代谢组学揭示了高遗传风险糖尿病男性餐后碳水化合物餐后脂质代谢的改变。

Metabolomics Reveal Altered Postprandial Lipid Metabolism After a High-Carbohydrate Meal in Men at High Genetic Risk of Diabetes.

机构信息

Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland.

Center for Metabolomics and Bioanalysis (CEMBIO), Universidad CEU San Pablo, Madrid, Spain.

出版信息

J Nutr. 2019 Jun 1;149(6):915-922. doi: 10.1093/jn/nxz024.

DOI:10.1093/jn/nxz024

PMID:31049566

Abstract

BACKGROUND

The transcription factor 7-like 2 (TCF7L2) gene confers one of the strongest genetic predispositions to type 2 diabetes, but diabetes development can be modified by diet.

OBJECTIVE

The aim of our study was to evaluate postprandial metabolic alterations in healthy men with a high genetic risk of diabetes, after two meals with varying macronutrient content.

METHODS

The study was conducted in 21 homozygous nondiabetic men carrying the high-risk (HR, n = 8, age: 31.2 ± 6.3 y, body mass index (BMI, kg/m2) 28.5 ± 8.1) or low-risk (LR, n = 13, age: 35.2 ± 10.3 y, BMI: 28.1 ± 6.4) genotypes at the rs7901695 locus. During two meal challenge test visits subjects received standardized isocaloric (450 kcal) liquid meals: high-carbohydrate (HC, carbohydrates: 89% of energy) and normo-carbohydrate (NC, carbohydrates: 45% of energy). Fasting (0 min) and postprandial (30, 60, 120, 180 min) plasma samples were analyzed for metabolite profiles through untargeted metabolomics. Metabolic fingerprinting was performed on an ultra-high-performance liquid chromatography (UHPLC) system connected to an iFunnel quadrupole-time-of-flight (Q-TOF) mass spectrometer.

RESULTS

In HR-genotype men, after the intake of an HC-meal, we noted a significantly lower area under the curves (AUCs) of postprandial plasma concentrations of most of the phospholipids (-37% to -53%, variable importance in the projection (VIP) = 1.2-1.5), lysophospholipids (-29% to -86%, VIP = 1.1-2.6), sphingolipids (-32% to -47%, VIP = 1.1-1.3), as well as arachidonic (-36%, VIP = 1.4) and oleic (-63%, VIP = 1.3) acids, their metabolites: keto- and hydoxy-fatty acids (-38% to -78%, VIP = 1.3-2.5), leukotrienes (-65% to -83%, VIP = 1.4-2.2), uric acid (-59%, VIP = 1.5), and pyroglutamic acid (-65%, VIP = 1.8). The AUCs of postprandial sphingosine concentrations were higher (125-832%, VIP = 1.9-3.2) after the NC-meal, AUCs of acylcarnitines were lower (-21% to -61%, VIP = 1.1-2.4), and AUCs of fatty acid amides were higher (51-508%, VIP = 1.7-3.1) after the intake of both meals.

CONCLUSIONS

In nondiabetic men carrying the TCF7L2 HR genotype, subtle but detectable modifications in intermediate lipid metabolism are induced by an HC-meal. This trial was registered at www.clinicaltrials.gov as NCT03792685.

摘要

背景

转录因子 7 样 2（TCF7L2）基因赋予了 2 型糖尿病最强的遗传易感性，但糖尿病的发展可以通过饮食来改变。

目的

本研究旨在评估具有高糖尿病遗传风险的健康男性在摄入两种不同宏量营养素含量的餐后，其餐后代谢的变化。

方法

这项研究在 21 名同型非糖尿病男性中进行，他们携带 rs7901695 位点的高风险（HR，n=8，年龄：31.2±6.3 岁，体重指数（BMI，kg/m2）28.5±8.1）或低风险（LR，n=13，年龄：35.2±10.3 岁，BMI：28.1±6.4）基因型。在两次膳食挑战测试访问期间，受试者接受了标准化的等热量（450 千卡）液体餐：高碳水化合物（HC，碳水化合物：能量的 89%）和正常碳水化合物（NC，碳水化合物：能量的 45%）。空腹（0 分钟）和餐后（30、60、120、180 分钟）采集血浆样本，通过非靶向代谢组学分析代谢物图谱。代谢指纹图谱在超高效液相色谱（UHPLC）系统上进行，连接到 iFunnel 四极杆-飞行时间（Q-TOF）质谱仪。

结果

在 HR 基因型男性中，摄入 HC 餐后，我们注意到大多数磷脂（-37%至-53%，变量重要性投影（VIP）=1.2-1.5）、溶血磷脂（-29%至-86%，VIP=1.1-2.6）、鞘脂（-32%至-47%，VIP=1.1-1.3）以及花生四烯酸（-36%，VIP=1.4）和油酸（-63%，VIP=1.3）酸的餐后血浆浓度 AUC 显著降低，其代谢物：酮基和羟基脂肪酸（-38%至-78%，VIP=1.3-2.5）、白三烯（-65%至-83%，VIP=1.4-2.2）、尿酸（-59%，VIP=1.5）和焦谷氨酸（-65%，VIP=1.8）。NC 餐后，鞘氨醇的 AUC 更高（125-832%，VIP=1.9-3.2），酰基肉碱的 AUC 更低（-21%至-61%，VIP=1.1-2.4），而脂肪酸酰胺的 AUC 更高（51%-508%，VIP=1.7-3.1）。