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Free keywords:
Endocrinology & Metabolism; Integrins; Kindlin-2; Insulin resistance; Adipose tissue; Obesity; Brown
fat; Insulin receptor; Lipodystrophy;
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.
