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

Ruiz-Ojeda, Francisco Javier; Wang, Jiefu; Baecker, Theresa; Krueger, Martin; Zamani, Samira; Rosowski, Simon; Gruber, Tim; Onogi, Yasuhiro; Feuchtinger, Annette; Schulz, Tim J.; Faessler, Reinhard; Mueller, Timo D.; Garcia-Caceres, Cristina; Meier, Matthias; Blueher, Matthias; Ussar, Siegfried

doi:10.1016/j.molmet.2020.101147

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

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Faessler, Reinhard
Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society;

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Citation

Ruiz-Ojeda, F. J., Wang, J., Baecker, T., Krueger, M., Zamani, S., Rosowski, S., et al. (2021). Active integrins regulate white adipose tissue insulin sensitivity and brown fat thermogenesis. Molecular Metabolism, 45: 101147. doi:10.1016/j.molmet.2020.101147.

Cite as: https://hdl.handle.net/21.11116/0000-0008-A85A-6

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 celle-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 beta 1 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. (C) 2020 The Author(s). Published by Elsevier GmbH.