@article{10.1172/jci.insight.128405, author = {Huanqing Gao AND Yuxi Guo AND Qinnan Yan AND Wei Yang AND Ruxuan Li AND Simin Lin AND Xiaochun Bai AND Chuanju Liu AND Di Chen AND Huiling Cao AND Guozhi Xiao}, journal = {JCI Insight}, publisher = {The American Society for Clinical Investigation}, title = {Lipoatrophy and metabolic disturbance in mice with adipose-specific deletion of kindlin-2}, year = {2019}, month = {7}, volume = {4}, url = {https://insight.jci.org/articles/view/128405}, abstract = {Kindlin-2 regulates integrin-mediated cell adhesion to 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. In this study, we generated adipose tissue–specific conditional knockout of kindlin-2 in mice by using Adipoq-Cre BAC–transgenic mice. 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 blood levels of nonesterified fatty acids and triglycerides, 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 PPARγ, mTOR, AKT, and β-catenin proteins, and suppressed adipocyte gene expression and differentiation. Finally, kindlin-2 loss drastically reduced leptin production and caused a high bone mass phenotype. Collectively, these studies establish a critical role of kindlin-2 in control of adipogenesis and lipid metabolism as well as bone homeostasis.}, number = {13}, doi = {10.1172/jci.insight.128405}, url = {https://doi.org/10.1172/jci.insight.128405}, }