Baier L J, Bogardus C, Sacchettini J C
NIDDK, National Institutes of Health, Phoenix, Arizona 85016, USA.
J Biol Chem. 1996 May 3;271(18):10892-6. doi: 10.1074/jbc.271.18.10892.
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.
人肠脂肪酸结合蛋白（IFABP）在体外能结合长链脂肪酸，但其细胞内功能一直存在推测。编码IFABP的基因中的一种多态性导致第54位密码子处的丙氨酸（Ala54）被苏氨酸（Thr54）取代，这改变了该蛋白对长链脂肪酸的体外结合亲和力。为了确定Ala54和Thr54 IFABP之间潜在的功能差异，我们建立了永久转染的Caco-2细胞系，分别表达Ala54或Thr54 IFABP。我们发现，表达Thr54 IFABP的Caco-2细胞比表达Ala54 IFABP的Caco-2细胞能更大量地转运长链脂肪酸并分泌甘油三酯。这些结果首次证明IFABP参与长链脂肪酸的细胞内转运。此外，观察到表达Thr54 IFABP的细胞跨膜脂肪酸转运增加，这为我们之前的观察结果提供了一种合理的生理机制，即具有Thr54 IFABP基因型的皮马印第安人在吸收后脂质氧化率增加，且比具有Ala54 IFABP基因型的皮马人更具胰岛素抵抗性。
