Characterization of the fasting-induced adipose factor FIAF, a novel peroxisome proliferator-activated receptor target gene

Fasting is associated with significant changes in nutrient metabolism, many of which are governed by transcription factors that regulate the expressio n of rate-limiting enzymes. One factor that plays an important role in the metabolic response to fasting is the peroxisome proliferator-activated rece ptor alpha (PPAR alpha). To gain more insight into the role of PPAR alpha d uring fasting, and into the regulation of metabolism during fasting in gene ral, a search for unknown PPAR alpha target genes was performed. Using subt ractive hybridization (SABRE) comparing liver mRNA from wild-type and PPAR alpha null mice, we isolated a novel PPAR alpha target gene, encoding the s ecreted 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 whit e adipose tissue and liver. Moreover, FIAF mRNA is decreased in white adipo se tissue of PPAR gamma +/- mice. FIAF protein can be detected in various t issues 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 signa l involved in the regulation of metabolism, especially under fasting condit ions.