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Is Obesity an Infectious Disease? Adenovirus and its link to obesity. Alecia Sturgill April 18, 2008 Advisor: Dr. Bill Grimes. Introduction. Why is it easy for some people to lose weight and difficult for others? Caloric intake Physical activity Genetic predisposition Socioeconomic status

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Is Obesity an Infectious Disease? Adenovirus and its link to obesity


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    1. Is Obesity an Infectious Disease?Adenovirus and its link to obesity Alecia Sturgill April 18, 2008 Advisor: Dr. Bill Grimes

    2. Introduction • Why is it easy for some people to lose weight and difficult for others? • Caloric intake • Physical activity • Genetic predisposition • Socioeconomic status • Some other unknown factors

    3. Background • What does overweight and obesity mean? • CDC states, ranges of weight that are greater than what is considered healthy for a given height. • BMI (Body Mass Index)  25-29.9 = overweight, 30+ = obese

    4. Why is it important to determine the causes of obesity? • Some associated diseases with obesity are: • Type II Diabetes • Hypertension • Coronary Heart Disease • Stroke • Dyslipidemia • Osteoarthritis

    5. Other Negative Effects Associated with Obesity • Economic issues • Account for 9.1 percent of the national medical expenditure nearly 92.6 billion dollars • Psychological issue • Discrimination in work and school

    6. Epidemiology of Obesity • WHO has proclaimed a global epidemic of obesity estimates 300 million worldwide • Obesity has doubled in adults and tripled in children in the last thirty years • Since the 1970s, prevalence has sharply increased from 15% to 32.9% in a 2003-2004 survey • NHANES survey (combined overweight & obesity) went from 46% in 1976-1980 to 61% in 1999

    7. Obesity: A Global Epidemic • Dr. Leah Whigham, stated that this dramatic increase has not been found in an other chronic disease in the past and has only been witnessed in the spread of an infectious disease. • Is obesity actually being caused by an infectious process? • Could a virus, bacterium, etc. be interrupting the regulatory controls of our bodies and causing people to gain weight? • Many were skeptical at first but this theory has recently been given more credibility • Ex) Recent discovery of bacterium Helicobacter pylori as an etiologic agent in peptic ulcer disease.

    8. Research • Nikhil V. Dhurandhar, previously of Wayne State University and currently with Pennington Biomedical Research Center • Six viruses and a scrapie agent that has been shown to produce obesity in animals • Two viruses, an avian adenovirus and a human adenovirus (Adenovirus-36) have been linked to human obesity.

    9. Questions about the Virus • How is the virus transmitted? • Does the virus act alone or does it require other factors to increase obesity? • How does the virus act on the body to increase obesity? • Could there be other agents that may act in a similar way? • What can be done about this problem in the realm of screening and prevention?

    10. Adenovirus • Virus getting most attention • Medium-sized, nonenveloped icosahedral virus containing double-stranded DNA. • 49 immunologically distinct types that can cause human infections.

    11. Adenovirus • Usually does not cause severe illnesses • Most commonly cause respiratory illnesses, but can cause gastroenteritis, conjunctivitis, rashes, and cystitis • Severity depends on serotype and state of patient’s immune system • Adenovirus-36 (Ad-36) most often causes the common cold and pink eye

    12. Adenovirus • Transmission varies slightly by serotype being from fecal-oral, direct-contact and water-borne transmission • Severity can be dependent on transmission • Some adenoviruses are capable of existing in tonsils, adenoids and intestines of hosts without symptoms • Some are endemic to certain parts of the world

    13. Diagnosis of an adenovirus infection • Can be diagnosed in multiple ways • Polymerase chain reaction assays (PCR) • Antigen detection • Virus isolation • Serology

    14. Treatment and prevention of an adenovirus infection • Treatment • Since most are mild, they usually require no treatment • Treat complications of infections • Prevention • Hygiene practices  washing hands, cleaner drinking water, better medical practice, etc. • Vaccine • Exists but only given to the military • Live, oral vaccine that is attenuated in the intestine • Known to have an oncogenic potential

    15. Review of Literature • Dhurandhar’s first attempt (Dhurandhar, 2000) • Goal of study is to see if animals inoculated with Ad-36 would have increased adipose tissue • The results of this study showed those inoculated with Ad-36 had increased adipose tissue with contradictory low serum triglycerides and cholesterol, this did not occur in those inoculated with the avian adenovirus • This allowed Dhurandhar to believe that a virus could be involved and more research must be done

    16. Dhurandhar’s next attempt (Dhurandhar 2001) • Goal was to determine if Ad-36 could be transmitted from infected chickens sharing the same cage and if the virus could be transmitted through blood • This was found to be true in both cases. The transmission of the Ad-36 induced adiposity should raise concerns in the transmission in humans

    17. Further research (Dhurandhar, 2002) • He decided to study nonhuman primates to investigate the adiposity-promoting potential of Ad-36 • In the first study he observed spontaneously occurring Ad-36 antibodies in male rhesus monkeys and an association of positive antibody status with weight gain and decreased plasma cholesterol. • The next experiment showed that marmoset monkeys had a threefold body weight gain, an increase in body fat and lower serum cholesterol compared to control groups

    18. More Research (Vangipuram, 2004) • Next experiment determined that Ad-36 enhances differentiation of preadipocytes • Also, Ad-36 increased the number of differentiated adipocytes, GPDH enzyme levels, and the total cellular lipid content. • This may be a contributing mechanism in its adipogenic effect. It also proved that this is not a common factor in all adenoviruses since the same result was not found in Ad-2

    19. More research (Atkinson, 2005) • The result of another study showed a significant association of obesity and a positive Ad-36 status. It was found that 30% of obese participants were positive for Ad-36 antibodies and 11% in the non obese. • There was also lower serum cholesterol and triglyceride levels in Ad-36 antibody positive subjects. There was no association in the other adenoviruses and obesity. • Would it be logical to do viral antibody tests on obese individuals with low levels of cholesterol?

    20. Summary • Obesity is a global epidemic • It contributes to morbidity and mortality by its association with other chronic diseases • It is essential that all the etiologic agents associated with obesity is identified • It is now evident that obesity being partially infectious should not be disregarded • It is known that Ad-36 induces adiposity by increasing body fat, enhancing differentiation of preadipocytes, lowering serum lipids and triglycerides, increasing leptin production, and altering glucose metabolism • Other infectious agents needs to be considered • More research needs to be done so that vaccines and screening tests can be utilized to combat the problem

    21. Conclusion • It is important that this is not used as an excuse for being overweight • Other causes of obesity should not be forgotten • What measures will be taken if this theory is fully accepted? • Vaccines cover all serotypes known to cause obesity • Anti-viral medications Cidofovir prevents adiposity in mice cells • Screening tests expensive but may be worth it • New biotech company that developed an antibody screening test • Criticized by peers because there is not very effective treatment for an adenovirus infection • However, if a normal weight individual received a positive antibody test they would know that they are at risk and could possibly change their lifestyle

    22. Conclusion • If this theory does not follow through, it will still raise awareness that infectious agents should be considered as the causative agents in other disease processes • No matter what the solution (vaccines, screening tests, health & fitness programs, etc.) the problem of obesity needs to be conquered!

    23. References Atkinson, R.L., N.V. Dhurandhar, D.B. Allison, R.L. Bowen, B.A. Israel, J.B. Albu, and A.S. Augustus. Human adenovirus-36 is associated with increased body weight and paradoxical reduction of serum lipids. International Journal of Obesity 2005; 29:281-286. Center of Disease Control and Prevention, Adenoviruses. January 21, 2005, Available at: http://www.cdc.gov/Ncidod/dvrd/revb/respiratory/eadfeat.htm, Accessed on December 21, 2007. Center of Disease Control and Prevention, Obesity and Overweight. November 17, 2007, Available at http://www.cdc.gov/nccdphp/dnpa/obesity/index.htm, Accessed on December 21, 2007. Christakis, N.A. and J. H. Fowler. The spread of obesity in a large social network over 32 years. The New England Journal of Medicine 2007; 357; 370-379. Coglan, A. Common virus may trigger obesity. New Scientist. 2007; 195: 21. Dhurandhar, N.V. Infections and body weight: an emerging relationship? International Journal of Obesity. 2002; 26: 745-746. Dhurandhar, N.V., L.D. Whigham, D.H. Abbott, N.J. Schultz-Darken, B.A. Israel, S.M. Bradley, J.W. Kemnitz, D.B. Allison, and R.L. Atkinson. Human adenovirus Ad-36 promotes weight gain in male rhesus and marmoset monkeys. The Journal of Nutrition. 2002; 132: 3155-3160. Dhurandhar, N.V., B.A. Israel, J.M. Kolesar, G.F. Mayhew, M.E. Cook and R.L. Atkinson. Increased adiposity in animals due to a human virus. International Journal of Obesity. 2000; 24:989-996. Dhurandhar, N.V., B.A. Israel, J.M. Kolesar, G.F. Mayhew, M.E. Cook and R.L. Atkinson. Transmissibility of adenovirus-induced adiposity in a chicken model. International Journal of Obesity. 2001; 25; 990-996. Greenway, F. Virus-induced obesity. Am J Physiol Regulatory Integrative Comp Physiol 2006; 290:188-189. Kelly, J. Third human adenovirus linked to fat. Medscape Medical News 2006. Marsh and Bernstein. Common virus may contribute to obesity in some people, new study shows. American Chemical Society. Boston, public release date: Aug. 20, 2007. Pasarica, M., A.C. Shin, M. Yu, H.M. Ou Yang, M. Rathod, K.L. Jen, S. Mohankumar, P.S. Mohankumar, N. Markward, and N.V. Durandhar. Human Adenovirus 36 Induces Adiposity, Increases Insulin Sensitivity, and Alters Hypothalamic Monoamines in Rats. 2006; 15;1905-1913.

    24. Pennington Biomedical Research Center, The Explorers. 2007, Available at: http://www.pbrc.edu/About_Us/The_Explorers/Faculty_Bio.asp?EmployeeID=2449, Accessed on December 21, 2007. Powledge, T.M. Is obesity an infectious disease? Infectious Diseases. 2004; 4: 599. Rathod, M., S.D. Vangipuram, B. Krishnan, A.R. Heydari, T.C. Holland, and N.V. Dhurandhar. Viral mRNA expression but not DNA replication is required for lipogenic effect of human adenovirus Ad-36 in preadipocytes. International Journal of Obesity. 2007; 31; 78-86. Stanford University, The Adenovirus Family. March 7, 1998, Available at: http://virus.stanford.edu/adeno/adeno.html, Accessed on December 21, 2007. Vangipuram, S.D., M. Yu, K.L. Stanhope, M. Pasarica, P.J. Havel, A.R. Heydari, and N.V. Dhurandhar. Adipogenic human adenovirus-36 reduces leptin expression and secretion and increases glucose uptake by fat cells. International Journal of Obesity. 2007; 31:87-96. Vangipuram, S.D., J. Sheele, R.L. Atkinson, T.C. Holland, and N.V. Dhurandhar. A human adenovirus enhances preadipocyte differentiation. Obesity Research. 2004; 12:770-776. Vasilakopoulou, A and C.W le Roux. Could a virus contribute to weight gain? International Journal of Obesity. 2007; 31; 1350-1356. Vastag, B. Infectious Obesity. Science News. 2007; 172: 115-116. Whigham, L.D., B.A. Israel, and R.L. Atkinson. Adipogenic potential of multiple human adenoviruses in vivo and in vitro in animals. Am J Physiol Regulatory Integrative Comp Physiol 2005; 290; 190-194. Zimmerman, R.L. The obesity epidemic in America. Clinics in Family Practice. 2002; 4:229-247.