| Autor: |
Shuangying Leng, Song Lu, Ying Yao, Zhisheng Kan, Morris, Gabriel S., Stair, Brad R., Cherny, Mathew A., Black, Dennis D. |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Gastrointestinal & Liver Physiology; Aug2007, Vol. 293, pG478-G483, 9p, 7 Graphs |
| Abstrakt: |
Hepatocyte nuclear factor-4α (HNF-4α) regulates transcription of several genes involved in lipid metabolism, including that of apolipoprotein (apo) A-lV, which is tightly regulated by lipid absorption and enhances enterocyte chylomicron secretion. Studies were performed to define the role of HNF-4α in the regulation of apo A-IV gene transcription by dietary fatty acid in neonatal swine small intestine. HNF-4α mRNA was expressed in liver > intestine > kidney in suckling, weanling, and weaned pigs. Jejunal HNF-4α mRNA and protein and apo A-IV and swine microsornal 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-4α, apo A-IV, and MTP mRNA, similar to that observed in vivo. When HNF-4α expression was driven by doxycycline by using the TET-On system in the absence of OA to observe the effect of HNF-4α 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-lV and MTP expression were increased. In luciferase reporter gene assays in IPEC-l cells using apo A-IV/C-III intergenic region constructs, lET-On-regulated HNF-4α 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-lV and MTP genes by dietary lipid in newborn intestine occurs, at least in part, via ligand-independent transactivation by HNF-4α that is itself induced by a lipid-mediated mechanism. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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