Mechanisms underlying the biological function of fatty acids

脂肪酸生物学功能的机制

• 批准号: RGPIN-2015-06018
• 负责人: Ma, David
• 金额: $ 2.4万
• 依托单位: University of Guelph
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=590784
• 关键词: Mechanisms; underlying; biological; function; fatty

By virtue of a diversity of form, individual fatty acids (FA) have unique biological effects. Therefore, the long term objective of objective of my research program is to a) determine mechanisms by which FA regulate signalling pathways, b) define individual effects of major FA and c) their impact on cellular function. In the past 6 years, I have produced knowledge regarding physiological levels of FA, which will greatly inform future studies. Also, we defined an anti-inflammatory role for alpha-linolenic acid (ALA) using the novel delta 6 desaturase knock out mouse model. This finding debunks dogma that ALA has no biological activity. These results also led to a new line of research to understand the modulatory role of desaturases on FA signalling. Further support for this mechanism was provided in our work on stearoyl CoA desaturase (SCD1). We show that SCD1, a delta 9 desaturase enzyme, influences levels of conjugated linoleic acid (CLA) from trans vaccenic acid. We have previously shown that CLA influences caveolae-mediated signalling by altering caveolae membrane composition and protein localization. In tandem, these observations suggest that de novo synthesis influences cell signalling by controlling FA supply.

由于形式的多样性，单个脂肪酸（FA）具有独特的生物学效应。因此，我的研究计划的长期目标是：a）确定FA调节信号通路的机制，B）确定主要FA的个体效应，c）它们对细胞功能的影响。在过去的6年里，我已经产生了关于FA的生理水平的知识，这将极大地为未来的研究提供信息。此外，我们使用新的δ 6去饱和酶敲除小鼠模型确定了α-亚麻酸（ALA）的抗炎作用。这一发现推翻了ALA没有生物活性的教条。这些结果也导致了一个新的研究路线，以了解去饱和酶对FA信号的调节作用。在我们对硬脂酰辅酶A去饱和酶（SCD 1）的研究中，进一步支持了这一机制。我们发现，SCD 1，一个δ 9去饱和酶，影响共轭亚油酸（CLA）从反式异油酸的水平。我们以前已经表明，CLA影响小窝介导的信号通过改变小窝膜组成和蛋白定位。在串联，这些观察结果表明，从头合成影响细胞信号通过控制FA供应。