The transcription factor HNF-4α: a key factor of the intestinal uptake of fatty acids in mouse

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 transcri...

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Published in:American journal of physiology: Gastrointestinal and liver physiology 2012-06, Vol.302 (11), p.G1253-G1263
Main Authors: Frochot, Vincent, Alqub, Malik, Cattin, Anne-Laure, Carrière, Véronique, Houllier, Anne, Baraille, Floriane, Barbot, Laurence, Saint-Just, Susan, Ribeiro, Agnès, Lacasa, Michel, Cardot, Philippe, Chambaz, Jean, Rousset, Monique, Lacorte, Jean-Marc
Format: Article
Language:English
Subjects:
Animals
Coenzyme A Ligases - genetics
Coenzyme A Ligases - metabolism
Dietary Fats - metabolism
Enterocytes - drug effects
Enterocytes - metabolism
Fatty Acid Transport Proteins - genetics
Fatty Acid Transport Proteins - metabolism
Fatty Acids - metabolism
Hepatocyte Nuclear Factor 4 - genetics
Hepatocyte Nuclear Factor 4 - metabolism
Intestinal Absorption - drug effects
Intestinal Absorption - genetics
Intestinal Mucosa - drug effects
Intestinal Mucosa - metabolism
Intestines - drug effects
Intestines - metabolism
Mice
Mice, Knockout
Polyethylene Glycols - pharmacology
Postprandial Period - physiology
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Summary: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.
ISSN:0193-1857
1522-1547
DOI:10.1152/ajpgi.00329.2011