Effect of Lorenzo's Oil on Hepatic Gene Expression and the Serum Fatty Acid Level in abcd1-Deficient Mice.
Effect of Lorenzo's Oil on Hepatic Gene Expression and the Serum Fatty Acid Level in abcd1-Deficient Mice.
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洛伦佐油对 abcd1 缺陷小鼠肝脏基因表达和血清脂肪酸水平的影响。
DOI：
10.1007/8904_2017_32
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Imanaka T.
中科院分区：
文献类型：
--
作者：
Morita M;Honda A;Kobayashi A;Watanabe Y;Watanabe S;Kawaguchi K;Takashima S;Shimozawa N;Imanaka T.
众所周知，洛伦佐的油可以降低X连锁肾上腺脑白质营养不良(ALD)患者血浆和皮肤成纤维细胞中饱和超长链脂肪酸(VLCFA)的水平。然而，Lorenzo‘s油在体内脂肪酸代谢中的作用尚未得到很好的阐明。为了研究洛伦佐油对脂肪酸代谢的影响，我们分析了洛伦佐油处理的野生型和abcd1基因缺陷小鼠的肝脏基因表达和血清脂肪酸水平。洛伦佐油治疗abcd1缺陷小鼠的血清脂肪酸水平的变化与补充洛伦佐油的ALD患者的血浆脂肪酸水平的变化非常相似。此外，我们还发现，两种过氧化物体酶Dbanda Scp2和三种微粒体酶Elovl1、2和3的肝脏基因表达被洛伦佐油显著刺激。我们的发现表明，洛伦佐的油在转录水平上激活了肝脏过氧化体脂肪酸的β氧化。相比之下，Lorenzo‘s油对Elovl1、2和3的转录刺激不会引起血清脂肪酸水平的变化。看来，洛伦佐的油抑制这些伸长活性可能会导致饱和VLCFA的下降。因此，这些结果不仅有助于阐明洛伦佐油治疗降低ALD患者血清中饱和VLCFA水平的机制，而且也为开发一种新的治疗方法来治疗过氧化体β氧化酶缺乏症，特别是轻度DBP缺乏症。
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 andabcd1-deficient mice. The change in the serum fatty acid level in Lorenzo’s oil-treatedabcd1-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,DbpandScp2, and three microsomal enzymes,Elovl1, 2,and3, 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 ofElovl1, 2,and3by 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.
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DOI：
10.1016/j.bbalip.2014.12.005
发表时间：
2015-02-01
影响因子：
4.8
作者：
Schackmann, Martin J. A.;Ofman, Rob;Kemp, Stephan
通讯作者：
Kemp, Stephan
影响因子：
4.8
作者：
Brolinson, Annelie;Fourcade, Stephane;Jacobsson, Anders
通讯作者：
Jacobsson, Anders
影响因子：
3.5
作者：
Fourcade, Stephane;Ruiz, Montserrat;Pujol, Aurora
通讯作者：
Pujol, Aurora
膳食脂肪对大鼠组织中总脂肪酸和过氧化物酶体脂肪酸氧化的影响。
DOI：
--
发表时间：
1986
期刊：
Biochimica et Biophysica Acta
影响因子：
--
作者：
J. Veerkamp;J. Zevenbergen
通讯作者：
J. Zevenbergen
洛伦佐油对健康小鼠过氧化物酶体的影响。
影响因子：
2.9
作者：
D. Craemer;C. Branden;Monique Fontaine;Joseph Vamecq
通讯作者：
Joseph Vamecq