Caveolin-1 (cav1) is an important structural and signaling component of plasma membrane invaginations called caveolae and is abundant in adipocytes. As previously reported, adipocyte-specific ablation of the cav1 gene (ad-cav1KO mouse) does not result in elimination of the protein, as cav1 protein traffics to adipocytes from neighboring endothelial cells. However, this mouse is a functional knockout as adipocyte caveolar structures are depleted. Compared to controls, ad-cav1KO mice on a high-fat diet (HFD) display improved whole-body glucose clearance despite complete loss of glucose-stimulated insulin secretion, blunted insulin-stimulated AKT activation in metabolic tissues and partial lipodystrophy. The cause is increased insulin-independent glucose uptake by white adipose tissue (AT) and reduced hepatic gluconeogenesis. Furthermore, high fat fed ad-cav1KO mice display significant AT inflammation, fibrosis, mitochondrial dysfunction, and dysregulated lipid metabolism. The glucose clearance phenotype of the ad-cav1KO mice is at least partially mediated by AT small extracellular vesicles (AT-sEVs). Injection of control mice with AT-sEVs from ad-cav1KO mice phenocopies ad-cav1KO characteristics. Interestingly, AT-sEVs from ad-cav1KO mice propagate the phenotype of the AT to the liver. These data indicate that adipocyte cav1 is essential for healthy adaptation of the AT to overnutrition and prevents aberrant propagation of negative phenotypes to other organs by EVs.

中文翻译：

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脂肪细胞中的 Caveolin-1 合成不足会通过细胞外囊泡刺激全身胰岛素依赖性葡萄糖摄取


Caveolin-1 (cav1) 是质膜内陷（称为小窝）的重要结构和信号传导成分，在脂肪细胞中含量丰富。正如之前报道的，脂肪细胞特异性消除 cav1 基因（ad-cav1KO 小鼠）不会导致该蛋白质的消除，因为 cav1 蛋白质从邻近的内皮细胞转移到脂肪细胞。然而，该小鼠是功能性基因敲除小鼠，因为脂肪细胞小窝结构被耗尽。与对照组相比，高脂饮食（HFD）的 ad-cav1KO 小鼠尽管葡萄糖刺激的胰岛素分泌完全丧失、代谢组织中胰岛素刺激的 AKT 激活减弱以及部分脂肪营养不良，但其全身葡萄糖清除率有所改善。原因是白色脂肪组织 (AT) 增加了胰岛素依赖性葡萄糖摄取，并减少了肝脏糖异生作用。此外，高脂肪喂养的 ad-cav1KO 小鼠表现出明显的 AT 炎症、纤维化、线粒体功能障碍和脂质代谢失调。 ad-cav1KO 小鼠的葡萄糖清除表型至少部分由 AT 小细胞外囊泡 (AT-sEV) 介导。向对照小鼠注射来自 ad-cav1KO 小鼠的 AT-sEV，其表型复制了 ad-cav1KO 特征。有趣的是，来自 ad-cav1KO 小鼠的 AT-sEV 将 AT 表型传播到肝脏。这些数据表明脂肪细胞 cav1 对于 AT 健康适应营养过剩至关重要，并防止 EV 向其他器官异常传播负面表型。