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- Title
The Role of Inflammatory Cytokines as Intermediates in the Pathway from Increased Adiposity to Disease.
- Authors
Kalaoja, Marita; Corbin, Laura J.; Tan, Vanessa Y.; Ahola‐Olli, Ari V.; Havulinna, Aki S.; Santalahti, Kristiina; Pitkänen, Niina; Lehtimäki, Terho; Lyytikäinen, Leo‐Pekka; Raitoharju, Emma; Seppälä, Ilkka; Kähönen, Mika; Ripatti, Samuli; Palotie, Aarno; Perola, Markus; Viikari, Jorma S.; Jalkanen, Sirpa; Maksimow, Mikael; Salomaa, Veikko; Salmi, Marko
- Abstract
<bold>Objective: </bold>This study aimed to investigate the role of cytokines as intermediates in the pathway from increased adiposity to disease.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
HEPATOCYTE growth factor; INFLAMMATORY bowel diseases; CYTOKINES; OBESITY complications; ADIPOSE tissue physiology; RESEARCH; RESEARCH methodology; MEDICAL cooperation; EVALUATION research; COMPARATIVE studies; RESEARCH funding; BODY mass index; LONGITUDINAL method
- Publication
Obesity (19307381), 2021, Vol 29, Issue 2, p428
- ISSN
1930-7381
- Publication type
journal article
- DOI
10.1002/oby.23060