Human adenoviruses may cause human obesity, but more research is needed before a screening test and vaccine become reality. Meanwhile, one researcher advises, 'Eat right, exercise, wash your hands.'

The study, by Whigham, Barbara A. Israel and Richard L. Atkinson of the University of Wisconsin, Madison, found that the human adenovirus Ad-37 causes obesity in chickens. This finding builds on studies that two related viruses, Ad-36 and Ad-5, also cause obesity in animals. Ad-37, Ad-36 and Ad-5 are part of a family of approximately 50 viruses known as human adenoviruses.

Ad-36 has been associated with obesity not only in animals, but also in humans, leading researchers to suspect that Ad-37 may be implicated in human obesity as well. More research is needed on this question, Whigham said. In one study, only a handful of people showed evidence of infection with Ad-37 -- not enough to draw any conclusions.

Vaccine Long Way Off

The challenges ahead for researchers in this area are daunting. They must identify the viruses that cause human obesity; devise a screening test to identify people who are infected; and develop a vaccine. Availability of a screening test and vaccine are most likely still a long way off.

"If Ad-36 is responsible for a significant portion of human obesity, the logical therapeutic intervention would be to develop a vaccine to prevent future infections," comments Frank Greenway, professor in the Department of Clinical Trials at Louisiana State University's Pennington Biomedical Research Center, in an editorial published in the same journal.

"If a vaccine were to be developed, one would want to ensure that all the serotypes of human adenoviruses responsible for human obesity were covered in the vaccine," he adds.

"If one could predict the potential of an adenovirus to cause human obesity by using an in vitro assay or even by animal testing, screening of the approximately 50 human adenoviruses might be accelerated, shortening the time required for vaccine formulation," Greenway suggests.

"Human antibody prevalence in obese and lean human populations appears to be the only reliable method to screen adenoviruses for their potential to cause obesity in humans at the present time," he notes.

Resistance to Obesity Contagion Theory

The notion that viruses can cause obesity has been a contentious one among scientists, Whigham says, in spite of evidence that factors other than poor diet or lack of exercise may be at work in the obesity epidemic.

"The prevalence of obesity has doubled in adults in the United States in the last 30 years and has tripled in children," the study notes. "With the exception of infectious diseases, no other chronic disease in history has spread so rapidly, and the etiological factors producing this epidemic have not been clearly identified."

"It makes people feel more comfortable to think that obesity stems from lack of control," Whigham reasons. "It's a big mental leap to think you can catch obesity." However, other diseases once thought to be the product of environmental factors are now known to stem from infectious agents. For example, ulcers were once thought to be the result of stress, but researchers eventually implicated bacteria, H. pylori, as a cause.

"The nearly simultaneous increase in the prevalence of obesity in most countries of the world is difficult to explain by changes in food intake and exercise alone, and suggest that adenoviruses could have contributed," the study maintains. "The role of adenoviruses in the worldwide epidemic of obesity is a critical question that demands additional research."

Viruses Implicated in Animal Obesity

The theory that viruses could play a part in obesity began a few decades ago when Nikhil Dhurandhar, now at Pennington Biomedical Research Center at LSU, noticed that chickens in India infected with the avian adenovirus SMAM-1 had significantly more fat than non-infected chickens. The discovery was intriguing because the explosion of human obesity, even in poor countries, has led to suspicions that overeating and lack of exercise weren't the only culprits in the rapidly widening human girth. Since then, Ad-36 has been found to be more prevalent in obese humans.

In the current study, Whigham et al. attempted to determine which adenoviruses (in addition to Ad-36 and Ad-5) might be associated with obesity in chickens. The animals were separated into four groups and exposed to either Ad-2, Ad-31, or Ad-37. There was also a control group that was not exposed to any of the viruses. The researchers measured food intake and tracked weight over three weeks before ending the experiment and measuring the chickens' visceral fat, total body fat, serum lipids, and viral antibodies.

Chickens inoculated with Ad-37 had much more visceral fat and body fat compared with the chickens infected with Ad-2, Ad-31 or the control group, even though they didn't eat any more. The Ad-37 group was also generally heavier compared to the other three groups, but the difference wasn't great enough to be significant by scientific standards.

The authors conclude that Ad-37 increases obesity in chickens, but Ad-2 and Ad-31 do not. "Ad-37 is the third human adenovirus to increase adiposity in animals, but not all adenoviruses produce obesity," the study notes.

Many Questions Remain

There is still much to learn about how these viruses work, Whigham says. "There are people and animals that get infected and don't get fat. We don't know why." Among the possibilities: The virus hasn't been in the body long enough to produce the additional fat; or the virus creates a tendency to obesity that must be triggered by overeating.

Mass screening for these viruses is impractical right now because there is no simple blood test available that would quickly identify exposure to a suspect virus, say the researchers. More work is needed to develop such a test.