Identification of the major intestinal fatty acid transport protein.
While intestinal transport systems for metabolites such as carbohydrates have been well characterized, the molecular mechanisms of fatty acid (FA) transport across the apical plasmalemma of enterocytes have remained largely unclear. 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 293 cells facilitates uptake of long chain FAs with the same specificity as enterocytes, while reduction of FATP4 expression in primary enterocytes by antisense oligonucleotides inhibits FA uptake by 50%. This suggests that FATP4 is the principal fatty acid transporter in enterocytes and may constitute a novel target for antiobesity therapy.
Stahl
A
A
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Massachusetts 02142, USA.
Hirsch
D J
DJ
Gimeno
R E
RE
Punreddy
S
S
Ge
P
P
Watson
N
N
Patel
S
S
Kotler
M
M
Raimondi
A
A
Tartaglia
L A
LA
Lodish
H F
HF
D001667:Binding, Competitive; D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D016764:Cell Polarity; D020895:Enterocytes / Q000378:metabolism* / Q000648:ultrastructure; D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D007421:Intestine, Small / Q000378:metabolism* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D026901:Membrane Transport Proteins; D008715:Methionine / Q000378:metabolism; D008871:Microvilli / Q000737:chemistry / Q000648:ultrastructure; D019301:Oleic Acid / Q000378:metabolism; D016376:Oligonucleotides, Antisense; D010168:Palmitates / Q000378:metabolism; D013379:Substrate Specificity
D002352:Carrier Proteins; D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D016376:Oligonucleotides, Antisense; D010168:Palmitates; C493571:SLC27A4 protein, human; C493572:Slc27a4 protein, mouse; D019301:Oleic Acid; D008715:Methionine