Rämö Joel T, Kaye Sanna M, Jukarainen Sakari, Bogl Leonie H, Hakkarainen Antti, Lundbom Jesper, Lundbom Nina, Rissanen Aila, Kaprio Jaakko, Matikainen Niina, Pietiläinen Kirsi H
Obesity Research Unit, Research Programs Unit, Diabetes and Obesity, FI-00029, Helsinki, Finland.
Institute for Molecular Medicine Finland, FI-00014, Helsinki, Finland.
J Clin Endocrinol Metab. 2017 Jan 1;102(1):220-231. doi: 10.1210/jc.2015-3512.
The associations of body mass index (BMI) and liver fat (LF) with circulating prandial metabolomic markers are incompletely understood.
We aimed to characterize circulating metabolite excursions during an oral glucose tolerance test (OGTT) and evaluate whether the metabolomic signatures of BMI discordance coassociate with LF content.
DESIGN, SETTING, AND PARTICIPANTS: We measured 80 metabolite parameters by nuclear magnetic resonance, together with glucose and insulin, during a 2-hour OGTT in 64 monozygotic (MZ) and 73 dizygotic (DZ) twin pairs (aged 22.8 to 36.2 years). Metabolite excursions during the OGTT were compared within BMI-discordant (intrapair difference, BMI ≥ 3 kg/m2) cotwins separately within MZ and DZ pairs. Insulin-based indices were calculated from the OGTT. LF was measured by magnetic resonance spectroscopy in 25 BMI-discordant MZ pairs. Metabolite profiles were compared with respect to LF discordance (ΔLF% ≥ 2%).
We replicated many previously reported OGTT-induced metabolite excursions in all 274 individuals and report novel lipoprotein excursions. The associations between some metabolite excursions and BMI differed in MZ and DZ twins. In BMI-discordant MZ pairs (mean ΔBMI = 4.9 kg/m2) who were concordant for LF (Δ0.2%), few metabolites differed between the cotwins: very-low-density lipoprotein (VLDL) cholesterol and apolipoprotein B were elevated, and high-density lipoprotein size and concentration were decreased in the cotwins with higher BMI. In contrast, in BMI-discordant MZ pairs (ΔBMI = 6.1 kg/m2) who were discordant for LF (Δ6.8%), cotwins with higher BMI exhibited lower insulin sensitivity and widespread metabolomic differences: elevations in small VLDL and low-density lipoprotein particles, fatty acids (FAs), and isoleucine. Within all 64 MZ twin pairs, lower insulin sensitivity associated with higher levels of VLDLs, triglycerides, FAs, and isoleucine.
BMI-discordant MZ twin pairs who also are discordant for LF have more pronounced within-pair differences in metabolomics profiles during an OGTT than BMI-discordant pairs without LF discordance.
体重指数（BMI）和肝脏脂肪（LF）与循环餐后代谢组学标志物之间的关联尚未完全明确。
我们旨在描述口服葡萄糖耐量试验（OGTT）期间循环代谢物的变化情况，并评估BMI不一致的代谢组学特征是否与LF含量共同相关。
设计、地点和参与者：我们在64对同卵（MZ）双胞胎和73对异卵（DZ）双胞胎（年龄22.8至36.2岁）进行的2小时OGTT期间，通过核磁共振测量了80种代谢物参数，同时测量了葡萄糖和胰岛素。在MZ和DZ双胞胎对中，分别比较了BMI不一致（双胞胎内差异，BMI≥3kg/m²）的双胞胎在OGTT期间的代谢物变化。基于胰岛素的指标从OGTT中计算得出。通过磁共振波谱法在25对BMI不一致的MZ双胞胎中测量LF含量。比较了代谢物谱在LF不一致方面（ΔLF%≥2%）的差异。
我们在所有274名个体中重复了许多先前报道的OGTT诱导的代谢物变化，并报告了新的脂蛋白变化。一些代谢物变化与BMI之间的关联在MZ和DZ双胞胎中有所不同。在LF一致（Δ0.2%）的BMI不一致的MZ双胞胎对（平均ΔBMI = 4.9kg/m²）中，双胞胎之间几乎没有代谢物差异：极低密度脂蛋白（VLDL）胆固醇和载脂蛋白B升高，而高密度脂蛋白大小和浓度在BMI较高的双胞胎中降低。相比之下，在LF不一致（Δ6.8%）的BMI不一致的MZ双胞胎对（ΔBMI = 6.1kg/m²）中，BMI较高的双胞胎表现出较低的胰岛素敏感性和广泛的代谢组学差异：小VLDL和低密度脂蛋白颗粒、脂肪酸（FAs）和异亮氨酸升高。在所有64对MZ双胞胎对中，较低的胰岛素敏感性与较高水平的VLDL、甘油三酯、FAs和异亮氨酸相关。
与无LF不一致情况的BMI不一致的双胞胎对相比，LF也不一致的BMI不一致的MZ双胞胎对在OGTT期间的代谢组学谱内对差异更明显。
