Key Points
The chapter reviews the literature pertaining to the role of obesity in modulating immune function. Obesity is found in both genetic and diet-induced obese animal models as well as in obese humans to impair immune response; both innate and acquired immune functions are affected. The immune dysfunction during obesity increases host susceptibility to infections and to chronic inflammatory diseases.
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References
Calle EE, Thun MJ, Petrelli JM, Rodriguez C, Heath CW Jr (1999) Body-mass index and mortality in a prospective cohort of U.S. adults. N Engl J Med 341:1097–1105
WHO (2004) Global strategy on diet, physical activity and health. Obesity and overweight. http://www.who.int/dietphysicalactivity/media/en/gsfsobesity.pdf
National Health Center for Statistics (2003–2004) Prevalence of overweight and obesity among adults. www.CDC.gov/nchs http://www.CDC.gov/nchs
Dalla Vecchia CF, Susin C, Rosing CK, Oppermann RV, Albandar JM (2005) Overweight and obesity as risk indicators for periodontitis in adults. J Periodontol 76:1721–1728
Miranda PJ, DeFronzo RA, Califf RM, Guyton JR (2005) Metabolic syndrome: definition, pathophysiology, and mechanisms. Am Heart J 149:33–45
Miranda PJ, DeFronzo RA, Califf RM, Guyton JR (2005) Metabolic syndrome: evaluation of pathological and therapeutic outcomes. Am Heart J 149:20–32
Linden G, Patterson C, Evans A, Kee F (2007) Obesity and periodontitis in 60–70-year-old men. J Clin Periodontol 34:461–466
Stallone DD (1994) The influence of obesity and its treatment on the immune system. Nutr Rev 52:37–50
Fasol R, Schindler M, Schumacher B, Schlaudraff K, Hannes W, Seitelberger R, Schlosser V (1992) The influence of obesity on perioperative morbidity: retrospective study of 502 aortocoronary bypass operations. Thorac Cardiovasc Surg 40:126–129
Gottschlich MM, Mayes T, Khoury JC, Warden GD (1993) Significance of obesity on nutritional, immunologic, hormonal, and clinical outcome parameters in burns. J Am Diet Assoc 93:1261–1268
Weber DJ, Rutala WA, Samsa GP, Santimaw JE, Lemon SM (1985) Obesity as a predictor of poor antibody response to hepatitis B plasma vaccine. JAMA 254:3187–3189
Amar S, Zhou Q, Shaik-Dasthagirisaheb Y, Leeman S (2007) Diet-induced obesity in mice causes changes in immune responses and bone loss manifested by bacterial challenge. Proc Natl Acad Sci USA 104:20466–20471
Zhou Q, Leeman SE, Amar S (2009) Signaling mechanisms involved in altered function of macrophages from diet-induced obese mice affect immune responses. Proc Natl Acad Sci USA 106:10740–10745
Smith AG, Sheridan PA, Harp JB, Beck MA (2007) Diet-induced obese mice have increased mortality and altered immune responses when infected with influenza virus. J Nutr 137:1236–1243
Dunn SL, Bjornholm M, Bates SH, Chen Z, Seifert M, Myers MG Jr (2005) Feedback inhibition of leptin receptor/Jak2 signaling via Tyr1138 of the leptin receptor and suppressor of cytokine signaling 3. Mol Endocrinol 19:925–938
Taildeman J, Perez-Novo CA, Rottiers I, Ferdinande L, Waeytens A, De Colvenaer V, Bachert C, Demetter P, Waelput W, Braet K, Cuvelier CA (2009) Human mast cells express leptin and leptin receptors. Histochem Cell Biol 131:703–711
Vernooy JH, Drummen NE, van Suylen RJ, Cloots RH, Moller GM, Bracke KR, Zuyderduyn S, Dentener MA, Brusselle GG, Hiemstra PS, Wouters EF (2009) Enhanced pulmonary leptin expression in patients with severe COPD and asymptomatic smokers. Thorax 64:26–32
Zarkesh-Esfahani H, Pockley G, Metcalfe RA, Bidlingmaier M, Wu Z, Ajami A, Weetman AP, Strasburger CJ, Ross RJ (2001) High-dose leptin activates human leukocytes via receptor expression on monocytes. J Immunol 167:4593–4599
Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372:425–432
Lord GM, Matarese G, Howard JK, Baker RJ, Bloom SR, Lechler RI (1998) Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature 394:897–901
La Cava A, Matarese G (2004) The weight of leptin in immunity. Nat Rev Immunol 4:371–379
Loffreda S, Yang SQ, Lin HZ, Karp CL, Brengman ML, Wang DJ, Klein AS, Bulkley GB, Bao C, Noble PW, Lane MD, Diehl AM (1998) Leptin regulates proinflammatory immune responses. FASEB J 12:57–65
Tian Z, Sun R, Wei H, Gao B (2002) Impaired natural killer (NK) cell activity in leptin receptor deficient mice: leptin as a critical regulator in NK cell development and activation. Biochem Biophys Res Commun 298:297–302
Bresson JL, Jeay S, Gagnerault MC, Kayser C, Beressi N, Wu Z, Kinet S, Dardenne M, Postel-Vinay MC (1999) Growth hormone (GH) and prolactin receptors in human peripheral blood mononuclear cells: relation with age and GH-binding protein. Endocrinology 140:3203–3209
Poppi L, Dixit VD, Baratta M, Giustina A, Tamanini C, Parvizi N (2002) Growth hormone secretagogue (GHS) analogue, hexarelin stimulates GH from peripheral lymphocytes. Exp Clin Endocrinol Diabetes 110:343–347
Hattori N, Shimatsu A, Sugita M, Kumagai S, Imura H (1990) Immunoreactive growth hormone (GH) secretion by human lymphocytes: augmented release by exogenous GH. Biochem Biophys Res Commun 168:396–401
Taub DD, Tsarfaty G, Lloyd AR, Durum SK, Longo DL, Murphy WJ (1994) Growth hormone promotes human T cell adhesion and migration to both human and murine matrix proteins in vitro and directly promotes xenogeneic engraftment. J Clin Invest 94:293–300
Dixit VD, Mielenz M, Taub DD, Parvizi N (2003) Leptin induces growth hormone secretion from peripheral blood mononuclear cells via a protein kinase C- and nitric oxide-dependent mechanism. Endocrinology 144:5595–5603
Kadowaki T, Yamauchi T (2005) Adiponectin and adiponectin receptors. Endocr Rev 26:439–451
Zacharioudaki V, Androulidaki A, Arranz A, Vrentzos G, Margioris AN, Tsatsanis C (2009) Adiponectin promotes endotoxin tolerance in macrophages by inducing IRAK-M expression. J Immunol 182:6444–6451
Tilg H, Moschen AR (2006) Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol 6:772–783
Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA (2001) The hormone resistin links obesity to diabetes. Nature 409:307–312
Reilly MP, Lehrke M, Wolfe ML, Rohatgi A, Lazar MA, Rader DJ (2005) Resistin is an inflammatory marker of atherosclerosis in humans. Circulation 111:932–939
Bokarewa M, Nagaev I, Dahlberg L, Smith U, Tarkowski A (2005) Resistin, an adipokine with potent proinflammatory properties. J Immunol 174:5789–5795
Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K, Matsuki Y, Murakami M, Ichisaka T, Murakami H, Watanabe E, Takagi T, Akiyoshi M, Ohtsubo T, Kihara S, Yamashita S, Makishima M, Funahashi T, Yamanaka S, Hiramatsu R, Matsuzawa Y, Shimomura I (2005) Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science 307:426–430
Jia SH, Li Y, Parodo J, Kapus A, Fan L, Rotstein OD, Marshall JC (2004) Pre-B cell colony-enhancing factor inhibits neutrophil apoptosis in experimental inflammation and clinical sepsis. J Clin Invest 113:1318–1327
Moschen AR, Kaser A, Enrich B, Mosheimer B, Theurl M, Niederegger H, Tilg H (2007) Visfatin, an adipocytokine with proinflammatory and immunomodulating properties. J Immunol 178:1748–1758
Pond CM (2005) Adipose tissue and the immune system. Prostaglandins Leukot Essent Fatty Acids 73:17–30
Nguyen MT, Favelyukis S, Nguyen AK, Reichart D, Scott PA, Jenn A, Liu-Bryan R, Glass CK, Neels JG, Olefsky JM (2007) A subpopulation of macrophages infiltrates hypertrophic adipose tissue and is activated by free fatty acids via Toll-like receptors 2 and 4 and JNK-dependent pathways. J Biol Chem 282:35279–35292
Shi H, Kokoeva MV, Inouye K, Tzameli I, Yin H, Flier JS (2006) TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest 116:3015–3025
Lumeng CN, Deyoung SM, Bodzin JL, Saltiel AR (2007) Increased inflammatory properties of adipose tissue macrophages recruited during diet-induced obesity. Diabetes 56:16–23
Martinez FO, Sironi M, Vecchi A, Colotta F, Mantovani A, Locati M (2004) IL-8 induces a specific transcriptional profile in human neutrophils: synergism with LPS for IL-1 production. Eur J Immunol 34:2286–2292
Hevener AL, Olefsky JM, Reichart D, Nguyen MT, Bandyopadyhay G, Leung HY, Watt MJ, Benner C, Febbraio MA, Nguyen AK, Folian B, Subramaniam S, Gonzalez FJ, Glass CK, Ricote M (2007) Macrophage PPAR gamma is required for normal skeletal muscle and hepatic insulin sensitivity and full antidiabetic effects of thiazolidinediones. J Clin Invest 117:1658–1669
Odegaard JI, Ricardo-Gonzalez RR, Goforth MH, Morel CR, Subramanian V, Mukundan L, Red Eagle A, Vats D, Brombacher F, Ferrante AW, Chawla A (2007) Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance. Nature 447:1116–1120
Rausch ME, Weisberg S, Vardhana P, Tortoriello DV (2008) Obesity in C57BL/6J mice is characterized by adipose tissue hypoxia and cytotoxic T-cell infiltration. Int J Obes (Lond) 32:451–463
Zhang X, Li M, Lian D, Zheng X, Zhang ZX, Ichim TE, Xia X, Huang X, Vladau C, Suzuki M, Garcia B, Jevnikar AM, Min WP (2008) Generation of therapeutic dendritic cells and regulatory T cells for preventing allogeneic cardiac graft rejection. Clin Immunol 127:313–321
Tiemessen MM, Jagger AL, Evans HG, van Herwijnen MJ, John S, Taams LS (2007) CD4+CD25+Foxp3+ regulatory T cells induce alternative activation of human monocytes/macrophages. Proc Natl Acad Sci USA 104:19446–19451
Askenasy N, Kaminitz A, Yarkoni S (2008) Mechanisms of T regulatory cell function. Autoimmun Rev 7:370–375
Gonzalez-Rey E, Gonzalez MA, Varela N, O’Valle F, Hernandez-Cortes P, Rico L, Buscher D, Delgado M (2009) Human adipose-derived mesenchymal stem cells reduce inflammatory and T-cell responses and induce regulatory T cells in vitro in rheumatoid arthritis. Ann Rheum Dis 69(1):241–248
Hollenberg CH, Vost A (1969) Regulation of DNA synthesis in fat cells and stromal elements from rat adipose tissue. J Clin Invest 47:2485–2498
Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP, Hedrick MH (2001) Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 7:211–228
Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH (2002) Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13:4279–4295
Boquest AC, Shahdadfar A, Fronsdal K, Sigurjonsson O, Tunheim SH, Collas P, Brinchmann JE (2005) Isolation and transcription profiling of purified uncultured human stromal stem cells: alteration of gene expression after in vitro cell culture. Mol Biol Cell 16:1131–1141
Gimble JM, Robinson CE, Wu X, Kelly KA (1996) The function of adipocytes in the bone marrow stroma: an update. Bone 19:421–428
Naveiras O, Nardi V, Wenzel PL, Hauschka PV, Fahey F, Daley GQ (2009) Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment. Nature 460:259–263
Taub DD, Longo DL (2005) Insights into thymic aging and regeneration. Immunol Rev 205:72–93
Howard JK, Lord GM, Matarese G, Vendetti S, Ghatei MA, Ritter MA, Lechler RI, Bloom SR (1999) Leptin protects mice from starvation-induced lymphoid atrophy and increases thymic cellularity in ob/ob mice. J Clin Invest 104:1051–1059
Palmer G, Aurrand-Lions M, Contassot E, Talabot-Ayer D, Ducrest-Gay D, Vesin C, Chobaz-Peclat V, Busso N, Gabay C (2006) Indirect effects of leptin receptor deficiency on lymphocyte populations and immune response in db/db mice. J Immunol 177:2899–2907
MacQueen HA, Sadler D, Mattacks C (2000) Dietary fatty acids influence the appearance of tumour necrosis factor-alpha receptors on adipocytes following an immune challenge. Br J Nutr 84:387–392
Moshyedi AK, Josephs MD, Abdalla EK, Mackay SL, Edwards CK 3rd, Copeland EM 3rd, Moldawer LL (1998) Increased leptin expression in mice with bacterial peritonitis is partially regulated by tumor necrosis factor alpha. Infect Immun 66:1800–1802
Tanaka S, Isoda F, Yamakawa T, Ishihara M, Sekihara H (1998) T lymphopenia in genetically obese rats. Clin Immunol Immunopathol 86:219–225
Moriguchi S, Kato M, Sakai K, Yamamoto S, Shimizu E (1998) Decreased mitogen response of splenic lymphocytes in obese Zucker rats is associated with the decreased expression of glucose transporter 1 (GLUT-1). Am J Clin Nutr 67:1124–1129
Plotkin BJ, Paulson D (1996) Zucker rat (fa/fa), a model for the study of immune function in type-II diabetes mellitus: effect of exercise and caloric restriction on the phagocytic activity of macrophages. Lab Anim Sci 46:682–684
Smith AG, Sheridan PA, Tseng RJ, Sheridan JF, Beck MA (2009) Selective impairment in dendritic cell function and altered antigen-specific CD8+ T-cell responses in diet-induced obese mice infected with influenza virus. Immunology 126:268–279
Arsenijevic D, Onuma H, Pecqueur C, Raimbault S, Manning BS, Miroux B, Couplan E, Alves-Guerra MC, Goubern M, Surwit R, Bouillaud F, Richard D, Collins S, Ricquier D (2000) Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production. Nat Genet 26:435–439
Nieman DC, Henson DA, Nehlsen-Cannarella SL, Ekkens M, Utter AC, Butterworth DE, Fagoaga OR (1999) Influence of obesity on immune function. J Am Diet Assoc 99:294–299
Tanaka R, Yoshikawa N, Kitano Y, Ito H, Nakamura H (1993) Long-term ciclosporin treatment in children with steroid-dependent nephrotic syndrome. Pediatr Nephrol 7:249–252
Nieman DC, Nehlsen-Cannarella SI, Henson DA, Butterworth DE, Fagoaga OR, Warren BJ, Rainwater MK (1996) Immune response to obesity and moderate weight loss. Int J Obes Relat Metab Disord 20:353–360
Tanaka S, Isoda F, Ishihara Y, Kimura M, Yamakawa T (2001) T lymphopaenia in relation to body mass index and TNF-alpha in human obesity: adequate weight reduction can be corrective. Clin Endocrinol (Oxf) 54:347–354
Espejo B, Torres A, Valentin M, Bueno B, Andres A, Praga M, Morales JM (2003) Obesity favors surgical and infectious complications after renal transplantation. Transplant Proc 35:1762–1763
Choban PS, Heckler R, Burge JC, Flancbaum L (1995) Increased incidence of nosocomial infections in obese surgical patients. Am Surg 61:1001–1005
Canturk Z, Canturk NZ, Cetinarslan B, Utkan NZ, Tarkun I (2003) Nosocomial infections and obesity in surgical patients. Obes Res 11:769–775
Curhan GC, Chertow GM, Willett WC, Spiegelman D, Colditz GA, Manson JE, Speizer FE, Stampfer MJ (1996) Birth weight and adult hypertension and obesity in women. Circulation 94:1310–1315
Baik I, Curhan GC, Rimm EB, Bendich A, Willett WC, Fawzi WW (2000) A prospective study of age and lifestyle factors in relation to community-acquired pneumonia in US men and women. Arch Intern Med 160:3082–3088
Jedrychowski W, Maugeri U, Flak E, Mroz E, Bianchi I (1998) Predisposition to acute respiratory infections among overweight preadolescent children: an epidemiologic study in Poland. Public Health 112:189–195
Monto A, Alonzo J, Watson JJ, Grunfeld C, Wright TL (2002) Steatosis in chronic hepatitis C: relative contributions of obesity, diabetes mellitus, and alcohol. Hepatology 36:729–736
Ortiz V, Berenguer M, Rayon JM, Carrasco D, Berenguer J (2002) Contribution of obesity to hepatitis C-related fibrosis progression. Am J Gastroenterol 97:2408–2414
Janniger CK, Schwartz RA, Szepietowski JC, Reich A (2005) Intertrigo and common secondary skin infections. Am Fam Physician 72:833–838
Scheinfeld NS (2004) Obesity and dermatology. Clin Dermatol 22:303–309
Chan MK, Chong LY (2002) A prospective epidemiologic survey on the prevalence of foot disease in Hong Kong. J Am Podiatr Med Assoc 92:450–456
Roujeau JC, Sigurgeirsson B, Korting HC, Kerl H, Paul C (2004) Chronic dermatomycoses of the foot as risk factors for acute bacterial cellulitis of the leg: a case-control study. Dermatology 209:301–307
Ikejima S, Sasaki S, Sashinami H, Mori F, Ogawa Y, Nakamura T, Abe Y, Wakabayashi K, Suda T, Nakane A (2005) Impairment of host resistance to Listeria monocytogenes infection in liver of db/db and ob/ob mice. Diabetes 54:182–189
Saito T, Shimazaki Y, Sakamoto M (1998) Obesity and periodontitis. N Engl J Med 339:482–483
Al-Zahrani MS, Bissada NF, Borawskit EA (2003) Obesity and periodontal disease in young, middle-aged, and older adults. J Periodontol 74:610–615
Saito T, Shimazaki Y, Koga T, Tsuzuki M, Ohshima A (2001) Relationship between upper body obesity and periodontitis. J Dent Res 80:1631–1636
Al-Zahrani MS, Bissada NF, Borawski EA (2005) Diet and periodontitis. J Int Acad Periodontol 7:21–26
Al-Zahrani MS, Borawski EA, Bissada NF (2005) Increased physical activity reduces prevalence of periodontitis. J Dent 33:703–710
Al-Zahrani MS, Borawski EA, Bissada NF (2005) Periodontitis and three health-enhancing behaviors: maintaining normal weight, engaging in recommended level of exercise, and consuming a high-quality diet. J Periodontol 76:1362–1366
Perlstein MI, Bissada NF (1977) Influence of obesity and hypertension on the severity of periodontitis in rats. Oral Surg Oral Med Oral Pathol 43:707–719
Lundin M, Yucel-Lindberg T, Dahllof G, Marcus C, Modeer T (2004) Correlation between TNFalpha in gingival crevicular fluid and body mass index in obese subjects. Acta Odontol Scand 62:273–277
Hossain P, Kawar B, El Nahas M (2007) Obesity and diabetes in the developing world – a growing challenge. N Engl J Med 356:213–215
Kahn BB, Flier JS (2000) Obesity and insulin resistance. J Clin Invest 106:473–481
Saltiel AR (2001) New perspectives into the molecular pathogenesis and treatment of type 2 diabetes. Cell 104:517–529
Ozcan U, Cao Q, Yilmaz E, Lee AH, Iwakoshi N, Ozdelen E, Tuncman G, Gorgun C, Glimcher LH, Hotamisligil GS (2004) Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science 306:457–461
Wang Y, Vera L, Fischer WH, Montminy M (2009) The CREB coactivation CRTC2 links hepatic ER stress and fasting gluconeogenesis. Nature 460:534–537
Crowe S, Wu LE, Economou C, Turpin SM, Matzaris M, Hoehn KL, Hevener AL, James DE, Duh EJ, Watt MJ (2009) Pigment epithelium-derived factor contributes to insulin resistance in obesity. Cell Metab 10:40–47
Nakamura K, Yamagishi S, Adachi H, Kurita-Nakamura Y, Matsui T, Inoue H (2009) Serum levels of pigment epithelium-derived factor (PEDF) are positively associated with visceral adiposity in Japanese patients with type 2 diabetes. Diabetes Metab Res Rev 25:52–56
Ruan H, Pownall HJ (2009) The adipocyte IKK/NFkappaB pathway: a therapeutic target for insulin resistance. Curr Opin Investig Drugs 10:346–352
Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J (2005) Global burden of hypertension: analysis of worldwide data. Lancet 365:217–223
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This work was supported by a grant from the National Institute of Dental and Craniofacial Research DE15989 (SA).
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Zhou, Q., Amar, S. (2010). Obesity and Immune Functions. In: Watson, R., Zibadi, S., Preedy, V. (eds) Dietary Components and Immune Function. Nutrition and Health. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-061-8_7
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