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)

Vol. 13 4 1800173

Subject Categories

Endocrinology and Diabetes

Other Clinical Medicine

Nutrition and Dietetics

DOI

10.1002/prca.201800173

More information

Latest update

8/26/2019