Endogenous Oils Derived From Human Adipocytes Are Potent Adjuvants That Promote IL-1α–Dependent Inflammation
- Graham A. Tynan1,2,
- Claire H. Hearnden1,
- Ewa Oleszycka1,
- Claire L. Lyons3,
- Graham Coutts4,
- Jean O’Connell5,
- Michelle A. Corrigan5,
- Lydia Lynch5,
- Matthew Campbell6,
- John J. Callanan7,
- Kenneth H. Mok8,
- Justin Geoghegan9,
- Cliona O’Farrelly10,
- Stuart M. Allan4,
- Helen M. Roche3,
- Donal B. O’Shea5 and
- Ed C. Lavelle1,2⇑
- 1Adjuvant Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland
- 2Immunology Research Centre, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland
- 3Nutrigenomics Research Group, University College Dublin Conway Institute, University College Dublin, Dublin, Ireland
- 4Faculty of Life Sciences, University of Manchester, Manchester, U.K.
- 5Obesity Immunology Group, Education and Research Centre, St. Vincent’s University Hospital, University College Dublin, Dublin, Ireland
- 6Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland
- 7Veterinary Pathobiology, University College Dublin School of Veterinary Medicine, University College Dublin, Dublin, Ireland
- 8Protein Folding and Biomolecular Nuclear Magnetic Resonance Spectroscopy Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland
- 9Department of Hepatobiliary Surgery, St. Vincent’s University Hospital, Dublin, Ireland
- 10Comparative Immunology Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland
- Corresponding author: Ed C. Lavelle, .
Obesity is characterized by chronic inflammation associated with neutrophil and M1 macrophage infiltration into white adipose tissue. However, the mechanisms underlying this process remain largely unknown. Based on the ability of oil-based adjuvants to induce immune responses, we hypothesized that endogenous oils derived from necrotic adipocytes may function as an immunological “danger signal.” Here we show that endogenous oils of human origin are potent adjuvants, enhancing antibody responses to a level comparable to Freund’s incomplete adjuvant. The endogenous oils were capable of promoting interleukin (IL)-1α–dependent recruitment of neutrophils and M1-like macrophages, while simultaneously diminishing M2-like macrophages. We found that endogenous oils from subcutaneous and omental adipocytes, and from healthy and unhealthy obese individuals, promoted comparable inflammatory responses. Furthermore, we also confirmed that white adipocytes in visceral fat of metabolically unhealthy obese (MUO) individuals are significantly larger than those in metabolically healthy obese individuals. Since adipocyte size is positively correlated with adipocyte death, we propose that endogenous oils have a higher propensity to be released from hypertrophied visceral fat in MUO individuals and that this is the key factor in driving inflammation. In summary, this study shows that adipocytes contain a potent oil adjuvant which drives IL-1α–dependent proinflammatory responses in vivo.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db13-1476/-/DC1.
See accompanying article, p. 1844.
- Received September 24, 2013.
- Accepted January 19, 2014.
- © 2014 by the American Diabetes Association.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.