Metabolism Section, Department of Veterans Affairs Medical Center, University of California San Francisco, San Francisco, CA 94121, USA.
Biochem Biophys Res Commun. 2010 Jan 22;391(4):1737-41. doi: 10.1016/j.bbrc.2009.12.145. Epub 2009 Dec 31.
The acute phase response is characterized by elevations in serum triglyceride levels due to both an increase in hepatic VLDL production and a delay in the clearance of triglyceride rich lipoproteins secondary to a decrease in lipoprotein lipase (LPL) activity. Recently there has been a marked increase in our understanding of factors that regulate LPL activity. GPIHBP1 facilitates the interaction of LPL and lipoproteins thereby allowing lipolysis to occur. Angiopoietin like proteins (ANGPTL) 3 and 4 inhibit LPL activity. In the present study, treatment of mice with LPS, an activator of TLR4 and a model of Gram-negative infections, did not alter the expression of GPIHBP1 in heart or adipose tissue. However, LPS decreased the expression of ANGPTL3 in liver and increased the expression of ANGPTL4 in heart, muscle, and adipose tissue. Serum ANGPTL4 protein levels were markedly increased at 8 and 16h following LPS treatment. Administration of zymosan, an activator of TLR2 and a model of fungal infections, also increased serum ANGPTL4 protein and mRNA levels in liver, heart, muscle, and adipose tissue. Finally, treatment of 3T3-L1 adipocytes with LPS or cytokines (TNF alpha, IL-1 beta, and interferon gamma) stimulated ANGPTL4 expression. These studies demonstrate that ANGPTL4 is a positive acute phase protein and the increase in ANGPTL4 could contribute to the hypertriglyceridemia that characteristically occurs during the acute phase response by inhibiting LPL activity.
急性期反应的特征是血清甘油三酯水平升高，这是由于肝 VLDL 产生增加以及脂蛋白脂肪酶 (LPL) 活性降低导致富含甘油三酯的脂蛋白清除延迟所致。最近，我们对调节 LPL 活性的因素有了更深入的了解。GPIHBP1 促进 LPL 和脂蛋白之间的相互作用，从而允许脂肪分解发生。血管生成素样蛋白 (ANGPTL)3 和 4 抑制 LPL 活性。在本研究中，用 LPS（TLR4 的激动剂和革兰氏阴性感染的模型）处理小鼠不会改变心脏或脂肪组织中 GPIHBP1 的表达。然而，LPS 降低了肝脏中 ANGPTL3 的表达，增加了心脏、肌肉和脂肪组织中 ANGPTL4 的表达。LPS 处理后 8 和 16 小时，血清 ANGPTL4 蛋白水平显著升高。用酵母聚糖（TLR2 的激动剂和真菌感染的模型）处理也会增加肝脏、心脏、肌肉和脂肪组织中血清 ANGPTL4 蛋白和 mRNA 水平。最后，用 LPS 或细胞因子（TNFα、IL-1β 和干扰素γ）处理 3T3-L1 脂肪细胞会刺激 ANGPTL4 的表达。这些研究表明，ANGPTL4 是一种急性期正向蛋白，其增加可能通过抑制 LPL 活性导致急性期反应中典型的高甘油三酯血症。
