Elsevier

Molecular Metabolism

Volume 45, March 2021, 101147
Molecular Metabolism

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

Under a Creative Commons license
open access

Highlights

β1 and β3 integrins interact with insulin signaling to regulate white adipocyte insulin sensitivity and systemic metabolism.

Impaired integrin activity results in lipodystrophy in the absence of hepatosteatosis.

β1 integrin activity regulates energy expenditure and vascular permeability in brown adipose tissue.

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.

Keywords

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