APOE Genotype Modifies the Plasma Oxylipin Response to Omega-3 Polyunsaturated Fatty Acid Supplementation in Healthy Individuals.
APOE Genotype Modifies the Plasma Oxylipin Response to Omega-3 Polyunsaturated Fatty Acid Supplementation in Healthy Individuals.
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DOI：
10.3389/fnut.2021.723813
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发表时间：
2021
影响因子：
5
通讯作者：
Minihane AM
中科院分区：
文献类型：
--
作者：
Saleh RNM;West AL;Ostermann AI;Schebb NH;Calder PC;Minihane AM
ω-3多不饱和脂肪酸（n-3 PUFA）、二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）在很大程度上通过影响促炎和抗炎/促消退氧化脂素浓度来介导炎症。常见的基因变异被认为是响应于n-3 PUFA补充的氧脂素水平的大的个体间差异的基础，这反过来可能有助于响应于n-3 PUFA干预的整体异质性。鉴于其在炎症中的已知作用，并作为EPA和DHA的生理反应的调节剂，在这里，我们探索，第一次，根据载脂蛋白E（APOE）基因型的血浆羟基-，环氧-和二羟基-花生四烯酸，EPA和DHA氧化脂质的差异反应，使用来自剂量-反应平行设计RCT的样品。健康参与者被给予相当于每周摄入1，2和4份油性鱼的EPA+DHA剂量，持续12个月。在补充n-3 PUFA 3个月或12个月后，野生型APOE 3/E3和APOE 4携带者组之间的EPA、DHA或ARA血浆水平没有差异。在12个月时，APOE 4携带者的羟基EPA（HEPE）和羟基DHA（HDHAs）较高，在最高EPA+DHA摄入量时差异最明显。对于β-ω羟化酶产物19-HEPE（p = 0.027）和20-HEPE（p = 0.011），观察到显著的APOE*n-3 PUFA剂量效应。8-HEPE与其他几种血浆氧脂素沿着是过氧化物酶体增殖物激活受体（PPARs）的激活剂，与APOE 3/E3（4倍）相比，8-HEPE在APOE 4携带者中显示出最高的倍数变化（14倍）（p = 0.014）。与高基础EPA水平（EPA >总脂肪酸的1.22%）相比，低基础血浆EPA水平（EPA <总脂肪酸的0.85%）与5-HEPE、9-HEPE、11-HEPE和20-HEPE的更大变化相关。总之，APOE基因型调节了血浆氧脂素对EPA+DHA摄入量增加的反应，APOE 4携带者在高剂量n-3 PUFA补充12个月后出现最大增加。
The omega-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), mediate inflammation in large part by affecting pro-inflammatory and anti-inflammatory/pro-resolving oxylipin concentrations. Common gene variants are thought to underlie the large inter-individual variation in oxylipin levels in response to n-3 PUFA supplementation, which in turn is likely to contribute to the overall heterogeneity in response to n-3 PUFA intervention. Given its known role in inflammation and as a modulator of the physiological response to EPA and DHA, here we explore, for the first time, the differential response of plasma hydroxy-, epoxy- and dihydroxy-arachidonic acid, EPA and DHA oxylipins according to apolipoprotein E (APOE) genotype using samples from a dose-response parallel design RCT. Healthy participants were given doses of EPA+DHA equivalent to intakes of 1, 2, and 4 portions of oily fish per week for 12 months. There was no difference in the plasma levels of EPA, DHA or ARA between the wildtype APOE3/E3 and APOE4 carrier groups after 3 or 12 months of n-3 PUFA supplementation. At 12 months, hydroxy EPAs (HEPEs) and hydroxy-DHAs (HDHAs) were higher in APOE4 carriers, with the difference most evident at the highest EPA+DHA intake. A significant APOE*n-3 PUFA dose effect was observed for the CYP-ω hydroxylase products 19-HEPE (p = 0.027) and 20-HEPE (p = 0.011). 8-HEPE, which, along with several other plasma oxylipins, is an activator of peroxisome proliferator activated receptors (PPARs), showed the highest fold change in APOE4 carriers (14-fold) compared to APOE3/E3 (4-fold) (p = 0.014). Low basal plasma EPA levels (EPA < 0.85% of total fatty acids) were associated with a greater change in 5-HEPE, 9-HEPE, 11-HEPE, and 20-HEPE compared to high basal EPA levels (EPA > 1.22% of total fatty acids). In conclusion, APOE genotype modulated the plasma oxylipin response to increased EPA+DHA intake, with APOE4 carriers presenting with the greatest increases following high dose n-3 PUFA supplementation for 12 months.
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影响因子：
5.9
作者：
Griffin BA;Walker CG;Jebb SA;Moore C;Frost GS;Goff L;Sanders TAB;Lewis F;Griffin M;Gitau R;Lovegrove JA
通讯作者：
Lovegrove JA
影响因子：
5.9
作者：
D'Angelo S;Motti ML;Meccariello R
通讯作者：
Meccariello R
影响因子：
6.5
作者：
Fischer, Robert;Konkel, Anne;Schunck, Wolf-Hagen
通讯作者：
Schunck, Wolf-Hagen
影响因子：
32.4
作者：
Buckley, Christopher D.;Gilroy, Derek W.;Serhan, Charles N.
通讯作者：
Serhan, Charles N.
影响因子：
4.1
作者：
Demler OV;Liu Y;Luttmann-Gibson H;Watrous JD;Lagerborg KA;Dashti H;Giulianini F;Heath M;Camargo CA Jr;Harris WS;Wohlgemuth JG;Andres AM;Tivari S;Long T;Najhawan M;Dao K;Prentice JG;Larsen JA;Okereke OI;Costenbader KH;Buring JE;Manson JE;Cheng S;Jain M;Mora S
通讯作者：
Mora S