Brain arachidonic acid incorporation is decreased in heart fatty acid binding protein gene-ablated mice
Brain arachidonic acid incorporation is decreased in heart fatty acid binding protein gene-ablated mice
复制标题
DOI：
10.1021/bi047292r
复制
发表时间：
2005-04-26
期刊：
影响因子：
2.9
通讯作者：
Glatz, JFC
中科院分区：
文献类型：
--
作者：
Murphy, EJ;Owada, Y;Glatz, JFC
心脏脂肪酸结合蛋白(H-FABP)在神经元中表达，但其在脑脂肪酸合成和代谢中的作用尚不清楚。我们在体内检测了H-FABP基因切除对花生四烯酸([I-C-14]20：4N-6)或棕榈酸([1-C-14]16：0)脑内掺入的影响。脑部信使核糖核酸的分析证实了基因消融，并且在基因消融的小鼠中其他FABP信使核糖核酸的水平没有补偿性变化。在H-FABP基因去除小鼠的脑中，[1-C-14]20：4N-6的掺入系数降低了24%，而[1-C-14]16：0的掺入系数未受影响。在有机组分和水相组分中，更多的[1-14C]20：4N-6分布到水相组分中，这表明20：4N-6在这些小鼠体内的代谢靶向性被破坏。[1-C-14]20：4N-6在总磷脂中的掺入较少，胆碱甘油磷脂(ChoGpl)的掺入水平显著降低(51%)。因为FABP可以影响稳态脂肪质量，所以我们测量了大脑个体的脂肪质量。基因去除后，脑内总磷脂质量减少了17%，归因于ChoGpl和鞘磷脂的质量分别减少了27%和32%。血浆纤维蛋白原亚类质量也减少，提示H-FABP可能促进脑内纤维蛋白原的合成。在基因去除的小鼠中，磷脂酰肌醇20：4n-6水平降低了25%，而主要磷脂类中总n-6脂肪酸的比例降低。因此，这些结果首次证明了H-FABP的表达影响了大脑20：4N-6的摄取和转运以及稳态脑脂水平。
Heart fatty acid binding protein (H-FABP) is expressed in neurons, but its role in brain fatty acid incorporation and metabolism is poorly defined. We examined the effect of H-FABP gene ablation on brain incorporation of arachidonic ([I-C-14]20:4n-6) or palmitic ([1-C-14]16:0) acid in vivo. Analysis of brain mRNA confirmed gene ablation and demonstrated no compensatory changes in the levels of other FABP mRNA in the gene-ablated mice. In brains from H-FABP gene-ablated mice, the incorporation coefficient for [1-C-14]20:4n-6 was reduced 24%, while that for [1-C-14]16:0 was unaffected. Within the organic and aqueous fractions, significantly more [1-14C]20:4n-6 was distributed into the aqueous fraction, suggesting a disruption in the metabolic targeting of 20:4n-6 in these mice. There was less incorporation of [1-C-14]20:4n-6 into total phospholipids and a marked reduction (51%) in the level of incorporation into the choline glycerophospholipids (ChoGpl). Because FABP can influence steady-state lipid mass, brain individual lipid masses were measured. The brain total phospholipid mass was reduced 17% by gene ablation, ascribed to a 27% and 32% reduction in the masses of ChoGpl and sphingomyelin, respectively. Plasmalogen subclass masses were also reduced, suggesting that H-FABP may augment brain plasmalogen synthesis. In gene-ablated mice, the phosphatidylinositol 20:4n-6 level was reduced 25%, while the proportion of total n-6 fatty acids was reduced in the major phospholipid classes. Thus, these results demonstrate for the first time that H-FABP expression influences brain 20:4n-6 uptake and trafficking as well as steady-state brain lipid levels.