Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
J Extracell Vesicles. 2022 Sep;11(9):e12262. doi: 10.1002/jev2.12262.
Transmembrane 4 L six family member 5 (TM4SF5) is involved in chronic liver disease, although its role in glucose homeostasis remains unknown. TM4SF5 deficiency caused age-dependent glucose (in)tolerance with no link to insulin sensitivity. Further, hepatic TM4SF5 binding to GLUT1 promoted glucose uptake and glycolysis. Excessive glucose repletion caused hepatocytes to secrete small extracellular vesicles (sEVs) loaded with TM4SF5 (hep-sEV ), suggesting a role for sEV in glucose metabolism and homeostasis. Hep-sEV were smaller than sEV and recruit proteins for efficient organ tropism. Liver-derived sEVs, via a liver-closed vein circuit (LCVC) using hepatic TM4SF5-overexpressing (Alb-Tm4sf5 TG) mice (liv-sEV ), improved glucose tolerance in Tm4sf5 KO mice and targeted brown adipose tissues (BATs), possibly allowing the clearance of blood glucose as heat independent of UCP1. Taken together, hep-sEV might clear high extracellular glucose levels more efficiently by targeting BAT compared with hep-sEV , suggesting an insulin-like role for sEV™ in affecting age-related metabolic status and thus body weight (BW).
跨膜 4 L 六家族成员 5（TM4SF5）参与慢性肝病，尽管其在葡萄糖稳态中的作用尚不清楚。TM4SF5 缺乏导致年龄依赖性葡萄糖（耐）受，与胰岛素敏感性无关。此外，肝 TM4SF5 与 GLUT1 的结合促进葡萄糖摄取和糖酵解。过多的葡萄糖补充导致肝细胞分泌富含 TM4SF5 的小细胞外囊泡（sEV）（肝 sEV），表明 sEV 在葡萄糖代谢和稳态中起作用。肝 sEV 比 sEV 小，并募集蛋白质以实现有效的器官靶向。肝来源的 sEV 通过使用过表达肝 TM4SF5（Alb-Tm4sf5 TG）小鼠的肝封闭静脉循环（LCVC）（liv-sEV），改善了 Tm4sf5 KO 小鼠的葡萄糖耐量，并靶向棕色脂肪组织（BATs），可能允许清除血糖作为热量，而不依赖于 UCP1。总之，与肝 sEV 相比，肝 sEV 可能通过靶向 BAT 更有效地清除高细胞外葡萄糖水平，提示 sEV 在影响与年龄相关的代谢状态和体重（BW）方面具有类似胰岛素的作用。
