Clarke S D, Baillie R, Jump D B, Nakamura M T
Department of Human Ecology, University of Texas, Austin 78712, USA.
Ann N Y Acad Sci. 1997 Sep 20;827:178-87. doi: 10.1111/j.1749-6632.1997.tb51833.x.
Dietary polyenoic (n-6) and (n-3) fatty acids uniquely regulate fatty acid biosynthesis and fatty acid oxidation. They exercise this effect by modulating the expression of genes coding for key metabolic enzymes and, in doing this, PUFA govern the intracellular as well as the interorgan metabolism of glucose and fatty acids. During the past 20 years, we have gradually elucidated the cellular and molecular mechanism by which dietary PUFA regulate lipid metabolism. Central to this mechanism has been our ability to determine that dietary PUFA regulate the transcription of genes. We have only begun to elucidate the nuclear mechanisms by which PUFA govern gene expression, but one point is clear and that is that it is unlikely that one mechanism will explain the variety of genes governed by PUFA. The difficulty in providing a unifying hypothesis at this time stems from (a) the many metabolic routes taken by PUFA upon entering a cell and (b) the lack of identity of a specific PUFA-regulated trans-acting factor. Nevertheless, our studies have revealed that PUFA are not only utilized as fuel and structural components of cells, but also serve as important mediators of gene expression, and that in this way they influence the metabolic directions of fuels and they modulate the development of nutritionally related pathophysiologies such as diabetes.
膳食多烯(n-6)和(n-3)脂肪酸对脂肪酸生物合成和脂肪酸氧化具有独特的调节作用。它们通过调节编码关键代谢酶的基因表达来发挥这种作用,在此过程中,多不饱和脂肪酸(PUFA)控制着细胞内以及器官间葡萄糖和脂肪酸的代谢。在过去20年里,我们逐渐阐明了膳食PUFA调节脂质代谢的细胞和分子机制。该机制的核心在于我们确定膳食PUFA可调节基因转录的能力。我们才刚刚开始阐明PUFA调控基因表达的核机制,但有一点是明确的,即不太可能有一种机制能解释由PUFA调控的各种基因。目前难以提出统一假说的原因在于:(a)PUFA进入细胞后有许多代谢途径;(b)缺乏特定的PUFA调控反式作用因子。然而,我们的研究表明,PUFA不仅可作为细胞的燃料和结构成分,还可作为基因表达的重要介质,并且通过这种方式影响燃料的代谢方向,调节诸如糖尿病等营养相关病理生理学的发展。