Vimentin Deficiency Prevents High-Fat Diet-Induced Obesity and Insulin Resistance in Mice

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

Automated summary

This study showed that genetic deletion of vimentin in mice fed a high-fat diet led to less weight gain, reduced adiposity, improved glucose tolerance, but higher levels of serum triglycerides and non-esterified fatty acids. Vimentin deficiency in adipocytes resulted in decreased CD36 and GLUT4 levels, indicating defects in intracellular trafficking. These findings suggest that vimentin may play a central role in linking obesity and type 2 diabetes mellitus.