Vasopressin mediates fructose-induced metabolic syndrome by activating the V1b receptor
Vasopressin mediates fructose-induced metabolic syndrome by activating the V1b receptor
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DOI：
10.1172/jci.insight.140848
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发表时间：
2021-01-11
期刊：
影响因子：
8
通讯作者：
Lanaspa, Miguel A.
中科院分区：
文献类型：
--
作者：
Andres-Hernando, Ana;Jensen, Thomas J.;Lanaspa, Miguel A.
肥胖患者血清加压素水平经常升高，通过测量稳定的类似物和肽素来观察。加压素主要通过尿浓缩作用重吸收水分。然而，脂肪也是代谢水的来源，增加了加压素可能在脂肪积累中发挥作用的可能性。据报道，果糖也能刺激血管加压素。在这里，我们测试的假设，果糖诱导的代谢综合征是由血管加压素介导的。口服果糖、葡萄糖或高果糖玉米糖浆可增加血管加压素（和肽素）浓度，并由果糖激酶（一种果糖代谢特异性酶）介导。抑制加压素与水化预防和改善果糖诱导的代谢综合征。加压素的作用是由加压素1b受体（V1 bR）介导的，因为V1 bR-KO小鼠完全受到保护，而V1 a-KO小鼠反而表现出更差的代谢综合征。该机制可能部分由肝脏中V1 bR的从头表达介导，其响应于果糖而放大果糖激酶的表达。因此，我们的研究证明了加压素通过脂肪的积累作为代谢水的来源在水保护中的作用。在临床上，他们还建议增加水的摄入量可能是预防或治疗代谢综合征的有益方法。
Subjects with obesity frequently have elevated serum vasopressin levels, noted by measuring the stable analog, copeptin. Vasopressin acts primarily to reabsorb water via urinary concentration. However, fat is also a source of metabolic water, raising the possibility that vasopressin might have a role in fat accumulation. Fructose has also been reported to stimulate vasopressin. Here, we tested the hypothesis that fructose-induced metabolic syndrome is mediated by vasopressin. Orally administered fructose, glucose, or high-fructose corn syrup increased vasopressin (copeptin) concentrations and was mediated by fructokinase, an enzyme specific for fructose metabolism. Suppressing vasopressin with hydration both prevented and ameliorated fructose-induced metabolic syndrome. The vasopressin effects were mediated by the vasopressin 1b receptor (V1bR), as V1bR-KO mice were completely protected, whereas V1a-KO mice paradoxically showed worse metabolic syndrome. The mechanism is likely mediated in part by de novo expression of V1bR in the liver that amplifies fructokinase expression in response to fructose. Thus, our studies document a role for vasopressin in water conservation via the accumulation of fat as a source of metabolic water. Clinically, they also suggest that increased water intake may be a beneficial way to both prevent or treat metabolic syndrome.