FADS genetic and metabolomic analyses identify the ∆5 desaturase (FADS1) step as a critical control point in the formation of biologically important lipids.
FADS genetic and metabolomic analyses identify the ∆5 desaturase (FADS1) step as a critical control point in the formation of biologically important lipids.
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DOI：
10.1038/s41598-020-71948-1
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发表时间：
2020-09-28
影响因子：
4.6
通讯作者：
Chilton FH
中科院分区：
文献类型：
--
作者：
Reynolds LM;Dutta R;Seeds MC;Lake KN;Hallmark B;Mathias RA;Howard TD;Chilton FH
人类经历了激烈的进化选择，以优化其产生必要数量的长链（LC-）多不饱和脂肪酸（PUFA）的脂质的能力。为了更好地了解三个FADS基因（FADS 1，FADS 2和FADS 3）基因座内的遗传变异对不同脂质家族的影响，我们研究了247种脂质代谢物（包括四种主要的含LC-PUFA分子和信号分子）与位于FADS基因座内的常见和低频遗传变异的相关性。FADS基因座的遗传变异与52种含LC-PUFA的脂质和信号分子（包括游离脂肪酸、磷脂、溶血磷脂和内源性大麻素）密切相关（p < 1.2 × 10-8）。值得注意的是，大多数（80%）FADS相关脂质与该FADS基因座以外的遗传变异无关。这些发现强调了FADS基因座的遗传变异在调节生理关键的含LC-PUFA的脂质水平中发挥的核心作用，这些脂质参与先天免疫，能量稳态和大脑发育/功能。
Humans have undergone intense evolutionary selection to optimize their capacity to generate necessary quantities of long chain (LC-) polyunsaturated fatty acid (PUFA)-containing lipids. To better understand the impact of genetic variation within a locus of three FADS genes (FADS1, FADS2, and FADS3) on a diverse family of lipids, we examined the associations of 247 lipid metabolites (including four major classes of LC-PUFA-containing molecules and signaling molecules) with common and low-frequency genetic variants located within the FADS locus. Genetic variation in the FADS locus was strongly associated (p < 1.2 × 10–8) with 52 LC-PUFA-containing lipids and signaling molecules, including free fatty acids, phospholipids, lyso-phospholipids, and an endocannabinoid. Notably, the majority (80%) of FADS-associated lipids were not significantly associated with genetic variants outside of this FADS locus. These findings highlight the central role genetic variation at the FADS locus plays in regulating levels of physiologically critical LC-PUFA-containing lipids that participate in innate immunity, energy homeostasis, and brain development/function.
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