Hepatocyte nuclear factor-4 mediates apolipoprotein A-IV transcriptional regulation by fatty acid in newborn swine enterocytes
| Autor: | Gabriel Scott Morris, Zhisheng Kan, Ying Yao, Brad Ryan Stair, Song Lu, Dennis Black, Shuangying Leng, Mathew Aaron Cherny |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Apolipoprotein B
Transcription Genetic Physiology Molecular Sequence Data Sus scrofa Apolipoproteins A Apolipoprotein A-IV Transfection digestive system Cell Line Genes Reporter Physiology (medical) Chylomicrons medicine Transcriptional regulation Animals Amino Acid Sequence RNA Messenger Luciferases Hepatology biology Gastroenterology Lipid metabolism Dietary Fats Cell biology Up-Regulation medicine.anatomical_structure Enterocytes Jejunum Hepatocyte nuclear factor 4 Biochemistry Animals Newborn Hepatocyte Nuclear Factor 4 Hepatocyte biology.protein lipids (amino acids peptides and proteins) DNA Intergenic Female Carrier Proteins Chylomicron Oleic Acid Signal Transduction |
| Zdroj: | American journal of physiology. Gastrointestinal and liver physiology. 293(2) |
| ISSN: | 0193-1857 |
| Popis: | Hepatocyte nuclear factor-4alpha (HNF-4alpha) regulates transcription of several genes involved in lipid metabolism, including that of apolipoprotein (apo) A-IV, which is tightly regulated by lipid absorption and enhances enterocyte chylomicron secretion. Studies were performed to define the role of HNF-4alpha in the regulation of apo A-IV gene transcription by dietary fatty acid in neonatal swine small intestine. HNF-4alpha mRNA was expressed in liverintestinekidney in suckling, weanling, and weaned pigs. Jejunal HNF-4alpha mRNA and protein and apo A-IV and swine microsomal triglyceride transfer protein (MTP) large subunit mRNA expression were induced in parallel in 2-day-old swine by a 24-h high-fat intraduodenal infusion. In IPEC-1 cells, incubation with oleic acid (OA) resulted in coordinate induction of both HNF-4alpha, apo A-IV, and MTP mRNA, similar to that observed in vivo. When HNF-4alpha expression was driven by doxycycline by using the TET-On system in the absence of OA to observe the effect of HNF-4alpha directly on apo A-IV and MTP mRNA levels in the absence of other factors that might be concomitantly induced by fatty acid absorption, apo A-IV and MTP expression were increased. In luciferase reporter gene assays in IPEC-1 cells using apo A-IV/C-III intergenic region constructs, TET-On-regulated HNF-4alpha expression without OA increased luciferase activity, and incubation with OA did not further increase activity. These data suggest that acute induction of the apo A-IV and MTP genes by dietary lipid in newborn intestine occurs, at least in part, via ligand-independent transactivation by HNF-4alpha that is itself induced by a lipid-mediated mechanism. |
| Databáze: | OpenAIRE |
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