González-Muniesa Pedro, de Oliveira Cristiane, Pérez de Heredia Fátima, Thompson Mary P, Trayhurn Paul
Obesity Biology Research Unit, School of Clinical Sciences, University of Liverpool, UK.
J Nutrigenet Nutrigenomics. 2011;4(3):146-53. doi: 10.1159/000327774. Epub 2011 Jun 28.
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.
Human adipocytes were differentiated and incubated with fatty acids (250 μM) 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.
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.
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.
背景/目的：肥胖状态下白色脂肪组织会出现缺氧情况，这会调节特定炎症相关脂肪因子的表达和释放。血管生成素样蛋白4（血管生成素样蛋白4/禁食诱导脂肪因子）参与血管生成、脂质代谢和葡萄糖稳态，是一种主要的缺氧敏感基因；最近的研究表明，血管生成素样蛋白4的表达也受脂肪酸调节。我们研究了缺氧和脂肪酸单独及共同作用对人脂肪细胞血管生成素样蛋白4表达和释放的影响。
使人脂肪细胞分化，并在常氧（21% O₂）或缺氧（1% O₂）条件下与脂肪酸（250 μM）一起孵育。通过实时定量PCR检测血管生成素样蛋白4 mRNA水平，用酶联免疫吸附测定法测定培养基中的蛋白含量。
在常氧条件下，棕榈酸、油酸、花生四烯酸和二十碳五烯酸上调血管生成素样蛋白4基因表达，血管生成素样蛋白4释放增加。相比之下，月桂酸或肉豆蔻酸无此作用。单独缺氧增加血管生成素样蛋白4的表达和分泌，月桂酸、肉豆蔻酸、花生四烯酸和二十碳五烯酸均可进一步增加缺氧脂肪细胞中血管生成素样蛋白4的表达和释放。
人脂肪细胞中血管生成素样蛋白4的表达和分泌受缺氧和脂肪酸上调。在缺氧条件下，脂肪酸对血管生成素样蛋白4产生的刺激作用增强。
