The direct peroxisome proliferator-activated receptor target fasting-induced adipose factor (FIAF/PGAR/ANGPTL4) is present in blood plasma as a truncated protein that is increased by fenofibrate treatment
The direct peroxisome proliferator-activated receptor target fasting-induced adipose factor (FIAF/PGAR/ANGPTL4) is present in blood plasma as a truncated protein that is increased by fenofibrate treatment
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DOI：
10.1074/jbc.m403058200
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发表时间：
2004-08-13
影响因子：
4.8
通讯作者：
Kersten, S
中科院分区：
文献类型：
--
作者：
Mandard, S;Zandbergen, F;Kersten, S
禁食诱导的脂肪因子（FIAF、ANGPTL4、PGAR、HFARP）先前被鉴定为一种新型脂肪细胞因子，禁食、过氧化物酶体增殖物激活受体激动剂和缺氧会上调该因子。为了进一步表征 FIAF，我们研究了肝脏和脂肪细胞系以及人和小鼠血浆中 FIAF mRNA 和蛋白质的调节。在大鼠和人肝癌细胞系中，FIAF mRNA 的表达受到过氧化物酶体增殖物激活受体 α (PPARα) 和 PPARbeta/δ 激动剂的上调，在小鼠和人脂肪细胞中受到 PPARgamma 和 PPARbeta/δ 激动剂的上调。反式激活、染色质免疫沉淀和凝胶迁移实验鉴定了 FIAF 基因内含子 3 内的功能性 PPAR 反应元件。在蛋白质水平上，在人和小鼠血浆中，发现 FIAF 以天然蛋白质和截短形式存在。小鼠 3T3-L1 脂肪细胞的分化与截短的 FIAF 的产生相关，而在人白色脂肪组织和 SGBS 脂肪细胞中，只能检测到天然 FIAF。有趣的是，截短的 FIAF 是由人类肝脏产生的。非诺贝特（一种有效的 PPARα 激动剂）治疗可显着增加人类血浆中截短 FIAF 的水平，但不会增加天然 FIAF 的水平。截短的和天然的 FIAF 水平均显示出明显的个体差异，但与体重指数无关，并且不受长期半饥饿的影响。总之，这些数据表明，FIAF 与其他脂肪细胞因子（如脂联素）类似，可能通过截短形式部分发挥其功能。
The fasting-induced adipose factor (FIAF, ANGPTL4, PGAR, HFARP) was previously identified as a novel adipocytokine that was up-regulated by fasting, by peroxisome proliferator-activated receptor agonists, and by hypoxia. To further characterize FIAF, we studied regulation of FIAF mRNA and protein in liver and adipose cell lines as well as in human and mouse plasma. Expression of FIAF mRNA was up-regulated by peroxisome proliferator-activated receptor alpha( PPARalpha) and PPARbeta/delta agonists in rat and human hepatoma cell lines and by PPARgamma and PPARbeta/delta agonists in mouse and human adipocytes. Transactivation, chromatin immunoprecipitation, and gel shift experiments identified a functional PPAR response element within intron 3 of the FIAF gene. At the protein level, in human and mouse blood plasma, FIAF was found to be present both as the native protein and in a truncated form. Differentiation of mouse 3T3-L1 adipocytes was associated with the production of truncated FIAF, whereas in human white adipose tissue and SGBS adipocytes, only native FIAF could be detected. Interestingly, truncated FIAF was produced by human liver. Treatment with fenofibrate, a potent PPARalpha agonist, markedly increased plasma levels of truncated FIAF, but not native FIAF, in humans. Levels of both truncated and native FIAF showed marked interindividual variation but were not associated with body mass index and were not influenced by prolonged semistarvation. Together, these data suggest that FIAF, similar to other adipocytokines such as adiponectin, may partially exert its function via a truncated form.