Abstract
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.
Masashi Morita and Ayako Honda contributed equally to this work.
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Acknowledgements
We thank Akiko Ohba, Kayoko Toyoshi, and Noritake Taniguchi for technical assistance. This research was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (16K09961, 15H04875, 15K15389). Pacific Edit reviewed the manuscript prior to submission.
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Take-Home Message
Lorenzo’s oil activates hepatic peroxisomal fatty acid β-oxidation at the transcriptional level.
Conflict of Interest
Masashi Morita, Ayako Honda, Akira Kobayashi, Yuichi Watanabe, Shiro Watanabe, Kosuke Kawaguchi, Shigeo Takashima, Nobuyuki Shimozawa, and Tsuneo Imanaka declare that they have no conflict of interest.
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This article does not contain any studies with human participants performed by any of the authors.
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All institutional and national guidelines for the care and use of laboratory animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the University Committee for Animal Use and Care at the University of Toyama.
Author Contributions
TI conceived and supervised the study; TI, MM, AH, and NS designed experiments; MM, AH, AK, YW, KK, ST, and SW performed the experiments; MM, TI, and NS wrote the manuscript, which was discussed by all authors.
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Supplementary Fig. 1
Changes in body weight of LO-treated mice. Wild-type (WT) and abcd1-deficient (KO) 4-week-old mice (n = 4) were supplemented with or without LO for 5 weeks and weighed every 3 or 4 days. Intake of dietary LO was an average of 26 g/kg body weight/day. The values for the LO-treated mice were not significantly different from the non-treated mice in either WT or KO mice (PPTX 42 kb)
Supplementary Fig. 2
Effect of Lorenzo’s oil on C26:0 level in liver. Wild-type (WT) (n = 4) and abcd1-deficient (KO) mice (n = 4) were fed with or without LO for 5 weeks as in Table 1. The liver was prepared from each mouse and subjected to gas chromatography analysis. Values are the mean ± S.E. (n = 4 animals. *, p < 0.02) (PPTX 41 kb)
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Morita, M. et al. (2017). Effect of Lorenzo’s Oil on Hepatic Gene Expression and the Serum Fatty Acid Level in abcd1-Deficient Mice. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 38. JIMD Reports, vol 38. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2017_32
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DOI: https://doi.org/10.1007/8904_2017_32
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