title: The transcription factor HNF-4α: a key factor of the intestinal uptake of fatty acids in mouse.
abstract: 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-4α(intΔ)) mice compared with the Hnf-4α(loxP/loxP) control mice. These discrepancies were due to a net decrease of the intestinal uptake of fatty acid in Hnf-4α(intΔ) mice compared with Hnf-4α(loxP/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-4α(intΔ) 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.
authors.affiliation: Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, UMRS, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Frochot
authors.forename: Malik
authors.initials: M
authors.lastname: Alqub
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Cattin
authors.forename: Véronique
authors.initials: V
authors.lastname: Carrière
authors.forename: Anne
authors.initials: A
authors.lastname: Houllier
authors.forename: Floriane
authors.initials: F
authors.lastname: Baraille
authors.forename: Laurence
authors.initials: L
authors.lastname: Barbot
authors.forename: Susan
authors.initials: S
authors.lastname: Saint-Just
authors.forename: Agnès
authors.initials: A
authors.lastname: Ribeiro
authors.forename: Michel
authors.initials: M
authors.lastname: Lacasa
authors.forename: Philippe
authors.initials: P
authors.lastname: Cardot
authors.forename: Jean
authors.initials: J
authors.lastname: Chambaz
authors.forename: Monique
authors.initials: M
authors.lastname: Rousset
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Lacorte
mesh_terms: D000818:Animals; D003066:Coenzyme A Ligases / Q000235:genetics / Q000378:metabolism; D004041:Dietary Fats / Q000378:metabolism*; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism; D050612:Fatty Acid Transport Proteins / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics / Q000378:metabolism*; D007408:Intestinal Absorption / Q000187:drug effects / Q000235:genetics*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D011092:Polyethylene Glycols / Q000494:pharmacology; D019518:Postprandial Period / Q000502:physiology
chemical_list: D004041:Dietary Fats; D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids; D051557:Hepatocyte Nuclear Factor 4; C493572:Slc27a4 protein, mouse; D011092:Polyethylene Glycols; D003066:Coenzyme A Ligases; C016811:tyloxapol