Characterization of the fasting-induced adipose factor FIAF, a novel peroxisome proliferator-activated receptor target gene
Characterization of the fasting-induced adipose factor FIAF, a novel peroxisome proliferator-activated receptor target gene
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DOI：
10.1074/jbc.m004029200
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发表时间：
2000-09-15
影响因子：
4.8
通讯作者：
Wahli, W
中科院分区：
文献类型：
--
作者：
Kersten, S;Mandard, S;Wahli, W
禁食与营养代谢的显著变化有关，其中许多变化是由调节限速酶表达的转录因子控制的。在禁食代谢反应中起重要作用的一个因素是过氧化物酶体增殖物激活受体α (PPAR α)。为了更深入地了解PPAR α在禁食期间的作用，以及在禁食期间的代谢调节，研究人员对未知的PPAR α靶基因进行了搜索。利用减法杂交（SABRE）比较野生型和PPAR α缺失小鼠的肝脏mRNA，我们分离出一个新的PPAR α靶基因，编码分泌蛋白FIAF（空腹诱导脂肪因子），属于纤维蛋白原/血管生成素样蛋白家族。FIAF主要在脂肪组织中表达，并在白色脂肪组织和肝脏中通过禁食强烈上调。此外，PPAR γ +/-小鼠白色脂肪组织中FIAF mRNA表达减少。FIAF蛋白可在多种组织和血浆中检测到，提示FIAF具有内分泌功能。血浆丰度因禁食而增加，因长期高脂喂养而降低。这些数据表明，FIAF是一种新的内分泌信号，参与代谢调节，特别是在禁食条件下。
Fasting is associated with significant changes in nutrient metabolism, many of which are governed by transcription factors that regulate the expression of rate-limiting enzymes. One factor that plays an important role in the metabolic response to fasting is the peroxisome proliferator-activated receptor alpha (PPAR alpha). To gain more insight into the role of PPAR alpha during fasting, and into the regulation of metabolism during fasting in general, a search for unknown PPAR alpha target genes was performed. Using subtractive hybridization (SABRE) comparing liver mRNA from wild-type and PPAR alpha null mice, we isolated a novel PPAR alpha target gene, encoding the secreted protein FIAF (for fasting induced adipose factor), that belongs to the family of fibrinogen/angiopoietin-like proteins. FIAF is predominantly expressed in adipose tissue and is strongly up-regulated by fasting in white adipose tissue and liver. Moreover, FIAF mRNA is decreased in white adipose tissue of PPAR gamma +/- mice. FIAF protein can be detected in various tissues and in blood plasma, suggesting that FIAF has an endocrine function. Its plasma abundance is increased by fasting and decreased by chronic high fat feeding. The data suggest that FIAF represents a novel endocrine signal involved in the regulation of metabolism, especially under fasting conditions.