Tissue-specific suppression of aortic fatty-acid-binding protein in streptozotocin-induced diabetic rats

Fatty-acid-binding protein (FABP) expressed in rat aorta has been shown to be homologous to heart FABP (H-FABP) but its precise primary structure, cellular localization and function are not known. To establish the nucleotide identity between heart and aorta FABP, we performed an RNase protection assay with antisense RNA of rat H-FABP. The results demonstrate that the primary nucleotide sequence of aortic FABP is identical to that of rat H-FABP. In situ hybridization analysis revealed that aortic H-FABP mRNA is present in both smooth muscle cells and endothelial cells. In order to explore the function of aortic H-FABP, we examined whether a quantitative change in aortic H-FABP occurred in diabetes mellitus, since this pathological state has been shown to cause abnormalities in fatty acid metabolism. Northern blot analysis revealed that the level of aortic H-FABP mRNA was markedly decreased in rats made diabetic by streptozotocin treatment. The suppression of the mRNA level paralleled that of the protein level, as assessed by Western blot analysis. In distinct contrast, no major changes in the H-FABP mRNA level were observed in any other tissues examined, including heart, kidney and skeletal muscle, suggesting that this decrease is highly tissue-specific. The suppression of the aortic H-FABP in streptozotocin-diabetic rats was abolished by insulin supplementation. Taken together, these results suggest that the expression of the H-FABP gene in aorta may be specifically and dramatically suppressed in streptozotocin-diabetic rats, and that this suppression appears to be regulated by insulin.