Top

Published in:

01-01-2014 | Review

Obesity and infection: two sides of one coin

Authors: Giulia Genoni, Flavia Prodam, Agostina Marolda, Enza Giglione, Irene Demarchi, Simonetta Bellone, Gianni Bona

Published in: European Journal of Pediatrics | Issue 1/2014

Abstract

The prevalence of obesity has exponentially risen worldwide. The etiology of obesity is multifactorial, and genetic inheritance and behavioral/environmental causes are considered the main etiological factors. Moreover, evidence that specific infections might promote the development of obesity has steadily accumulated. Only a few works investigate the impact of obesity on the immune response to infections and the risk of infections in the obese population. The aim of this paper was to review the available data regarding the various aspects of the association between obesity and infections and to highlight the possibility that infectious agents may have an etiological role in obesity, an idea known as “infectobesity”. Several microbes have been considered as possible promoter of obesity, but most of the data concern adenovirus-36 that exerts an adipogenic action mainly via a direct effect on adipose tissue leading to weight gain, at least in animal models.

Obesity affects the immune response leading to an increased susceptibility to infections. Obese adults and children show an increased incidence of both nosocomial and community-acquired infections. Furthermore, obesity may alter the pharmacokinetics of antimicrobial drugs and impact on vaccine response. However, the various aspects of the association of obesity infections remain poorly studied, and a call to research is necessary to better investigate the problem.

In conclusion, obesity impacts millions globally, and greater understanding of its etiology and its effects on immunity, infections, and prevention and management strategies is a key public health concern.

Akiyama N, Segawa T, Ida H, Mezawa H, Noya M, Tamez S, Urashima M (2011) Bimodal effects of obesity ratio on disease duration of respiratory syncytial virus infection in children. Allergol Int 60:305–308PubMedCrossRef

Arens R, Muzumdar H (2008) Childhood obesity and obstructive sleep apnea syndrome. J Appl Physiol 108:436–444CrossRef

Atkinson RL, Dhurandhar NV, Allison DB, Bowen RL, Israel BA, Albu JB, Augustus AS (2005) Human adenovirus-36 is associated with increased body weight and paradoxical reduction of serum lipids. Int J Obes 29:281–286CrossRef

Atkinson RL, Lee I, Shin HJ, He J (2010) Human adenovirus-36 antibody status is associated with obesity in chidren. Int J Pediatr Obes 5:157–160PubMedCrossRef

Barlow SE, Committee E (2007) Expert committee recommendations regarding the prevention, assessment, and treatment of child and adolescent overweight and obesity. Summary Report. Pediatrics 120(Suppl 4):164–192CrossRef

Bauer LA, Black DJ, Lill JS (1998) Vancomycin dosing in morbidly obese patients. Eur J Clin Pharmacol 54:621–625PubMedCrossRef

Bearden DT, Rodvold KA (2000) Dosage adjustments for antibacterials in obese patients: applying clinical pharmacokinetics. Clin Pharmacokinet 38:415–426PubMedCrossRef

Bercault N, Boulain T, Kuteifan K, Wolf M, Runge I, Fleury JC (2004) Obesity-related excess mortality rate in an adult intensive care unit: a risk-adjusted matched cohort study. Crit Care Med 32:998–1003PubMedCrossRef

Bhattacharjee R, Kim J, Kheirandish-Gozal L, Gozal D (2011) Obesity and obstructive sleep apnea syndrome in children: a tale of inflammatory cascades. Pediatr Pulmonol 46:313–323PubMedCrossRef

10.

Binkin N, Fontana G, Lamberti A, Cattaneo C, Baglio G, Perra A, Spinelli A (2010) A national survey of the prevalence of childhood overweight and obesity in Italy. Obes Rev 11:2–10PubMedCrossRef

11.

Broderick MP, Hansen CJ, Irvine M, Metzgar D, Campbell K, Baker C, Russell KL (2010) Adenovirus 36 seropositivity is strongly associated with race and gender, but not obesity, among US military personnel. Int J Obes 34:302–308CrossRef

12.

Bulló M, García-Lorda P, Megias I, Salas-Salvadó J (2003) Systemic inflammation, adipose tissue tumor necrosis factor, and leptin expression. Obesity 11:525–531CrossRef

13.

Caldefie-Chezet F, Poulin A, Vasson MP (2003) Leptin regulates functional capacities of polymorphonuclear neutrophils. Free Radic Res 37:809–814PubMedCrossRef

14.

Claycombe K, King LE, Fraker PJ (2008) A role for leptin in sustaining lymphopoiesis and myelopoiesis. Proc Natl Acad Sci U S A 105:2017–2021PubMedCentralPubMedCrossRef

15.

Dhurandhar NV, Israel BA, Kolesar JM, Mayhew GF, Cook ME, Atkinson RL (2000) Increased adiposity in animals due to a human virus. Int J Obes Relat Metab Disord 24:989–996PubMedCrossRef

16.

Dhurandhar NV, Israel BA, Kolesar JM, Mayhew GF, Cook ME, Atkinson RL (2001) Transmissibility of adenovirus-induced adiposity in a chicken model. Int J Obes Relat Metab Disord 25:990–996PubMedCrossRef

17.

Dossett LA, Heffernan D, Lightfoot M, Collier B, Diaz JJ, Sawyer RG, May AK (2008) Obesity and pulmonary complications in critically injured adults. Chest 134:974–980PubMedCentralPubMedCrossRef

18.

Early GJ, Seifried SE (2012) Risk factors for community-associated Staphylococcus aureus skin infection in children of Maui, Hawaii. J Med Public Health 71:218–223

19.

Eliakim A, Schwindt C, Zaldivar F, Casali P, Cooper DM (2006) Reduced tetanus antibody titers in overweight children. Autoimmunity 39:137–141PubMedCrossRef

20.

Esposito S, Preti V, Consolo S, Nazzari E, Principi N (2012) Adenovirus 36 infection and obesity. J Clin Virol 55:95–100PubMedCrossRef

21.

Falagas ME, Kompoti M (2006) Obesity and infection. Lancet Infect Dis 6:438–446PubMedCrossRef

22.

Fantuzzi G (2005) Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol 115:911–919PubMedCrossRef

23.

Farooqi IS (2008) Monogenic human obesity. Front Horm Res 36:1–11PubMedCrossRef

24.

Farooqi IS, Matarese G, Lord GM, Keogh JM, Lawrence E, Agwu C, Sanna V, Jebb SA, Perna F, Fontana S, Lechler RI, DePaoli AM, O'Rahilly S (2002) Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest 110:1093–1094PubMedCentralPubMed

25.

Franchini R, Petri A, Migliario M, Rimondini L (2011) Poor oral hygiene and gingivitis are associated with obesity and overweight status in paediatric subjects. J Clin Periodontol 38:1021–1028PubMedCrossRef

26.

Gabbert C, Donohue M, Arnold J, Schwimmer JB (2010) Adenovirus 36 and obesity in children and adolescents. Pediatrics 126:721–726PubMedCrossRef

27.

Ghanim H, Aljada A, Hofmeyer D, Syed T, Mohanty P, Dandona P (2004) Circulating mononuclear cells in the obese are in a proinflammatory state. Circulation 110:1564–1571PubMedCrossRef

28.

Goossens VJ, deJager SA, Grauls GE, Gielen M, Vlietinck RF, Derom CA, Loos RJ, Rensen SS, Buurman WA, Greve JW, van Baak MA, Wolffs PF, Bruggeman CA, Hoebe CJ (2011) Lack of evidence for the role of human adenovirus-36 in obesity in a European cohort. Obesity 19:220–221PubMedCrossRef

29.

Guo SS, Chumlea WC (1999) Tracking of body mass index in children in relation to overweight in adulthood. Am J Clin Nutr 70(1 Part 2):145–148

30.

Healthy People (2010) DC: US Dept of Health and Human Services, 2nd ed. Washington 2000

31.

Hsu A, Aronoff DM, Phipps J, Goel D, Mancuso P (2007) Leptin improves pulmonary bacterial clearance and survival in ob/ob mice during pneumococcal pneumonia. Clin Exp Immunol 150:332–339PubMedCentralPubMedCrossRef

32.

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 54:182–189PubMedCrossRef

33.

Inyushkina EM, Merkulova NA, Inyushkin AN (2010) Mechanisms of the respiratory activity of leptin at the level of the solitary tract nucleus. Neurosci Behav Physiol 40:707–713PubMedCrossRef

34.

Jacobs SR, Herman CE, MacIver NJ, Wofford JA, Wieman HL, Hammen JJ, Rathmell JC (2008) Glucose uptake is limiting in T cell activation and requires CD28-mediated Akt-dependent and independent pathways. J Immunol 180:4476–4486PubMedCentralPubMed

35.

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 112:189–195PubMed

36.

Kapila M, Khosla P, Dhurandhar NV (2004) Novel short-term effects of adenovirus AD-36, on hamster lipoproteins. Int J Obes Relat Metab Disord 28:1521–1527PubMedCrossRef

37.

Karlsson EA, Sheridan PA, Beck MA (2010) Dietinduced obesity impairs the T cell memory response to influenza virus infection. J Immunol 184:3127–3133PubMedCrossRef

38.

Keith SW, Redden DT, Katzmarzyk PT, Boggiano MM, Hanlon EC, Benca RM, Ruden D, Pietrobelli A, Barger JL, Fontaine KR, Wang C, Aronne LJ, Wright SM, Baskin M, Dhurandhar NV, Lijoi MC, Grilo CM, DeLuca M, Westfall AO, Allison DB (2006) Putative contributors to the secular increase in obesity: exploring the roads less traveled. Int J Obes 30:1585–1594CrossRef

39.

Koenig SM (2001) Pulmonary complications of obesity. Am J Med Sci 321:249–279PubMedCrossRef

40.

Korndewal MJ, Geurts van Kessel WM, Jak LG, Uiterwaal CS, Rövekamp MH, van der Ent CK (2012) Influence of obesity on nocturnal oxygen saturation in young children. Eur J Pediatr 171:1687–1693PubMedCrossRef

41.

Kwong JC, Campitelli MA, Rosella LC (2011) Obesity and respiratory hospitalizations during influenza seasons in Ontario, Canada: a cohort study. Clin Infect Dis 53:413–421PubMedCrossRef

42.

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 2:57–65

43.

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 394:897–901PubMedCrossRef

44.

Louie JK, Acosta M, Samuel MC, Schechter R, Vugia DJ, Harriman K, Matyas BT, California Pandemic (H1N1) Working Group (2011) A novel risk factor for a novel virus: obesity and 2009 pandemic influenza A (H1N1). Clin Infect Dis 52:301–312PubMedCrossRef

45.

Lynch JP 3rd, Fishbein M, Echavarria M (2011) Adenovirus. Semin Respir Crit Care Med 32:494–511PubMedCrossRef

46.

Lyons MJ, Faust IM, Hemmes RB, Buskirk DR, Hirsch J, Zabriskie JB (1982) A virally induced obesity syndrome in mice. Science 216:82–85PubMedCrossRef

47.

Maciver NJ, Jacobs SR, Wieman HL, Wofford JA, Coloff JL, Rathmell JC (2008) Glucose metabolism in lymphocytes is a regulated process with significant effects on immune cell function and survival. J Leukoc Biol 84:949–957PubMedCrossRef

48.

Mancuso P (2010) Obesity and lung inflammation. J Appl Physiol 108:722–728PubMedCrossRef

49.

McAllister EJ, Dhurandhar NV, Keith SW, Aronne LJ, Barger J, Baskin M, Benca RM, Biggio J, Boggiano MM, Eisenmann JC, Elobeid M, Fontaine KR, Gluckman P, Hanlon EC, Katzmarzyk P, Pietrobelli A, Redden DT, Ruden DM, Wang C, Waterland RA, Wright SM, Allison DB (2009) Ten putative contributors to the obesity epidemic. Crit Rev Food Sci Nutr 49:868–913PubMedCentralPubMedCrossRef

50.

Middleman AB, Anding R, Tung C (2010) Effect of needle length when immunizing obese adolescents with hepatitis B vaccine. Pediatrics 125:508–512CrossRef

51.

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

52.

Montecucco F, Bianchi G, Gnerre P, Bertolotto M, Dallegri F, Ottonello L (2006) Induction of neutrophil chemotaxis by leptin: crucial role for p38 and Src kinases. Ann N Y Acad Sci 1069:463–471PubMedCrossRef

53.

Na HN, Hong YM, Kim J, Kim HN, Jo I, Nam JH (2010) Association between human adenovirus-36 and lipid disorders in Korean schoolchildren. Int J Obes 34:89–93CrossRef

54.

Na HN, Kim J, Lee HS, Shim KW, Kimm H, Jee SH (2012) Association of human adenovirus-36 in overweight Korean adults. Int J Obes 36:281–285CrossRef

55.

Na HN, Nam JH (2012) Adenovirus 36 as an obesity agent maintains the obesity state by increasing MCP-1 and inducing inflammation. J Infect Dis 205:914–922PubMedCrossRef

56.

Nadeau KJ, Maahs DM, Daniels SR, Eckel RH (2011) Childhood obesity and cardiovascular disease: links and prevention strategies. Nat Rev Cardiol 8:513–525PubMedCrossRef

57.

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 99:294–299PubMedCrossRef

58.

Nino M, Franzese A, Ruggiero Perrino N, Balato N (2012) The effect of obesity on skin disease and epidermal permeability barrier status in children. Pediatr Dermatol 29:567–570PubMedCrossRef

59.

Ogden CL, Carroll MD, Kit BK, Flegal KM (2012) Prevalence of obesity in the United States, 2009–2010. NCHS Data Brief 82:1–8PubMed

60.

Olds T, Maher C, Zumin S, Péneau S, Lioret S, Castetbon K, Bellisle, de Wilde J, Hohepa M, Maddison R, Lissner L, Sjöberg A, Zimmermann M, Aeberli I, Ogden C, Flegal K, Summerbell C (2011) Evidence that the prevalence of childhood overweight is plateauing: data from nine countries. Int J Pediatr Obes 6:342–360PubMedCrossRef

61.

Ozata M, Ozdemir LC, Licinio J (1999) Human leptin deficiency caused by a missense mutation: multiple endocrine defects, decreased sympathetic tone, and immune system dysfunction indicate new targets for leptin action, greater central than peripheral resistance to the effects of leptin, and spontaneous correction of leptin of leptin mediated defects. J Clin Endocrinol Metab 84:3686–3695PubMed

62.

Parsarica M, Shin AC, Yu M, Ou Yang HM, Rathod M, Jen KL, MohanKumar S, MohanKumar PS, Markward N, Dhurandhar NV (2006) Human adenovirus 36 induces adiposity, increases insulin sensitivity, and alters hypothalamic monoamines in rats. Obesity 14:1905–1913CrossRef

63.

Pasarica M, Dhurandhar NV (2007) Infectobesity: obesity of infectious origin. Adv Food Nutr Res 52:61–102PubMed

64.

Pasarica M, Mashtalir N, McAllister EJ, Kilroy GE, Koska J, Permana P, de Courten B, Yu M, Ravussin E, Gimble JM, Dhurandhar NV (2008) Adipogenic human adenovirus Ad-36 induces commitment, differentiation and lipid accumulation in human adipose-derived stem cells. Stem Cells 26:969–978PubMedCentralPubMedCrossRef

65.

Plotkin BJ, Paulson D, Chelich A, Jurak D, Cole J, Kasimos J, Burdick JR, Casteel N (1996) Immune responsiveness in a rat model for type II diabetes (Zucker rat, fa/fa): susceptibility to Candida albicans infection and leucocyte function. J Med Microbiol 44:277–283PubMedCrossRef

66.

Prodam F, Ricotti R, Genoni G, Parlamento S, Petri A, Balossini C, Savastio S, Bona G, Bellone S (2013) Comparison of two classifications of metabolic syndrome in the pediatric population and the impact of cholesterol. J Endocrinol Invest 36:466–473

67.

Rabec C, de Lucas RP, Veale D (2011) Respiratory complications of obesity. Arch Bronconeumol 47:252–261PubMedCrossRef

68.

Smith AG, Sheridan PA, Tseng RJ, Sheridan JF, Beck MA (2009) Selective impairment in dendritic cell function and altered antigenspecific CD8 T-cell responses in diet-induced obese mice infected with influenza virus. Immunology 26:268–279CrossRef

69.

Stein GE, Schooley SL, Peloquin CA, Kak V, Havlichek DH, Citron DM, Tyrrell KL, Goldstein EJ (2005) Pharmacokinetics and pharmacodynamics of linezolid in obese patients with cellulitis. Ann Pharmacother 39:427–432PubMedCrossRef

70.

Stentz FB, Kitabchi AE (2005) Hyperglycemia-induced activation of human T-lymphocytes with de novo emergence of insulin receptors and generation of reactive oxygen species. Biochem Biophys Res Commun 335:491–495PubMedCrossRef

71.

Tilg H, Moschen AR (2006) Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol 6:772–783PubMedCrossRef

72.

Trischitta V, Brunetti A, Chiavetta A, Benzi L, Papa V, Vigneri R (1989) Defects in insulin-receptor internalization and processing in monocytes of obese subjects and obese NIDDM patients. Diabetes 38:1579–1584PubMedCrossRef

73.

Trovato GM, Castro A, Tonzuso A, Garozzo A, Martines GF, Pirri C, Trovato F, Catalano D (2009) Human obesity relationship with Ad36 adenovirus and insulin resistance. Int J Obes 33:1402–1409CrossRef

74.

Vangipuram SD, Yu M, Tian J, Stanhope KL, Pasarica M, Havel PJ, Heydari AR, Dhurandhar NV (2007) Adipogenic human adenovirus-36 reduces leptin expression and secretion and increases glucose uptake by fat cells. Int J Obes 31:87–96CrossRef

75.

Viardot A, Grey ST, Mackay F, Chisholm D (2006) Potential antiinflammatory role of insulin via the preferential polarization of effector T cells toward a T helper 2 phenotype. Endocrinology 148:346–353PubMedCrossRef

76.

Vilar-Compte D, Mohar A, Sandoval S, de la Rosa M, Gordillo P, Volkow P (2000) Surgical site infections at the National Cancer Institute in Mexico: a case–control study. Am J Infect Control 28:14–20PubMedCrossRef

77.

Wang Y, Lobstein T (2006) Worldwide trends in childhood overweight and obesity. Int J Pediatr Obes 1:11–25PubMedCrossRef

78.

Weatherill AR, Lee JY, Zhao L, Lemay DG, Youn HS, Hwang DH (2005) Saturated and polyunsaturated fatty acids reciprocally modulate dendritic cell functions mediated through TLR4. J Immunol 174:5390–5397PubMed

79.

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

80.

Wigand R, Gelderblom H, Wadell G (1980) New human adenovirus (candidate adenovirus 36), a novel member of subgroup D. Arch Virol 64:225–233PubMedCrossRef

81.

Willershausen B, Haas G, Krummenauer F, Hohenfellner K (2004) Relationship between high weight and caries frequency in German elementary school children. Eur J Med Res 9:400–404PubMed

82.

Wolf AM, Wolf D, Rumpold H, Enrich B, Tilg H (2004) Adiponectin induces the anti-inflammatory cytokines IL-10 and IL-1RA in human leukocytes. Biochem Biophys Res Commun 323:630–635PubMedCrossRef

83.

Wood N, Johnson RB, Streckfus CF (2003) Comparison of body composition and periodontal disease using nutritional assessment techniques: Third National Health and Nutrition Examination Survey (NHANES III). J Clin Periodontol 30:321–327PubMedCrossRef

84.

World Health Organization (2001) Obesity: preventing and managing the global epidemic. Report of a WHO Consultation on Obesity, 3–5 June 1997, Geneva 2001. WHO/NUT/NCD 98.1

85.

Yang H, Youm YH, Vandanmagsar B, Rood J, Kumar KG, Butler AA, Dixit VD (2009) Obesity accelerates thymic aging. Blood 114:3803–3812PubMedCrossRef

86.

Younossi ZM, McCullough AJ, Ong JP, Barnes DS, Post A, Tavill A, Bringman D, Martin LM, Assmann J, Gramlich T, Mullen KD, O'Shea R, Carey WD, Ferguson R (2004) Obesity and non-alcoholic fatty liver disease in chronic hepatitis C. J Clin Gastroenterol 38:705–709PubMedCrossRef

87.

Zhao Y, Sun R, You L, Gao C, Tian Z (2003) Expression of leptin receptors and response to leptin stimulation of human natural killer cell lines. Biochem Biophys Res Commun 300:247–252PubMedCrossRef

Title: Obesity and infection: two sides of one coin
Authors: Giulia Genoni
Flavia Prodam
Agostina Marolda
Enza Giglione
Irene Demarchi
Simonetta Bellone
Gianni Bona
Publication date: 01-01-2014
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Pediatrics / Issue 1/2014
Print ISSN: 0340-6199
Electronic ISSN: 1432-1076
DOI: https://doi.org/10.1007/s00431-013-2178-1

At a glance: The STEP trials

Springer Medicine

Obesity and infection: two sides of one coin

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2014

Influence of mask type and mask position on the effectiveness of bag-mask ventilation in a neonatal manikin

Young male soccer players exhibit additional bone mineral acquisition during the peripubertal period: 1-year longitudinal study

Unexpected vertical transmission of HIV infection

Juvenile polyp

Early biomarkers as predictors for bronchopulmonary dysplasia in preterm infants: a systematic review

Initial anticonvulsant monotherapy in routine care of children and adolescents: levetiracetam fails more frequently than valproate and oxcarbazepine due to a lack of effectiveness