支链氨基酸和芳香族氨基酸与内脏脂肪组织相关，影响代谢健康风险标志物。

Branched-Chain and Aromatic Amino Acids Related to Visceral Adipose Tissue Impact Metabolic Health Risk Markers.

机构信息

Population Health Sciences, German Center for Neurodegenerative diseases (DZNE), 53127 Bonn, Germany.

Department of Food Quality and Nutrition, Research and Innovation Centre, Fondazione Edmund Mach (FEM), 38010 San Michele all'Adige, Italy.

出版信息

J Clin Endocrinol Metab. 2022 Jun 16;107(7):e2896-e2905. doi: 10.1210/clinem/dgac160.

DOI:10.1210/clinem/dgac160

PMID:35325166

Abstract

CONTEXT

Visceral (VAT) and subcutaneous adipose tissue (SAT) function as endocrine organs capable of influencing metabolic health across adiposity levels.

OBJECTIVE

We aimed to investigate whether metabolites associated with VAT and SAT impact metabolic health through metabolite concentrations.

METHODS

Analyses are based on 1790 participants from the population-based Rhineland Study. We assessed plasma levels of methionine (Met), branched-chain amino acids (BCAA), aromatic amino acids (AAA), and their metabolic downstream metabolites with liquid chromatography-mass spectrometry. VAT and SAT volumes were assessed by magnetic resonance imaging (MRI). Metabolically healthy and unhealthy phenotypes were defined using Wildman criteria.

RESULTS

Metabolically unhealthy participants had higher concentrations of BCAA than metabolically healthy participants (P < 0.001). In metabolically unhealthy participants, VAT volumes were significantly associated with levels of L-isoleucine, L-leucine, indole-3-lactic acid, and indole-3-propionic acid (in log SD units: β = 0.16, P = 0.003; β = 0.12, P = 0.038; β = 0.11, P = 0.035 and β = -0.16, P = 0.010, respectively). Higher concentrations of certain BCAA and AAA-downstream metabolites significantly increased the odds of cardiometabolic risk markers. The relation between VAT volume and cardiometabolic risk markers was mediated by BCAA (indirect effects 3.7%-11%, P = 0.02 to < 0.0001), while the effect of VAT on systemic inflammation was mediated through higher kynurenine concentrations (indirect effect 6.4%, P < 0.0001).

CONCLUSION

Larger volumes of VAT in metabolically unhealthy individuals are associated with altered concentrations of circulating BCAA and AAA-downstream metabolites, increasing the odds of cardiometabolic risk markers. This suggests that these metabolites are involved in the mechanisms that underlie the relationship of abdominal VAT with metabolic health.

摘要

背景

内脏（VAT）和皮下脂肪组织（SAT）作为内分泌器官，能够在不同的肥胖水平上影响代谢健康。

目的

我们旨在研究与 VAT 和 SAT 相关的代谢物是否通过代谢物浓度影响代谢健康。

方法

分析基于人群为基础的 Rhineland 研究中的 1790 名参与者。我们使用液相色谱-质谱法评估了血浆中甲硫氨酸（Met）、支链氨基酸（BCAA）、芳香族氨基酸（AAA）及其代谢下游代谢物的水平。通过磁共振成像（MRI）评估了 VAT 和 SAT 的体积。使用 Wildman 标准定义了代谢健康和不健康的表型。

结果

代谢不健康的参与者的 BCAA 浓度明显高于代谢健康的参与者（P<0.001）。在代谢不健康的参与者中，VAT 体积与 L-异亮氨酸、L-亮氨酸、吲哚-3-乳酸和吲哚-3-丙酸的水平显著相关（以对数 SD 单位表示：β=0.16，P=0.003；β=0.12，P=0.038；β=0.11，P=0.035 和 β=-0.16，P=0.010）。某些 BCAA 和 AAA 下游代谢物浓度的升高显著增加了心血管代谢风险标志物的发生几率。VAT 体积与心血管代谢风险标志物之间的关系通过 BCAA 介导（间接效应 3.7%-11%，P=0.02 至<0.0001），而 VAT 对全身炎症的影响则通过较高的犬尿氨酸浓度介导（间接效应 6.4%，P<0.0001）。