Endothelial Cell Surface Expressed Chemotaxis and Apoptosis Regulator (ECSCR) Regulates Lipolysis in White Adipocytes via the PTEN/AKT Signaling Pathway.
Endothelial Cell Surface Expressed Chemotaxis and Apoptosis Regulator (ECSCR) Regulates Lipolysis in White Adipocytes via the PTEN/AKT Signaling Pathway.
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DOI：
10.1371/journal.pone.0144185
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Wilkinson GA
中科院分区：
文献类型：
--
作者：
Kilari S;Cossette S;Pooya S;Bordas M;Huang YW;Ramchandran R;Wilkinson GA
血浆甘油三酯升高与心脏病和中风的易感性增加有关，但这种关系背后的机制尚不清楚。更清楚地了解影响血浆甘油三酯的基因产物可能有助于确定这些疾病的新治疗靶点。内皮细胞表面表达趋化和凋亡调节剂（ECSCR）最初被研究为内皮细胞标志物，但最近在白色脂肪细胞中被发现，白色脂肪细胞是甘油三酯的主要储存细胞类型。在这里，我们证实了ECSCR在白色脂肪细胞中的表达，并表明ECSCR敲除小鼠显示空腹血浆甘油三酯升高。在细胞水平上，培养的3T3-L1脂肪细胞对Ecscr沉默显示出迟钝的Akt磷酸化反应。此外，我们发现与ECSCR相关的磷酸酶和含有紧张素同源性的脂质磷酸酶（PTEN）在胰岛素刺激下增加。这些数据表明，ECSCR有助于控制白色脂肪细胞的脂肪分解。在这种情况下，缺乏Ecscr的白色脂肪细胞显示PTEN活性升高，从而降低AKT的激活并损害胰岛素介导的脂肪分解抑制。总之，这些结果表明ECSCR在调节白色脂肪组织的脂肪分解中起关键作用。
Elevated plasma triglycerides are associated with increased susceptibility to heart disease and stroke, but the mechanisms behind this relationship are unclear. A clearer understanding of gene products which influence plasma triglycerides might help identify new therapeutic targets for these diseases. The Endothelial Cell Surface expressed Chemotaxis and apoptosis Regulator (ECSCR) was initially studied as an endothelial cell marker, but has recently been identified in white adipocytes, the primary storage cell type for triglycerides. Here we confirm ECSCR expression in white adipocytes and show that Ecscr knockout mice show elevated fasting plasma triglycerides. At a cellular level, cultured 3T3-L1 adipocytes silenced for Ecscr show a blunted Akt phosphorylation response. Additionally we show that the phosphatase and tensin homology containing (PTEN) lipid phosphatase association with ECSCR is increased by insulin stimulation. These data suggest a scenario by which ECSCR contributes to control of white adipocyte lipolysis. In this scenario, white adipocytes lacking Ecscr display elevated PTEN activity, thereby reducing AKT activation and impairing insulin-mediated suppression of lipolysis. Collectively, these results suggest that ECSCR plays a critical function in regulating lipolysis in white adipose tissue.