Abdominal obesity and circulating metabolites: A twin study approach
Abdominal obesity and circulating metabolites: A twin study approach
复制标题
DOI：
10.1016/j.metabol.2015.10.027
复制
发表时间：
2016-03-01
影响因子：
9.8
通讯作者：
Pietilainen, Kirsi H.
中科院分区：
文献类型：
--
作者：
Bogl, Leonie H.;Kaye, Sanna M.;Pietilainen, Kirsi H.
目标。研究肥胖、胰岛素抵抗和低度炎症与循环代谢物之间的联系，以及这种联系是由于遗传因素还是环境因素。研究对象和方法。采用质子核磁共振光谱法测定循环血清代谢物。1368对双胞胎（531对同卵双胞胎和837对异卵双胞胎）的数据被用于双变量双胞胎建模，以获得腰围（WC）与血清代谢物之间的遗传（r(g)）和环境（re）相关性。对286对双胞胎进行了脂肪分布（DEXA）与代谢健康（HOMA-IR， CRP）之间的关系的详细检查，其中包括33对BMI不一致的MZ对（对内BMI差异>= 3 kg/m(2)）。脂肪，特别是腹部脂肪（即WC、脂肪百分比和脂肪与雌性脂肪的比例），以及HOMA-IR和CRP与致动脉粥样硬化脂蛋白谱、更高水平的支链（BCAA）和芳香氨基酸、更高水平的糖蛋白和更饱和的脂肪酸谱显著相关。相比之下，较高比例的雌性脂肪与有利的代谢物相关。WC与几种代谢物存在显著的遗传重叠，其中以苯丙氨酸（r(g) = 0.40）、糖蛋白（r(g) = 0.37）、血清甘油三酯（r(g) = 0.36）、BCAAs （r(g) = 0.30-0.40）、高密度脂蛋白颗粒直径（r(g) = -0.33）和高密度脂蛋白胆固醇（r(g) = -0.30）遗传重叠最为明显。在不一致的MZ对中，获得性肥胖对致动脉粥样硬化脂蛋白的影响尤其强烈。血清代谢组的一系列不利改变与腹部肥胖、胰岛素抵抗和低度炎症有关。双胞胎模型和肥胖-不一致双胞胎分析表明，这些关联部分是由共享基因解释的，但也反映了独立于遗传责任的机制。(C) 2015爱思唯尔公司版权所有。
Objective. To investigate how obesity, insulin resistance and low-grade inflammation link to circulating metabolites, and whether the connections are due to genetic or environmental factors.Subjects and methods. Circulating serum metabolites were determined by proton NMR spectroscopy. Data from 1368 (531 monozygotic (MZ) and 837 dizygotic (DZ)) twins were used for bivariate twin modeling to derive the genetic (r(g)) and environmental (re) correlations between waist circumference (WC) and serum metabolites. Detailed examination of the associations between fat distribution (DEXA) and metabolic health (HOMA-IR, CRP) was performed among 286 twins including 33 BMI-discordant MZ pairs (intrapair BMI difference >= 3 kg/m(2)).Results. Fat, especially in the abdominal area (i.e. WC, android fat % and android to gynoid fat ratio), together with HOMA-IR and CRP correlated significantly with an atherogenic lipoprotein profile, higher levels of branched-chain (BCAA) and aromatic amino acids, higher levels of glycoprotein, and a more saturated fatty acid profile. In contrast, a higher proportion of gynoid to total fat associated with a favorable metabolite profile. There was a significant genetic overlap between WC and several metabolites, most strongly with phenylalanine (r(g) = 0.40), glycoprotein (r(g) = 0.37), serum triglycerides (r(g) = 0.36), BCAAs (r(g) = 0.30-0.40), HDL particle diameter (r(g) = -0.33) and HDL cholesterol (r(g) = -0.30). The effect of acquired obesity within the discordant MZ pairs was particularly strong for atherogenic lipoproteins.Conclusions. A wide range of unfavorable alterations in the serum metabolome was associated with abdominal obesity, insulin resistance and low-grade inflammation. Twin modeling and obesity-discordant twin analysis suggest that these associations are partly explained by shared genes but also reflect mechanisms independent of genetic liability. (C) 2015 Elsevier Inc. All rights reserved.