HNF-4-dependent Induction of Apolipoprotein A-IV Gene Transcription by an Apical Supply of Lipid Micelles in Intestinal Cells
Abstract
Apolipoprotein (apo) A-IV, a component of triglyceride-rich lipoproteins secreted by the small intestine, has been shown to play an important role in the control of lipid homeostasis. Numerous studies have described the induction of apoA-IV gene expression by lipids, but the molecular mechanisms involved in this process remain unknown. In this study, we have demonstrated that a lipid bolus induced transcription of the apoA-IV gene in transgenic mice and that the regulatory region of the apoA-IV gene, composed of the apoC-III enhancer and the apoA-IV promoter (eC3-A4), was responsible for this induction. In enterocyte Caco-2/TC7 cells, a permanent supply of lipids at the basal pole induced expression of the apoA-IV gene both at the transcriptional level and through mRNA stabilization. ApoA-IV gene transcription and protein secretion were further induced by an apical supply of complex lipid micelles mimicking the composition of duodenal micelles, and this effect was not reproduced by apical delivery of different combinations of micelle components. Only induction of the apoA-IV gene by lipid micelles involved the participation of hepatic nuclear factor (HNF)-4, as demonstrated using a dominant negative form of this transcription factor. Accordingly, lipid micelles increased the DNA binding activity of HNF-4 on the eC3-A4 region. These results emphasize the importance of physiological delivery of dietary lipids on apoA-IV gene expression and the implication of HNF-4 in this regulation.
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BibTeX
@article{carriere2026hnf4dependent,
title = {{HNF-4-dependent Induction of Apolipoprotein A-IV Gene Transcription by an Apical Supply of Lipid Micelles in Intestinal Cells}},
author = {Véronique Carrière and Romain Vidal and Kristell Lazou and Michel Lacasa and François Delers and Agnès Ribeiro and Monique Rousset and Jean Chambaz and Jean Marc Lacorte},
journal = {Journal of Biological Chemistry},
year = {2026},
month = sep,
doi = {10.1074/jbc.m408002200},
url = {https://hal.science/hal-05754778v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - HNF-4-dependent Induction of Apolipoprotein A-IV Gene Transcription by an Apical Supply of Lipid Micelles in Intestinal Cells
AU - Véronique Carrière
AU - Romain Vidal
AU - Kristell Lazou
AU - Michel Lacasa
AU - François Delers
AU - Agnès Ribeiro
AU - Monique Rousset
AU - Jean Chambaz
AU - Jean Marc Lacorte
PY - 2026
DA - 2026/09/18
JO - Journal of Biological Chemistry
DO - 10.1074/jbc.m408002200
UR - https://hal.science/hal-05754778v1
AB - Apolipoprotein (apo) A-IV, a component of triglyceride-rich lipoproteins secreted by the small intestine, has been shown to play an important role in the control of lipid homeostasis. Numerous studies have described the induction of apoA-IV gene expression by lipids, but the molecular mechanisms involved in this process remain unknown. In this study, we have demonstrated that a lipid bolus induced transcription of the apoA-IV gene in transgenic mice and that the regulatory region of the apoA-IV gene, composed of the apoC-III enhancer and the apoA-IV promoter (eC3-A4), was responsible for this induction. In enterocyte Caco-2/TC7 cells, a permanent supply of lipids at the basal pole induced expression of the apoA-IV gene both at the transcriptional level and through mRNA stabilization. ApoA-IV gene transcription and protein secretion were further induced by an apical supply of complex lipid micelles mimicking the composition of duodenal micelles, and this effect was not reproduced by apical delivery of different combinations of micelle components. Only induction of the apoA-IV gene by lipid micelles involved the participation of hepatic nuclear factor (HNF)-4, as demonstrated using a dominant negative form of this transcription factor. Accordingly, lipid micelles increased the DNA binding activity of HNF-4 on the eC3-A4 region. These results emphasize the importance of physiological delivery of dietary lipids on apoA-IV gene expression and the implication of HNF-4 in this regulation.
SN - 0021-9258
SN - 1083-351X
ER -