Sickness behaviors, including anorexia, are evolutionarily conserved responses to acute infections. Inflammation-induced anorexia causes dramatic metabolic changes, of which components critical to survival are unique depending on the type of inflammation. Glucose supplementation during the anorectic period induced by bacterial inflammation suppresses adaptive fasting metabolic pathways, including fibroblast growth factor 21 (FGF21), and decreases survival. Consistent with this observation, FGF21-deficient mice are more susceptible to mortality from endotoxemia and polybacterial peritonitis. Here, we report that increased circulating FGF21 during bacterial inflammation is hepatic derived and required for survival through the maintenance of thermogenesis, energy expenditure, and cardiac function. FGF21 signaling downstream of its obligate coreceptor, β-Klotho (KLB), is required in bacterial sepsis. However, FGF21 modulates thermogenesis and chronotropy independent of the adipose, forebrain, and hypothalamus, which are operative in cold adaptation, suggesting that in bacterial inflammation, either FGF21 signals through a novel, undescribed target tissue or concurrent signaling of multiple KLB-expressing tissues is required.

中文翻译：

---

肝脏 FGF21 在细菌炎症期间保持体温调节和心血管功能


包括厌食症在内的疾病行为是对急性感染的进化保守反应。炎症引起的厌食症会引起剧烈的代谢变化，其中对生存至关重要的成分因炎症类型而异。在细菌炎症引起的厌食期补充葡萄糖会抑制适应性禁食代谢途径，包括成纤维细胞生长因子 21 (FGF21)，并降低存活率。与这一观察结果一致，FGF21 缺陷小鼠更容易因内毒素血症和多菌性腹膜炎而死亡。在此，我们报道细菌炎症期间循环中 FGF21 的增加来自肝脏，并且是通过维持产热、能量消耗和心脏功能来维持生存所必需的。细菌性败血症需要 FGF21 信号传导至其专性辅助受体 β-Klotho (KLB) 下游。然而，FGF21 独立于脂肪、前脑和下丘脑调节产热和变时性，而脂肪、前脑和下丘脑在冷适应中发挥作用，这表明在细菌炎症中，FGF21 通过新的、未描述的靶组织发出信号，或者通过多个表达 KLB 的组织同时发出信号。必需的。