Abstract
Background
Evidence for an infectious origin of obesity is emerging. We explored whether common viruses were associated with obesity and metabolic traits.
Methods
We used cross-sectional (n = 674) and prospective (n = 440) data from children participating at the 4 and 6 years of age follow-up in the Rhea birth cohort. Presence of IgG antibodies to ten polyomaviruses (BKPyV, JCPyV, KIPyV, WUPyV, HPyV6, HPyV7, TSPyV, MCPyV, HPyV9, and HPyV10) and four herpesviruses (EBV, CMV, HSV-1, and HSV-2) were measured at age 4. Body mass index, waist circumference, and skinfold thickness were measured at age 4 and 6. Data on serum lipids, leptin, and adiponectin were also available. Multivariable linear regression models were used to explore the associations.
Results
At 4 years of age, seroprevalence to polyomaviruses ranged from 21.0% for HPyV9 to 82.0% for HPyV10. Seroprevalence for EBV, CMV, HSV-1, and HSV-2 was 53.0%, 26.0%, 3.6%, and 1.5% respectively. BKPyV seropositivity was associated with lower BMI SD score at age 4 [−0.21 (95% CI: −0.39, −0.03)] and 6 [−0.27 (95% CI:-0.48, −0.05)], waist circumference at age 4 [−1.12 cm (95% CI: −2.10, −0.15)] and 6 [−1.73 cm (95% CI: −3.33, −0.12)], sum of four skinfolds [−2.97 mm (95% CI: −5.70, −0.24)], and leptin levels at age 4 [ratio of geometric means, 0.83 (95% CI: 0.70, 0.98)]. CMV seropositivity was associated with higher BMI SD score at age 4 [0.28 (95% CI: 0.11, 0.45)] and 6 [0.24 (95% CI: 0.03, 0.45)] and sum of four skinfolds at age 6 [4.75 mm (95% CI: 0.67, 8.83)]. Having “2–3 herpesviruses infections” (versus “0 herpesvirus infections”) was associated with higher BMI SD score [0.32, (95% CI: 0.12, 0.53)], waist circumference [1.22 cm (95% CI: 0.13, 2.31)], and sum of four skinfolds [3.26 mm (95% CI: 0.18, 6.35)] at age 4. Polyomaviruses burden was not associated with outcomes.
Conclusions
A higher herpesviruses burden and CMV seropositivity were associated with obesity traits in childhood.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Dietz WH, Baur LA, Hall K, Puhl RM, Taveras EM, Uauy R, et al. Management of obesity: improvement of health-care training and systems for prevention and care. Lancet. 2015;385:2521–33.
Na H-N, Nam J-H. Proof-of-concept for a virus-induced obesity vaccine; vaccination against the obesity agent adenovirus 36. Int J Obes. 2014;38:1470–4.
Dhurandhar NV, Geurts L, Atkinson RL, Casteilla L, Clement K, Gerard P, et al. Harnessing the beneficial properties of adipogenic microbes for improving human health: adipogenic microbes & human health. Obes Rev. 2013;14:721–35.
Mitra AK, Clarke K. Viral obesity: fact or fiction? Obes Rev. 2010;11:289–96.
Pasarica M, Dhurandhar NV. Infectobesity: obesity of infectious origin. Adv Food Nutr Res. 2007;52:61–102.
Ponterio E, Gnessi L. Adenovirus 36 and obesity: an overview. Viruses. 2015;7:3719–40.
Atkinson RL, Dhurandhar NV, Allison DB, Bowen RL, Israel BA, Albu JB, et al. Human adenovirus-36 is associated with increased body weight and paradoxical reduction of serum lipids. Int J Obes. 2005;29:281–6.
Atkinson RL. Human adenovirus-36 and childhood obesity. Int J Pediatr Obes. 2011;6:2–6.
Na H-N, Hong Y-M, Kim J, Kim H-K, Jo I, Nam J-H. Association between human adenovirus-36 and lipid disorders in Korean schoolchildren. Int J Obes. 2010;34:89–93.
Atkinson RL, Lee I, Shin H-J, He J. Human adenovirus-36 antibody status is associated with obesity in children. Int J Pediatr Obes. 2010;5:157–60.
Hamer M, Batty GD, Kivimäki M. Obesity, metabolic health, and history of cytomegalovirus infection in the general population. J Clin Endocrinol Metab. 2016;101:1680–5.
Firth C, Harrison R, Ritchie S, Wardlaw J, Ferro CJ, Starr JM, et al. Cytomegalovirus infection is associated with an increase in systolic blood pressure in older individuals. QJM. 2016. https://doi.org/10.1093/qjmed/hcw0266.
Sun Y, Pei W, Wu Y, Yang Y. An association of herpes simplex virus type 1 infection with type 2 diabetes. Diabetes Care. 2005;28:435–6.
Nabipour I, Vahdat K, Jafari SM, Pazoki R, Sanjdideh Z. The association of metabolic syndrome and Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, and herpes simplex virus type 1: the Persian Gulf Healthy Heart Study. Cardiovasc Diabetol. 2006;5:25.
Fernández-Real J-M, Ferri M-J, Vendrell J, Ricart W. Burden of infection and fat mass in healthy middle-aged men. Obesity. 2007;15:245–52.
Fernández-Real J-M, López-Bermejo A, Vendrell J, Ferri M-J, Recasens M, Ricart W. Burden of infection and insulin resistance in healthy middle-aged men. Diabetes Care. 2006;29:1058–64.
Leinonen M, Saikku P. Evidence for infectious agents in cardiovascular disease and atherosclerosis. Lancet Infect Dis. 2002;2:11–17.
Lutsey PL, Pankow JS, Bertoni AG, Szklo M, Folsom AR. Serological evidence of infections and Type 2 diabetes: the multi-ethnic study of atherosclerosis. Diabet Med. 2009;26:149–52.
Zhu J, Quyyumi AA, Norman JE, Csako G, Waclawiw MA, Shearer GM, et al. Effects of total pathogen burden on coronary artery disease risk and C-reactive protein levels. Am J Cardiol. 2000;85:140–6.
Schooling CM, Jones HE, Leung GM. Lifecourse infectious origins of sexual inequalities in central adiposity. Int J Epidemiol. 2011;40:1556–64.
Dhurandhar NV. A framework for identification of infections that contribute to human obesity. Lancet Infect Dis. 2011;11:963–9.
Li D-K, Chen H, Ferber J, Odouli R. Infection and antibiotic use in infancy and risk of childhood obesity: a longitudinal birth cohort study. Lancet Diabetes Endocrinol. 2016. https://doi.org/10.1016/S2213-8587(16)30281-9.
Karachaliou M, Waterboer T, Casabonne D, Chalkiadaki G, Roumeliotaki T, Michel A. et al. The natural history of human polyomaviruses and herpesviruses in early life—The Rhea Birth Cohort in Greece. Am J Epidemiol. 2016;183:671–9.
Karachaliou M, Chatzi L, Roumeliotaki T, Kampouri M, Kyriklaki A, Koutra K, et al. Common infections with polyomaviruses and herpesviruses and neuropsychological development at 4 years of age, the Rhea birth cohort in Crete, Greece. J Child Psychol Psychiatry. 2016. https://doi.org/10.1111/jcpp.12582.
Chatzi L, Leventakou V, Vafeiadi M, Koutra K, Roumeliotaki T, Chalkiadaki G, et al. Cohort profile: the mother-child cohort in Crete, Greece (Rhea Study). Int J Epidemiol. 2017. https://doi.org/10.1093/ije/dyx084.
Waterboer T, Sehr P, Michael KM, Franceschi S, Nieland JD, Joos TO, et al. Multiplex human papillomavirus serology based on in situ-purified glutathione s-transferase fusion proteins. Clin Chem. 2005;51:1845–53.
Cole TJ, Lobstein T. Extended international (IOTF) body mass index cut-offs for thinness, overweight and obesity. Pediatr Obes. 2012;7:284–94.
Ulijaszek SJ, Kerr DA. Anthropometric measurement error and the assessment of nutritional status. Br J Nutr. 1999;82:165–77.
Koinaki S, Georgiou V, Karachaliou M, Daraki V, Vassilaki M, et al. Early determinants of childhood obesity: mother-child cohort in Crete, Greece. 2nd International Conference on Nutrition and Growth. 2014;January 30th-February 1st. Barcelona, Spain
Leventakou V, Georgiou V, Chatzi L, Sarri K. Relative validity of an FFQ for pre-school children in the mother-child ‘Rhea’ birth cohort in Crete, Greece. Public Health Nutr. 2015;18:421–7.
Muenchhoff M, Goulder PJR. Sex differences in pediatric infectious diseases. J Infect Dis. 2014;209:S120–S126.
Dowd JB, Zajacova A, Aiello A. Early origins of health disparities: burden of infection, health, and socioeconomic status in U.S. children. Soc Sci Med. 2009;68:699–707.
Voss JD, Dhurandhar NV. Viral infections and obesity. Curr Obes Rep. 2017;6:28–37.
Grant RW, Dixit VD. Adipose tissue as an immunological organ: adipose tissue as an immunological organ. Obesity. 2015;23:512–8.
Bouwman JJM, Visseren FLJ, Bouter KP, Diepersloot RJA. Infection-induced inflammatory response of adipocytes in vitro. Int J Obes. 2008;32:892–901.
Sanchez V, Dong JJ. Alteration of lipid metabolism in cells infected with human cytomegalovirus. Virology. 2010;404:71–77.
Yu Y, Maguire TG, Alwine JC. Human cytomegalovirus infection induces adipocyte-like lipogenesis through activation of sterol regulatory element binding protein 1. J Virol. 2012;86:2942–9.
Sanchez EL, Lagunoff M. Viral activation of cellular metabolism. Virology. 2015;479–80:609–18.
Bassols J, Moreno JM, Ortega F, Ricart W, Fernandez-Real JM. Characterization of Herpes virus entry mediator as a factor linked to obesity. Obesity. 2010;18:239–46.
Bassols J, Botas P, Moreno-Navarrete JM, Delgado E, Ortega F, Ricart W, et al. Environmental and genetic factors influence the relationship between circulating IL-10 and obesity phenotypes. Obesity. 2010;18:611–8.
Fleck-Derderian S, McClellan W, Wojcicki JM. The association between cytomegalovirus infection, obesity, and metabolic syndrome in U.S. adult females. Obesity. 2017;25:626–33.
Tewari R, Nijhawan V, Mishra M, Dudeja P, Salopal T. Prevalence of Helicobacter pylori, cytomegalovirus, and Chlamydia pneumoniae immunoglobulin seropositivity in coronary artery disease patients and normal individuals in North Indian population. Med J Armed Forces India. 2012;68:53–57.
Thjodleifsson B, Olafsson I, Gislason D, Gislason T, Jögi R, Janson C. Infections and obesity: a multinational epidemiological study. Scand J Infect Dis. 2008;40:381–6.
Sorlie PD, Nieto FJ, Adam E, Folsom AR, Shahar E, Massing M. A prospective study of cytomegalovirus, herpes simplex virus 1, and coronary heart disease: the atherosclerosis risk in communities (ARIC) study. Arch Intern Med. 2000;160:2027–32.
Grahame-Clarke C, Chan NN, Andrew D, Ridgway GL, Betteridge DJ, Emery V, et al. Human cytomegalovirus seropositivity is associated with impaired vascular function. Circulation. 2003;108:678–83.
Gkrania-Klotsas E, Langenberg C, Sharp SJ, Luben R, Khaw K-T, Wareham NJ. Higher immunoglobulin G antibody levels against cytomegalovirus are associated with incident ischemic heart disease in the population-based EPIC-Norfolk cohort. J Infect Dis. 2012;206:1897–903.
Hirsch HH, Steiger J. Polyomavirus BK. Lancet Infect Dis. 2003;3:611–23.
Fuentes-Mattei E, Giza DE, Shimizu M, Ivan C, Manning JT, Tudor S, et al. Plasma viral miRNAs indicate a high prevalence of occult viral infections. EBioMedicine. 2017;20:182–92.
Painter SD, Ovsyannikova IG, Poland GA. The weight of obesity on the human immune response to vaccination. Vaccine. 2015;33:4422–9.
Falagas ME, Kompoti M. Obesity and infection. Lancet Infect Dis. 2006;6:438–46.
Dhurandhar NV, Bailey D, Thomas D. Interaction of obesity and infections. Obes Rev. 2015;16:1017–29.
Huttunen R, Syrjänen J. Obesity and the risk and outcome of infection. Int J Obes. 2013;37:333–40.
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;52:301–12.
Rothman KJ. No adjustments are needed for multiple comparisons. Epidemiology. 1990;1:43–46.
Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple. Test J R Stat Soc Ser B. 1995;57:289–300.
Acknowledgements
This work was funded by the European Union Social Fund and the Hellenic Ministry of Health (“Program of prevention and early diagnosis of obesity and neurodevelopment disorders in preschool age children in the prefecture of Heraklion, Crete, Greece “MIS number 349580, NSRF 2007–2013); Partial support for the development of this work was received from Spanish public grants from the Instituto de Salud Carlos III (grants FIS PI11/01810 and CIBERESP) and from the Agència de Gestió d’Ajuts Universitaris i de Recerca (grant 2014 SGR 756).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
Dr. Vassilaki receives research funding from Roche outside of current study. The remaining authors declare that they have no conflict of interest.
Electronic supplementary material
Rights and permissions
About this article
Cite this article
Karachaliou, M., de Sanjose, S., Waterboer, T. et al. Is early life exposure to polyomaviruses and herpesviruses associated with obesity indices and metabolic traits in childhood?. Int J Obes 42, 1590–1601 (2018). https://doi.org/10.1038/s41366-018-0017-1
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41366-018-0017-1
This article is cited by
-
A multi-etiological model of childhood obesity: a new biobehavioral perspective for prevention?
Italian Journal of Pediatrics (2019)
-
Multi-etiological Perspective on Child Obesity Prevention
Current Nutrition Reports (2019)