Effect of branched-chain fatty acid on lipid dynamics in mice lacking liver fatty acid binding protein gene
Effect of branched-chain fatty acid on lipid dynamics in mice lacking liver fatty acid binding protein gene
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DOI：
10.1152/ajpcell.00359.2004
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发表时间：
2005-03-01
影响因子：
5.5
通讯作者：
Schroeder, F
中科院分区：
文献类型：
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作者：
Atshaves, BP;McIntosh, AL;Schroeder, F
虽然肝脂肪酸蛋白（L-FABP）在支链脂肪酸代谢中的作用已被提出的基础上获得的数据与培养细胞，这一观察结果的生理意义仍有待证明。为了解决这个问题，在L-FABP基因消除的小鼠中测定了植烷酸（一种支链脂肪酸）的脂质表型和代谢，这些小鼠喂食含和不含1%植醇（植烷酸的代谢前体）的饮食。在响应饮食植醇，L-FABP基因消融表现出性别依赖性的脂质表型。与雄性L-FABP-/-小鼠相比，饲喂植物醇的雌性L-FABP-/-小鼠的肝脏具有显著更多的脂肪脂滴，而在饲喂植物醇的野生型L-FABP +/+小鼠中，雄性和雌性之间的差异不显著。因此，L-FABP基因消融加剧了脂肪滴的积累，在植物醇喂养的女性，但不是男性，小鼠。这些结果反映在脂质谱中，其中在植物醇喂养的雌性L-FABP -/-小鼠中的三酰甘油酯的肝脏水平显著高于雄性L-FABP -/-小鼠。此外，叶绿醇喂养的雌性L-FABP -/-小鼠的肝脏表现出比雄性小鼠更多的坏死，这与肝脏和血清中更高水平的叶绿醇代谢物（植烷酸，降植烷酸）的积累一致，此外，肝脏中甾醇载体蛋白（SCP）-x的水平也有所增加，SCP-x是支链脂肪酸氧化所需的唯一已知过氧化物酶体酶。总之，L-FABP基因切除在支链脂肪酸代谢中发挥了重要作用，特别是在雌性小鼠中。这些影响仅部分补偿伴随上调SCP-x响应L-FABP基因消融和饮食植醇。
Although a role for liver fatty acid protein (L-FABP) in the metabolism of branched-chain fatty acids has been suggested based on data obtained with cultured cells, the physiological significance of this observation remains to be demonstrated. To address this issue, the lipid phenotype and metabolism of phytanic acid, a branched-chain fatty acid, were determined in L-FABP gene-ablated mice fed a diet with and without 1% phytol ( a metabolic precursor to phytanic acid). In response to dietary phytol, L-FABP gene ablation exhibited a gender-dependent lipid phenotype. Livers of phytol-fed female L-FABP -/- mice had significantly more fatty lipid droplets than male L-FABP -/- mice, whereas in phytol-fed wild-type L-FABP +/+ mice differences between males and females were not significant. Thus L-FABP gene ablation exacerbated the accumulation of lipid droplets in phytol-fed female, but not male, mice. These results were reflected in the lipid profile, where hepatic levels of triacylglycerides in phytol-fed female L-FABP -/- mice were significantly higher than in male L-FABP -/- mice. Furthermore, livers of phytol-fed female L-FABP -/- mice exhibited more necrosis than their male counterparts, consistent with the accumulation of higher levels of phytol metabolites ( phytanic acid, pristanic acid) in liver and serum, in addition to increased hepatic levels of sterol carrier protein (SCP)-x, the only known peroxisomal enzyme specifically required for branched-chain fatty acid oxidation. In summary, L-FABP gene ablation exerted a significant role, especially in female mice, in branched-chain fatty acid metabolism. These effects were only partially compensated by concomitant upregulation of SCP-x in response to L-FABP gene ablation and dietary phytol.