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Plasma Proteomics Analysis Reveals Dysregulation of Complement Proteins and Inflammation in Acquired Obesity-A Study on Rare BMI-Discordant Monozygotic Twin Pairs
Univ Helsinki, Diabet & Obes Res Program, Res Programs Unit, Obes Res Unit, FIN-00014 Helsinki, Finland. araswat, Mayank; Joenvaara, Sakari; Renkonen, Risto.
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2019 (English)In: PROTEOMICS - Clinical Applications, ISSN 1862-8346, E-ISSN 1862-8354, Vol. 13, no 4, article id 1800173Article in journal (Refereed) Published
Abstract [en]

Purpose: 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. Experimental Design: 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−2, 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. Results: 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. Conclusions and Clinical Relevance: 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.

Place, publisher, year, edition, pages
Wiley-VCH Verlagsgesellschaft, 2019. Vol. 13, no 4, article id 1800173
Keywords [en]
acquired obesity, complement cascade, monozygotic twins, label-free proteomics, plasma proteomics
National Category
Biochemistry and Molecular Biology
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URN: urn:nbn:se:kth:diva-255773DOI: 10.1002/prca.201800173ISI: 000475990600007PubMedID: 30688043Scopus ID: 2-s2.0-85061063771OAI: oai:DiVA.org:kth-255773DiVA, id: diva2:1342188
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QC 20190813

Available from: 2019-08-13 Created: 2019-08-13 Last updated: 2019-08-13Bibliographically approved

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