| Title: |
Active integrins regulate white adipose tissue insulin sensitivity and brown fat thermogenesis |
| Authors: |
Ruiz Ojeda, Francisco Javier; Wang, Jiefu; Bäcker, Theresa; Krueger, Martin; Zamani, Samira; Rosowski, Simon; Gruber, Tim; Onogi, Yasuhiro; Feuchtinger, Annette; Schulz, Tim J; Fässler, Reinhard; Müller, Timo D; García-Cáceres, Cristina; Meier, Matthias; Blüher, Matthias; Ussar, Siegfried |
| Publication Year: |
2021 |
| Collection: |
DIGIBUG: Repositorio Institucional de la Universidad de Granada |
| Subject Terms: |
Integrins; Kindlin-2; Insulin resistance; Adipose tissue; obesity; Brown fat; Insulin receptor; Lipodystrophy |
| Description: |
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 β1 integrin (Itgb1adipo-cre) and Kindlin-2 (Kind2adipo-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 Kind2adipo-cre and Itgb1adipo-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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://hdl.handle.net/10481/100851; https://doi.org/10.1016/j.molmet.2020.101147 |
| DOI: |
10.1016/j.molmet.2020.101147 |
| Availability: |
https://hdl.handle.net/10481/100851; https://doi.org/10.1016/j.molmet.2020.101147 |
| Rights: |
Attribution-NonCommercial-NoDerivatives 4.0 Internacional ; http://creativecommons.org/licenses/by-nc-nd/4.0/ ; open access |
| Accession Number: |
edsbas.71ABEF9 |
| Database: |
BASE |