Adaptation to fasting by glycerol transport through aquaporin 7 in adipose tissue
Adaptation to fasting by glycerol transport through aquaporin 7 in adipose tissue
复制标题
DOI：
10.1073/pnas.0406230101
复制
发表时间：
2004-12-21
影响因子：
11.1
通讯作者：
Matsuzawa, Y
中科院分区：
文献类型：
--
作者：
Maeda, N;Funahashi, T;Matsuzawa, Y
脂肪细胞水解甘油三酯并分泌游离脂肪酸和甘油进入循环。甘油从脂肪细胞转运的分子机制尚未阐明。在这里，我们研究了缺乏水通道蛋白7（Aqp 7），在脂肪组织中表达的水甘油通道蛋白的成员，小鼠的甘油和葡萄糖代谢，并证明了Aqp 7作为甘油网关分子在体内的功能。与WT小鼠相比，Aqp 7敲除（KO）小鼠的血浆甘油水平较低，但血浆游离脂肪酸水平正常。在KO小鼠中，响应于β（3）-肾上腺素能激动剂的血浆甘油水平的增加严重受损。肾上腺素刺激的甘油分泌也受损Aqp 7敲低脂肪细胞。在长期禁食期间，WT小鼠的血浆甘油升高，血糖水平维持不变。相比之下，KO小鼠在长时间禁食期间显示出血浆甘油的中断增加和血浆葡萄糖的快速降低。我们的研究结果表明，缺乏有效的甘油转运脂肪细胞的甘油网关分子导致缺陷的适应长期禁食。
Adipocytes hydrolyze triglycerides and secrete free fatty acids and glycerol into the circulation. The molecular mechanism involved in glycerol transport from adipocytes has not been elucidated. Here, we investigated glycerol and glucose metabolism in mice lacking aquaporin 7 (Aqp7), a member of the aquaglyceroporins expressed in adipose tissue, and demonstrated that Aqp7 functions as a glycerol gateway molecule in vivo. Aqp7-knockout (KO) mice had lower plasma glycerol levels compared with WT mice but had normal plasma free fatty acid levels. The increase in plasma glycerol level in response to beta(3)-adrenergic agonist was severely impaired in KO mice. Epinephrine-stimulated glycerol secretion was also impaired in Aqp7 knockdown adipocytes. During prolonged fasting, plasma glycerol was elevated and the plasma glucose level was maintained in WT mice. In contrast, KO mice showed a disrupted increase of plasma glycerol and rapid reduction of plasma glucose during prolonged fasting. Our findings indicate that the lack of effective glycerol transport from adipocytes by glycerol gateway molecule causes defective adaptation to prolonged fasting.