Skip to main content
SpringerLink
Log in

Immune Function in Obesity

  • Chapter
  • First Online:
Pediatric Obesity

Part of the book series: Contemporary Endocrinology ((COE))

Abstract

Obesity is characterized by changes in immune cell number, location, and function, and the recruitment of pro-inflammatory immune cells into adipose tissue. Both the adipocytes and immune cells recruited to adipose fat stores secrete pro-inflammatory hormones, cytokines, and chemokines with paracrine and endocrine effects that promote an overall inflammatory environment. This pro-inflammatory phenotype has deleterious effects on health and has been shown to promote insulin resistance leading to type 2 diabetes, impair immune response to infection, and increase the risks of autoimmunity and cancer. Given that 500 million individuals are obese worldwide, the altered immune function in obesity presents a major public health problem. Future studies that target obesity-associated inflammation will be key for developing new treatments of many obesity-associated disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

Similar content being viewed by others

Abbreviations

EAE:

Experimental autoimmune encephalomyelitis

IBD:

Inflammatory bowel disease

IFN-γ:

Interferon-γ

IL:

Interleukin

JNK:

c-Jun N-terminal kinase

MCP-1:

Monocyte chemotactic protein 1

MS:

Multiple sclerosis

NF-κB:

Nuclear factor kappaB

NKT cells:

Natural killer T cells

PPARγ:

Peroxisome proliferator-activated receptor gamma

TCR:

T cell receptor

Th1:

T helper type 1

Th17:

T helper type 17

TNF-α:

Tumor necrosis factor-α

Treg:

Regulatory T cells

RA:

Rheumatoid arthritis

SLE:

Systemic lupus erythematosus

References

  1. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003;112(12):1796–808.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Lumeng CN, Bodzin JL, Saltiel AR. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest. 2007;117(1):175–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Gerriets VA, MacIver NJ. Role of T cells in malnutrition and obesity. Front Immunol. 2014;5:379.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Cipolletta D, Feuerer M, Li A, Kamei N, Lee J, Shoelson SE, et al. PPAR-gamma is a major driver of the accumulation and phenotype of adipose tissue Treg cells. Nature. 2012;486(7404):549–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Winer DA, Winer S, Chng MH, Shen L, Engleman EG. B Lymphocytes in obesity-related adipose tissue inflammation and insulin resistance. Cell Mol Life Sci. 2014;71(6):1033–43.

    Article  CAS  PubMed  Google Scholar 

  6. Lund FE. Cytokine-producing B lymphocytes-key regulators of immunity. Curr Opin Immunol. 2008;20(3):332–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Lynch L, O’Shea D, Winter DC, Geoghegan J, Doherty DG, O'Farrelly C. Invariant NKT cells and CD1d(+) cells amass in human omentum and are depleted in patients with cancer and obesity. Eur J Immunol. 2009;39(7):1893–901.

    Article  CAS  PubMed  Google Scholar 

  8. Huh JY, Kim JI, Park YJ, Hwang IJ, Lee YS, Sohn JH, et al. A novel function of adipocytes in lipid antigen presentation to iNKT cells. Mol Cell Biol. 2013;33(2):328–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Lynch L, Nowak M, Varghese B, Clark J, Hogan AE, Toxavidis V, et al. Adipose tissue invariant NKT cells protect against diet-induced obesity and metabolic disorder through regulatory cytokine production. Immunity. 2012;37(3):574–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Huh JY, Park YJ, Ham M, Kim JB. Crosstalk between adipocytes and immune cells in adipose tissue inflammation and metabolic dysregulation in obesity. Mol Cells. 2014 May;37(5):365–71.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Wu D, Molofsky AB, Liang HE, Ricardo-Gonzalez RR, Jouihan HA, Bando JK, et al. Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science. 2011;332(6026):243–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Coppack SW. Pro-inflammatory cytokines and adipose tissue. Proc Nutr Soc. 2001;60(3):349–56.

    Article  CAS  PubMed  Google Scholar 

  13. Friedman JM. The function of leptin in nutrition, weight, and physiology. Nutr Rev. 2002;60(10 Pt 2):S1–14; discussion S68–84, 85–7

    Article  PubMed  Google Scholar 

  14. Naylor C, Petri WA Jr. Leptin regulation of immune responses. Trends Mol Med. 2016;22(2):88–98.

    Article  CAS  PubMed  Google Scholar 

  15. Mandel MA, Mahmoud AA. Impairment of cell-mediated immunity in mutation diabetic mice (db/db). J Immunol. 1978;120(4):1375–7.

    CAS  PubMed  Google Scholar 

  16. Chandra RK, Au B. Spleen hemolytic plaque-forming cell response and generation of cytotoxic cells in genetically obese (C57Bl/6J ob/ob) mice. Int Arch Allergy Appl Immunol. 1980;62(1):94–8.

    Article  CAS  PubMed  Google Scholar 

  17. Gerriets VA, Danzaki K, Kishton RJ, Eisner W, Nichols AG, Saucillo DC, et al. Leptin directly promotes T-cell glycolytic metabolism to drive effector T-cell differentiation in a mouse model of autoimmunity. Eur J Immunol. 2016;46(8):1970–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Reis BS, Lee K, Fanok MH, Mascaraque C, Amoury M, Cohn LB, et al. Leptin receptor signaling in T cells is required for Th17 differentiation. J Immunol. 2015;194(11):5253–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Fantuzzi G. Adiponectin and inflammation: consensus and controversy. J Allergy Clin Immunol. 2008;121(2):326–30.

    Article  CAS  PubMed  Google Scholar 

  20. Pang TT, Narendran P. The distribution of adiponectin receptors on human peripheral blood mononuclear cells. Ann N Y Acad Sci. 2008;1150:143–5.

    Article  PubMed  Google Scholar 

  21. Wilk S, Jenke A, Stehr J, Yang CA, Bauer S, Goldner K, et al. Adiponectin modulates NK-cell function. Eur J Immunol. 2013;43(4):1024–33.

    Article  CAS  PubMed  Google Scholar 

  22. Ohashi K, Parker JL, Ouchi N, Higuchi A, Vita JA, Gokce N, et al. Adiponectin promotes macrophage polarization toward an anti-inflammatory phenotype. J Biol Chem. 2010;285(9):6153–60.

    Article  CAS  PubMed  Google Scholar 

  23. Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 1993;259(5091):87–91.

    Article  CAS  PubMed  Google Scholar 

  24. Ghigliotti G, Barisione C, Garibaldi S, Fabbi P, Brunelli C, Spallarossa P, et al. Adipose tissue immune response: novel triggers and consequences for chronic inflammatory conditions. Inflammation. 2014;37(4):1337–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Gregor MF, Hotamisligil GS. Inflammatory mechanisms in obesity. Annu Rev Immunol. 2011;29:415–45.

    Article  CAS  PubMed  Google Scholar 

  26. Kraakman MJ, Kammoun HL, Allen TL, Deswaerte V, Henstridge DC, Estevez E, et al. Blocking IL-6 trans-signaling prevents high-fat diet-induced adipose tissue macrophage recruitment but does not improve insulin resistance. Cell Metab. 2015;21(3):403–16.

    Article  CAS  PubMed  Google Scholar 

  27. Christiansen T, Richelsen B, Bruun JM. Monocyte chemoattractant protein-1 is produced in isolated adipocytes, associated with adiposity and reduced after weight loss in morbid obese subjects. Int J Obes. 2005;29(1):146–50.

    Article  CAS  Google Scholar 

  28. Carr MW, Roth SJ, Luther E, Rose SS, Springer TA. Monocyte chemoattractant protein 1 acts as a T-lymphocyte chemoattractant. Proc Natl Acad Sci U S A. 1994;91(9):3652–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Silswal N, Singh AK, Aruna B, Mukhopadhyay S, Ghosh S, Ehtesham NZ. Human resistin stimulates the pro-inflammatory cytokines TNF-alpha and IL-12 in macrophages by NF-kappaB-dependent pathway. Biochem Biophys Res Commun. 2005;334(4):1092–101.

    Article  CAS  PubMed  Google Scholar 

  30. Moschen AR, Kaser A, Enrich B, Mosheimer B, Theurl M, Niederegger H, et al. Visfatin, an adipocytokine with proinflammatory and immunomodulating properties. J Immunol. 2007;178(3):1748–58.

    Article  CAS  PubMed  Google Scholar 

  31. Bullo M, Garcia-Lorda P, Megias I, Salas-Salvado J. Systemic inflammation, adipose tissue tumor necrosis factor, and leptin expression. Obes Res. 2003;11(4):525–31.

    Article  CAS  PubMed  Google Scholar 

  32. Martinez FO, Helming L, Gordon S. Alternative activation of macrophages: an immunologic functional perspective. Annu Rev Immunol. 2009;27:451–83.

    Article  CAS  PubMed  Google Scholar 

  33. Makki K, Froguel P, Wolowczuk I. Adipose tissue in obesity-related inflammation and insulin resistance: cells, cytokines, and chemokines. ISRN Inflamm. 2013;2013:139239.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Couper KN, Blount DG, Riley EM. IL-10: the master regulator of immunity to infection. J Immunol. 2008;180(9):5771–7.

    Article  CAS  PubMed  Google Scholar 

  35. Vasanthakumar A, Moro K, Xin A, Liao Y, Gloury R, Kawamoto S, et al. Erratum: the transcriptional regulators IRF4, BATF and IL-33 orchestrate development and maintenance of adipose tissue-resident regulatory T cells. Nat Immunol. 2015;16(5):544.

    Article  CAS  PubMed  Google Scholar 

  36. Perrier S, Darakhshan F, Hajduch E. IL-1 receptor antagonist in metabolic diseases: Dr Jekyll or Mr Hyde? FEBS Lett. 2006;580(27):6289–94.

    Article  CAS  PubMed  Google Scholar 

  37. Sakaue S, Nishihira J, Hirokawa J, Yoshimura H, Honda T, Aoki K, et al. Regulation of macrophage migration inhibitory factor (MIF) expression by glucose and insulin in adipocytes in vitro. Mol Med. 1999;5(6):361–71.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Surmi BK, Hasty AH. Macrophage infiltration into adipose tissue: initiation, propagation and remodeling. Future Lipidol. 2008;3(5):545–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324(5930):1029–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. MacIver NJ, Michalek RD, Rathmell JC. Metabolic regulation of T lymphocytes. Annu Rev Immunol. 2013;31:259–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Macintyre AN, Gerriets VA, Nichols AG, Michalek RD, Rudolph MC, Deoliveira D, et al. The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function. Cell Metab. 2014;20(1):61–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Michalek RD, Gerriets VA, Jacobs SR, Macintyre AN, MacIver NJ, Mason EF, et al. Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets. J Immunol. 2011;186(6):3299–303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Shi LZ, Wang R, Huang G, Vogel P, Neale G, Green DR, et al. HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J Exp Med. 2011;208(7):1367–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Magrone T, Jirillo E. Childhood obesity: immune response and nutritional approaches. Front Immunol. 2015;6:76.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007;56(7):1761–72.

    Article  CAS  PubMed  Google Scholar 

  46. Cho I, Yamanishi S, Cox L, Methe BA, Zavadil J, Li K, et al. Antibiotics in early life alter the murine colonic microbiome and adiposity. Nature. 2012;488(7413):621–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Gibbs BG, Forste R. Socioeconomic status, infant feeding practices and early childhood obesity. Pediatr Obes. 2014;9(2):135–46.

    Article  CAS  PubMed  Google Scholar 

  48. Mesquita DN, Barbieri MA, Goldani HA, Cardoso VC, Goldani MZ, Kac G, et al. Cesarean section is associated with increased peripheral and central adiposity in young adulthood: cohort study. PLoS One. 2013;8(6):e66827.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Riley LW, Raphael E, Faerstein E. Obesity in the United States—dysbiosis from exposure to low-dose antibiotics? Front Public Health. 2013;1:69.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Shu CJ, Benoist C, Mathis D. The immune system’s involvement in obesity-driven type 2 diabetes. Semin Immunol. 2012;24(6):436–42.

    Article  CAS  PubMed  Google Scholar 

  51. Uysal KT, Wiesbrock SM, Marino MW, Hotamisligil GS. Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. Nature. 1997;389(6651):610–4.

    Article  CAS  PubMed  Google Scholar 

  52. Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA. 2001;286(3):327–34.

    Article  CAS  PubMed  Google Scholar 

  53. Rocha VZ, Folco EJ, Sukhova G, Shimizu K, Gotsman I, Vernon AH, et al. Interferon-gamma, a Th1 cytokine, regulates fat inflammation: a role for adaptive immunity in obesity. Circ Res. 2008;103(5):467–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. O'Rourke RW, White AE, Metcalf MD, Winters BR, Diggs BS, Zhu X, et al. Systemic inflammation and insulin sensitivity in obese IFN-gamma knockout mice. Metab Clin Exp. 2012;61(8):1152–61.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Olefsky JM, Glass CK. Macrophages, inflammation, and insulin resistance. Annu Rev Physiol. 2010;72:219–46.

    Article  CAS  PubMed  Google Scholar 

  56. Patsouris D, Li PP, Thapar D, Chapman J, Olefsky JM, Neels JG. Ablation of CD11c-positive cells normalizes insulin sensitivity in obese insulin resistant animals. Cell Metab. 2008;8(4):301–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Wentworth JM, Naselli G, Brown WA, Doyle L, Phipson B, Smyth GK, et al. Pro-inflammatory CD11c+CD206+ adipose tissue macrophages are associated with insulin resistance in human obesity. Diabetes. 2010;59(7):1648–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Khan IM, Dai Perrard XY, Perrard JL, Mansoori A, Smith CW, Wu H, et al. Attenuated adipose tissue and skeletal muscle inflammation in obese mice with combined CD4+ and CD8+ T cell deficiency. Atherosclerosis. 2014;233(2):419–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Nishimura S, Manabe I, Nagasaki M, Eto K, Yamashita H, Ohsugi M, et al. CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med. 2009;15(8):914–20.

    Article  CAS  PubMed  Google Scholar 

  60. Winer DA, Winer S, Shen L, Wadia PP, Yantha J, Paltser G, et al. B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nat Med. 2011;17(5):610–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Arkan MC, Hevener AL, Greten FR, Maeda S, Li ZW, Long JM, et al. IKK-beta links inflammation to obesity-induced insulin resistance. Nat Med. 2005;11(2):191–8.

    Article  CAS  PubMed  Google Scholar 

  62. Hirosumi J, Tuncman G, Chang L, Gorgun CZ, Uysal KT, Maeda K, et al. A central role for JNK in obesity and insulin resistance. Nature. 2002;420(6913):333–6.

    Article  CAS  PubMed  Google Scholar 

  63. Dominguez H, Storgaard H, Rask-Madsen C, Steffen Hermann T, Ihlemann N, Baunbjerg Nielsen D, et al. Metabolic and vascular effects of tumor necrosis factor-alpha blockade with etanercept in obese patients with type 2 diabetes. J Vasc Res. 2005;42(6):517–25.

    Article  CAS  PubMed  Google Scholar 

  64. Gonzalez-Gay MA, De Matias JM, Gonzalez-Juanatey C, Garcia-Porrua C, Sanchez-Andrade A, Martin J, et al. Anti-tumor necrosis factor-alpha blockade improves insulin resistance in patients with rheumatoid arthritis. Clin Exp Rheumatol. 2006;24(1):83–6.

    CAS  PubMed  Google Scholar 

  65. Stanley TL, Zanni MV, Johnsen S, Rasheed S, Makimura H, Lee H, et al. TNF-alpha antagonism with etanercept decreases glucose and increases the proportion of high molecular weight adiponectin in obese subjects with features of the metabolic syndrome. J Clin Endocrinol Metab. 2011;96(1):E146–50.

    Article  CAS  PubMed  Google Scholar 

  66. Kim MS, Yamamoto Y, Kim K, Kamei N, Shimada T, Liu L, et al. Regulation of diet-induced adipose tissue and systemic inflammation by salicylates and pioglitazone. PLoS One. 2013;8(12):e82847.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Larsen CM, Faulenbach M, Vaag A, Volund A, Ehses JA, Seifert B, et al. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N Engl J Med. 2007;356(15):1517–26.

    Article  CAS  PubMed  Google Scholar 

  68. Versini M, Jeandel PY, Rosenthal E, Shoenfeld Y. Obesity in autoimmune diseases: not a passive bystander. Autoimmun Rev. 2014;13(9):981–1000.

    Article  CAS  PubMed  Google Scholar 

  69. Duntas LH, Biondi B. The interconnections between obesity, thyroid function, and autoimmunity: the multifold role of leptin. Thyroid. 2013;23(6):646–53.

    Article  CAS  PubMed  Google Scholar 

  70. Harper JW, Zisman TL. Interaction of obesity and inflammatory bowel disease. World J Gastroenterol. 2016;22(35):7868–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Harpsoe MC, Basit S, Andersson M, Nielsen NM, Frisch M, Wohlfahrt J, et al. Body mass index and risk of autoimmune diseases: a study within the Danish National Birth Cohort. Int J Epidemiol. 2014;43(3):843–55.

    Article  PubMed  Google Scholar 

  72. Hedstrom AK, Lima Bomfim I, Barcellos L, Gianfrancesco M, Schaefer C, Kockum I, et al. Interaction between adolescent obesity and HLA risk genes in the etiology of multiple sclerosis. Neurology. 2014;82(10):865–72.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Kavak KS, Teter BE, Hagemeier J, Zakalik K, Weinstock-Guttman B. Higher weight in adolescence and young adulthood is associated with an earlier age at multiple sclerosis onset. Mult Scler. 2015 Jun;21(7):858–65.

    Article  PubMed  Google Scholar 

  74. Gianfrancesco MA, Acuna B, Shen L, Briggs FB, Quach H, Bellesis KH, et al. Obesity during childhood and adolescence increases susceptibility to multiple sclerosis after accounting for established genetic and environmental risk factors. Obes Res Clin Pract. 2014;8(5):e435–47.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Langer-Gould A, Brara SM, Beaber BE, Koebnick C. Childhood obesity and risk of pediatric multiple sclerosis and clinically isolated syndrome. Neurology. 2013;80(6):548–52.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Ong KK, Kuh D, Pierce M, Franklyn JA, Medical Research Council National Survey of Health and Development Scientific and Data Collection Teams. Childhood weight gain and thyroid autoimmunity at age 60–64 years: the 1946 British birth cohort study. J Clin Endocrinol Metab. 2013;98(4):1435–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Harder T, Roepke K, Diller N, Stechling Y, Dudenhausen JW, Plagemann A. Birth weight, early weight gain, and subsequent risk of type 1 diabetes: systematic review and meta-analysis. Am J Epidemiol. 2009;169(12):1428–36.

    Article  PubMed  Google Scholar 

  78. Cardwell CR, Stene LC, Joner G, Davis EA, Cinek O, Rosenbauer J, et al. Birthweight and the risk of childhood-onset type 1 diabetes: a meta-analysis of observational studies using individual patient data. Diabetologia. 2010;53(4):641–51.

    Article  CAS  PubMed  Google Scholar 

  79. Verbeeten KC, Elks CE, Daneman D, Ong KK. Association between childhood obesity and subsequent Type 1 diabetes: a systematic review and meta-analysis. Diabetic Med. 2011;28(1):10–8.

    Article  CAS  PubMed  Google Scholar 

  80. Teixeira LG, Leonel AJ, Aguilar EC, Batista NV, Alves AC, Coimbra CC, et al. The combination of high-fat diet-induced obesity and chronic ulcerative colitis reciprocally exacerbates adipose tissue and colon inflammation. Lipids Health Dis. 2011;10:204.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Harper JW, Sinanan MN, Zisman TL. Increased body mass index is associated with earlier time to loss of response to infliximab in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2013;19(10):2118–24.

    Article  PubMed  Google Scholar 

  82. Blain A, Cattan S, Beaugerie L, Carbonnel F, Gendre JP, Cosnes J. Crohn’s disease clinical course and severity in obese patients. Clin Nutr. 2002;21(1):51–7.

    Article  CAS  PubMed  Google Scholar 

  83. Hass DJ, Brensinger CM, Lewis JD, Lichtenstein GR. The impact of increased body mass index on the clinical course of Crohn’s disease. Clin Gastroenterol Hepatol. 2006;4(4):482–8.

    Article  PubMed  Google Scholar 

  84. Ahmed M, Gaffen SL. IL-17 in obesity and adipogenesis. Cytokine Growth Factor Rev. 2010;21(6):449–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Procaccini C, Pucino V, Mantzoros CS, Matarese G. Leptin in autoimmune diseases. Metabolism. 2015;64(1):92–104.

    Article  CAS  PubMed  Google Scholar 

  86. Yu Y, Liu Y, Shi FD, Zou H, Matarese G, La Cava A. Cutting edge: Leptin-induced RORgammat expression in CD4+ T cells promotes Th17 responses in systemic lupus erythematosus. J Immunol. 2013;190(7):3054–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Fujita Y, Fujii T, Mimori T, Sato T, Nakamura T, Iwao H, et al. Deficient leptin signaling ameliorates systemic lupus erythematosus lesions in MRL/Mp-Fas lpr mice. J Immunol. 2014;192(3):979–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Liu Y, Yu Y, Matarese G, La Cava A. Cutting edge: fasting-induced hypoleptinemia expands functional regulatory T cells in systemic lupus erythematosus. J Immunol. 2012;188(5):2070–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Matarese G, Sanna V, Di Giacomo A, Lord GM, Howard JK, Bloom SR, et al. Leptin potentiates experimental autoimmune encephalomyelitis in SJL female mice and confers susceptibility to males. Eur J Immunol. 2001;31(5):1324–32.

    Article  CAS  PubMed  Google Scholar 

  90. Matarese G, Di Giacomo A, Sanna V, Lord GM, Howard JK, Di Tuoro A, et al. Requirement for leptin in the induction and progression of autoimmune encephalomyelitis. J Immunol. 2001;166(10):5909–16.

    Article  CAS  PubMed  Google Scholar 

  91. De Rosa V, Procaccini C, La Cava A, Chieffi P, Nicoletti GF, Fontana S, et al. Leptin neutralization interferes with pathogenic T cell autoreactivity in autoimmune encephalomyelitis. J Clin Invest. 2006;116(2):447–55.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. Matarese G, Carrieri PB, La Cava A, Perna F, Sanna V, De Rosa V, et al. Leptin increase in multiple sclerosis associates with reduced number of CD4(+)CD25+ regulatory T cells. Proc Natl Acad Sci U S A. 2005;102(14):5150–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Kraszula L, Jasinska A, Eusebio M, Kuna P, Glabinski A, Pietruczuk M. Evaluation of the relationship between leptin, resistin, adiponectin and natural regulatory T cells in relapsing-remitting multiple sclerosis. Neurol Neurochir Pol. 2012;46(1):22–8.

    CAS  PubMed  Google Scholar 

  94. Emamgholipour S, Eshaghi SM, Hossein-nezhad A, Mirzaei K, Maghbooli Z, Sahraian MA. Adipocytokine profile, cytokine levels and foxp3 expression in multiple sclerosis: a possible link to susceptibility and clinical course of disease. PLoS One. 2013;8(10):e76555.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Siegmund B, Sennello JA, Lehr HA, Batra A, Fedke I, Zeitz M, et al. Development of intestinal inflammation in double IL-10- and leptin-deficient mice. J Leukoc Biol. 2004;76(4):782–6.

    Article  CAS  PubMed  Google Scholar 

  96. Singh UP, Singh NP, Guan H, Busbee B, Price RL, Taub DD, et al. Leptin antagonist ameliorates chronic colitis in IL-10(−)/(−) mice. Immunobiology. 2013;218(12):1439–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Singh UP, Singh NP, Guan H, Busbee B, Price RL, Taub DD, et al. The emerging role of leptin antagonist as potential therapeutic option for inflammatory bowel disease. Int Rev Immunol. 2014;33(1):23–33.

    Article  CAS  PubMed  Google Scholar 

  98. Tuzun A, Uygun A, Yesilova Z, Ozel AM, Erdil A, Yaman H, et al. Leptin levels in the acute stage of ulcerative colitis. J Gastroenterol Hepatol. 2004;19(4):429–32.

    Article  CAS  PubMed  Google Scholar 

  99. Biesiada G, Czepiel J, Ptak-Belowska A, Targosz A, Krzysiek-Maczka G, Strzalka M, et al. Expression and release of leptin and proinflammatory cytokines in patients with ulcerative colitis and infectious diarrhea. J Physiol Pharmacol. 2012;63(5):471–81.

    CAS  PubMed  Google Scholar 

  100. Wang S, Baidoo SE, Liu Y, Zhu C, Tian J, Ma J, et al. T cell-derived leptin contributes to increased frequency of T helper type 17 cells in female patients with Hashimoto’s thyroiditis. Clin Exp Immunol. 2013;171(1):63–8.

    Article  CAS  PubMed  Google Scholar 

  101. MacIver NJ, Thomas SM, Green CL, Worley G. Increased leptin levels correlate with thyroid autoantibodies in nonobese males. Clin Endocrinol. 2016;85(1):116–21.

    Article  CAS  Google Scholar 

  102. Lukens JR, Dixit VD, Kanneganti TD. Inflammasome activation in obesity-related inflammatory diseases and autoimmunity. Discov Med. 2011;12(62):65–74.

    PubMed  PubMed Central  Google Scholar 

  103. Morgan OW, Bramley A, Fowlkes A, Freedman DS, Taylor TH, Gargiullo P, et al. Morbid obesity as a risk factor for hospitalization and death due to 2009 pandemic influenza A(H1N1) disease. PLoS One. 2010;5(3):e9694.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  104. Louie JK, Acosta M, Samuel MC, Schechter R, Vugia DJ, Harriman K, et al. A novel risk factor for a novel virus: obesity and 2009 pandemic influenza A (H1N1). Clin Infect Dis. 2011;52(3):301–12.

    Article  PubMed  Google Scholar 

  105. Sheridan PA, Paich HA, Handy J, Karlsson EA, Hudgens MG, Sammon AB, et al. Obesity is associated with impaired immune response to influenza vaccination in humans. Int J Obes. 2012;36(8):1072–7.

    Article  CAS  Google Scholar 

  106. Smith AG, Sheridan PA, Harp JB, Beck MA. Diet-induced obese mice have increased mortality and altered immune responses when infected with influenza virus. J Nutr. 2007;137(5):1236–43.

    CAS  PubMed  Google Scholar 

  107. Karlsson EA, Sheridan PA, Beck MA. Diet-induced obesity impairs the T cell memory response to influenza virus infection. J Immunol. 2010;184(6):3127–33.

    Article  CAS  PubMed  Google Scholar 

  108. Jedrychowski W, Maugeri U, Flak E, Mroz E, Bianchi I. Predisposition to acute respiratory infections among overweight preadolescent children: an epidemiologic study in Poland. Public Health. 1998;112(3):189–95.

    CAS  PubMed  Google Scholar 

  109. Akiyama N, Segawa T, Ida H, Mezawa H, Noya M, Tamez S, et al. Bimodal effects of obesity ratio on disease duration of respiratory syncytial virus infection in children. Allergol Int. 2011;60(3):305–8.

    Article  PubMed  Google Scholar 

  110. Ylostalo P, Suominen-Taipale L, Reunanen A, Knuuttila M. Association between body weight and periodontal infection. J Clin Periodontol. 2008;35(4):297–304.

    Article  PubMed  Google Scholar 

  111. Milner JJ, Beck MA. The impact of obesity on the immune response to infection. Proc Nutr Soc. 2012;71(02):298–306.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Weber DJ, Rutala WA, Samsa GP, Bradshaw SE, Lemon SM. Impaired immunogenicity of hepatitis B vaccine in obese persons. N Engl J Med. 1986;314(21):1393.

    CAS  PubMed  Google Scholar 

  113. Weber DJ, Rutala WA, Samsa GP, Santimaw JE, Lemon SM. Obesity as a predictor of poor antibody response to hepatitis B plasma vaccine. JAMA. 1985;254(22):3187–9.

    Article  CAS  PubMed  Google Scholar 

  114. Eliakim A, Schwindt C, Zaldivar F, Casali P, Cooper DM. Reduced tetanus antibody titers in overweight children. Autoimmunity. 2006;39(2):137–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Schottenfeld D, Beebe-Dimmer JL, Buffler PA, Omenn GS. Current perspective on the global and United States cancer burden attributable to lifestyle and environmental risk factors. Annu Rev Public Health. 2013;34:97–117.

    Article  PubMed  Google Scholar 

  116. Wolin KY, Carson K, Colditz GA. Obesity and cancer. Oncologist. 2010;15(6):556–65.

    Article  PubMed  PubMed Central  Google Scholar 

  117. Font-Burgada J, Sun B, Karin M. Obesity and cancer: the oil that feeds the flame. Cell Metab. 2016;23(1):48–62.

    Article  CAS  PubMed  Google Scholar 

  118. Warburg O. On the origin of cancer cells. Science. 1956;123(3191):309–14.

    Article  CAS  PubMed  Google Scholar 

  119. Karin M, Lin A. NF-kappaB at the crossroads of life and death. Nat Immunol. 2002;3(3):221–7.

    Article  CAS  PubMed  Google Scholar 

  120. Louis P, Hold GL, Flint HJ. The gut microbiota, bacterial metabolites and colorectal cancer. Nat Rev Microbiol. 2014;12(10):661–72.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Pediatric Endocrinology and Diabetes, Duke University, Durham, NC, USA

    Yazan Alwarawrah PhD

  2. Division of Pediatric Endocrinology and Diabetes and the Departments of Pediatrics, Immunology, and Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, USA

    Nancie J. MacIver MD, PhD

Authors
  1. Yazan Alwarawrah PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nancie J. MacIver MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nancie J. MacIver MD, PhD .

Editor information

Editors and Affiliations

  1. Duke University School of Medicine , Durham, North Carolina, USA

    Michael S. Freemark

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG

About this chapter

Cite this chapter

Alwarawrah, Y., MacIver, N.J. (2018). Immune Function in Obesity. In: Freemark, M. (eds) Pediatric Obesity. Contemporary Endocrinology. Humana Press, Cham. https://doi.org/10.1007/978-3-319-68192-4_22

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-68192-4_22

  • Published:

  • Publisher Name: Humana Press, Cham

  • Print ISBN: 978-3-319-68191-7

  • Online ISBN: 978-3-319-68192-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation