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 HNF-4α in this process. We used transgenic mice with a specific and inducible intestinal knockout of Hnf-4alpha gene. One hour after a lipid bolus, in the presence of the lipase inhibitor tyloxapol, lower amounts of triglycerides were found both in plasma and intestinal epithelium of the intestine-specific Hnf-4alpha KO (Hnf-4alphaint∆) mice as compared to the Hnf-4alphaloxP/loxP control mice. These discrepancies were due to a net decrease of the intestinal uptake of fatty acid in Hnf-4alphaint∆ mice as compared to Hnf-4alphaloxP/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-4alphaint∆ mice as compared to 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.
- HNF-4a knock out
- dietary fat