The George Institute for Global Health, University of New South Wales, Sydney, NSW 2042, Australia.
Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, 751 22 Uppsala, Sweden.
Nutrients. 2018 Nov 17;10(11):1791. doi: 10.3390/nu10111791.
Fatty acid desaturases (FADS) catalyze the formation of unsaturated fatty acids and have been related to insulin sensitivity (IS). FADS activities differ between tissues and are influenced by genetic factors that may impact the link to IS. Genome-wide association studies of δ-5-desaturase (D5D), δ-6-desaturase (D6D) and stearoyl-CoA desaturase-1 (SCD) activities (estimated by product-to-precursor ratios of fatty acids analyzed by gas chromatography) in serum cholesterol esters ( = 1453) and adipose tissue ( = 783, all men) were performed in two Swedish population-based cohorts. Genome-wide significant associated loci were evaluated for associations with IS measured with a hyperinsulinemic euglycemic clamp ( = 554). Variants at the were strongly associated with D5D in both cholesterol esters ( = 1.9 × 10) and adipose tissue ( = 1.1 × 10). Variants in three further loci were associated with D6D in cholesterol esters (, = 3.0 × 10; , = 4.8 × 10; and near , = 3.7 × 10) but no associations with D6D in adipose tissue attained genome-wide significance. One locus was associated with SCD in adipose tissue (, = 2.2 × 10). Genetic variants near were associated with IS ( = 3.8 × 10). The cluster was the main genetic determinant of estimated FADS activity. However, fatty acid (FA) ratios in adipose tissue and cholesterol esters represent FADS activities in separate tissues and are thus influenced by different genetic factors with potential varying effects on IS.
脂肪酸去饱和酶（FADS）催化不饱和脂肪酸的形成，与胰岛素敏感性（IS）有关。FADS 的活性在不同组织之间存在差异，并且受到可能影响与 IS 联系的遗传因素的影响。对血清胆固醇酯（= 1453）和脂肪组织（= 783，均为男性）中 δ-5-去饱和酶（D5D）、δ-6-去饱和酶（D6D）和硬脂酰辅酶 A 去饱和酶-1（SCD）活性（通过气相色谱分析的脂肪酸产物与前体比值估算）进行了两项基于瑞典人群的队列研究。对与通过高胰岛素正葡萄糖钳夹法测量的 IS 具有关联的全基因组显著相关的基因座进行了评估（= 554）。在胆固醇酯（= 1.9×10）和脂肪组织（= 1.1×10）中，与 D5D 强烈相关的 基因座在两种组织中均具有全基因组显著关联。在另外三个基因座中，三种变体与胆固醇酯中的 D6D 相关（，= 3.0×10；，= 4.8×10；以及接近，= 3.7×10），但在脂肪组织中，与 D6D 相关的变体未达到全基因组显著水平。一个基因座与脂肪组织中的 SCD 相关（，= 2.2×10）。 基因座附近的遗传变异与 IS 相关（= 3.8×10）。 簇是估计 FADS 活性的主要遗传决定因素。然而，脂肪组织和胆固醇酯中的脂肪酸（FA）比值代表了不同组织中的 FADS 活性，因此受到不同遗传因素的影响，这些因素可能对 IS 产生不同的影响。
