Obesity Research Unit, Research Programs Unit, Diabetes and Obesity Research Program, University of Helsinki, 00014, Helsinki, Finland.
Transplantation Laboratory, Faculty of Medicine, University of Helsinki, 00014, Helsinki, Finland.
Proteomics Clin Appl. 2019 Jul;13(4):e1800173. doi: 10.1002/prca.201800173. Epub 2019 Feb 5.
The purpose of this study is to elucidate the effect of excess body weight and liver fat on the plasma proteome without interference from genetic variation.
The effect of excess body weight is assessed in young, healthy monozygotic twins from pairs discordant for body mass index (intrapair difference (Δ) in BMI > 3 kg m , n = 26) with untargeted LC-MS proteomics quantification. The effect of liver fat is interrogated via subgroup analysis of the BMI-discordant twin cohort: liver fat discordant pairs (Δliver fat > 2%, n = 12) and liver fat concordant pairs (Δliver fat < 2%, n = 14), measured by magnetic resonance spectroscopy.
Seventy-five proteins are differentially expressed, with significant enrichment for complement and inflammatory response pathways in the heavier co-twins. The complement dysregulation is found in obesity in both the liver fat subgroups. The complement and inflammatory proteins are significantly associated with adiposity measures, insulin resistance and impaired lipids.
The early pathophysiological mechanisms in obesity are incompletely understood. It is shown that aberrant complement regulation in plasma is present in very early stages of clinically healthy obese persons, independently of liver fat and in the absence of genetic variation that typically confounds human studies.
本研究旨在阐明超重和肝脂肪对血浆蛋白质组的影响，而不受遗传变异的干扰。
通过对体重指数（BMI）不匹配的同卵双胞胎（BMI 差值（Δ）> 3 kg/m2，n = 26）进行非靶向 LC-MS 蛋白质组学定量分析，评估超重的影响。通过对 BMI 不匹配的双胞胎队列进行亚组分析来研究肝脂肪的影响：肝脂肪不匹配组（Δ肝脂肪> 2%，n = 12）和肝脂肪匹配组（Δ肝脂肪< 2%，n = 14），通过磁共振波谱法测量。
有 75 种蛋白质表达差异，超重同卵双胞胎中补体和炎症反应途径显著富集。在两个肝脂肪亚组中均发现肥胖时补体失调。补体和炎症蛋白与肥胖指标、胰岛素抵抗和脂质受损显著相关。
肥胖的早期病理生理机制尚未完全阐明。研究表明，在临床健康肥胖个体的早期阶段，血浆中异常的补体调节独立于肝脂肪且不受通常会干扰人类研究的遗传变异的影响。
