Department of Physiology, University of Lausanne, 1005 Lausanne, Switzerland.
Department of Physiology, University of Lausanne, 1005 Lausanne, Switzerland.
Cell Metab. 2019 Oct 1;30(4):833-844.e7. doi: 10.1016/j.cmet.2019.08.004. Epub 2019 Aug 29.
The hypothalamus plays a key role in the detection of energy substrates to regulate energy homeostasis. Tanycytes, the hypothalamic ependymo-glia, are located at a privileged position to integrate multiple peripheral inputs. We observed that tanycytes produce and secrete Fgf21 and are located close to Fgf21-sensitive neurons. Fasting, likely via the increase in circulating fatty acids, regulates this central Fgf21 production. Tanycytes store palmitate in lipid droplets and oxidize it, leading to the activation of a reactive oxygen species (ROS)/p38-MAPK signaling pathway, which is essential for tanycytic Fgf21 expression upon palmitate exposure. Tanycytic Fgf21 deletion triggers an increase in lipolysis, likely due to impaired inhibition of key neurons during fasting. Mice deleted for tanycytic Fgf21 exhibit increased energy expenditure and a reduction in fat mass gain, reminiscent of a browning phenotype. Our results suggest that tanycytes sense free fatty acids to maintain body lipid homeostasis through Fgf21 signaling within the hypothalamus.
下丘脑在检测能量底物以调节能量平衡方面发挥着关键作用。室管膜下细胞（tanycytes）位于下丘脑的室管膜下，处于整合多种外周输入的有利位置。我们观察到 tanycytes 产生并分泌 Fgf21，并且靠近 Fgf21 敏感神经元。禁食可能通过增加循环脂肪酸来调节这种中枢 Fgf21 的产生。tanycytes 将棕榈酸储存在脂滴中并氧化它，导致活性氧物质（ROS）/p38-MAPK 信号通路的激活，这对于棕榈酸暴露时 tanycytic Fgf21 的表达至关重要。tanycytic Fgf21 的缺失会引发脂肪分解增加，可能是由于在禁食期间关键神经元的抑制作用受损。缺失 tanycytic Fgf21 的小鼠表现出能量消耗增加和脂肪质量增加减少，类似于褐色表型。我们的研究结果表明，tanycytes 通过下丘脑内的 Fgf21 信号感知游离脂肪酸，以维持身体脂质的平衡。
