Adiponectin is secreted via caveolin 1-dependent mechanisms in white adipocytes
Adiponectin is secreted via caveolin 1-dependent mechanisms in white adipocytes
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DOI：
10.1530/joe-20-0078
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发表时间：
2020-10-01
影响因子：
4
通讯作者：
Olofsson, Charlotta S.
中科院分区：
文献类型：
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作者：
Brannmark, Cecilia;Kay, Emma, I;Olofsson, Charlotta S.
在这里，我们研究了蛋白质小窝蛋白1（Cav 1）和小窝在分泌的白色脂肪细胞激素脂联素的作用。使用小鼠原代皮下脂肪细胞基因耗尽Cav 1，我们表明，脂联素分泌，刺激肾上腺素或胰岛素，被废除，而基础（未刺激）释放脂联素升高。脂联素分泌在野生型小鼠和人脂肪细胞中受到类似的影响，其中小窝结构被化学破坏。从Cav 1基因敲除小鼠分离的脂肪细胞中的离体分泌的改变伴随着高分子量（HMW）形式的脂联素的血清水平降低，而脂联素的总浓度不变。有趣的是，高分子量脂联素的水平保持在脂肪组织从Cav 1耗尽的小鼠，这意味着分泌缺陷的存在。已知参与cAMP/肾上腺素能触发的脂联素胞吐作用的关键调节蛋白（β-3-肾上腺素能受体和交换蛋白直接由cAMP激活）的基因表达在Cav 1缺失脂肪细胞中保持完整。显微镜和分馏研究表明，脂联素囊泡不与Cav 1共定位，但一些囊泡与特定部分的小窝。我们的研究表明，Cav 1在高分子量脂联素的分泌中具有重要作用，尽管脂联素囊泡与该蛋白没有明显的相关性。我们认为，Cav 1，和/或小窝结构域，是必不可少的组织参与调节高分子量脂联素胞吐的信号转导途径，一个功能，在Cav 1/小窝耗尽脂肪细胞被破坏。
Here we have investigated the role of the protein caveolin 1 (Cav1) and caveolae in the secretion of the white adipocyte hormone adiponectin. Using mouse primary subcutaneous adipocytes genetically depleted of Cav1, we show that the adiponectin secretion, stimulated either adrenergically or by insulin, is abrogated while basal (unstimulated) release of adiponectin is elevated. Adiponectin secretion is similarly affected in wildtype mouse and human adipocytes where the caveolae structure was chemically disrupted. The altered ex vivo secretion in adipocytes isolated from Cav1 null mice is accompanied by lowered serum levels of the high-molecular weight (HMW) form of adiponectin, whereas the total concentration of adiponectin is unaltered. Interestingly, levels of HMW adiponectin are maintained in adipose tissue from Cav1-depleted mice, signifying that a secretory defect is present. The gene expression of key regulatory proteins known to be involved in cAMP/adrenergically triggered adiponectin exocytosis (the beta-3-adrenergic receptor and exchange protein directly activated by cAMP) remains intact in Cav1 null adipocytes. Microscopy and fractionation studies indicate that adiponectin vesicles do not co-localise with Cav1 but that some vesicles are associated with a specific fraction of caveolae. Our studies propose that Cav1 has an important role in secretion of HMW adiponectin, even though adiponectin-containing vesicles are not obviously associated with this protein. We suggest that Cav1, and/or the caveolae domain, is essential for the organisation of signalling pathways involved in the regulation of HMW adiponectin exocytosis, a function that is disrupted in Cav1/caveolae-depleted adipocytes.