人类MASLD是一种日间疾病,由多系统胰岛素抵抗和夜间胰岛素可用性降低所驱动
Thomas Marjot1, Kieran Smith2, Felix Westcott2
1Oxford Centre for Diabetes Endocrinology and Metabolism (OCDEM), Churchill Hospital, Radcliffe Department of Medicine, University of Oxford, Oxford, UK; Translational Gastroenterology and Liver Unit (TGLU), Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK; NIHR Oxford Health Biomedical Research Centre, University of Oxford, Oxford, UK.
夜间代谢功能障碍对人类的代谢功能障碍相关的脂肪性肝病 (MASLD) 有显著影响. 这些发现强调了昼夜节律在肝脏脂肪积累中的重要性,并建议新的治疗时间策略.
科学领域:
- 时间生物学 时间生物学
- 代谢性疾病研究研究.
- 肝病学 肝病学是一种肝病学.
背景情况:
- 肝脂和葡萄糖代谢的循环控制在临床前模型中已经确立.
- 人体肝脏内脂质积累的日间模式在很大程度上仍然没有表征.
研究的目的:
- 为了研究控制人体肝脏内脂质积累的功能过程中的日间模式.
- 评估夜间代谢功能障碍对代谢功能障碍相关的脂肪性肝病 (MASLD) 的影响.
主要方法:
- 在白天和晚上使用稳定同位素技术进行代谢表型化.
- 患有MASLD的患者与体重过重的对照人群之间的比较 (NCT05962099).
- 血,脂肪和骨肌肉组织的综合蛋白质组学.
主要成果:
- 夜间代谢功能障碍是MASLD的标志,肝脏和外周胰岛素耐药性上调,新型脂质生成 (DNL) 和全身非化脂肪酸 (NEFA) 暴露.
- 胰岛素抵抗因夜间血胰岛素水平较低而加剧.
- 即使在减肥后,白天的差异仍然存在,这表明夜间功能障碍是肥胖症的主要驱动因素.
结论:
- 夜间代谢功能障碍是MASLD的关键病原特征.
- 研究结果表明,最优的时间是干预措施,如能量摄入,运动和药物.
- 已识别的分子标可能为代谢性疾病提供治疗潜力.
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