The Transcription Factor HNF-4α: A Key Factor of The Intestinal Uptake of Fatty Acids in Mouse

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Journal Title, Volume, Page: 
Am J Physiol Gastrointest Liver Physiol 302: G1253–G1263
Year of Publication: 
2012
Authors: 
Malik Alqub
Institut National de la Santé et de la Recherche Médicale, U872, Paris, France
Current Affiliation: 
Faculty of Medicine & Health Sciences, Department of Biomedical Sciences, An-Najah National University, Nablus, Palestine
Vincent Frochot
Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, UMRS 872, Paris, France
Anne-Laure Cattin
Université Paris Descartes, UMRS 872, Paris, France
Véronique Carrière
Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, UMRS 872, Paris, France
Anne Houllier
Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, UMRS 872, Paris, France
Floriane Baraille
Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, UMRS 872, Paris, France
Laurence Barbot
Laboratoire de Coprologie, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
Susan Saint-Just
Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, UMRS 872, Paris, France
Agnès Ribeiro
Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, UMRS 872, Paris, France
Michel Lacasa
Université Paris Descartes, UMRS 872, Paris, France
Philippe Cardot
Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, UMRS 872, Paris, France
Jean Chambaz
Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, UMRS 872, Paris, France
Monique Rousset
Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, UMRS 872, Paris, France
Jean-Marc Lacorte
Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, UMRS 872, Paris, France
Preferred Abstract (Original): 

With an excessive postprandial accumulation of intestine-derived, triglyceride-rich lipoproteins being a risk factor of cardiovascular diseases, it is essential to characterize the mechanisms controlling the intestinal absorption of dietary lipids. Our aim was to investigate the role of the transcription factor hepatocyte nuclear factor (HNF)-4α in this process. We used transgenic mice with a specific and inducible intestinal knockout of Hnf-4α gene. One hour after a lipid bolus, in the presence of the lipase inhibitor tyloxapol, lower amounts of triglycerides were found in both plasma and intestinal epithelium of the intestine-specific Hnf-4α knockout (Hnf-4αintΔ) mice compared with the Hnf-4αloxP/loxP control mice. These discrepancies were due to a net decrease of the intestinal uptake of fatty acid in Hnf-4αintΔ mice compared with Hnf-4αloxP/loxP mice, as assessed by the amount of radioactivity that was recovered in intestine and plasma after gavage with labeled triolein or oleic acid, or in intestinal epithelial cells isolated from jejunum after a supply of labeled oleic acid-containing micelles. This decreased fatty acid uptake was associated with significant lower levels of the fatty acid transport protein-4 mRNA and protein along the intestinal tract and with a lower acyl-CoA synthetase activity in Hnf-4αintΔ mice compared with the control mice. We conclude that the transcription factor HNF-4α is a key factor of the intestinal absorption of dietary lipids, which controls this process as early as in the initial step of fatty acid uptake by enterocytes.

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