Lorenzo's oil is known to decrease the saturated very long chain
fatty acid (VLCFA) level in the plasma and skin fibroblasts of
X-linked adrenoleukodystrophy (ALD) patients. However, the involvement of
Lorenzo's oil in in vivo
fatty acid metabolism has not been well elucidated. To investigate the effect of
Lorenzo's oil on
fatty acid metabolism, we analyzed the hepatic gene expression together with the serum
fatty acid level in
Lorenzo's oil-treated wild-type and abcd1-deficient mice. The change in the serum
fatty acid level in
Lorenzo's oil-treated abcd1-defcient mice was quite similar to that in the plasma
fatty acid level in ALD patients supplemented with
Lorenzo's oil. In addition, we found that the hepatic gene expression of two peroxisomal
enzymes, Dbp and Scp2, and three microsomal
enzymes, Elovl1, 2, and 3, were significantly stimulated by
Lorenzo's oil. Our findings indicate that
Lorenzo's oil activates hepatic peroxisomal
fatty acid β-oxidation at the transcriptional level. In contrast, the transcriptional stimulation of Elovl1, 2, and 3 by
Lorenzo's oil does not cause changes in the serum
fatty acid level. It seems likely that the inhibition of these elongation activities by
Lorenzo's oil results in a decrease in saturated VLCFA. Thus, these results not only contribute to a clarification of the mechanism by which the saturated VLCFA level is reduced in the serum of ALD patients by
Lorenzo's oil-treatment, but also suggest the development of a new therapeutic approach to peroxisomal β-oxidation
enzyme deficiency, especially mild phenotype of DBP deficiency.