TNF-α stimulates endothelial palmitic acid transcytosis and promotes insulin resistance.
TNF-α stimulates endothelial palmitic acid transcytosis and promotes insulin resistance.
复制标题
TNF-α刺激内皮棕榈酸转胞吞作用并促进胰岛素抵抗
DOI：
10.1038/srep44659
复制
发表时间：
2017-03-17
影响因子：
4.6
通讯作者：
Jin S
中科院分区：
文献类型：
--
作者：
Li W;Yang X;Zheng T;Xing S;Wu Y;Bian F;Wu G;Li Y;Li J;Bai X;Wu D;Jia X;Wang L;Zhu L;Jin S
血浆TNF-α持续升高是低度全身性炎症的标志物。棕榈酸是人体内最丰富的饱和脂肪酸。PA在血浆中与白蛋白结合，不能自由通过内皮屏障。白蛋白结合的PA必须通过细胞内转胞吞作用而不是细胞间扩散穿过单层内皮细胞。在本研究中，我们发现TNF-α可刺激PA跨心肌微血管内皮细胞的胞吞，从而进一步损害胰岛素刺激的心肌细胞葡萄糖摄取，并促进胰岛素抵抗。在此过程中，TNF-α刺激的内皮细胞自噬和NF-κB信号相互交叉协调，最终导致内皮细胞脂肪酸转运蛋白4（FATP 4）表达增加，并介导PA跨微血管内皮细胞的转胞吞。希望本研究发现了低度全身性炎症和胰岛素抵抗之间的一个新的缺失环节。
Persistent elevation of plasma TNF-α is a marker of low grade systemic inflammation. Palmitic acid (PA) is the most abundant type of saturated fatty acid in human body. PA is bound with albumin in plasma and could not pass through endothelial barrier freely. Albumin-bound PA has to be transported across monolayer endothelial cells through intracellular transcytosis, but not intercellular diffusion. In the present study, we discovered that TNF-α might stimulate PA transcytosis across cardiac microvascular endothelial cells, which further impaired the insulin-stimulated glucose uptake by cardiomyocytes and promoted insulin resistance. In this process, TNF-α-stimulated endothelial autophagy and NF-κB signaling crosstalk with each other and orchestrate the whole event, ultimately result in increased expression of fatty acid transporter protein 4 (FATP4) in endothelial cells and mediate the increased PA transcytosis across microvascular endothelial cells. Hopefully the present study discovered a novel missing link between low grade systemic inflammation and insulin resistance.