Department of Molecular Medicine, University of Pavia, Pavia, Italy.
PLoS One. 2013;8(1):e54474. doi: 10.1371/journal.pone.0054474. Epub 2013 Jan 29.
Glycerol outflow from adipocytes has been considered for a decade to be mediated by aquaporin-7, an aquaglyceroporin highly expressed in the adipose tissue. Its involvement in glycerol metabolism has been widely studied also in humans. Recent studies in different aquaporin-7 KO mice models pose two different questions 1) the exact localization of aquaporin-7 in human white adipose tissue; 2) the existence of other aquaglyceroporins that work with aquaporin-7 to guarantee glycerol efflux and thus a normal adiposity in humans. To this purpose we investigated the expression, the localization and the functioning of aquaglyceroporin-10 in subcutaneous white adipose tissue, in isolated and cultured differentiated adipocytes.
METHODOLOGY/PRINCIPAL FINDINGS: Aquaporin-7 and -10 were expressed in the white adipose tissue both at mRNA and at protein level. Immunofluorescence revealed aquaporin-7 and -10 labelling in the human adipose tissue both to the plasma membrane and to a thin rim of cytoplasm of adipocytes. Aquaporin-7, but not aquaporin-10, colocalized with the endothelial marker CD34. Human cultured differentiated adipocytes showed an aquaporin-7 and -10 labelling mainly in the cytoplasm and in the lipid droplets with insulin reinforcing the lipid droplets staining and isoproterenol inducing its translocation to the plasma membrane compartment. Water and glycerol permeability measurements using adipocytes and adipose membrane vesicles confirmed the presence of functioning aquaglyceroporins. Aquaporin-10 silencing in human differentiated adipocytes resulted in a 50% decrease of glycerol and osmotic water permeability.
CONCLUSIONS/SIGNIFICANCE: The results indicate that aquaporin-7, differently from mice, is present in both adipocyte and capillary plasma membranes of human adipose tissue. Aquaporin-10, on the contrary, is expressed exclusively in the adipocytes. The expression of two aquaglyceroporins in human adipose tissue is particularly important for the maintenance of normal or low glycerol contents inside the adipocyte, thus protecting humans from obesity.
十年来，人们一直认为脂肪细胞中的甘油外流是由水通道蛋白-7（一种在脂肪组织中高度表达的水甘油通道蛋白）介导的。其在甘油代谢中的作用也在人类中得到了广泛研究。最近在不同的水通道蛋白-7 KO 小鼠模型中的研究提出了两个不同的问题：1）水通道蛋白-7在人白色脂肪组织中的精确定位；2）是否存在其他与水通道蛋白-7一起工作以保证甘油外排从而维持人类正常肥胖的水甘油通道蛋白。为此，我们研究了水通道蛋白-10 在皮下白色脂肪组织中的表达、定位和功能，包括在分离和培养的分化脂肪细胞中。
方法/主要发现：水通道蛋白-7 和 -10 在白色脂肪组织中均在 mRNA 和蛋白质水平上表达。免疫荧光显示水通道蛋白-7 和 -10 在人脂肪组织中均定位于质膜和脂肪细胞的细胞质薄环。水通道蛋白-7 而非水通道蛋白-10 与内皮标志物 CD34 共定位。人培养的分化脂肪细胞显示水通道蛋白-7 和 -10 的标记主要位于细胞质和脂滴中，胰岛素增强脂滴染色，异丙肾上腺素诱导其向质膜区室转位。使用脂肪细胞和脂肪膜囊泡进行水和甘油通透性测量证实了功能性水甘油通道蛋白的存在。在人分化脂肪细胞中沉默水通道蛋白-10 导致甘油和渗透水通透性降低 50%。
结论/意义：结果表明，与小鼠不同，水通道蛋白-7 存在于人脂肪组织的脂肪细胞和毛细血管质膜中。相反，水通道蛋白-10 仅在脂肪细胞中表达。两种水甘油通道蛋白在人脂肪组织中的表达对于维持脂肪细胞内正常或低甘油含量特别重要，从而保护人类免受肥胖的影响。
