Identification of the major intestinal fatty acid transport protein

While intestinal transport systems for metabolites such as carbohydrates ha ve been well characterized, the molecular mechanisms of fatty acid (FA) tra nsport across the apical plasmalemma of enterocytes have remained largely u nclear. Here, we show that FATP4 a member of a large family of FA transport proteins (FATPs), is expressed at high levels on the apical side of mature enterocytes in the small intestine. Further, overexpression of FATP4 in 29 3 cells facilitates uptake of long chain FAs with the same specificity as e nterocytes, while reduction of FATP4 expression in primary enterocytes by a ntisense oligonucleotides inhibits FA uptake by 50%. This suggests that FAT P4 is the principal fatty acid transporter in enterocytes and may constitut e a novel target for antiobesity therapy.