Obesity Surgery

, Volume 28, Issue 9, pp 2774–2782 | Cite as

Tissue-Specific Phenotype and Activation of iNKT Cells in Morbidly Obese Subjects: Interaction with Adipocytes and Effect of Bariatric Surgery

  • Soledad LópezEmail author
  • Sara García-Serrano
  • Carolina Gutierrez-Repiso
  • Francisca Rodríguez-Pacheco
  • Ailec Ho-Plagaro
  • Concepción Santiago-Fernandez
  • Gonzalo Alba
  • Marta Cejudo-Guillen
  • Alberto Rodríguez-Cañete
  • Sergio Valdes
  • Lourdes Garrido-Sanchez
  • David Pozo
  • Eduardo García-FuentesEmail author
Original Contributions



The immune response of visceral adipose tissue (VAT) in obesity, in particular the role of invariant natural killer T (iNKT) cells, has not yet been fully elucidated.


To characterize iNKT cells and its activation status in VAT and peripheral blood mononuclear cells (PBMC) in morbidly obese subjects (MO), and to analyze their association with metabolic parameters.

Subjects and Methods

Twenty non-obese and 20 MO subjects underwent Roux-en-Y gastric bypass (RYGB) and were studied before and 6 months after RYGB. VAT and PBMC were obtained.


A decrease in VAT iNKT cells from MO was found, however, not in PBMC. Visceral adipocytes from MO presented increased CD1d expression (p = 0.032). MO presented an increase in early activated CD69+ iNKT cells in PBMC before RYGB (p < 0.001), but not after RYGB nor in VAT, and an increase in later activated CD25+ iNKT in VAT (p = 0.046), without differences in PBMC. The co-expression of early and later markers (CD69+CD25+) in iNKT cells was increased in MO in VAT (p = 0.050) and PBMC (p = 0.006), decreasing after RYGB (p = 0.050). CD69+ iNKT and CD69+CD25+ iNKT cells in PBMC after RYGB correlated negatively with glucose, insulin, and insulin resistance levels.


There is a tissue-specific phenotype and activation of iNKT cells in VAT in morbid obesity, which could be involved in VAT immunometabolism dysregulation. Also, the increase in CD1d expression could be to offset the lack of VAT iNKT cells.


Natural killer T cells Inflammation Obesity Adipose tissue 



CIBERObn is an ISCIII project. We gratefully acknowledge the Imaging platform of the Institute of Biomedical Research in Malaga (IBIMA), as well as the technical assistance from Gomez-Conde, AI.


This study has been supported by the Instituto de Salud Carlos III (ISCIII) (PI09/01016) (“A way to make Europe”), the Andalusian Ministry of Health (PI-2013-575), and the Andalusian Ministry of Economy, Science and Innovation (P10-CTS6928, P11-CTS8161 and P11-CTS8081) and co-financed by the European Regional Development Fund (FEDER) (“Andalusia moves with Europe”).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no competing interests.

Supplementary material

11695_2018_3215_MOESM1_ESM.pptx (658 kb)
ESM 1 (PPTX 657 kb)
11695_2018_3215_MOESM2_ESM.docx (40 kb)
ESM 2 (DOCX 40 kb)


  1. 1.
    Barbarroja N, Lopez-Pedrera R, Mayas MD, et al. The obese healthy paradox: is inflammation the answer? Biochem J. 2010;430:141–9.CrossRefGoogle Scholar
  2. 2.
    Medzhitov R. Origin and physiological roles of inflammation. Nature. 2008;454:428–35.CrossRefGoogle Scholar
  3. 3.
    Huh JY, Park YJ, Ham M, et al. Crosstalk between adipocytes and immune cells in adipose tissue inflammation and metabolic dysregulation in obesity. Mol Cells. 2014;37:365–71.CrossRefGoogle Scholar
  4. 4.
    Huh JY, Kim JI, Park YJ, et al. A novel function of adipocytes in lipid antigen presentation to iNKT cells. Mol Cell Biol. 2013;33:328–39.CrossRefGoogle Scholar
  5. 5.
    Bertola A, Ciucci T, Rousseau D, et al. Identification of adipose tissue dendritic cells correlated with obesity-associated insulin-resistance and inducing Th17 responses in mice and patients. Diabetes. 2012;61:2238–47.CrossRefGoogle Scholar
  6. 6.
    Elgazar-Carmon V, Rudich A, Hadad N, et al. Neutrophils transiently infiltrate intra-abdominal fat early in the course of high-fat feeding. J Lipid Res. 2008;49:1894–903.CrossRefGoogle Scholar
  7. 7.
    Schipper HS, Rakhshandehroo M, van de Graaf SF, et al. Natural killer T cells in adipose tissue prevent insulin resistance. J Clin Invest. 2012;122:3343–54.CrossRefGoogle Scholar
  8. 8.
    Lynch L, Nowak M, Varghese B, et al. Adipose tissue invariant NKT cells protect against diet-induced obesity and metabolic disorder through regulatory cytokine production. Immunity. 2012;37:574–87.CrossRefGoogle Scholar
  9. 9.
    Cipolletta D. Adipose tissue-resident regulatory T cells: phenotypic specialization, functions and therapeutic potential. Immunology. 2014;142:517–25.CrossRefGoogle Scholar
  10. 10.
    Ferrante Jr AW. The immune cells in adipose tissue. Diabetes Obes Metab. 2013;15(Suppl 3):34–8.CrossRefGoogle Scholar
  11. 11.
    Godfrey DI, Pellicci DG, Patel O, et al. Antigen recognition by CD1d-restricted NKT T cell receptors. Semin Immunol. 2010;22:61–7.CrossRefGoogle Scholar
  12. 12.
    Berzins SP, Smyth MJ, Baxter AG. Presumed guilty: natural killer T cell defects and human disease. Nat Rev Immunol. 2011;11:131–42.CrossRefGoogle Scholar
  13. 13.
    Lynch L, O'Shea D, Winter DC, et al. Invariant NKT cells and CD1d(+) cells amass in human omentum and are depleted in patients with cancer and obesity. Eur J Immunol. 2009;39:1893–901.CrossRefGoogle Scholar
  14. 14.
    Garrido-Sanchez L, Escote X, Coin-Araguez L, et al. Munc18c in adipose tissue is downregulated in obesity and is associated with insulin. PLoS One. 2013;8:e63937.CrossRefGoogle Scholar
  15. 15.
    Rodríguez-Pacheco F, Gutierrez-Repiso C, García-Serrano S, et al. Growth hormone-releasing hormone is produced by adipocytes and regulates lipolysis through growth hormone receptor. Int J Obes. 2017;41:1547–55.CrossRefGoogle Scholar
  16. 16.
    Rodriguez-Pacheco F, Garcia-Serrano S, Garcia-Escobar E, et al. Effects of obesity/fatty acids on the expression of GPR120. Mol Nutr Food Res. 2014;58:1852–60.CrossRefGoogle Scholar
  17. 17.
    Huh JY, Park J, Kim JI, et al. Deletion of CD1d in adipocytes aggravates adipose tissue inflammation and insulin resistance in obesity. Diabetes. 2017;66:835–47.CrossRefGoogle Scholar
  18. 18.
    Reddy M, Eirikis E, Davis C, et al. Comparative analysis of lymphocyte activation marker expression and cytokine secretion profile in stimulated human peripheral blood mononuclear cell cultures: an in vitro model to monitor cellular immune function. J Immunol Methods. 2004;293:127–42.CrossRefGoogle Scholar
  19. 19.
    Koh YI, Shim JU, Wi JO, et al. Inverse association of peripheral blood CD4(+) invariant natural killer T cells with atopy in human asthma. Hum Immunol. 2010;71:186–91.CrossRefGoogle Scholar
  20. 20.
    Dhodapkar KM, Cirignano B, Chamian F, et al. Invariant natural killer T cells are preserved in patients with glioma and exhibit antitumor lytic activity following dendritic cell-mediated expansion. Int J Cancer. 2004;109:893–9.CrossRefGoogle Scholar
  21. 21.
    Hogan AE, Corrigan MA, O'Reilly V, et al. Cigarette smoke alters the invariant natural killer T cell function and may inhibit anti-tumor responses. Clin Immunol. 2011;140:229–35.CrossRefGoogle Scholar
  22. 22.
    Lang ML. How do natural killer T cells help B cells? Expert Rev Vaccines. 2009;8:1109–21.CrossRefGoogle Scholar
  23. 23.
    Malide D, Yewdell JW, Bennink JR, et al. The export of major histocompatibility complex class I molecules from the endoplasmic reticulum of rat brown adipose cells is acutely stimulated by insulin. Mol Biol Cell. 2001;12:101–14.CrossRefGoogle Scholar
  24. 24.
    Mantell BS, Stefanovic-Racic M, Yang X, et al. Mice lacking NKT cells but with a complete complement of CD8+ T-cells are not protected against the metabolic abnormalities of diet-induced obesity. PLoS One. 2011;6:e19831.CrossRefGoogle Scholar
  25. 25.
    Koh YI, Shim JU. Association between sputum natural killer T cells and eosinophilic airway inflammation in human asthma. Int Arch Allergy Immunol. 2010;153:239–48.CrossRefGoogle Scholar
  26. 26.
    Sancho D, Gomez M, Sanchez-Madrid F. CD69 is an immunoregulatory molecule induced following activation. Trends Immunol. 2005;26:136–40.CrossRefGoogle Scholar
  27. 27.
    Gonzalez-Amaro R, Cortes JR, Sanchez-Madrid F, et al. Is CD69 an effective brake to control inflammatory diseases? Trends Mol Med. 2013;19:625–32.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Soledad López
    • 1
    • 2
    • 3
    Email author
  • Sara García-Serrano
    • 4
    • 5
  • Carolina Gutierrez-Repiso
    • 6
  • Francisca Rodríguez-Pacheco
    • 4
  • Ailec Ho-Plagaro
    • 7
  • Concepción Santiago-Fernandez
    • 7
  • Gonzalo Alba
    • 1
  • Marta Cejudo-Guillen
    • 2
  • Alberto Rodríguez-Cañete
    • 8
  • Sergio Valdes
    • 5
    • 6
  • Lourdes Garrido-Sanchez
    • 4
    • 9
  • David Pozo
    • 1
    • 2
  • Eduardo García-Fuentes
    • 7
    • 9
    • 10
    Email author
  1. 1.Department of Medical Biochemistry, Molecular Biology and ImmunologyUniversity of Seville Medical SchoolSevilleSpain
  2. 2.CABIMER-Andalusian Center for Molecular Biology and Regenerative Medicine (CSIC-University of Seville-UPO-Junta de Andalucia)SevilleSpain
  3. 3.Dpto. Bioquímica Médica, Biología Molecular e Inmunología, Facultad de MedicinaUniversidad de SevillaSevillaSpain
  4. 4.Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA)Hospital Regional UniversitarioMalagaSpain
  5. 5.CIBER de Diabetes y Enfermedades Metabólicas asociadas (CIBERDEM), Instituto de Salud Carlos IIIMalagaSpain
  6. 6.Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA)Hospital Universitario Virgen de la VictoriaMalagaSpain
  7. 7.Unidad de Gestión Clínica de Aparato Digestivo, Instituto de Investigación Biomédica de Málaga (IBIMA)Hospital Universitario Virgen de la VictoriaMalagaSpain
  8. 8.Unidad de Gestión Clínica de Cirugía General, Digestiva y TrasplantesHospital Regional UniversitarioMalagaSpain
  9. 9.CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos IIIMalagaSpain
  10. 10.Laboratorio de InvestigaciónHospital CivilMalagaSpain

Personalised recommendations