Hepatocyte nuclear factor-4 mediates apolipoprotein A-IV transcriptional regulation by fatty acid in newborn swine enterocytes

Shuangying Leng, Song Lu, Ying Yao, Zhisheng Kan, Gabriel S. Morris, Brad R. Stair, Mathew A. Cherny, Dennis Black

Research output: Contribution to journalArticle

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Abstract

Hepatocyte nuclear factor-4α (HNF-4α) 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-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 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-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-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-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-IV 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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume293
Issue number2
DOIs
StatePublished - Aug 1 2007

Fingerprint

Hepatocyte Nuclear Factor 4
Enterocytes
Swine
Fatty Acids
Oleic Acid
Messenger RNA
Luciferases
Lipids
Intestines
Genes
apolipoprotein A-IV
Chylomicrons
Intergenic DNA
Doxycycline
Protein Subunits
Staphylococcal Protein A
Reporter Genes
Lipid Metabolism
Transcriptional Activation
Small Intestine

All Science Journal Classification (ASJC) codes

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Cite this

Hepatocyte nuclear factor-4 mediates apolipoprotein A-IV transcriptional regulation by fatty acid in newborn swine enterocytes. / Leng, Shuangying; Lu, Song; Yao, Ying; Kan, Zhisheng; Morris, Gabriel S.; Stair, Brad R.; Cherny, Mathew A.; Black, Dennis.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 293, No. 2, 01.08.2007.

Research output: Contribution to journalArticle

Leng, Shuangying ; Lu, Song ; Yao, Ying ; Kan, Zhisheng ; Morris, Gabriel S. ; Stair, Brad R. ; Cherny, Mathew A. ; Black, Dennis. / Hepatocyte nuclear factor-4 mediates apolipoprotein A-IV transcriptional regulation by fatty acid in newborn swine enterocytes. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2007 ; Vol. 293, No. 2.
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abstract = "Hepatocyte nuclear factor-4α (HNF-4α) 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-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 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-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-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-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-IV 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.",
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