与FGF21结合的高血GDF15表明,在神经性厌食症患者的一个亚组中,线粒体功能障碍
Jingjing Xu1,2, Ruyue Zhang3,4, Vincent Millischer5,6,7,8
1Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. jingjing.xu@ki.se.
Translational psychiatry
|June 25, 2025
概括
增长和分化因子15 (GDF15) 与神经性厌食症 (AN) 有关. 虽然总体GDF15水平相似,但AN患者的一个子集显示GDF15升高,与线粒体功能障碍和像FGF21这样的炎症标志物有关.
科学领域:
- 生物化学 生物化学
- 遗传学 是一个遗传学.
- 精神病学是一个精神病学.
背景情况:
- 增长和分化因子15 (GDF15) 是细胞应激和能量平衡的关键调节者.
- 在诸如癌症缓解症,化疗诱导的厌食症,重症性过高和线粒体疾病等条件下观察到高GDF15.
- 神经性厌食症 (AN) 是一种精神疾病,由低体重和持续的食物摄入限制来定义.
研究的目的:
- 研究GDF15在神经性厌食症 (AN) 中的作用.
- 确定与AN中GDF15水平相关的潜在生物标志物.
- 探索GDF15,线粒体功能障碍和AN之间的联系.
主要方法:
- 对活跃AN,恢复AN和健康对照组中的血GDF15度的分析.
- 稀疏部分最小方程区分分析 (sPLS-DA) 用于识别区分标记.
- 对纤维细胞生长因子21 (FGF21) 血度和线粒体多基因风险评分 (PRS) 的评估.
- 在厌食症小鼠模型中检查肝脏GDF15表达.
主要成果:
- 在AN和对照组之间,总体血GDF15没有显著差异,但在AN患者中确定了高GDF15的亚组.
- sPLS-DA确定了6个标记,包括FGF21,区分高GDF15.0的AN.
- 在高GDF15 AN亚组中,FGF21的血度显著更高,这表明线粒体功能障碍.
- 在大型队列中,线粒体PRS与AN风险有显著的关联.
- 在小鼠的厌食症相关的线粒体功能障碍中观察到肝脏GDF15表达的升高.
结论:
- 线粒体功能障碍是AN的潜在贡献因素,需要进一步调查.
- GDF15可能在一小部分AN患者中发挥作用,特别是那些水平较高的患者.
- FGF21是与GDF15和AN中的线粒体功能障碍相关的潜在生物标志物.
- 针对GDF15的临床试验,例如免疫中和,可以考虑用于高GDF15.5的AN患者.
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