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 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...