Apolipoprotein A5 regulates intracellular triglyceride metabolism in adipocytes.

Apolipoprotein A5 regulates intracellular triglyceride metabolism in adipocytes.
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载脂蛋白 A5 调节脂肪细胞内甘油三酯代谢

DOI:
10.3892/mmr.2017.7461
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发表时间:
2017-11
影响因子:
3.4
通讯作者:
Wu CL
Wu CL
中科院分区:
医学4区
文献类型:
--
作者:
Zheng XY;Yu BL;Xie YF;Zhao SP;Wu CL

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先前已经证明载脂蛋白A5 (apoA5)可以被人类脂肪细胞内化,并显著降低细胞内甘油三酯含量。本研究研究了不同条件下脂肪细胞对apoA5的内吞作用,以及apoA5调节细胞甘油三酯储存的潜在机制。结果表明,apoA5蛋白存在于人皮下腹部脂肪组织中。此外,apoA5的摄取在人类肥胖脂肪组织和肥胖或胰岛素抵抗的培养脂肪细胞中减弱。脂肪细胞中低密度脂蛋白受体蛋白1 (LRP1)敲低导致内化apoA5含量降低,提示LRP1在apoA5摄取中起作用。用apoA5处理脂肪细胞可降低脂滴相关蛋白如cidec和perilipin的表达。apoa5处理的脂肪细胞显示出脂肪分解活性和解偶联蛋白1的表达增加,解偶联蛋白1是棕色脂肪细胞中产热的分子效应。这些结果表明,apoA5诱导的脂肪细胞中甘油三酯积累的减少可能与脂肪分解和能量消耗的增加有关,这可能是由于cidec和perilipin的表达减少所致。总之,本研究证明了apoA5在调节脂肪细胞内甘油三酯代谢中的新作用。本研究结果提示apoA5可能作为治疗肥胖及其相关疾病的潜在治疗靶点。
It has previously been demonstrated that apolipoprotein A5 (apoA5) can be internalized by human adipocytes and significantly decreases intracellular triglyceride content. In the present study, endocytosis of apoA5 by adipocytes under different conditions, and the underlying mechanism by which apoA5 regulates cellular triglyceride storage, was investigated. The results revealed that the apoA5 protein was detected in human subcutaneous abdominal adipose tissues. In addition, the uptake of apoA5 was attenuated in human obese adipose tissues and in cultured adipocytes with hypertrophy or insulin resistance. Low-density lipoprotein receptor protein 1 (LRP1) knockdown in adipocytes resulted in a decrease in internalized apoA5 content, suggesting that LRP1 serves a role in apoA5 uptake. Treatment of adipocytes with apoA5 decreased the expression of the lipid droplet-associated proteins such as cidec and perilipin. ApoA5-treated adipocytes demonstrated an increase in lipolysis activity and expression of uncoupling protein 1, which is the molecular effector of thermogenesis in brown adipocytes. These results suggested that decreased triglyceride accumulation in adipocytes induced by apoA5 may be associated with enhanced lipolysis and energy expenditure, which may result from reduced expression of cidec and perilipin. In conclusion, the present study demonstrated a novel role of apoA5 in regulating the intracellular triglyceride metabolism of adipocytes. The results of the present study suggested that apoA5 may serve as a potential therapeutic target for the treatment of obesity and its related disorders.
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