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Ruiz Ojeda, F.J. ; Wang, J. ; Bäcker, T. ; Krueger, M.* ; Zamani, S. ; Rosowski, S. ; Gruber, T. ; Onogi, Y. ; Feuchtinger, A. ; Schulz, T.J.* ; Fässler, R.* ; Müller, T.D. ; García-Cáceres, C. ; Meier, M. ; Blüher, M. ; Ussar, S.

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

Mol. Metab. 45:101147 (2021)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Adipose Tissue ; Brown Fat ; Insulin Receptor ; Insulin Resistance ; Integrins ; Kindlin-2 ; Lipodystrophy ; Obesity
ISSN (print) / ISBN 2212-8778
e-ISSN 2212-8778
Journal Molecular Metabolism
Quellenangaben Volume: 45, Issue: , Pages: , Article Number: 101147 Supplement: ,
Publisher Elsevier
Publishing Place Amsterdam
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Obesity (IDO)
Institute of Developmental Genetics (IDG)
Helmholtz Pioneer Campus (HPC)
Research Unit Analytical Pathology (AAP)
Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
Grants European Research Council ERC
Deutsche Forschungsgemeinschaft
Fundación Alfonso Martín Escudero