Loss of prion protein is associated with the development of insulin resistance and obesity
Loss of prion protein is associated with the development of insulin resistance and obesity
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DOI：
10.1042/bcj20170137
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发表时间：
2017-09-01
影响因子：
4.1
通讯作者：
Hajj, Glaucia N.
中科院分区：
文献类型：
--
作者：
de Brito, Giovanna;Lupinacci, Fernanda C.;Hajj, Glaucia N.
朊蛋白（PrPC）最初被描述是因为它与传染性海绵状脑病有关。它随后被证明是一个参与许多生理过程的细胞表面分子，如囊泡运输。在这里，我们研究了PrPC在胰岛素和肥胖发展反应中的作用。2只独立PrPC敲除（KO）小鼠模型和1只PrPC过表达（TG20）小鼠模型分别饲喂高脂饲料，监测胰岛素抵抗和肥胖的发展情况。喂食高脂肪饮食的PrPC KO小鼠表现出与胰岛素抵抗发展相关的所有症状：高血糖、高胰岛素血症和肥胖。相反，喂食高脂肪食物的TG20动物表现出体重减轻和胰岛素抵抗。相应地，过氧化物酶体增殖物激活受体γ (PPAR.)在PrPC KO小鼠中的表达减少，而在TG20小鼠中表达增加。PrPC KO细胞在胰岛素刺激下也表现出葡萄糖摄取减少，这是由于葡萄糖转运蛋白Glut4的易位减少。因此，我们的研究结果表明，PrPC反映了胰岛素抵抗和代谢综合征的易感性。
Prion protein (PrPC) was initially described due to its involvement in transmissible spongiform encephalopathies. It was subsequently demonstrated to be a cell surface molecule involved in many physiological processes, such as vesicle trafficking. Here, we investigated the roles of PrPC in the response to insulin and obesity development. Two independent PrPC knockout (KO) and one PrPC overexpressing (TG20) mouse models were fed high-fat diets, and the development of insulin resistance and obesity was monitored. PrPC KO mice fed high-fat diets presented all of the symptoms associated with the development of insulin resistance: hyperglycemia, hyperinsulinemia, and obesity. Conversely, TG20 animals fed high-fat diets showed reduced weight and insulin resistance. Accordingly, the expression of peroxisome proliferator-activated receptor gamma (PPAR.) was reduced in PrPC KO mice and increased in TG20 animals. PrPC KO cells also presented reduced glucose uptake upon insulin stimulation, due to reduced translocation of the glucose transporter Glut4. Thus, our results suggest that PrPC reflects susceptibility to the development of insulin resistance and metabolic syndrome.