Plasma N-Glycoproteomics in monozygotic twin pairs discordant for body mass index reveals an obesity signature related to inflammation and iron metabolism.

IF 5.7 2区 生物学 Q1 BIOLOGY
Maheswary Muniandy, Sakari Joenväärä, Birgitta W van der Kolk, Tiialotta Tohmola, Hanna Haltia, Sina Saari, Antti Hakkarainen, Jesper Lundbom, Juho Kuula, Per-Henrik Groop, Jaakko Kaprio, Sini Heinonen, Risto Renkonen, Kirsi H Pietiläinen
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Abstract

Background: N-glycosylation is a complex, post-translational modification which influences protein function and is sensitive to physiological changes. Obesity is associated with alterations in protein function; however, little is known about the glycoproteome in obesity beyond observations of association with types and structures of selected glycopeptides. Most often, due to technical challenges, glycan composition and structure information are missing. Here, we combined label-free data-independent proteomics and targeted quantitative glycoproteomics to study N-glycosylation of plasma proteins in obesity. Using a monozygotic twin study design, we controlled for genetic variation and focused only on the acquired effects of obesity.

Methods: Using plasma samples of 48 monozygotic twin pairs discordant for BMI (intrapair difference > 2.5 kg/m2), we identified using mass spectrometry, differential protein and glycopeptide levels between heavier and leaner co-twins. We used a within-twin paired analysis model and considered p < 0.05 as significant.

Results: We identified 48 protein and 33 N-glycosylation expression differences (p < 0.05) between co-twins. These differences occurred either both in the protein expression and glycoprotein (sometimes in opposing directions) or independently from each other. Haptoglobin protein was upregulated (Fold Change = 1.10, p = 0.001) in heavier co-twins along with seven upregulated glycan compositions at N-glycosylation site Asn241. The complement protein C3 was upregulated (Fold Change = 1.08, p = 0.014) along with one upregulated glycopeptide at Asn85. Additionally, many glycopeptides were upregulated despite non-significant differences in protein-backbone plasma levels.

Conclusion: Differential protein expression related to cholesterol biosynthesis and acute phase signalling as well as N-glycosylation of proteins related to iron metabolism and inflammation can be linked to acquired obesity.

在体重指数不一致的同卵双胞胎中,血浆n -糖蛋白组学揭示了与炎症和铁代谢相关的肥胖特征。
背景:n -糖基化是一种复杂的翻译后修饰,影响蛋白质功能,对生理变化敏感。肥胖与蛋白质功能的改变有关;然而,除了与选定的糖肽的类型和结构相关的观察外,对肥胖中的糖蛋白组知之甚少。大多数情况下,由于技术上的挑战,多糖的组成和结构信息是缺失的。在这里,我们结合无标签数据不依赖的蛋白质组学和靶向定量糖蛋白组学来研究肥胖血浆蛋白的n -糖基化。采用单卵双胞胎研究设计,我们控制了遗传变异,只关注肥胖的获得性影响。方法:使用48对BMI不一致的同卵双胞胎的血浆样本(对内差异> 2.5 kg/m2),我们使用质谱法鉴定了体重较重和较瘦的同卵双胞胎之间的差异蛋白质和糖肽水平。结果:我们鉴定了48种蛋白质和33种n-糖基化表达差异(p结论:与胆固醇生物合成和急性期信号相关的蛋白质差异表达以及与铁代谢和炎症相关的蛋白质n-糖基化可能与获得性肥胖有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biology Direct
Biology Direct 生物-生物学
CiteScore
6.40
自引率
10.90%
发文量
32
审稿时长
7 months
期刊介绍: Biology Direct serves the life science research community as an open access, peer-reviewed online journal, providing authors and readers with an alternative to the traditional model of peer review. Biology Direct considers original research articles, hypotheses, comments, discovery notes and reviews in subject areas currently identified as those most conducive to the open review approach, primarily those with a significant non-experimental component.
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