Fatty Acids and Hypoxia Stimulate the Expression and Secretion of the Adipokine ANGPTL4 (Angiopoietin-Like Protein 4/Fasting-Induced Adipose Factor) by Human Adipocytes
Fatty Acids and Hypoxia Stimulate the Expression and Secretion of the Adipokine ANGPTL4 (Angiopoietin-Like Protein 4/Fasting-Induced Adipose Factor) by Human Adipocytes
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DOI：
10.1159/000327774
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发表时间：
2011-01-01
影响因子：
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通讯作者：
Trayhurn, Paul
中科院分区：
文献类型：
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作者：
Gonzalez-Muniesa, Pedro;de Oliveira, Cristiane;Trayhurn, Paul
背景/目的：缺氧发生在肥胖的白色脂肪组织中，调节特定炎症相关脂肪因子的表达和释放。ANGPTL 4（血管生成素样蛋白4/禁食诱导脂肪因子）与血管生成、脂质代谢和葡萄糖稳态有关，是一种主要的缺氧敏感基因;最近的研究表明ANGPTL 4的表达也受到脂肪酸的调节。我们已经研究了缺氧和脂肪酸单独和一起对人脂肪细胞表达和释放ANGPTL 4的影响。方法：将人脂肪细胞分化并与脂肪酸（250 μ M）在常氧（21%O（2））或缺氧（1%O（2））中孵育。用实时荧光定量PCR法检测ANGPTL 4 mRNA的表达，用ELISA法检测培养液中ANGPTL 4蛋白的含量。结果如下：在常氧下，ANGPTL 4基因表达被棕榈酸、油酸、花生四烯酸和二十碳五烯酸上调，ANGPTL 4释放增加。相比之下，月桂酸或肉豆蔻酸没有影响。缺氧单独增加ANGPTL 4的表达和分泌，并且月桂酸、肉豆蔻酸、花生四烯酸和二十碳五烯酸各自进一步增加缺氧脂肪细胞中的表达和释放。结论：缺氧和脂肪酸均可上调人脂肪细胞ANGPTL 4的表达和分泌。脂肪酸对ANGPTL 4产生的刺激作用在缺氧条件下增强。版权所有（C）2011 S. Karger AG，巴塞尔
Background/Aims: Hypoxia occurs in white adipose tissue in obesity, modulating the expression and release of specific inflammation-related adipokines. ANGPTL4 (angiopoietin-like protein 4/fasting-induced adipose factor), which is implicated in angiogenesis, lipid metabolism and glucose homeostasis, is a major hypoxia-sensitive gene; recent studies indicate that ANGPTL4 expression is also regulated by fatty acids. We have examined the effects of hypoxia and fatty acids, alone and together, on the expression and release of ANGPTL4 by human adipocytes. Methods: Human adipocytes were differentiated and incubated with fatty acids (250 mu M) in normoxia (21% O(2)) or hypoxia (1% O(2)). ANGPTL4 mRNA was measured by real-time PCR and the protein in the medium determined by ELISA. Results: In normoxia, ANGPTL4 gene expression was upregulated by palmitic, oleic, arachidonic and eicosapentaenoic acids, and ANGPTL4 release was increased. In contrast, there was no effect of lauric or myristic acids. Hypoxia alone increased the expression and secretion of ANGPTL4, and lauric, myristic, arachidonic and eicosapentaenoic acids each further increased expression and release in hypoxic adipocytes. Conclusion: The expression and secretion of ANGPTL4 by human adipocytes is upregulated by both hypoxia and fatty acids. The stimulatory effect of fatty acids on ANGPTL4 production is augmented under hypoxic conditions. Copyright (C) 2011 S. Karger AG, Basel