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人水通道蛋白7作为3T3-L1脂肪细胞中水和甘油通道的生物物理评估。

Biophysical assessment of human aquaporin-7 as a water and glycerol channel in 3T3-L1 adipocytes.

作者信息

Madeira Ana, Camps Marta, Zorzano Antonio, Moura Teresa F, Soveral Graça

机构信息

Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal ; Departmento de Bioquímica e Biologia Humana, Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal.

Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain ; Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain.

出版信息

PLoS One. 2013 Dec 20;8(12):e83442. doi: 10.1371/journal.pone.0083442. eCollection 2013.

Abstract

The plasma membrane aquaporin-7 (AQP7) has been shown to be expressed in adipose tissue and its role in glycerol release/uptake in adipocytes has been postulated and correlated with obesity onset. However, some studies have contradicted this view. Based on this situation, we have re-assessed the precise localization of AQP7 in adipose tissue and analyzed its function as a water and/or glycerol channel in adipose cells. Fractionation of mice adipose tissue revealed that AQP7 is located in both adipose and stromal vascular fractions. Moreover, AQP7 was the only aquaglyceroporin expressed in adipose tissue and in 3T3-L1 adipocytes. By overexpressing the human AQP7 in 3T3-L1 adipocytes it was possible to ascertain its role as a water and glycerol channel in a gain-of-function scenario. AQP7 expression had no effect in equilibrium cell volume but AQP7 loss of function correlated with higher triglyceride content. Furthermore it is also reported for the first time a negative correlation between water permeability and the cell non-osmotic volume supporting the observation that AQP7 depleted cells are more prone to lipid accumulation. Additionally, the strong positive correlation between the rates of water and glycerol transport highlights the role of AQP7 as both a water and a glycerol channel and reflects its expression levels in cells. In all, our results clearly document a direct involvement of AQP7 in water and glycerol transport, as well as in triglyceride content in adipocytes.

摘要

质膜水通道蛋白7(AQP7)已被证明在脂肪组织中表达,并且其在脂肪细胞甘油释放/摄取中的作用已被提出并与肥胖症的发生相关。然而,一些研究对此观点提出了反驳。基于这种情况,我们重新评估了AQP7在脂肪组织中的精确定位,并分析了其作为脂肪细胞中水和/或甘油通道的功能。对小鼠脂肪组织进行分级分离显示,AQP7存在于脂肪和基质血管部分中。此外,AQP7是在脂肪组织和3T3-L1脂肪细胞中表达的唯一水甘油通道蛋白。通过在3T3-L1脂肪细胞中过表达人AQP7,可以在功能获得的情况下确定其作为水和甘油通道的作用。AQP7的表达对细胞平衡体积没有影响,但AQP7功能丧失与较高的甘油三酯含量相关。此外,首次报道了水渗透性与细胞非渗透体积之间的负相关,支持了AQP7缺失的细胞更容易发生脂质积累的观察结果。另外,水和甘油运输速率之间的强正相关突出了AQP7作为水和甘油通道的作用,并反映了其在细胞中的表达水平。总之,我们的结果清楚地证明了AQP7直接参与水和甘油运输,以及脂肪细胞中的甘油三酯含量。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbe3/3869813/2332e56cf319/pone.0083442.g001.jpg

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