Deep Lipidomics in Human Plasma: Cardiometabolic Disease Risk and Effect of Dietary Fat Modulation.
Deep Lipidomics in Human Plasma: Cardiometabolic Disease Risk and Effect of Dietary Fat Modulation.
复制标题
人类血浆中的深层脂质组学：饮食脂肪调节对心脏代谢疾病的风险和影响。
DOI：
10.1161/circulationaha.121.056805
复制
发表时间：
2022-07-05
期刊：
影响因子：
37.8
通讯作者：
Schulze, Matthias B.
中科院分区：
文献类型：
--
作者：
Eichelmann, Fabian;Sellem, Laury;Wittenbecher, Clemens;Jaeger, Susanne;Kuxhaus, Olga;Prada, Marcela;Cuadrat, Rafael;Jackson, Kim G.;Lovegrove, Julie A.;Schulze, Matthias B.
关键词：
在血液和组织中，膳食和内源性产生的脂肪酸（FA）以游离形式或作为复合脂质分子的一部分存在，这些分子共同代表相应组织的脂质组。我们评估了来自高分辨率脂质组学的血浆脂质与心脏代谢疾病的相关性，并随后测试了所确定的风险相关脂质是否对膳食脂肪改变敏感。EPIC波茨坦队列研究（欧洲癌症和营养前瞻性研究）包括从德国波茨坦周围的一般人群中招募的27548名年龄范围为35至65岁的参与者。我们根据固定随机子样本（n=1262）和所有相应队列范围内确定的原发性心血管疾病（致死性和非致死性心肌梗死和卒中的复合物; n=551）和2型糖尿病（n=775）病例生成了2个疾病特异性病例队列。我们估计了282种类别特异性FA丰度（从15种脂质类别的940种不同分子种类计算）的基线血浆浓度与多变量校正考克斯模型结果的相关性。我们在DIVAS随机对照试验（膳食干预和血管功能; n=113）中测试了等能量膳食脂肪改良对风险相关脂质的影响。参与者食用富含饱和脂肪酸（对照）、单不饱和脂肪酸或单不饱和脂肪酸和n-6多不饱和脂肪酸的混合物的饮食16周。69种脂质与至少1种结局相关（错误发现率<0.05）（两者均为8;仅心血管疾病为49;仅2型糖尿病为12）。简而言之，几种单酰基甘油和二酰基甘油中的FA 16：0和FA 18：0与两种结局相关;胆固醇酯、游离脂肪酸和鞘脂主要是心血管疾病特异性的;几种（甘油）磷脂是2型糖尿病特异性的。此外，与饱和脂肪饮食相比，富含不饱和脂肪酸的饮食影响了19种风险相关脂质（错误发现率<0.05）（17种方向与长期心脏代谢风险的潜在有益影响一致）。例如，富含单不饱和FA的饮食使二酰基甘油（FA 16：0）减少0.4（95%CI，0.5-0.3）SD单位，并使三酰基甘油（FA 22：1）增加0.5（95%CI，0.4-0.7）SD单位。我们确定了几种与心脏代谢疾病风险相关的脂质。一个子集是有益的改变饮食脂肪干预，支持替代饮食饱和脂肪酸与不饱和脂肪酸作为一种潜在的工具，初级疾病的预防。
In blood and tissues, dietary and endogenously generated fatty acids (FAs) occur in free form or as part of complex lipid molecules that collectively represent the lipidome of the respective tissue. We assessed associations of plasma lipids derived from high-resolution lipidomics with incident cardiometabolic diseases and subsequently tested if the identified risk-associated lipids were sensitive to dietary fat modification. The EPIC Potsdam cohort study (European Prospective Investigation into Cancer and Nutrition) comprises 27 548 participants recruited within an age range of 35 to 65 years from the general population around Potsdam, Germany. We generated 2 disease-specific case cohorts on the basis of a fixed random subsample (n=1262) and all respective cohort-wide identified incident primary cardiovascular disease (composite of fatal and nonfatal myocardial infarction and stroke; n=551) and type 2 diabetes (n=775) cases. We estimated the associations of baseline plasma concentrations of 282 class-specific FA abundances (calculated from 940 distinct molecular species across 15 lipid classes) with the outcomes in multivariable-adjusted Cox models. We tested the effect of an isoenergetic dietary fat modification on risk-associated lipids in the DIVAS randomized controlled trial (Dietary Intervention and Vascular Function; n=113). Participants consumed either a diet rich in saturated FAs (control), monounsaturated FAs, or a mixture of monounsaturated and n-6 polyunsaturated FAs for 16 weeks. Sixty-nine lipids associated (false discovery rate<0.05) with at least 1 outcome (both, 8; only cardiovascular disease, 49; only type 2 diabetes, 12). In brief, several monoacylglycerols and FA16:0 and FA18:0 in diacylglycerols were associated with both outcomes; cholesteryl esters, free fatty acids, and sphingolipids were largely cardiovascular disease specific; and several (glycero)phospholipids were type 2 diabetes specific. In addition, 19 risk-associated lipids were affected (false discovery rate<0.05) by the diets rich in unsaturated dietary FAs compared with the saturated fat diet (17 in a direction consistent with a potential beneficial effect on long-term cardiometabolic risk). For example, the monounsaturated FA-rich diet decreased diacylglycerol(FA16:0) by 0.4 (95% CI, 0.5–0.3) SD units and increased triacylglycerol(FA22:1) by 0.5 (95% CI, 0.4–0.7) SD units. We identified several lipids associated with cardiometabolic disease risk. A subset was beneficially altered by a dietary fat intervention that supports the substitution of dietary saturated FAs with unsaturated FAs as a potential tool for primary disease prevention.