Gamma-linolenic acid, Dihommo-gamma linolenic, Eicosanoids and Inflammatory Processes.
Gamma-linolenic acid, Dihommo-gamma linolenic, Eicosanoids and Inflammatory Processes.
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DOI：
10.1016/j.ejphar.2016.04.020
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发表时间：
2016-08-15
影响因子：
5
通讯作者：
Chilton FH
中科院分区：
文献类型：
--
作者：
Sergeant S;Rahbar E;Chilton FH
γ-亚麻酸 (GLA, 18:3n-6) 是一种 omega-6 (n-6)、18 碳 (18C-) 多不饱和脂肪酸 (PUFA)，存在于母乳和多种植物种子油中，通常作为膳食补充剂的一部分食用。虽然有大量的体外和体内动物模型表明补充 GLA 的饮食可减轻炎症反应，但利用 GLA 或 GLA 与 omega-3 (n-3) PUFA 组合的临床研究尚无定论。本综述的一个中心前提是，存在影响 GLA 转化为二高γ亚麻酸（DGLA，20:3n-6）和花生四烯酸（AA，20:4n-6）的关键代谢和遗传因素，从而影响 DGLA 和 AA 衍生代谢物的平衡。因此，这些因素会影响 GLA 或 GLA/n-3 PUFA 补充剂治疗炎症的临床效果。具体来说，这些因素包括：1）不同人体细胞和组织将GLA转化为DGLA和AA以及将DGLA和AA代谢为生物活性代谢物的能力； 2) DGLA 和 AA 代谢物对炎症过程和疾病的相反作用； 3) 脂肪酸去饱和酶 (FADS) 基因簇内遗传变异的影响，特别是对 AA/DGLA 比率和生物活性代谢物的影响。我们假设这些因素影响基于 GLA 补充剂的临床试验中观察到的结果的异质性，并表明利用基于 PUFA 的补充剂的“一刀切”方法可能不再适合预防和治疗复杂的人类疾病。
Gamma-linolenic acid (GLA, 18:3n-6) is an omega-6 (n-6), 18 carbon (18C-) polyunsaturated fatty acid (PUFA) found in human milk and several botanical seed oils and is typically consumed as part of a dietary supplement. While there have been numerous in vitro and in vivo animal models which illustrate that GLA-supplemented diets attenuate inflammatory responses, clinical studies utilizing GLA or GLA in combination with omega-3 (n-3) PUFAs have been much less conclusive. A central premise of this review is that there are critical metabolic and genetic factors that affect the conversion of GLA to dihommo-gamma linolenic acid (DGLA, 20:3n-6) and arachidonic acid (AA, 20:4n-6), which consequently affects the balance of DGLA- and AA- derived metabolites. As a result, these factors impact the clinical effectiveness of GLA or GLA/n-3 PUFA supplementations in treating inflammatory conditions. Specifically, these factors include: 1) the capacity for different human cells and tissues to convert GLA to DGLA and AA and to metabolize DGLA and AA to bioactive metabolites; 2) the opposing effects of DGLA and AA metabolites on inflammatory processes and diseases; and 3) the impact of genetic variations within the fatty acid desaturase (FADS) gene cluster, in particular, on AA/DGLA ratios and bioactive metabolites. We postulate that these factors influence the heterogeneity of results observed in GLA supplement-based clinical trials and suggest that “one-size fits all” approaches utilizing PUFA-based supplements may no longer be appropriate for the prevention and treatment of complex human diseases.