Endogenous oils derived from human adipocytes are potent adjuvants that promote IL-1α-dependent inflammation.
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.
Adjuvant Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, IrelandImmunology Research Centre, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Graham A
GA
Tynan
Adjuvant Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Claire H
CH
Hearnden
Adjuvant Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Ewa
E
Oleszycka
Nutrigenomics Research Group, University College Dublin Conway Institute, University College Dublin, Dublin, Ireland.
Claire L
CL
Lyons
Faculty of Life Sciences, University of Manchester, Manchester, U.K.
Graham
G
Coutts
Obesity Immunology Group, Education and Research Centre, St. Vincent's University Hospital, University College Dublin, Dublin, Ireland.
Jean
J
O'Connell
Obesity Immunology Group, Education and Research Centre, St. Vincent's University Hospital, University College Dublin, Dublin, Ireland.
Michelle A
MA
Corrigan
Obesity Immunology Group, Education and Research Centre, St. Vincent's University Hospital, University College Dublin, Dublin, Ireland.
Lydia
L
Lynch
Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland.
Matthew
M
Campbell
Veterinary Pathobiology, University College Dublin School of Veterinary Medicine, University College Dublin, Dublin, Ireland.
John J
JJ
Callanan
Protein Folding and Biomolecular Nuclear Magnetic Resonance Spectroscopy Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Kenneth H
KH
Mok
Department of Hepatobiliary Surgery, St. Vincent's University Hospital, Dublin, Ireland.
Justin
J
Geoghegan
Comparative Immunology Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Cliona
C
O'Farrelly
Faculty of Life Sciences, University of Manchester, Manchester, U.K.
Stuart M
SM
Allan
Nutrigenomics Research Group, University College Dublin Conway Institute, University College Dublin, Dublin, Ireland.
Helen M
HM
Roche
Obesity Immunology Group, Education and Research Centre, St. Vincent's University Hospital, University College Dublin, Dublin, Ireland.
Donal B
DB
O'Shea
Adjuvant Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, IrelandImmunology Research Centre, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland lavellee@tcd.ie.
Ed C
EC
Lavelle
D017667:Adipocytes; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism; D007333:Insulin Resistance; D053582:Interleukin-1alpha / Q000276:immunology*; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D008297:Male; D051379:Mice; D009765:Obesity / Q000188:drug therapy / Q000276:immunology*; D009821:Oils / Q000494:pharmacology*
D018836:Inflammation Mediators; D053582:Interleukin-1alpha; D009821:Oils