Advertisement

Endocrine

, Volume 60, Issue 2, pp 368–371 | Cite as

Gain-of-function SNPs in NLRP3 and IL1B genes confer protection against obesity and T2D: undiscovered role of inflammasome genetics in metabolic homeostasis?

  • Juliana de Moraes Rodrigues
  • Dhemerson Souza de Lima
  • Vinicius N. C. Leal
  • Adriana A. Bosco
  • Valeria Sandrim
  • Alessandra Pontillo
Research Letter

Introduction

Inflammation represents a cause, but also a consequence of obesity, contributing to disrupt metabolic homeostasis. Previously associated to high fat diets and physical inactivity, the contribution of gut microbiota and genetic inheritance are also being evaluated as risk factors for obesity. [1]

Increasing, and sometimes contrasting, findings have revealed the involvement of inflammasome in the development of obesity and obesity-associated diseases in experimental models. Inflammasome is a cytoplasmic complex responsible for the activation of caspase-1 and the consequent production of the biologic active form of interleukin (IL)-1ß and IL-18. Several intracellular innate receptors (i.e., NLR Family Pyrin Domain Containing 1/NLRP1, NLRP3, NLRP6, Absent in Melanoma 2/AIM2) sense pathogen-associated and danger-associated molecular patterns (DAMPs), respectively, and became able to mount an inflammasome. These molecules are expressed in leucocytes, as well as in non-immune...

Notes

Funding

This study was supported by Sao Paulo Research Foundation (FAPESP) (Grants numbers: 2015/23395-6;) and “Conselho Nacional de Desenvolvimento Cientıfico e Tecnologico” (CNPq). A.P. is a recipient of a CNPq fellowship. J.M.R. was a recipient of a PIBIC Fellowship. V.N.C.L. is a recipient of a FAPESP-funded fellowship. D.L. is a recipient of a UFAM-funded PhD Fellowship.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

Research involved human participants. All procedures performed were in accordance with the ethical standards of the Institutional Review Board of the “Santa Casa de Belo Horizonte” hospital, and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

12020_2017_1343_MOESM1_ESM.docx (74 kb)
Supplementary File 1

References

  1. 1.
    L.P. Zambetti, A. Mortellaro, NLRPs, microbiota, and gut homeostasis: unravelling the connection. J. Pathol. 233(4), 321–330 (2014)CrossRefPubMedGoogle Scholar
  2. 2.
    M. Haneklaus, L.A. O’Neill, NLRP3 at the interface of metabolism and inflammation. Immunol. Rev. 265(1), 53–62 (2015)CrossRefPubMedGoogle Scholar
  3. 3.
    K. Esposito, A. Pontillo, M. Ciotola, C. Di Palo, E. Grella, G. Nicoletti, D. Giugliano, Weight loss reduces interleukin-18 levels in obese women. J. Clin. Endocrinol. Metab. 87(8), 3864–3866 (2002)CrossRefPubMedGoogle Scholar
  4. 4.
    A. Satpathy, S. Ravindra, S. Thakur, S. Kulkarni, A. Porwal, S. Panda, Serum interleukin-1β in subjects with abdominal obesity and periodontitis. Obes. Res. Clin. Pract 9(5), 513–521 (2015)CrossRefPubMedGoogle Scholar
  5. 5.
    K.M. Flegal, B.K. Kit, H. Orpana, B.I. Graubard, Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis. JAMA 309(1), 71–82 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    S.M. Grundy, J.I. Cleeman, S.R. Daniels, K.A. Donato, R.H. Eckel, B.A. Franklin, D.J. Gordon, R.M. Krauss, P.J. Savage, S.C. Smith Jr, J.A. Spertus, F. Costa; American Heart A, National Heart L, Blood I, Diagnosis and management of the metabolic syndrome: an American heart association/national heart, lung, and blood institute scientific statement. Circulation 112(17), 2735–2752 (2005)CrossRefPubMedGoogle Scholar
  7. 7.
    Y. Zhong, A. Kinio, M. Saleh, Functions of NOD-like receptors in human diseases. Front. Immunol. 4, 333 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    A.J. Murphy, M.J. Kraakman, H.L. Kammoun, D. Dragoljevic, M.K. Lee, K.E. Lawlor, J.M. Wentworth, A. Vasanthakumar, M. Gerlic, L.W. Whitehead, L. DiRago, L. Cengia, R.M. Lane, D. Metcalf, J.E. Vince, L.C. Harrison, A. Kallies, B.T. Kile, B.A. Croker, M.A. Febbraio, S.L. Masters, IL-18 production from the NLRP1 inflammasome prevents obesity and metabolic syndrome. Cell. Metab. 23(1), 155–164 (2016)CrossRefPubMedGoogle Scholar
  9. 9.
    M.G. Netea, L.A. Joosten, The NLRP1-IL18 connection: a stab in the back of obesity-induced inflammation. Cell. Metab. 23(1), 6–7 (2016)CrossRefPubMedGoogle Scholar
  10. 10.
    Y. Hitomi, M. Ebisawa, M. Tomikawa, T. Imai, T. Komata, T. Hirota, M. Harada, M. Sakashita, Y. Suzuki, N. Shimojo, Y. Kohno, K. Fujita, A. Miyatake, S. Doi, T. Enomoto, M. Taniguchi, N. Higashi, Y. Nakamura, M. Tamari, Associations of functional NLRP3 polymorphisms with susceptibility to food-induced anaphylaxis and aspirin-induced asthma. J. Allergy. Clin. Immunol. 124(4), 779–785 (2009). e6CrossRefPubMedGoogle Scholar
  11. 11.
    R. Stienstra, J.A. van Diepen, C.J. Tack, M.H. Zaki, F.L. van de Veerdonk, D. Perera, G.A. Neale, G.J. Hooiveld, A. Hijmans, I. Vroegrijk, S. van den Berg, J. Romijn, P.C. Rensen, L.A. Joosten, M.G. Netea, T.D. Kanneganti, Inflammasome is a central player in the induction of obesity and insulin resistance. Proc. Natl Acad. Sci. USA 108(37), 15324–15329 (2011)CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    E. Elinav, J. Henao-Mejia, R.A. Flavell, Integrative inflammasome activity in the regulation of intestinal mucosal immune responses. Mucosal Immunol. 6(1), 4–13 (2013)CrossRefPubMedGoogle Scholar
  13. 13.
    M. Levy, E. Blacher, Elinav E microbiome, metabolites and host immunity. Curr. Opin. Microbiol. 35, 8–15 (2016)CrossRefPubMedGoogle Scholar
  14. 14.
    J. Hung, B.M. McQuillan, C.M. Chapman, P.L. Thompson, J.P. Beilby, Elevated interleukin-18 levels are associated with the metabolic syndrome independent of obesity and insulin resistance. Arterioscler. Thromb. Vasc. Biol. 25(6), 1268–1273 (2005)CrossRefPubMedGoogle Scholar
  15. 15.
    M. Vijay-Kumar, A.T. Gewirtz, Is predisposition to NAFLD and obesity communicable? Cell. Metab. 15(4), 419–420 (2012)CrossRefPubMedGoogle Scholar
  16. 16.
    C. Bing, Is interleukin-1β a culprit in macrophage-adipocyte crosstalk in obesity? Adipocyte 4(2), 149–152 (2015)CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    J.1 Henao-Mejia, E. Elinav, C. Jin, L. Hao, W.Z. Mehal, T. Strowig, C.A. Thaiss, A.L. Kau, S.C. Eisenbarth, M.J. Jurczak, J.P. Camporez, G.I. Shulman, J.I. Gordon, H.M. Hoffman, R.A. Flavell, Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 482(7384), 179–185 (2012)CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Juliana de Moraes Rodrigues
    • 1
  • Dhemerson Souza de Lima
    • 1
  • Vinicius N. C. Leal
    • 1
  • Adriana A. Bosco
    • 2
  • Valeria Sandrim
    • 3
  • Alessandra Pontillo
    • 1
  1. 1.Laboratório de Imunogenética, Departamento of Imunologia, Instituto de Ciências BiomédicasUniversidade de São Paulo (USP)São PauloBrazil
  2. 2.Nucleo de Pos-Graduacao e Pesquisa—Santa Casa de Belo HorizonteBelo HorizonteBrazil
  3. 3.Departmento de Farmacologia, Instituto de BiocienciasUniversidade Estadual Paulista/UNESPBotucatuBrazil

Personalised recommendations