Regulation of angiopoietin-like 4 and lipoprotein lipase in human adipose tissue
Regulation of angiopoietin-like 4 and lipoprotein lipase in human adipose tissue
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DOI：
10.1016/j.jacl.2018.02.006
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发表时间：
2018-06-01
影响因子：
4.4
通讯作者：
Kersten, Sander
中科院分区：
文献类型：
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作者：
Dijk, Wieneke;Schutte, Sophie;Kersten, Sander
背景：血浆甘油三酯升高越来越多地被认为是冠状动脉疾病的一个危险因素。血管生成素样4（ANGPTL4）是一种能提高血浆甘油三酯水平并作为冠状动脉疾病风险调节剂的蛋白质。ANGPTL4通过抑制脂蛋白脂酶（LPL）升高血浆甘油三酯水平，脂蛋白脂酶（LPL）是催化毛细血管内皮细胞上循环甘油三酯水解的酶。目的：本研究的目的是评估人脂肪组织中ANGPTL4和LPL之间的关联，并检查营养状况对ANGPTL4表达的影响。我们测定了大量接受减肥手术的严重肥胖患者不同脂肪组织中ANGPTL4和LPL的mRNA和蛋白水平。结果：ANGPTL4 mRNA在皮下脂肪组织中表达最高，而LPL mRNA在肠系膜脂肪组织中表达最高。ANGPTL4和LPL mRNA水平在网膜和皮下脂肪组织中呈强正相关。相比之下，ANGPTL4和LPL蛋白水平在皮下脂肪组织中呈负相关，表明ANGPTL4对皮下脂肪组织中LPL蛋白丰度的抑制作用。ANGPTL4 mRNA水平在空腹时比餐后状态高38%。结论：我们的数据为人类脂肪组织中ANGPTL4和LPL之间的关系以及ANGPTL4在人类中的生理功能和调节提供了有价值的见解。(C)2018年全国脂质协会。All rights reserved.
BACKGROUND: Elevated plasma triglycerides are increasingly viewed as a causal risk factor for coronary artery disease. One protein that raises plasma triglyceride levels and that has emerged as a modulator of coronary artery disease risk is angiopoietin-like 4 (ANGPTL4). ANGPTL4 raises plasma triglyceride levels by inhibiting lipoprotein lipase (LPL), the enzyme that catalyzes the hydrolysis of circulating triglycerides on the capillary endothelium.OBJECTIVE: The objective of the present study was to assess the association between ANGPTL4 and LPL in human adipose tissue, and to examine the influence of nutritional status on ANGPTL4 expression.METHODS: We determined ANGPTL4 and LPL mRNA and protein levels in different adipose tissue depots in a large number of severely obese patients who underwent bariatric surgery. Furthermore, in 72 abdominally obese subjects, we measured ANGPTL4 and LPL mRNA levels in subcutaneous adipose tissue in the fasted and postprandial state.RESULTS: ANGPTL4 mRNA levels were highest in subcutaneous adipose tissue, whereas LPL mRNA levels were highest in mesenteric adipose tissue. ANGPTL4 and LPL mRNA levels were strongly positively correlated in the omental and subcutaneous adipose tissue depots. In contrast, ANGPTL4 and LPL protein levels were negatively correlated in subcutaneous adipose tissue, suggesting a suppressive effect of ANGPTL4 on LPL protein abundance in subcutaneous adipose tissue. ANGPTL4 mRNA levels were 38% higher in the fasted compared to the postprandial state.CONCLUSION: Our data provide valuable insights into the relationship between ANGPTL4 and LPL in human adipose tissue, as well as the physiological function and regulation of ANGPTL4 in humans. (C) 2018 National Lipid Association. All rights reserved.