Fitzpatrick Susan F, Gojkovic Milos, Macias David, Tegnebratt Tetyana, Lu Li, Samén Erik, Rundqvist Helene, Johnson Randall S
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
Front Physiol. 2018 Nov 22;9:1624. doi: 10.3389/fphys.2018.01624. eCollection 2018.
The response to lipopolysaccharide (LPS) occurs rapidly and has profound physiological and metabolic effects. The hypoxia inducible (HIF) transcription factor is an intrinsic and essential part of inflammation, and is induced by LPS. To determine the importance of the HIF response in regulating metabolism following an LPS response, glucose uptake was quantified in a time dependent manner in mice lacking HIF-1α in myeloid cells. We found that deletion of HIF-1α has an acute protective effect on LPS-induced hypoglycemia. Furthermore, reduced glucose uptake was observed in the heart and brown fat, in a time dependent manner, following loss of HIF-1α. To determine the physiological significance of these findings, cardiovascular, body temperature, and blood pressure changes were subsequently quantified in real time using radiotelemetry measurements. These studies reveal the temporal aspects of HIF-1α as a regulator of the metabolic response to acute LPS-induced inflammation.
对脂多糖（LPS）的反应迅速发生，并具有深远的生理和代谢影响。缺氧诱导（HIF）转录因子是炎症的内在和重要组成部分，由LPS诱导产生。为了确定HIF反应在调节LPS反应后代谢中的重要性，我们以时间依赖性方式对髓系细胞中缺乏HIF-1α的小鼠的葡萄糖摄取进行了定量。我们发现，HIF-1α的缺失对LPS诱导的低血糖具有急性保护作用。此外，在HIF-1α缺失后，心脏和棕色脂肪中的葡萄糖摄取以时间依赖性方式减少。为了确定这些发现的生理意义，随后使用无线电遥测测量实时定量心血管、体温和血压变化。这些研究揭示了HIF-1α作为急性LPS诱导炎症代谢反应调节因子的时间方面。
