A polymorphism in the human intestinal fatty acid binding protein alters fatty acid transport across Caco-2 cells.
The human intestinal fatty acid binding protein (IFABP) binds long-chain fatty acids in vitro, but its intracellular function has remained speculative. A polymorphism in the gene that encodes IFABP results in an alanine (Ala54) to threonine (Thr54) substitution at codon 54 that alters the in vitro binding affinity of the protein for long-chain fatty acids. To identify potential functional variability between Ala54 and Thr54 IFABP, we established permanently transfected Caco-2 cell lines that express either Ala54 or Thr54 IFABP. We found that Caco-2 cells expressing Thr54 IFABP transport long-chain fatty acids and secrete triglycerides to a greater degree than Caco-2 cells expressing Ala54 IFABP. These results provide the first demonstration that IFABP participates in the intracellular transport of long-chain fatty acids. In addition, the observed increase in transport of fatty acids across cells expressing Thr54 IFABP suggests a plausible physiologic mechanism for our prior observation that Pima Indians with a Thr54 IFABP genotype have increased post-absorptive lipid oxidation rates and are more insulin-resistant than Pimas with a Ala54 IFABP genotype.
Baier
L J
LJ
NIDDK, National Institutes of Health, Phoenix, Arizona 85016, USA.
Bogardus
C
C
Sacchettini
J C
JC
D001692:Biological Transport; D018938:Caco-2 Cells; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D003106:Colon / Q000378:metabolism*; D018076:DNA, Complementary; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance; D018996:Myelin P2 Protein / Q000235:genetics* / Q000378:metabolism; D009363:Neoplasm Proteins; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D025521:Tumor Suppressor Proteins
D002352:Carrier Proteins; D018076:DNA, Complementary; C107608:FABP7 protein, human; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D018996:Myelin P2 Protein; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins