van Schothorst Evert M, Flachs Pavel, Franssen-van Hal Nicole L W, Kuda Ondrej, Bunschoten Annelies, Molthoff Jos, Vink Carolien, Hooiveld Guido J E J, Kopecky Jan, Keijer Jaap
Food Bioactives Group, RIKILT Institute of Food Safety, Wageningen UR, Wageningen, The Netherlands.
BMC Genomics. 2009 Mar 16;10:110. doi: 10.1186/1471-2164-10-110.
Dietary polyunsaturated fatty acids (PUFA), in particular the long chain marine fatty acids docosahexaenoic (DHA) and eicosapentaenoic (EPA), are linked to many health benefits in humans and in animal models. Little is known of the molecular response to DHA and EPA of the small intestine, and the potential contribution of this organ to the beneficial effects of these fatty acids. Here, we assessed gene expression changes induced by DHA and EPA in the wildtype C57BL/6J murine small intestine using whole genome microarrays and functionally characterized the most prominent biological process.
The main biological process affected based on gene expression analysis was lipid metabolism. Fatty acid uptake, peroxisomal and mitochondrial beta-oxidation, and omega-oxidation of fatty acids were all increased. Quantitative real time PCR, and -- in a second animal experiment -- intestinal fatty acid oxidation measurements confirmed significant gene expression differences and showed in a dose-dependent manner significant changes at biological functional level. Furthermore, no major changes in the expression of lipid metabolism genes were observed in the colon.
We show that marine n-3 fatty acids regulate small intestinal gene expression and increase fatty acid oxidation. Since this organ contributes significantly to whole organism energy use, this effect on the small intestine may well contribute to the beneficial physiological effects of marine PUFAs under conditions that will normally lead to development of obesity, insulin resistance and diabetes.
膳食多不饱和脂肪酸(PUFA),尤其是长链海洋脂肪酸二十二碳六烯酸(DHA)和二十碳五烯酸(EPA),在人类和动物模型中与许多健康益处相关。关于小肠对DHA和EPA的分子反应以及该器官对这些脂肪酸有益作用的潜在贡献,人们了解甚少。在此,我们使用全基因组微阵列评估了野生型C57BL/6J小鼠小肠中DHA和EPA诱导的基因表达变化,并对最显著的生物学过程进行了功能表征。
基于基因表达分析,受影响的主要生物学过程是脂质代谢。脂肪酸摄取、过氧化物酶体和线粒体β-氧化以及脂肪酸的ω-氧化均增加。定量实时PCR以及在第二项动物实验中的肠道脂肪酸氧化测量证实了显著的基因表达差异,并在生物学功能水平上以剂量依赖方式显示出显著变化。此外,在结肠中未观察到脂质代谢基因表达的主要变化。
我们表明海洋n-3脂肪酸调节小肠基因表达并增加脂肪酸氧化。由于该器官对整个生物体的能量利用有显著贡献,在通常会导致肥胖、胰岛素抵抗和糖尿病发展的情况下,这种对小肠的作用很可能有助于海洋多不饱和脂肪酸的有益生理作用。