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 (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.

中文翻译：

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活性整合素调节白色脂肪组织胰岛素敏感性和棕色脂肪产热

客观的

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知之甚少。本研究的目的是确定整联蛋白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。

方法

我们在小鼠中使用 β1 整合素 (Itgb1 ^adipo-cre ) 和 Kindlin-2 (Kind2 ^adipo-cre ) 的脂肪选择性缺失来表征脂肪组织中的整合素活性及其对全身代谢的影响。

结果

我们证明整合素信号调节白色脂肪细胞胰岛素作用和全身代谢。因此，脂肪整合素活性的丧失，类似于脂肪胰岛素受体的丧失，导致脂肪营养不良样表型和全身性胰岛素抵抗。然而，Kind2 ^adipo-cre和 Itgb1 ^adipo-cre小鼠的棕色脂肪组织长期过度^活化，底物传递增加，内皮基底膜厚度减少，内皮囊泡运输增加。

结论

因此，我们建立了整合素-细胞外基质相互作用作为白色和棕色脂肪组织功能和全身代谢的关键调节剂。