调节。这个微生物生态系统与宿主共生共存，在免疫成熟中起关键作用，微生物防御机制，和代谢功能对营养和激素稳态至关重要。补充E2可有效预防雌性大鼠双侧卵巢切除术（OVX）后NAFLD的发展。补充E2部分恢复了由OVX引起的肠道微生物群的变化，例如脂肪酸的生物合成代谢异常。肝脏转录组学和代谢组学分析的结合显示，亚油酸（LA）代谢，脂肪酸代谢的一个关键途径主要在NAFLD的诱导和治疗过程中被操纵。进一步的相关性分析表明，肠道微生物与血清指标异常和不同的LA代谢产物有关。这些代谢产物也与NAFLD的血清指标密切相关。体外研究证实LA是肝性脂肪变性的诱导剂。LA代谢途径中的转录变化可以通过E2处理来标准化。LA的代谢扰动可能直接和二手影响绝经后个体NAFLD的发展。这项研究集中于NAFLD的性别特异性病理生理学和治疗。为HRT提供更多证据，并呼吁对NAFLD进行多层管理。
