Active integrins regulate white adipose tissue insulin sensitivity and brown fat thermogenesis

Francisco Javier Ruiz-Ojeda, Jiefu Wang, Theresa Bäcker, Martin Krueger, Samira Zamani, Simon Rosowski, Tim Gruber, Yasuhiro Onogi, Annette Feuchtinger, Tim J. Schulz, Reinhard Fässler, Timo D. Müller, Cristina García-Cáceres, Matthias Meier, Matthias Blüher, Siegfried Ussar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

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.

Original languageEnglish
Article number101147
JournalMolecular Metabolism
Volume45
DOIs
StatePublished - 2021/03

Keywords

  • Adipose tissue
  • Brown fat
  • Insulin receptor
  • Insulin resistance
  • Integrins
  • Kindlin-2
  • Lipodystrophy
  • Obesity

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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