Apolipoprotein A5 internalized by human adipocytes modulates cellular triglyceride content
Apolipoprotein A5 internalized by human adipocytes modulates cellular triglyceride content
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DOI：
10.1515/hsz-2011-0259
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发表时间：
2012-03
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影响因子：
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通讯作者：
Xiao-yan Zheng;Shuiping Zhao;Bi‐lian Yu;Chenfang Wu;Ling Liu
中科院分区：
文献类型：
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作者：
Xiao-yan Zheng;Shuiping Zhao;Bi‐lian Yu;Chenfang Wu;Ling Liu
摘要载脂蛋白A5（apoA5）是血浆甘油三酯（TG）水平的重要决定因素，近年来研究发现，apoA5可调节肝细胞TG代谢。在这项研究中，我们研究了apoA5是否可以被脂肪细胞内化并调节细胞TG储存。人前脂肪细胞来源于接受腹部手术的患者的皮下脂肪组织，分化为成熟脂肪细胞。脉冲追踪实验表明，apoA5被内化到人脂肪细胞中，并且在脉冲期间内化的apoA5的约70%在24小时追踪内保持在细胞内，而30%被降解。预孵育肝素和受体相关蛋白，这两者都防止了apoA5与低密度脂蛋白受体基因家族成员的相互作用，显着降低了apoA5的摄取分别为61%和52%，随后证实了蛋白质印迹分析。使用共聚焦显微镜，我们证明了标记的载脂蛋白A5包围在人类脂肪细胞的脂滴和共定位与已知的脂滴蛋白perilipin。重要的是，用apoA5处理脂肪细胞显著降低了细胞TG储存。总之，载脂蛋白A5可以内化的人脂肪细胞，并可能作为一种新的调节剂，以控制TG储存在人脂肪细胞。
Abstract Apolipoprotein A5 (apoA5), an important determinant of plasma triglyceride (TG) levels, has been recently reported to modulate TG metabolism in hepatocytes. In this study, we investigated whether apoA5 can be internalized by adipocytes and regulate cellular TG storage. Human preadipocytes, derived from subcutaneous adipose tissue of patients undergoing abdominal surgery, were differentiated into mature adipocytes. Pulse-chase experiments revealed that apoA5 was internalized into human adipocytes, and ∼70% of the apoA5 internalized during the pulse remained intracellular within a 24-h chase, while 30% was degraded. Preincubation with heparin and the receptor-associated protein, both of which prevented the apoA5 interaction with members of the low-density lipoprotein receptor gene family, markedly reduced the uptake of apoA5 by 61% and 52%, respectively, which were subsequently confirmed by Western blot analysis. Using confocal microscopy, we demonstrated that labeled apoA5 surrounded lipid droplets in human adipocytes and colocalized with the known lipid droplet protein perilipin. Importantly, treatment of adipocytes with apoA5 significantly decreased cellular TG storage. In conclusion, apoA5 can be internalized by human adipocytes and may act as a novel regulator to control TG storage in human adipocytes.