The Expression of GHIBP1, an Endothelial Cell Binding Site for Lipoprotein Lipase and Chylomicrons, Is Induced by Peroxisome Proliferator-Activated Receptor-γ
The Expression of GHIBP1, an Endothelial Cell Binding Site for Lipoprotein Lipase and Chylomicrons, Is Induced by Peroxisome Proliferator-Activated Receptor-γ
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DOI：
10.1210/me.2008-0146
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发表时间：
2008-11-01
影响因子：
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通讯作者：
Young, Stephen G.
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文献类型：
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作者：
Davies, Brandon S. J.;Waki, Hironori;Young, Stephen G.
糖基磷脂酰肌醇锚定高密度脂蛋白结合蛋白1（GPIHBP 1）是淋巴细胞抗原6（Ly-6）家族中的一种蛋白，在富含磷脂酰肌醇的脂蛋白的脂解加工中起关键作用。GPIHBP 1结合脂蛋白脂肪酶和乳糜微粒，并沿微血管内皮细胞的管腔表面沿着表达。已知脂解受代谢因素调节，并在多个水平上受到控制，包括毛细血管上LPL结合位点的数量。在这里，我们测试的可能性，GPIHBP 1的表达可以调节饮食扰动和过氧化物酶体增殖物激活受体（PPARs）。心脏、棕色和白色脂肪组织中的gpihbp 1转录水平随着禁食而增加，再进食后恢复到基线水平。一个过氧化物酶体增殖物激活物受体γ激动剂增加Gpihbp 1在脂肪组织，心脏和骨骼肌的表达，而过氧化物酶体增殖物激活物受体α和过氧化物酶体增殖物激活物受体δ激动剂没有影响。Gpihbp 1在由小鼠胚胎干细胞产生的胚状体的内皮细胞中表达，并且Gpihbp 1在胚状体中的表达被PPAR γ激动剂上调。Gpihbp 1外显子1上游序列含有一个强的PPAR结合位点，该位点在荧光素酶报告基因检测中表现出活性。在棕色和白色脂肪组织中，内皮细胞PPAR γ基因敲除小鼠的Gpihbp 1转录水平低于同窝对照小鼠，表明PPAR γ在体内调节Gpihbp 1表达。我们的结论是，GPIHBP 1受到饮食因素和PPAR γ的调节。（分子内分泌学22：2496-2504，2008）
Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1), a protein in the lymphocyte antigen 6 (Ly-6) family, plays a key role in the lipolytic processing of triglyceride-rich lipoproteins. GPIHBP1 binds lipoprotein lipase and chylomicrons and is expressed along the luminal surface of microvascular endothelial cells. Lipolysis is known to be regulated by metabolic factors and is controlled at multiple levels, including the number of LPL binding sites on capillaries. Here, we tested the possibility that GPIHBP1 expression could be regulated by dietary perturbations and by peroxisome proliferator-activated receptors (PPARs). Gpihbp1 transcript levels in the heart and in brown and white adipose tissue increased with fasting and returned toward baseline after refeeding. A PPAR gamma agonist increased Gpihbp1 expression in adipose tissue, heart, and skeletal muscle, whereas PPAR alpha and PPAR delta agonists had no effect. Gpihbp1 was expressed in endothelial cells of embryoid bodies generated from mouse embryonic stem cells, and Gpihbp1 expression in embryoid bodies was up-regulated by a PPAR gamma agonist. Sequences upstream from exon 1 of Gpihbp1 contain a strong PPAR binding site, and that site exhibited activity in a luciferase reporter assay. Gpihbp1 transcript levels in brown and white adipose tissue were lower in endothelial cell PPAR gamma knockout mice than in littermate control mice, suggesting that PPAR gamma regulates Gpihbp1 expression in vivo. We conclude that GPIHBP1 is regulated by dietary factors and by PPAR gamma. (Molecular Endocrinology 22: 2496-2504, 2008)