RG Adipocytes and Metabolism, Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, 85764, Neuherberg, Germany; German Center for Diabetes Research (DZD), 85764, Neuherberg, Germany.
Institute for Anatomy, University of Leipzig, 04103, Leipzig, Germany.
Mol Metab. 2021 Mar;45:101147. doi: 10.1016/j.molmet.2020.101147. Epub 2021 Jan 7.
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.
We characterized integrin activity in adipose tissue and its consequences on whole-body metabolism using adipose-selective deletion of β1 integrin (Itgb1) and Kindlin-2 (Kind2) in mice.
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 and Itgb1 mice is chronically hyperactivated and has increased substrate delivery, reduced endothelial basement membrane thickness, and increased endothelial vesicular transport.
Thus, we establish integrin-extracellular matrix interactions as key regulators of white and brown adipose tissue function and whole-body metabolism.
细胞外基质的重组是健康脂肪组织扩张的先决条件，而纤维化是脂肪功能障碍和炎症的关键特征。然而，关于受损的细胞-基质相互作用对脂肪细胞功能和胰岛素敏感性的直接影响，我们知之甚少。本研究的目的是确定整合素活性是否可以调节脂肪细胞中的胰岛素敏感性，从而调节全身代谢。
我们使用脂肪组织中β1 整合素（Itgb1）和 Kindlin-2（Kind2）的脂肪选择性缺失来描述整合素活性及其对全身代谢的影响。
我们证明整合素信号调节白色脂肪细胞的胰岛素作用和全身代谢。因此，失去脂肪组织中的整合素活性，类似于失去脂肪组织中的胰岛素受体，会导致脂肪营养不良样表型和全身胰岛素抵抗。然而，Kind2 和 Itgb1 小鼠的棕色脂肪组织呈慢性过度激活状态，并且具有增加的底物输送、减少的内皮基底膜厚度和增加的内皮小泡运输。
因此，我们将整合素-细胞外基质相互作用确立为白色和棕色脂肪组织功能及全身代谢的关键调节因子。
