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Proteomics Clin Appl. 2019 Jan 27:e1800173. doi: 10.1002/prca.201800173. [Epub ahead of print]

Plasma Proteomics Analysis Reveals Dysregulation of Complement Proteins and Inflammation in Acquired Obesity-A Study on Rare BMI-Discordant Monozygotic Twin Pairs.

Author information

1
Obesity Research Unit, Research Programs Unit, Diabetes and Obesity Research Program, University of Helsinki, 00014, Helsinki, Finland.
2
Transplantation Laboratory, Faculty of Medicine, University of Helsinki, 00014, Helsinki, Finland.
3
HUSLAB, Helsinki University Hospital, 00029, Helsinki, Finland.
4
Science for Life Laboratory, KTH-Royal Institute of Technology, 17121, Stockholm, Sweden.
5
Department of Biology and Biological Engineering, Chalmers University of Technology, 41296, Gothenburg, Sweden.
6
Centre for Host-Microbiome Interactions, Dental Institute, King's College London, SE19RT, London, UK.
7
Department of Public Health, Finnish Twin Cohort Study, University of Helsinki, 00014, Helsinki, Finland.
8
Institute for Molecular Medicine Finland, FIMM, University of Helsinki, 00014, Helsinki, Finland.
9
Abdominal Center, Endocrinology, Helsinki University Central Hospital and University of Helsinki, 00014, Helsinki, Finland.

Abstract

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.

KEYWORDS:

acquired obesity; complement cascade; label-free proteomics; monozygotic twins; plasma proteomics

PMID:
30688043
DOI:
10.1002/prca.201800173

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