Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, United States.
Front Endocrinol (Lausanne). 2023 Sep 25;14:1264530. doi: 10.3389/fendo.2023.1264530. eCollection 2023.
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.
各种线粒体应激模型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。这是线粒体整合应激反应的下游适应性机制，常与全身代谢健康的改善相关。已经证明，FGF21 和 GDF15 都可以调节能量平衡和葡萄糖稳态，并且它们的药理学给药在临床前模型中导致针对肥胖和相关代谢疾病的有希望的有益效果。此外，FGF21 和 GDF15 的内源性上调与抵抗饮食诱导的肥胖（DIO）、改善葡萄糖稳态和增加胰岛素敏感性相关。在这篇综述中，我们强调了几种线粒体应激的转基因小鼠模型的研究，并将比较 FGF21 和 GDF15 在这些模型中报道的全身代谢适应中的特定作用。
