Mechanisms underlying the biological function of fatty acids

单种脂肪酸(FA)形式多样，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，我积累了有关FA生理水平的知识，这将极大地促进未来的研究。此外，我们使用新的delta6去饱和酶基因敲除小鼠模型定义了α-亚麻酸(ALA)的抗炎作用。这一发现揭穿了ALA没有生物活性的教条。这些结果还导致了一条新的研究路线，以了解去饱和酶在FA信号中的调制作用。我们对硬脂酰辅酶A去饱和酶(SCD1)的研究进一步支持了这一机制。我们发现，SCD1，一种Delta9去饱和酶，影响反式母牛油酸中共轭亚油酸(CLA)的水平。我们以前已经证明，CLA通过改变小窝的膜成分和蛋白质定位来影响小窝介导的信号转导。这些观察结果表明，从头合成通过控制FA供应来影响细胞信号转导。

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.