Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Medicine (Rheumatology), Yale University School of Medicine, New Haven, CT 06520, USA.
Cell. 2019 Aug 22;178(5):1231-1244.e11. doi: 10.1016/j.cell.2019.07.033. Epub 2019 Aug 8.
Growth and differentiation factor 15 (GDF15) is an inflammation-associated hormone with poorly defined biology. Here, we investigated the role of GDF15 in bacterial and viral infections. We found that inflammation induced GDF15, and that GDF15 was necessary for surviving both bacterial and viral infections, as well as sepsis. The protective effects of GDF15 were largely independent of pathogen control or the magnitude of inflammatory response, suggesting a role in disease tolerance. Indeed, we found that GDF15 was required for hepatic sympathetic outflow and triglyceride metabolism. Failure to defend the lower limit of plasma triglyceride levels was associated with impaired cardiac function and maintenance of body temperature, effects that could be rescued by exogenous administration of lipids. Together, we show that GDF15 coordinates tolerance to inflammatory damage through regulation of triglyceride metabolism.
生长分化因子 15（GDF15）是一种与炎症相关的激素，其生物学功能尚未完全明确。在这里，我们研究了 GDF15 在细菌和病毒感染中的作用。我们发现炎症会诱导 GDF15 的产生，并且 GDF15 对于细菌和病毒感染以及败血症的存活都是必需的。GDF15 的保护作用在很大程度上独立于病原体的控制或炎症反应的程度，这表明它在疾病耐受中发挥作用。事实上，我们发现 GDF15 是肝脏交感神经输出和甘油三酯代谢所必需的。未能维持血浆甘油三酯水平的下限与心脏功能受损和体温维持有关，这些影响可以通过外源性给予脂质来挽救。总之，我们表明 GDF15 通过调节甘油三酯代谢来协调对炎症损伤的耐受。
