在過去的一個世紀(jì)中，西方飲食習(xí)慣的變化改變了人們飲食結(jié)構(gòu)中ω-6脂肪酸（w6,，存在于肉類和植物油中）和ω-3脂肪酸（w3，存在于亞麻油和魚油中）的攝入比例,。很多研究顯示,，這樣的變化會造成炎癥類疾病的風(fēng)險升高（伴隨有自身免疫和過敏）,，目前研究者通過調(diào)節(jié)志愿者飲食情況進行研究，發(fā)現(xiàn)了引起這些變化的生物學(xué)基礎(chǔ),。
人類學(xué)研究顯示,，歷史上人類祖先飲食中的w6/w3比例一直維持在2:1,，但是目前西方國家的這個比例已經(jīng)高達10:1。由于ω-脂肪酸能被轉(zhuǎn)化成炎癥性分子,，有人認(rèn)為這種飲食變化也會破壞促炎因子和抗炎因子，導(dǎo)致全身性炎癥反應(yīng)以及哮喘,、過敏,、糖尿病和關(guān)節(jié)炎等問題發(fā)生率升高。
Floyd Chilton及其同事希望搞清這些脂肪酸是否還會產(chǎn)生其他影響，他們對27名健康的志愿者采取一種飲食干預(yù)的方法,，在5周的時間內(nèi)，使他們的飲食情況類似于早期人類,。然后，他們檢測了一些血液細(xì)胞中影響自身免疫及過敏的免疫信號和細(xì)胞因子（蛋白質(zhì)免疫信使）的相關(guān)基因表達水平,，他們發(fā)現(xiàn),與常規(guī)飲食者相比,，很多促炎癥的關(guān)鍵信號因子基因表達大幅度減少，包括一種名為PI3K的信號因子蛋白質(zhì),，它是自身免疫和炎癥過敏反應(yīng)早期階段中的一個關(guān)鍵因子,。
這項研究首次說明，ω-脂肪酸在臨床中有巨大的潛在應(yīng)用價值,，它具有重要的生理機制,，能夠引起人類基因表達發(fā)生巨大變化。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
