| First Author | Ruiz-Ojeda FJ | Year | 2021 |
| Journal | Mol Metab | Volume | 45 |
| Pages | 101147 | PubMed ID | 33359386 |
| Mgi Jnum | J:302197 | Mgi Id | MGI:6507659 |
| Doi | 10.1016/j.molmet.2020.101147 | Citation | Ruiz-Ojeda FJ, et al. (2021) Active integrins regulate white adipose tissue insulin sensitivity and brown fat thermogenesis. Mol Metab 45:101147 |
| abstractText | OBJECTIVE: Reorganization of the extracellular matrix is a prerequisite for healthy adipose tissue expansion, whereas fibrosis is a key feature of adipose dysfunction and inflammation. However, very little is known about the direct effects of impaired cell-matrix interaction in adipocyte function and insulin sensitivity. The objective of this study was to determine whether integrin activity can regulate insulin sensitivity in adipocytes and thereby systemic metabolism. METHODS: We characterized integrin activity in adipose tissue and its consequences on whole-body metabolism using adipose-selective deletion of beta1 integrin (Itgb1(adipo-cre)) and Kindlin-2 (Kind2(adipo-cre)) in mice. RESULTS: We demonstrate that integrin signaling regulates white adipocyte insulin action and systemic metabolism. Consequently, loss of adipose integrin activity, similar to loss of adipose insulin receptors, results in a lipodystrophy-like phenotype and systemic insulin resistance. However, brown adipose tissue of Kind2(adipo-cre) and Itgb1(adipo-cre) mice is chronically hyperactivated and has increased substrate delivery, reduced endothelial basement membrane thickness, and increased endothelial vesicular transport. CONCLUSIONS: Thus, we establish integrin-extracellular matrix interactions as key regulators of white and brown adipose tissue function and whole-body metabolism. |
