Apelin, a newly identified adipokine up-regulated by insulin and obesity
Apelin, a newly identified adipokine up-regulated by insulin and obesity
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DOI：
10.1210/en.2004-1427
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发表时间：
2005-04-01
期刊：
影响因子：
4.8
通讯作者：
Valet, P
中科院分区：
文献类型：
--
作者：
Boucher, J;Masri, B;Valet, P
本文呈现的结果表明，人和小鼠脂肪细胞均表达和分泌爱帕琳。分离的脂肪细胞中的爱帕琳mRNA水平接近于存在于白色脂肪组织或已知表达爱帕琳的其他器官（例如肾脏、心脏）中的其他细胞类型，并且在较小程度上接近于棕色脂肪组织。Apelin在脂肪细胞分化阶段表达增加。在小鼠中的四种不同肥胖模型的比较显示，在所有高胰岛素血症相关的肥胖中，脂肪细胞中的apelin表达和apelin血浆水平都大幅增加，并且清楚地表明肥胖或高脂肪喂养不是apelin表达上升的主要决定因素。链脲佐菌素处理的小鼠中胰岛素的缺乏与脂肪细胞中apelin表达的降低有关。此外，脂肪细胞中的爱帕琳蛋白表达被禁食强烈抑制，并在再喂养后恢复，与胰岛素类似。在人类和小鼠脂肪细胞中均观察到胰岛素对爱帕琳肽表达的直接调节，并且明显与磷脂酰肌醇3-激酶、蛋白激酶C和MAPK的刺激相关。这些数据提供了证据表明，胰岛素直接控制脂肪细胞中的爱帕琳基因表达。在肥胖患者中，血浆apelin和胰岛素水平均显著较高，表明胰岛素对apelin的调节可影响apelin的血液浓度。目前的工作确定爱帕琳作为一种新的脂肪细胞内分泌，并集中在其与肥胖相关的胰岛素敏感性状态的变化的潜在联系。
The results presented herein demonstrate that apelin is expressed and secreted by both human and mouse adipocytes. Apelin mRNA levels in isolated adipocytes are close to other cell types present in white adipose tissue or other organs known to express apelin such as kidney, heart, and to a lesser extent brown adipose tissue. Apelin expression is increased during adipocyte differentiation stage. A comparison of four different models of obesity in mice showed a large increase in both apelin expression in fat cells and apelin plasma levels in all the hyperinsulinemia-associated obesities and clearly demonstrated that obesity or high-fat feeding are not the main determinants of the rise of apelin expression. The lack of insulin in streptozotocin-treated mice is associated with a decreased expression of apelin in adipocytes. Furthermore, apelin expression in fat cells is strongly inhibited by fasting and recovered after refeeding, in a similar way to insulin. A direct regulation of apelin expression by insulin is observed in both human and mouse adipocytes and clearly associated with the stimulation of phosphatidylinositol 3-kinase, protein kinase C, and MAPK. These data provide evidence that insulin exerts a direct control on apelin gene expression in adipocytes. In obese patients, both plasma apelin and insulin levels were significantly higher, suggesting that the regulation of apelin by insulin could influence blood concentrations of apelin. The present work identifies apelin as a novel adipocyte endocrine secretion and focuses on its potential link with obesity-associated variations of insulin sensitivity status.