Department of Molecular Medicine, College of Medicine, Ewha Womans University, Seoul, Korea.
Immune and Vascular Cell Network Research Center, National Creative Initiatives, Department of Life Sciences, Ewha Womans University, Seoul, Korea.
Diabetes Metab J. 2021 Jan;45(1):97-108. doi: 10.4093/dmj.2019.0198. Epub 2020 Jun 15.
Obesity and type 2 diabetes mellitus are world-wide health problems, and lack of understanding of their linking mechanism is one reason for limited treatment options. We determined if genetic deletion of vimentin, a type 3 intermediate filament, affects obesity and type 2 diabetes mellitus.
We fed vimentin-null (Vim-/-) mice and wild-type mice a high-fat diet (HFD) for 10 weeks and measured weight change, adiposity, blood lipids, and glucose. We performed intraperitoneal glucose tolerance tests and measured CD36, a major fatty acid translocase, and glucose transporter type 4 (GLUT4) in adipocytes from both groups of mice.
Vim-/- mice fed an HFD showed less weight gain, less adiposity, improved glucose tolerance, and lower serum level of fasting glucose. However, serum triglyceride and non-esterified fatty acid levels were higher in Vim-/- mice than in wild-type mice. Vimentin-null adipocytes showed 41.1% less CD36 on plasma membranes, 27% less uptake of fatty acids, and 50.3% less GLUT4, suggesting defects in intracellular trafficking of these molecules.
We concluded that vimentin deficiency prevents obesity and insulin resistance in mice fed an HFD and suggest vimentin as a central mediator linking obesity and type 2 diabetes mellitus.
肥胖和 2 型糖尿病是全球性的健康问题，对其发病机制缺乏了解是治疗选择有限的原因之一。我们确定了 3 型中间丝波形蛋白（vimentin）的基因缺失是否会影响肥胖和 2 型糖尿病。
我们用高脂肪饮食（HFD）喂养波形蛋白缺失（Vim-/-）小鼠和野生型小鼠 10 周，测量体重变化、肥胖程度、血脂和血糖。我们进行了腹腔内葡萄糖耐量试验，并测量了两组小鼠脂肪细胞中的主要脂肪酸转运蛋白 CD36 和葡萄糖转运蛋白 4（GLUT4）。
喂食 HFD 的 Vim-/- 小鼠体重增加较少，肥胖程度较低，葡萄糖耐量改善，空腹血糖水平较低。然而，Vim-/- 小鼠的血清甘油三酯和非酯化脂肪酸水平高于野生型小鼠。Vim-/- 脂肪细胞的质膜上 CD36 减少了 41.1%，脂肪酸摄取减少了 27%，GLUT4 减少了 50.3%，提示这些分子的细胞内转运存在缺陷。
我们得出结论，波形蛋白缺失可预防 HFD 喂养的小鼠肥胖和胰岛素抵抗，并提示波形蛋白作为肥胖和 2 型糖尿病之间的中心介质。
