Abstract: SA-PO804
Lipoatrophy and Metabolic Disturbance in Mice with Adipose-Specific Deletion of Kindlin 2
Session Information
- Health Maintenance, Nutrition, Metabolism - II
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Health Maintenance, Nutrition, and Metabolism
- 1300 Health Maintenance, Nutrition, and Metabolism
Authors
- Gao, Huanqing, Southern University of Science and Technology, Shenzhen, Comoros
- Xiao, Guozhi, Southern University of Science and Technology, Shenzhen, Comoros
Background
Kindlin-2 regulates the integrin-mediated cell adhesion and migration on the extracellular matrix. Our recent studies demonstrate important roles of Kindlin-2 in regulation of mesenchymal stem cell differentiation and skeletal development.
Methods
In this study we generated adipose tissue-specific conditional knock-out Kindlin-2 mice by using the Adipoq-Cre BAC transgenic mice. We used GTT to assess the glucose tolerance and ITT to assess insulin sensitivity.
Results
The results showed that deleting Kindlin-2 expression in adipocytes in mice caused a severe lipodystrophy with drastically reduced adipose tissue mass. Kindlin-2 ablation elevated the levels of blood nonesterified fatty acids (NEFA) and triglyceride, resulting in massive fatty livers in the mutant mice fed with high fat diet (HFD). Furthermore, HFD-fed mutant mice displayed type II diabetes-like phenotypes, including elevated levels of fasting blood glucose, glucose intolerance, and peripheral insulin resistance. Kindlin-2 loss dramatically reduced the expression levels of multiple key factors, including PPARg, mTOR, AKT, and b-catenin proteins, and suppressed adipocyte gene expression and differentiation. Finally, Kindlin-2 loss drastically reduced leptin production and caused a high bone mass phenotype.
Conclusion
Our study established a critical role of Kindlin-2 in control of adipogenesis and lipid metabolism as well as bone homeostasis.
Funding
- Government Support - Non-U.S.