Liver-secreted RBP4 does not impair glucose homeostasis in mice
Liver-secreted RBP4 does not impair glucose homeostasis in mice
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DOI：
10.1074/jbc.ra118.004294
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发表时间：
2018-09-28
影响因子：
4.8
通讯作者：
Schupp, Michael
中科院分区：
文献类型：
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作者：
Fedders, Ronja;Muenzner, Matthias;Schupp, Michael
视黄醇结合蛋白4(RBP4)是血液中视黄醇的主要转运蛋白。最近来自遗传小鼠模型的证据表明，循环中的RBP4仅来自肝细胞。由于RBP4在肥胖患者中升高，并与糖耐量异常和胰岛素抵抗的发展有关，我们测试了小鼠肝脏特异性的RBP4过度表达是否破坏了葡萄糖稳态。我们使用腺相关病毒(AAV)来驱动小鼠RBP4在成年小鼠肝脏中的表达，AAV含有高度肝脏特异性启动子。这些小鼠血清RBP4水平的升高与肥胖报告的水平相当。令人惊讶的是，我们发现增加循环RBP4对葡萄糖稳态没有影响。同样，在高脂饮食挑战期间，循环中RBP4水平的升高未能加剧全身血糖和能量平衡参数的恶化。这些发现表明，肝脏分泌的RBP4不会破坏葡萄糖的动态平衡。我们的结论是，在肥胖和胰岛素抵抗状态下观察到的小鼠循环中它的水平的适度增加，不太可能是葡萄糖稳态受损的原因。
Retinol-binding protein 4 (RBP4) is the major transport protein for retinol in blood. Recent evidence from genetic mouse models shows that circulating RBP4 derives exclusively from hepatocytes. Because RBP4 is elevated in obesity and associates with the development of glucose intolerance and insulin resistance, we tested whether a liver-specific overexpression of RBP4 in mice impairs glucose homeostasis. We used adeno-associated viruses (AAV) that contain a highly liver-specific promoter to drive expression of murine RBP4 in livers of adult mice. The resulting increase in serum RBP4 levels in these mice was comparable with elevated levels that were reported in obesity. Surprisingly, we found that increasing circulating RBP4 had no effect on glucose homeostasis. Also during a high-fat diet challenge, elevated levels of RBP4 in the circulation failed to aggravate the worsening of systemic parameters of glucose and energy homeostasis. These findings show that liver-secreted RBP4 does not impair glucose homeostasis. We conclude that a modest increase of its circulating levels in mice, as observed in the obese, insulin-resistant state, is unlikely to be a causative factor for impaired glucose homeostasis.