Chen Xiaoyuan, Liu Chao, Ruan Litao
Department of Ultrasound, Women and Children's Hospital of Northwest, Xi'an, 710061, Shaanxi, China.
Department of Ultrasound, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, Shaanxi, China.
Dig Dis Sci. 2021 Apr;66(4):1090-1096. doi: 10.1007/s10620-020-06280-9. Epub 2020 May 5.
GPR120 plays a crucial role in insulin sensitization, inflammatory responses and obesity and is considered as an attractive potential target for the treatment of metabolic dysfunctions. However, the mechanisms of GPR120 agonist III in NAFLD/NASH treatment are still unclear.
We aimed to evaluate the effect and molecular mechanisms of GPR120 agonist III on NASH, and search for future treatments of human NAFLD/NASH.
The effects of GPR120 agonist III on steatohepatitis were evaluated in mice fed with HFHC diet and MCD diet. The ultrastructural changes of ER were assessed by TEM. Hepatic ROS production was evaluated by DHE staining. Apoptosis and macrophage infiltration were determined by IHC staining. Inflammatory cytokines secretion were examined using mouse XL cytokine array.
GPR120 agonist III significantly suppressed macrophage infiltration and ROS production and reversed hepatic inflammation, ER stress and apoptosis in dietary-induced steatohepatitis.
GPR120 agonist III will be an attractive treatment method in steatohepatitis, which opens up a new sight for future treatments of human NAFLD/NASH.
GPR120在胰岛素增敏、炎症反应和肥胖中起关键作用，被认为是治疗代谢功能障碍的一个有吸引力的潜在靶点。然而，GPR120激动剂III在非酒精性脂肪性肝病/非酒精性脂肪性肝炎（NAFLD/NASH）治疗中的机制仍不清楚。
我们旨在评估GPR120激动剂III对NASH的作用及分子机制，并寻找人类NAFLD/NASH的未来治疗方法。
在喂食高糖高脂（HFHC）饮食和蛋氨酸胆碱缺乏（MCD）饮食的小鼠中评估GPR120激动剂III对脂肪性肝炎的影响。通过透射电子显微镜（TEM）评估内质网（ER）的超微结构变化。通过二氢乙锭（DHE）染色评估肝脏活性氧（ROS）的产生。通过免疫组化（IHC）染色确定细胞凋亡和巨噬细胞浸润。使用小鼠XL细胞因子阵列检测炎症细胞因子的分泌。
GPR120激动剂III显著抑制巨噬细胞浸润和ROS产生，并逆转饮食诱导的脂肪性肝炎中的肝脏炎症、内质网应激和细胞凋亡。
GPR120激动剂III将是脂肪性肝炎中一种有吸引力的治疗方法，为人类NAFLD/NASH的未来治疗开辟了新视野。
