与代谢功能障碍相关的脂肪性肝病中单碳代谢的改变可能会被塞马格卢提德修改
Mikkel Parsberg Werge1, Adrian McCann2, Elias Badal Rashu1
1Gastro Unit, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
Annals of hepatology
|September 1, 2025
概括
脂肪肝疾病 (MASLD) 的代谢功能障碍涉及单碳代谢的改变. 在小鼠模型中,塞马格卢提德治疗逆转了这些变化,这表明MASLD的治疗潜力.
科学领域:
- 生物化学
- 代谢学
- 基因组学
背景情况:
- 单碳代谢 (OCM) 的破坏与心脏代谢疾病有关.
- 非酒精性脂肪肝 (NAFLD) 和其渐进的形式 - - 代谢功能障碍相关的脂肪肝炎 (MASH) 是全球日益严重的健康问题.
- 了解MASLD的代谢基础对于开发有效治疗至关重要.
研究的目的:
- 研究MASLD患者的OCM代谢物和酶的变化.
- 在饮食诱导的MASH小鼠模型中评估semaglutide对OCM的影响.
主要方法:
- 针对100名MASLD患者和50名对照患者的血和肝脏样本的目标代谢量和批量转录量.
- 由饮食引起的肥胖和MASH (DIO-MASH) 治疗的小鼠的肝脏和血上的非向代谢和转录量.
- 分析叶酸,维生素B6,贝他因,血清,甘氨酸和谷氨酸水平,以及关键酶活动.
主要成果:
- 在MASLD患者中,OCM代谢物 (叶酸,维生素B6,贝他因,血清,甘氨酸) 的度发生变化,同类半氨酸和谷氨酸的度增加,表明转硫和甲氨酸/叶酸循环受损.
- 这些代谢变化与酶活动的改变相关,并且在DIO- MASH小鼠中反映.
- 在DIO-MASH小鼠中,塞马格卢提德治疗降低了体重,肝炎和纤维化,并且在很大程度上逆转了观察到的代谢和基因表达变化.
结论:
- MASLD与OCM代谢物和酶的显著变化有关.
- 观察到的MASLD患者的代谢变化在临床前的小鼠模型中进行了回顾.
- 在MASH小鼠模型中,塞马格卢提德在逆转这些代谢障碍和改善肝脏病理方面表现出有效性.
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