Maeda Norikazu, Funahashi Tohru, Shimomura Iichiro
Graduate School of Medicine, Osaka University, Osaka, Japan.
Nat Clin Pract Endocrinol Metab. 2008 Nov;4(11):627-34. doi: 10.1038/ncpendmet0980. Epub 2008 Oct 14.
The discovery of aquaporins, which are plasma-membrane-associated water channels, has greatly influenced the medical sciences. So far, thirteen aquaporins have been identified in humans. Among them, types 3, 7, 9, and 10 are subcategorized as aquaglyceroporins, which enable the transport of glycerol as well as water. Although aquaporins have a proven crucial role in water homeostasis, the physiological and pathological importance of aquaporins as glycerol channels is not fully understood. Adipocytes are a major source of glycerol, one of the substrates for hepatic gluconeogenesis. Aquaporin subtypes 7 and 9 (AQP7 and AQP9) are the glycerol channels in adipocytes and hepatocytes, respectively. The coordinated regulation of these channels leads to the optimum balance between release of glycerol by adipocytes and its uptake by the liver. In addition, studies of AQP7 and AQP9 knockout or knockdown mice have clearly demonstrated in vivo the pathophysiological relevance of glycerol channels through effects on glycerol metabolism. Associations between various AQP7 gene mutations and obesity in humans have also been shown. Thus, further research of these two aquaporins might uncover novel targets for therapy.
水通道蛋白是与质膜相关的水通道,其发现对医学科学产生了重大影响。迄今为止,已在人类中鉴定出13种水通道蛋白。其中,3型、7型、9型和10型被归类为水甘油通道蛋白,可转运甘油和水。尽管水通道蛋白在水稳态中起着至关重要的作用,但其作为甘油通道的生理和病理重要性尚未完全明确。脂肪细胞是甘油的主要来源之一,甘油是肝脏糖异生的底物。水通道蛋白7型和9型(AQP7和AQP9)分别是脂肪细胞和肝细胞中的甘油通道。这些通道的协调调节导致脂肪细胞释放甘油与肝脏摄取甘油之间达到最佳平衡。此外,对AQP7和AQP9基因敲除或敲低小鼠的研究清楚地在体内证明了甘油通道通过对甘油代谢的影响而具有的病理生理相关性。在人类中也已显示各种AQP7基因突变与肥胖之间存在关联。因此,对这两种水通道蛋白的进一步研究可能会发现新的治疗靶点。