Hara-Chikuma Mariko, Sohara Eisei, Rai Tatemitsu, Ikawa Masahito, Okabe Masaru, Sasaki Sei, Uchida Shinichi, Verkman A S
Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, California 94143, USA.
J Biol Chem. 2005 Apr 22;280(16):15493-6. doi: 10.1074/jbc.C500028200. Epub 2005 Mar 3.
Aquaporin-7 (AQP7) is a water/glycerol transporting protein expressed in adipocyte plasma membranes. We report here remarkable age-dependent hypertrophy in adipocytes in AQP7-deficient mice. Wild type and AQP7 null mice had similar growth at 0-16 weeks as assessed by body weight; however, by 16 weeks AQP7 null mice had 3.7-fold increased body fat mass. Adipocytes from AQP7 null mice of age 16 weeks were greatly enlarged (diameter 118 mum) compared with wild type mice (39 mum). Adipocytes from AQP7 null mice also accumulated excess glycerol (251 versus 86 nmol/mg of protein) and triglycerides (3.4 versus 1.7 mumol/mg of protein). In contrast, at age 4 weeks, adipocyte volume and body fat mass were comparable in wild type and AQP7 null mice. To investigate the mechanism(s) responsible for the progressive adipocyte hypertrophy, glycerol permeability and fat metabolism were studied in adipocytes isolated from the younger mice. Plasma membrane glycerol permeability measured by [(14)C]glycerol uptake was 3-fold reduced in AQP7-deficient adipocytes. However, adipocyte lipolysis, measured by free fatty acid release and hormone-sensitive lipase activity, and lipogenesis, measured by [(14)C]glucose incorporation into triglycerides, were not affected by AQP7 deletion. These data suggest that adipocyte hypertrophy in AQP7 deficiency results from defective glycerol exit and consequent accumulation of glycerol and triglycerides. Increasing AQP7 expression/function in adipocytes may reduce adipocyte volume and fat mass in obesity.
水通道蛋白7（AQP7）是一种在脂肪细胞质膜中表达的水/甘油转运蛋白。我们在此报告，AQP7基因敲除小鼠的脂肪细胞出现了显著的年龄依赖性肥大。通过体重评估，野生型和AQP7基因敲除小鼠在0至16周时生长情况相似；然而，到16周时，AQP7基因敲除小鼠的体脂量增加了3.7倍。与野生型小鼠（直径39μm）相比，16周龄的AQP7基因敲除小鼠的脂肪细胞大幅增大（直径118μm）。AQP7基因敲除小鼠的脂肪细胞还积累了过量的甘油（251对86 nmol/mg蛋白质）和甘油三酯（3.4对1.7μmol/mg蛋白质）。相比之下，在4周龄时，野生型和AQP7基因敲除小鼠的脂肪细胞体积和体脂量相当。为了研究导致脂肪细胞逐渐肥大的机制，我们对从较年轻小鼠分离的脂肪细胞的甘油通透性和脂肪代谢进行了研究。通过[¹⁴C]甘油摄取测量的质膜甘油通透性在AQP7缺陷型脂肪细胞中降低了3倍。然而，通过游离脂肪酸释放和激素敏感性脂肪酶活性测量的脂肪细胞脂解作用，以及通过[¹⁴C]葡萄糖掺入甘油三酯测量的脂肪生成作用，均不受AQP7缺失的影响。这些数据表明，AQP7缺陷导致的脂肪细胞肥大是由于甘油排出缺陷以及随之而来甘油和甘油三酯的积累。增加脂肪细胞中AQP7的表达/功能可能会减少肥胖症中的脂肪细胞体积和脂肪量。
