The roles of FGF21 and GDF15 in mediating the mitochondrial integrated stress response.
The roles of FGF21 and GDF15 in mediating the mitochondrial integrated stress response.
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DOI：
10.3389/fendo.2023.1264530
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发表时间：
2023
影响因子：
5.2
通讯作者：
中科院分区：
文献类型：
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线粒体应激的不同模式导致应激反应细胞因子成纤维细胞生长因子21(FGF21)和生长分化因子15(GDF15)的诱导。这是线粒体综合应激反应下游的一种适应机制，经常与全身代谢健康的改善有关。FGF21和GDF15都被证明可以调节能量平衡和葡萄糖稳态，在临床前模型中，它们的药理作用导致了对肥胖和相关代谢性疾病的良好效果。此外，内源性FGF21和GDF15的上调与抵抗饮食诱导的肥胖(DIO)、改善血糖稳态和提高胰岛素敏感性有关。在这篇综述中，我们重点介绍了几个关于线粒体应激的转基因小鼠模型的研究，并将比较FGF21和GDF15在这些模型中所报道的系统代谢适应中所起的特定作用。
Various models of mitochondrial stress result in induction of the stress-responsive cytokines fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15). This is an adaptive mechanism downstream of the mitochondrial integrated stress response frequently associated with improvements in systemic metabolic health. Both FGF21 and GDF15 have been shown to modulate energy balance and glucose homeostasis, and their pharmacological administration leads to promising beneficial effects against obesity and associated metabolic diseases in pre-clinical models. Furthermore, endogenous upregulation of FGF21 and GDF15 is associated with resistance to diet-induced obesity (DIO), improved glucose homeostasis and increased insulin sensitivity. In this review, we highlight several studies on transgenic mouse models of mitochondrial stress and will compare the specific roles played by FGF21 and GDF15 on the systemic metabolic adaptations reported in these models.
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