Apolipoprotein E (APOE) genotype regulates body weight and fatty acid utilization-Studies in gene-targeted replacement mice
Apolipoprotein E (APOE) genotype regulates body weight and fatty acid utilization-Studies in gene-targeted replacement mice
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DOI：
10.1002/mnfr.201400636
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发表时间：
2015-02-01
影响因子：
5.2
通讯作者：
Rimbach, Gerald
中科院分区：
文献类型：
--
作者：
Huebbe, Patricia;Dose, Janina;Rimbach, Gerald
研究范围：在人类载脂蛋白E （APOE）的三个等位基因中，epsilon 3等位基因最为常见，这可能是适应性进化的结果。在本研究中，我们研究了APOE基因型是否通过调节脂肪酸利用来影响体重和能量代谢。方法和结果：与APOE4小鼠相比，表达人类APOE3的靶向替代小鼠在低脂和高脂饮食中明显更重。特别是在高脂肪喂养中，APOE3小鼠的食物摄入量和膳食能量产量以及脂肪量都增加了。脂肪酸动员（脂肪组织脂肪酶激活）和空腹血浆非酯化脂肪酸水平在APOE3小鼠中显著低于APOE4小鼠。相比之下，APOE4小鼠在骨骼肌中表现出更高的与脂肪酸氧化有关的蛋白质表达。结论：我们的数据表明，APOE3与更有效地获取膳食能量和在脂肪组织中沉积脂肪的潜力有关，而APOE4携带者倾向于增加脂肪酸的动员和利用，尤其是在高脂肪摄入的情况下。对饮食能量的不同处理可能促成了epsilon 3等位基因的进化和在世界范围内的分布。
Scope: Of the three human apolipoprotein E (APOE) alleles, the epsilon 3 allele is most common, which may be a result of adaptive evolution. In this study, we investigated whether the APOE genotype affects body weight and energy metabolism through regulation of fatty acid utilization.Methods and results: Targeted replacement mice expressing the human APOE3 were significantly heavier on low- and high-fat diets compared to APOE4 mice. Particularly on high-fat feeding, food intake and dietary energy yields as well as fat mass were increased in APOE3 mice. Fatty acid mobilization determined as activation of adipose tissue lipase and fasting plasma nonesterified fatty acid levels were significantly lower in APOE3 than APOE4 mice. APOE4 mice, in contrast, exhibited higher expression of proteins involved in fatty acid oxidation in skeletal muscle.Conclusion: Our data suggest that APOE3 is associated with the potential to more efficiently harvest dietary energy and to deposit fat in adipose tissue, while APOE4 carriers tend to increase fatty acid mobilization and utilization as fuel substrates especially under high-fat intake. The different handling of dietary energy may have contributed to the evolution and worldwide distribution of the epsilon 3 allele.