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High-fat meals induce systemic cytokine release without evidence of endotoxemia-mediated cytokine production from circulating monocytes or myeloid dendritic cells

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Abstract

Aims

Dietary fats have been shown to promote the translocation of bacterial endotoxins from the gut into circulation, which may induce systemic inflammation and modulate the inflammatory response of circulating immune cells. The aim of this study was to determine the effect of the postprandial milieu on inflammation and the inflammatory response of antigen presenting cells in the context of type 1 diabetes (T1D).

Materials and methods

Eleven patients with T1D and eleven nondiabetic controls were recruited as part of the FinnDiane study and given two fatty meals during 1 day. Cytokine responses in monocytes and myeloid dendritic cells (mDCs) as well as serum lipopolysaccharide activity levels, triglyceride concentrations and cytokine concentrations were measured from fasting and postprandial blood samples.

Results

Postprandially, patients with T1D and controls showed significant increases in eight inflammatory cytokines (IL-6, TNF-α, IL-1β, IFN-α, IL-10, IFN-γ, IL-12 and MIP-1β) without concomitant increase in serum LPS activity. Serum cytokine production was similar in both groups. No postprandial change was seen in the IL-6, TNF-α or IL-1β production of mDCs or monocytes. At fasting, diabetic mDCs exhibited higher LPS-induced IL-6 and IL-1β production than controls.

Conclusions

Acute high-fat meals increase circulating cytokines but have no effect on serum lipopolysaccharide activity levels or cytokine production in circulating mDCs or monocytes. Our results suggest that postprandial increase in serum cytokine levels is neither mediated by circulating endotoxins nor the activation of circulating innate cells. The production of high-fat meal-induced inflammatory markers is most likely regulated at the tissue level.

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Acknowledgments

The study was supported by Folkhälsan Research Foundation (PHG), Wilhelm and Else Stockmann Foundation (PHG, ML, MIL, CF), Academy of Finland (134379 to PHG, 257545 to MJ), Liv och Hälsa Foundation (MIL, PHG), Waldemar von Frenckells stiftelse (MIL), Svenska kulturfonden (MIL), Kyllikki and Uolevi Lehikoinen Foundation (MIL), Finnish Cardiovascular Foundation (SH), Helsinki University Central Hospital Research Foundation (MRT), the Sigrid Juselius Foundation (MRT, PJP, SH), Diabetes Research Foundation (ML) and The Novo Nordisk Foundation (PHG, ML). We acknowledge the nurses A. Sandelin, J. Tuomikangas and T. Soppela at the Folkhälsan Institute of Genetics for their excellent contribution to this work.

Conflict of interest

Christopher L. Fogarty, Janne K. Nieminen, Lina Peräneva, Mariann I. Lassenius, Aila J. Ahola, Marja-Riitta Taskinen, Matti Jauhiainen, Juha Kirveskari, Pirkko Pussinen, Sohvi Hörkkö, Ville-Petteri Mäkinen, Daniel Gordin, Carol Forsblom, Per-Henrik Groop, Outi Vaarala and Markku Lehto declare that they have no conflict of interest.

Statement of ethical disclosure

The study protocol was approved by the local ethical committee (221/13/03/01/2009; Ethics Committee, Department of Medicine, Helsinki University Central Hospital).

Statement of human and animal rights

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.

Statement of informed consent

Informed consent was obtained from all patients for being included in the study.

Author information

Authors and Affiliations

  1. Folkhälsan Research Center, Biomedicum Helsinki (Room C317b), Haartmaninkatu 8, 00290, Helsinki, Finland

    Christopher L. Fogarty, Lina Peräneva, Mariann I. Lassenius, Aila J. Ahola, Daniel Gordin, Carol Forsblom, Per-Henrik Groop & Markku Lehto

  2. Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Biomedicum Helsinki (Room C318b), Haartmaninkatu 8, 00290, Helsinki, Finland

    Christopher L. Fogarty, Lina Peräneva, Mariann I. Lassenius, Aila J. Ahola, Daniel Gordin, Carol Forsblom, Per-Henrik Groop & Markku Lehto

  3. Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland

    Christopher L. Fogarty, Lina Peräneva, Mariann I. Lassenius, Aila J. Ahola, Marja-Riitta Taskinen, Daniel Gordin, Carol Forsblom, Per-Henrik Groop & Markku Lehto

  4. Immune Response Unit, Department of Vaccination and Immune Protection, National Institute for Health and Welfare, Helsinki, Finland

    Janne K. Nieminen & Outi Vaarala

  5. Heart and Lung Center, Cardiovascular Research Group, HUCH, Helsinki, Finland

    Marja-Riitta Taskinen

  6. Public Health Genomics Unit, National Institute for Health and Welfare, Biomedicum, Helsinki, Finland

    Matti Jauhiainen

  7. Department of Bacteriology, HUSLAB, Helsinki, Finland

    Juha Kirveskari

  8. Institute of Dentistry, University of Helsinki, Helsinki, Finland

    Pirkko Pussinen

  9. Department of Medical Microbiology and Immunology, University of Oulu, Oulu, Finland

    Sohvi Hörkkö

  10. Department of Integrative Biology and Physiology, University of California, Los Angeles, CA, USA

    Ville-Petteri Mäkinen

  11. IDI Baker Heart and Diabetes Institute, Melbourne, VIC, Australia

    Per-Henrik Groop

Authors
  1. Christopher L. Fogarty
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  2. Janne K. Nieminen
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  3. Lina Peräneva
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  4. Mariann I. Lassenius
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  7. Matti Jauhiainen
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  8. Juha Kirveskari
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  9. Pirkko Pussinen
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  12. Daniel Gordin
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Corresponding authors

Correspondence to Per-Henrik Groop or Markku Lehto.

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Fogarty, C.L., Nieminen, J.K., Peräneva, L. et al. High-fat meals induce systemic cytokine release without evidence of endotoxemia-mediated cytokine production from circulating monocytes or myeloid dendritic cells. Acta Diabetol 52, 315–322 (2015). https://doi.org/10.1007/s00592-014-0641-8

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  • DOI: https://doi.org/10.1007/s00592-014-0641-8

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