Role of fatty acids in health and disease.

在过去的一年里，我们在与该项目相关的两个主要课题上取得了进展，这导致了以下出版物和多项专利的申请。使用小鼠模型，我们证明了在食物中补充常规大豆油可以降低血脂，但会增加动脉粥样硬化的发展。相比之下，补充一种富含油酸、亚油酸含量较低的改性大豆油并不能有效地降低血脂，但能减少小鼠的动脉粥样硬化。此外，我们发现，亚油酸在传统大豆油的小鼠中转化为花生四烯酸，并增加了它们的炎症倾向，这可能是为什么传统大豆油会增加动脉粥样硬化的可能解释。 这些结果最近发表，对改善人类饮食以预防心血管疾病具有潜在的重要意义，但必须在未来的人体临床试验中进行检查。 在我们与脂肪酸相关的另一个主要项目中，我们给老年（>12个月）apoE-KO小鼠喂食了一种从富含C24：5的鱼油中纯化的极长链脂肪酸（VLCPUFA）的新型混合物。 虽然视网膜和大脑中的VLCPUFA通常超过30个碳原子长，但我们发现C24：5具有良好的生物利用度，并且在靶器官中被拉长。 经过两个月的补充，通过ERG测量，小鼠的视力有所改善，并且在一系列测试中改善了认知功能。我们还证明了VLPUFA是比EPA和DHA更有效的PPAR-alpha激动剂，并且降低了血浆脂质和葡萄糖以及减少了动脉粥样硬化。目前正在对该项目的手稿进行审查，我们对这些发现申请了几项专利。

We made progress on two major topics related to this project in the past year, which has resulted in the below publications and the filing of several patents. Using a mouse model, we demonstrated that supplementation of chow with a conventional soybean oil lowers plasma lipids but increases development of atherosclerosis. In contrast, supplementation with a modified soybean oil designed to be enriched in oleic acid and lower in linoleic acid did not as effectively lower plasma lipids but decreased atherosclerosis in mice. Furthermore, we showed that linoleic acid is converted to arachidonic acid in mice on the conventional soybean oil and increases their propensity for inflammation, which may be a possible explanation for why conventional soybean oil increases atherosclerosis. These results have recently been published and have potentially important implications in improving the diet in humans for the prevention of cardiovascular disease but will have to be examined in a future human clinical trial. In our other major project related to fatty acids, we fed old (>12 months) apoE-KO mice a novel blend of Very Long Chain Fatty acids (VLCPUFA) purified from fish oil that were enriched in C24:5. Although the VLCPUFAs in the retina and brain are often over 30 carbons long, we found that C24:5 has good bioavailability and is elongated in target organs. After two month supplementation, the mice showed improved vision as measured by ERG, as well as improved cognitive function in a battery of tests. We also demonstrated that VLPUFAs are more potent PPAR-alpha agonists than either EPA and DHA and lowered plasma lipids and glucose and decreased atherosclerosis. A manuscript is currently be reviewed on this project and we filed several patents on these findings.