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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

Author: Mandard, S. · Zandbergen, F. · Nguan, S.T. · Escher, P. · Patsouris, D. · Koenig, W. · Kleemann, R. · Bakker, A. · Veenman, F. · Wahli, W. · Müller, M. · Kersten, S.
Institution: TNO Preventie en Gezondheid
Source:Journal of Biological Chemistry, 33, 279, 34411-34420
Identifier: 237938
doi: doi:10.1074/jbc.M403058200
Keywords: Biology · Biomedical Research · Biochemistry · Biological membranes · Blood · Precipitation (chemical) · RNA · Tissue · Adipose tissue · Blood plasma · Fasting induced adipose factors · Immunoprecipitation · Proteins · Cytokine · Fasting induced adipose factor · Fenofibrate · Messenger RNA · Peroxisome proliferator activated receptor alpha · Peroxisome proliferator activated receptor delta · Peroxisome proliferator activated receptor gamma · Unclassified drug · Adiponectin · ANGPTL4 protein, human · cell receptor · protein · RNA · Signal peptide · Transcription factor · Adipocyte · Animal cell · Blood level · Body mass · Cell differentiation · Chromatin · Controlled study · DNA responsive element · Gene control · Hepatoma cell · Human · Human cell · Human tissue · Immunoprecipitation · Intron · Liver · Mouse · Nonhuman · Rat · Transactivation · Upregulation · White adipose tissue · Animal · Blood · C57BL mouse · Cell culture · Cell line · Cell strain 3T3 · Genetic transcription · Metabolism · Molecular genetics · Nucleotide sequence · Reverse transcription polymerase chain reaction · Serodiagnosis · Tumor cell line · Western blotting · Animalia · Eukaryota · 3T3-L1 Cells · Adipocytes · Adiponectin · Adipose Tissue · Animals · Base Sequence · Blotting, Western · Cell Differentiation · Cell Line · Cell Line, Tumor · Cells, Cultured · Chromatin · Cytokines · Humans · Intercellular Signaling Peptides and Proteins · Introns · Liver · Mice · Mice, Inbred C57BL · Molecular Sequence Data · Precipitin Tests · Procetofen · Proteins · Rats · Receptors, Cytoplasmic and Nuclear · Reverse Transcriptase Polymerase Chain Reaction · RNA · RNA, Messenger · Trans-Activation (Genetics) · Transcription Factors · Transcription, Genetic · Up-Regulation


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 α (PPARα) and PPARβ/δ agonists in rat and human hepatoma cell lines and by PPARγ and PPARβ/δ 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 PPARα 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. Chemicals / CAS: fenofibrate, 49562-28-9; peroxisome proliferator activated receptor alpha, 147258-70-6; peroxisome proliferator activated receptor delta, 173359-81-4; adiponectin, 283182-39-8; protein, 67254-75-5; RNA, 63231-63-0; Adiponectin; ANGPTL4 protein, human; Chromatin; Cytokines; Intercellular Signaling Peptides and Proteins; Procetofen, 49562-28-9; Proteins; Receptors, Cytoplasmic and Nuclear; RNA, 63231-63-0; RNA, Messenger; Transcription Factors