在暴露于寒冷环境下,FGF21通过棕色化热源性脂肪组织促进热生成
Chen-Xi Li1,2, Chuan-Fei Tan1,3, Qi-Min Zhang1,3
1Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, China.
Annals of nutrition & metabolism
|November 7, 2025
概括
纤维细胞生长因子21 (FGF21) 通过不同的肝脏和脂肪细胞机制调节能量消耗. 针对这些途径,特别是脂肪衍生的FGF21,是有效的肥胖治疗的关键.
科学领域:
- 代谢调节 代谢调节 代谢调节
- 脂肪组织生物学 脂肪组织生物学
- 肥胖治疗方法 肥胖治疗方法
背景情况:
- 全球肥胖流行需要加强能源支出策略.
- 在棕色/色脂肪组织中,非的热生成 (NST) 是一个关键的目标.
- 纤维细胞生长因子21 (FGF21) 是脂肪可塑性和线粒体功能的关键调节者,但其在NST中的分泌和作用尚未完全理解.
研究的目的:
- 阐明FGF21在调节非发热的发生过程中的独特的时空机制.
- 为了研究肝脏和脂肪衍生的FGF21在对寒冷暴露的反应中的作用.
- 了解衰老和他类药物对FGF21信号和NST的影响.
主要方法:
- 在急性和慢性寒冷暴露下分析FGF21分泌途径.
- 通过脂肪组织中的FGFR1/β-Klotho复合体对FGF21信号的研究.
- 评估衰老和他类药物对线粒体功能和FGF21水平的影响.
- 在激活脂肪FGFR1/β-Klotho信号传递中,完全和部分FGF21激动剂的比较.
主要成果:
- 急性寒冷暴露通过β3-上腺素-脂解-PPARα轴刺激肝脏FGF21.
- 慢性感冒适应涉及脂肪衍生的FGF21,激活用于UCP1表达的PLCγ-Ca2+-CREB通路.
- 衰老和他类药物通过线粒体功能障碍和CoQ10耗尽来损害NST,导致补偿FGF21上调.
- 完全的FGF21激动剂通过完全激活脂肪FGFR1/β-Klotho信号来证明其卓越的疗效.
结论:
- FGF21表现出双重调节:肝脏用于急性脂质调动,脂肪基用于慢性色.
- 针对脂肪的FGF21输送对于治疗成功至关重要.
- 未来的肥胖治疗应该考虑将FGF21与UCP1独立途径集成.
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