Plasma Proteomics Analysis Reveals Dysregulation of Complement Proteins and Inflammation in Acquired Obesity—A Study on Rare BMI-Discordant Monozygotic Twin Pairs
Journal article, 2019
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.
acquired obesity
complement cascade
monozygotic twins
plasma proteomics
label-free proteomics
Author
Navid Sahebekhtiari
University of Helsinki
Mayank Saraswat
University of Helsinki
Helsinki University Central Hospital
Sakari Joenväärä
Helsinki University Central Hospital
University of Helsinki
Riikka Jokinen
University of Helsinki
Alen Lovric
Royal Institute of Technology (KTH)
Sanna Kaye
University of Helsinki
Adil Mardinoglu
Royal Institute of Technology (KTH)
King's College London
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
Aila Rissanen
University of Helsinki
Jaakko Kaprio
University of Helsinki
Risto Renkonen
University of Helsinki
Helsinki University Central Hospital
K. H. Pietilainen
Helsinki University Central Hospital
University of Helsinki
Proteomics - Clinical Applications
1862-8346 (ISSN) 1862-8354 (eISSN)
Vol. 13 4 1800173Subject Categories
Endocrinology and Diabetes
Other Clinical Medicine
Nutrition and Dietetics
DOI
10.1002/prca.201800173