FGF21 improves glucose homeostasis in an obese diabetes-prone mouse model independent of body fat changes.
FGF21 improves glucose homeostasis in an obese diabetes-prone mouse model independent of body fat changes.
复制标题
DOI：
10.1007/s00125-017-4389-x
复制
发表时间：
2017-11
期刊：
影响因子：
8.2
通讯作者：
Schürmann A
中科院分区：
文献类型：
--
作者：
Laeger T;Baumeier C;Wilhelmi I;Würfel J;Kamitz A;Schürmann A
成纤维细胞生长因子21 （FGF21）被认为是治疗2型糖尿病的有前途的候选药物。然而，由于FGF21水平在肥胖和糖尿病条件下升高，我们旨在测试外源性FGF21是否足以预防新西兰肥胖（NZO）小鼠（多基因肥胖和2型糖尿病的模型）的糖尿病和β细胞损失。雄性NZO小鼠用一种特定的饮食方案治疗，导致糖尿病在1周内发作。小鼠皮下注射PBS或FGF21，以评估葡萄糖稳态、能量消耗、食物摄入和其他代谢终点的变化。FGF21治疗可防止胰岛破坏和高血糖的发生，并改善葡萄糖清除率。FGF21通过诱导皮下白色脂肪组织褐变增加能量消耗。然而，由于代偿性的食物摄入增加，体脂并没有随着FGF21的治疗而减少，而是表现出Glut4表达的升高。FGF21可以预防饮食引起的糖尿病，而不会改变身体脂肪量。有益作用是通过白色脂肪组织褐变和产热升高介导的。此外，这些数据表明肥胖不会诱导NZO小鼠对FGF21产生抗性。本文的在线版本（doi:10.1007/s00125-017-4389-x）包含同行评审但未经编辑的补充材料，授权用户可使用。
Fibroblast growth factor 21 (FGF21) is considered to be a promising therapeutic candidate for the treatment of type 2 diabetes. However, as FGF21 levels are elevated in obese and diabetic conditions we aimed to test if exogenous FGF21 is sufficient to prevent diabetes and beta cell loss in New Zealand obese (NZO) mice, a model for polygenetic obesity and type 2 diabetes. Male NZO mice were treated with a specific dietary regimen that leads to the onset of diabetes within 1 week. Mice were treated subcutaneously with PBS or FGF21 to assess changes in glucose homeostasis, energy expenditure, food intake and other metabolic endpoints. FGF21 treatment prevented islet destruction and the onset of hyperglycaemia, and improved glucose clearance. FGF21 increased energy expenditure by inducing browning in subcutaneous white adipose tissue. However, as a result of a compensatory increased food intake, body fat did not decrease in response to FGF21 treatment, but exhibited elevated Glut4 expression. FGF21 prevents the onset of diet-induced diabetes, without changing body fat mass. Beneficial effects are mediated via white adipose tissue browning and elevated thermogenesis. Furthermore, these data indicate that obesity does not induce FGF21 resistance in NZO mice. The online version of this article (doi:10.1007/s00125-017-4389-x) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
登录
查看更多内容
影响因子：
8.2
作者：
Kluth, O.;Mirhashemi, F.;Scherneck, S.;Kaiser, D.;Kluge, R.;Neschen, S.;Joost, H. -G.;Schuermann, A.
通讯作者：
Schuermann, A.
DOI：
10.1016/j.bbalip.2015.01.013
发表时间：
2015-05-01
影响因子：
4.8
作者：
Baumeier, Christian;Kaiser, Daniel;Schuermann, Annette
通讯作者：
Schuermann, Annette
正常受试者和新诊断 2 型糖尿病患者的循环 FGF-21 水平
影响因子：
1.8
作者：
Chen, W. -W.;Li, L.;Boden, G.
通讯作者：
Boden, G.
影响因子：
5.6
作者：
Kharitonenkov, Alexei;Dunbar, James D.;Shanafelt, Armen B.
通讯作者：
Shanafelt, Armen B.
影响因子：
10.6
作者：
Alejandro, Emilyn U.;Gregg, Brigid;Blandino-Rosano, Manuel;Cras-Meneur, Corentin;Bernal-Mizrachi, Ernesto
通讯作者：
Bernal-Mizrachi, Ernesto