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Kalaoja, M., Corbin, L.J., Tan, V.Y., Ahola‐Olli, A.V., Havulinna, A.S., Santalahti, K., Pitkänen, N., Lehtimäki, T., Lyytikäinen, L.‐P., Raitoharju, E., Seppälä, I., Kähönen, M., Ripatti, S., Palotie, A., Perola, M., Viikari, J.S., Jalkanen, S., Maksimow, M., Salomaa, V., Salmi, M., Raitakari, O.T., Kettunen, J. and Timpson, N.J. (2021), The Role of Inflammatory Cytokines as Intermediates in the Pathway from Increased Adiposity to Disease. Obesity, 29: 428-437. https://doi.org/10.1002/oby.23060

The role of inflammatory cytokines as intermediates in the pathway from increased adiposity to disease

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Author: Kalaoja, Marita1,2; Corbin, Laura J.3,4; Tan, Vanessa Y.3,4;
Organizations: 1Computational Medicine, Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland
2Biocenter Oulu, University of Oulu, Oulu, Finland
3MRC Integrative Epidemiology Unit at University of Bristol, Bristol, UK
4Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
5Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
6Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
7Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland
8Finnish Institute for Health and Welfare, Helsinki, Finland
9Medicity Research Laboratory and Institute of Biomedicine, University of Turku, Turku, Finland
10Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
11Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland
12Department of Clinical Chemistry, Finnish Cardiovascular Research Center Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
13Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland
14Department of Clinical Physiology, Finnish Cardiovascular Research Center Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
15Department of Public Health, University of Helsinki, Helsinki, Finland
16Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
17Psychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA
18Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA
19Department of Medicine, University of Turku, Turku, Finland
20Division of Medicine, Turku University Hospital, Turku, Finland
21Centre for Population Health Research, University of Turku, Turku University Hospital, Turku, Finland
22Department of Clinical Physiology and Nuclear Medicine, University of Turku, Turku, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.7 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe202103298647
Language: English
Published: John Wiley & Sons, 2021
Publish Date: 2021-03-29
Description:

Abstract

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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Series: Obesity
ISSN: 1930-7381
ISSN-E: 1930-739X
ISSN-L: 1930-7381
Volume: 29
Issue: 2
Pages: 428 - 437
DOI: 10.1002/oby.23060
OADOI: https://oadoi.org/10.1002/oby.23060
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Subjects:
Article
Funding: NJT, LJC, and VYT work in the Medical Research Council (MRC) Integrative Epidemiology Unit at the University of Bristol, which is supported by the MRC (MC_UU_00011) and the University of Bristol. NJT is a Wellcome Trust Investigator (202802/Z/16/Z) and works within the University of Bristol National Institute for Health Research Biomedical Research Centre. LJC is supported by NJT’s Wellcome Trust Investigator grant (202802/Z/16/Z). NJT and VYT are supported by the Cancer Research UK Integrative Cancer Epidemiology Programme (C18281/A19169). JK is supported by the Academy of Finland (297338 and 307247) and the Novo Nordisk Foundation (NNF17OC0026062). MK was funded by Biocenter Oulu. VS is supported by the Finnish Foundation for Cardiovascular Research. The Young Finns Study has been financially supported by the Academy of Finland (grants 322098, 286284, 134309 [Eye], 126925, 121584, 124282, 129378 [Salve], 117787 [Gendi], and 41071 [Skidi]); the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere and Turku University Hospitals (grant X51001); Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research; Finnish Cultural Foundation; The Sigrid Juselius Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrjö Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; Diabetes Research Foundation of Finnish Diabetes Association; EU Horizon 2020 (grant 755320 for TAXINOMISIS and grant 848146 for TO‐AITION); European Research Council (grant 742927 for MULTIEPIGEN project); Tampere University Hospital Supporting Foundation; and the Finnish Society of Clinical Chemistry. SR is supported by the Academy of Finland Center of Excellence in Complex Disease Genetics (grant 312062), Academy of Finland (grant 285380), the Finnish Foundation for Cardiovascular Research, the Sigrid Juselius Foundation, and University of Helsinki HiLIFE Fellow grant. MS is funded by Academy of Finland (grant 141136).
Academy of Finland Grant Number: 297338
307247
322098
Detailed Information: 297338 (Academy of Finland Funding decision)
307247 (Academy of Finland Funding decision)
322098 (Academy of Finland Funding decision)
Copyright information: © 2021 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society (TOS). This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
  https://creativecommons.org/licenses/by/4.0/