在过去的一个世纪中,西方饮食习惯的变化改变了人们饮食结构中ω-6脂肪酸(w6,存在于肉类和植物油中)和ω-3脂肪酸(w3,存在于亚麻油和鱼油中)的摄入比例。很多研究显示,这样的变化会造成炎症类疾病的风险升高(伴随有自身免疫和过敏),目前研究者通过调节志愿者饮食情况进行研究,发现了引起这些变化的生物学基础。
人类学研究显示,历史上人类祖先饮食中的w6/w3比例一直维持在2:1,但是目前西方国家的这个比例已经高达10:1。由于ω-脂肪酸能被转化成炎症性分子,有人认为这种饮食变化也会破坏促炎因子和抗炎因子,导致全身性炎症反应以及哮喘、过敏、糖尿病和关节炎等问题发生率升高。
Floyd Chilton及其同事希望搞清这些脂肪酸是否还会产生其他影响,他们对27名健康的志愿者采取一种饮食干预的方法,在5周的时间内,使他们的饮食情况类似于早期人类。然后,他们检测了一些血液细胞中影响自身免疫及过敏的免疫信号和细胞因子(蛋白质免疫信使)的相关基因表达水平,他们发现,与常规饮食者相比,很多促炎症的关键信号因子基因表达大幅度减少,包括一种名为PI3K的信号因子蛋白质,它是自身免疫和炎症过敏反应早期阶段中的一个关键因子。
这项研究首次说明,ω-脂肪酸在临床中有巨大的潜在应用价值,它具有重要的生理机制,能够引起人类基因表达发生巨大变化。(生物谷Bioon.com)
生物谷推荐原始出处:
J. Biol. Chem., Vol. 284, Issue 23, 15400-15407, June 5, 2009
Effect of Dietary Fatty Acids on Inflammatory Gene Expression in Healthy Humans*
Kelly L. Weaver, Priscilla Ivester1, Michael Seeds, L. Douglas Case?, Jonathan P. Arm||, and Floyd H. Chilton
From the From the Department of Internal Medicine, Section on Molecular Medicine, and , Departments of Physiology and Pharmacology and , ?Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157 and the , ||Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115
ABSTRACT
Over the past 100 years, changes in the food supply in Western nations have resulted in alterations in dietary fatty acid consumption, leading to a dramatic increase in the ratio of omega-6 (ω6) to ω3 polyunsaturated fatty acids (PUFA) in circulation and in tissues. Increased ω6/ω3 ratios are hypothesized to increase inflammatory mediator production, leading to higher incidence of inflammatory diseases, and may impact inflammatory gene expression. To determine the effect of reducing the ω6/ω3 ratio on expression of inflammatory pathway genes in mononuclear cells, healthy humans were placed on a controlled diet for 1 week, then given fish oil and borage oil for an additional 4 weeks. Serum and neutrophil fatty acid composition and ex vivo leukotriene B4 production from stimulated neutrophils were measured at the start and end of the supplementation period and after a 2-week washout. RNA was isolated from mononuclear cells and expression of PI3K, Akt, NFB, and inflammatory cytokines was measured by real-time PCR. A marked increase was seen in serum and neutrophil levels of long-chain 3 PUFA concomitant with a reduction in the ω6/ω3 PUFA ratio (40%). The ex vivo capacity of stimulated neutrophils to produce leukotriene B4 was decreased by 31%. Expression of PI3K and PI3K and the quantity of PI3K protein in mononuclear cells was reduced after supplementation, as was the expression of several proinflammatory cytokines. These data reveal that PUFA may exert their clinical effects via their capacity to regulate the expression of signal transduction genes and genes for proinflammatory cytokines.