Abstract
The dysfunction of ABCD1, a peroxisomal ABC protein, leads to the perturbation of very long chain fatty acid (VLCFA) metabolism and is the cause of X-linked adrenoleukodystrophy. Abcd1-deficient mice exhibit an accumulation of saturated VLCFAs, such as C26:0, in all tissues, especially the brain. The present study sought to measure microsomal fatty acid elongation activity in the brain of wild-type (WT) and abcd1-deficient mice during the course of development. The fatty acid elongation activity in the microsomal fraction was measured by the incorporation of [2-14C]malonyl-CoA into fatty acids in the presence of C16:0-CoA or C20:0-CoA. Cytosolic fatty acid synthesis activity was completely inhibited by the addition of N-ethylmaleimide (NEM). The microsomal fatty acid elongation activity in the brain was significantly high at 3 weeks after birth and decreased substantially at 3 months after birth. Furthermore, we detected two different types of microsomal fatty acid elongation activity by using C16:0-CoA or C20:0-CoA as the substrate and found the activity toward C20:0-CoA in abcd1-deficient mice was higher than the WT 3-week-old animals. These results suggest that during the active myelination phase the microsomal fatty acid elongation activity is stimulated in abcd1-deficient mice, which in turn perturbs the lipid composition in myelin.
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Acknowledgments
This research was supported in part by a Grant-in-Aid for Intractable Diseases from the Ministry of Health, Labour and Welfare of Japan, and for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (22590060, 23590072, 26460063). Pacific Edit reviewed the manuscript prior to submission.
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This article dose not contain any studies with human participants performed by any of the authors. 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.
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Morita, M., Kawamichi, M., Shimura, Y. et al. Brain microsomal fatty acid elongation is increased in abcd1-deficient mouse during active myelination phase. Metab Brain Dis 30, 1359–1367 (2015). https://doi.org/10.1007/s11011-015-9701-1
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DOI: https://doi.org/10.1007/s11011-015-9701-1