当前位置: X-MOL 学术iScience › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Differential Expression of Ormdl Genes in the Islets of Mice and Humans with Obesity.
iScience ( IF 5.8 ) Pub Date : 2020-06-29 , DOI: 10.1016/j.isci.2020.101324
Hugo Lee 1 , Rachel J Fenske 2 , Tugce Akcan 1 , Elliot Domask 1 , Dawn B Davis 3 , Michelle E Kimple 4 , Feyza Engin 5
Affiliation  

The orosomucoid-like (Ormdl) proteins play a critical role in sphingolipid homeostasis, inflammation, and ER stress, all of which are associated with obesity and βcell dysfunction. However, their roles in β cells and obesity remain unknown. Here, we show that islets from overweight/obese human donors displayed marginally reduced ORMDL1-2 expression, whereas ORMDL3 expression was significantly downregulated compared with islets from lean donors. In contrast, Ormdl3 was substantially upregulated in the islets of leptin-deficient obese (ob/ob) mice compared with lean mice. Treatment of ob/ob mice and their islets with leptin markedly reduced islet Ormld3 expression. Ormdl3 knockdown in a β cell line induced expression of pro-apoptotic markers, which was rescued by ceramide synthase inhibitor fumonisin B1. Our results reveal differential expression of Ormdl3 in the islets of a mouse model and humans with obesity, highlight the potential effect of leptin in this differential regulation, and suggest a role for Ormdl3 in β cell apoptosis.



中文翻译:

Ormdl基因在肥胖小鼠和人类胰岛中的差异表达。

类类类骨胶蛋白(Ormdl)在鞘脂稳态,炎症和内质网应激中起关键作用,所有这些都与肥胖症和β细胞功能障碍有关。然而,它们在β细胞和肥胖中的作用仍然未知。在这里,我们显示来自超重/肥胖人类供体的胰岛显示出略微降低的ORMDL1-2表达,而与瘦体供体相比,ORMDL3表达显着下调。相反,与瘦小鼠相比,瘦素缺乏型肥胖(ob / ob)小鼠的胰岛中Ormdl3基本上上调。用瘦素显着减少胰岛Ormld3治疗ob / ob小鼠及其胰岛表达。β细胞系中的Ormdl3敲低诱导了促凋亡标记物的表达,其被神经酰胺合酶抑制剂伏马菌素B1拯救。我们的结果揭示了Ormdl3在小鼠模型和肥胖人群的胰岛中的差异表达,突出了瘦素在这种差异调节中的潜在作用,并暗示了Ormdl3在β细胞凋亡中的作用。

更新日期:2020-06-29
down
wechat
bug