Premium
Plasma Proteomics Analysis Reveals Dysregulation of Complement Proteins and Inflammation in Acquired Obesity—A Study on Rare BMI‐Discordant Monozygotic Twin Pairs
Author(s) -
Sahebekhtiari Navid,
Saraswat Mayank,
Joenväärä Sakari,
Jokinen Riikka,
Lovric Alen,
Kaye Sanna,
Mardinoglu Adil,
Rissanen Aila,
Kaprio Jaakko,
Renkonen Risto,
Pietiläinen Kirsi H.
Publication year - 2019
Publication title -
proteomics – clinical applications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.948
H-Index - 54
eISSN - 1862-8354
pISSN - 1862-8346
DOI - 10.1002/prca.201800173
Subject(s) - obesity , medicine , endocrinology , monozygotic twin , body mass index , complement system , insulin resistance , biology , immunology , genetics , immune system
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.