A1 Journal article – refereed

The Role of Inflammatory Cytokines as Intermediates in the Pathway from Increased Adiposity to Disease

List of Authors: Kalaoja M, Corbin LJ, Tan VY, Ahola-Olli AV, Havulinna AS, Santalahti K, Pitkänen N, Lehtimäki T, Lyytikäinen LP, Raitoharju E, Seppälä I, Kähönen M, Ripatti S, Palotie A, Perola M, Viikari JS, Jalkanen S, Maksimow M, Salomaa V, Salmi M, Raitakari OT, Kettunen J, Timpson NJ, Timpson NJ

Publisher: WILEY

Publication year: 2021

Journal: Obesity

Journal name in source: OBESITY

Journal acronym: OBESITY

Volume number: 29

Issue number: 2

Number of pages: 10

ISSN: 1930-7381

eISSN: 1930-739X

DOI: http://dx.doi.org/10.1002/oby.23060

Objective This study aimed to investigate the role of cytokines as intermediates in the pathway from increased adiposity to disease.Methods BMI and circulating levels of up to 41 cytokines were measured in individuals from three Finnish cohort studies (n = 8,293). Mendelian randomization (MR) was used to assess the impact of BMI on circulating cytokines and the impact of BMI-driven cytokines on risk of obesity-related diseases.Results Observationally, BMI was associated with 19 cytokines. For every SD increase in BMI, causal effect estimates were strongest for hepatocyte growth factor, monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and were as ratios of geometric means 1.13 (95% CI: 1.08-1.19), 1.08 (95% CI: 1.04-1.14), and 1.13 (95% CI: 1.04-1.21), respectively. TRAIL was associated with a small increase in the odds of coronary artery disease (odds ratio: 1.03; 95% CI: 1.00-1.06). There was inconsistent evidence for a protective role of MCP-1 against inflammatory bowel diseases.Conclusions Observational and MR estimates of the effect of BMI on cytokine levels were generally concordant. There was little evidence for an effect of raised levels of BMI-driven cytokines on disease. These findings illustrate the challenges of MR when applied in the context of molecular mediation.

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Last updated on 2021-24-06 at 11:23