In 2004, Atkinson and Dhurandhar were ready to move to humans. All of the 50 strains of human adenoviruses cause infections that are usually mild and transient, the kind that people pass off as a cold, a stomach bug or pink eye. The symptoms are so minor that people who have been infected often don’t remember ever having been sick. Even with such an innocuous virus, it would be unethical, of course, for a scientist to infect a human deliberately just to see if the person gets fat. Human studies are, therefore, always retrospective, a hunt for antibodies that would signal the presence of an infectious agent at some point in the past. To carry out this research, Atkinson developed — and patented — a screening test to look for the presence of Ad-36 antibodies in the blood.

Image Credit... Gary Schneider for The New York Times

The scientists found 502 volunteers from Wisconsin, Florida and New York willing to be screened for antibodies, 360 of them obese and 142 of them of not obese. Of the leaner subjects, 11 percent had antibodies to Ad-36, indicating an infection at some point in the past. (Ad-36 was identified relatively recently, in 1978.) Among the obese subjects, 30 percent had antibodies— a difference large enough to suggest it was not just chance. In addition, subjects who were antibody-positive weighed significantly more than subjects who were uninfected. Those who were antibody-positive also had cholesterol and triglyceride readings that were significantly lower than people who were antibody-negative — just as in the infected chickens — a finding that held true whether or not they were obese.

Were fat people just more prone to infection? Probably not, because the scientists also screened for antibodies to two other strains of adenovirus, and there was no difference between those who were obese and those who were not. Could the differences be explained by genes instead of by viruses? Probably not, because the scientists controlled for genes in a follow-up study that involved 90 pairs of twins. In the twin study, they found 20 identical-twin pairs who were “discordant” for antibodies to Ad-36, meaning one twin had been exposed to the virus and the other twin had not. In the discordant pairs, the infected twin tended to be fatter, with an average of almost 2 percent more body fat (29.6 percent versus 27.5 percent) than the uninfected twin — even though they shared exactly the same genes.

If Ad-36 is a cause of obesity, Atkinson says, you’re more likely to catch it from a newly infected and still-contagious thin person than from someone who has already gained weight because of its effects. Exactly what the virus does to create this kind of long-term perturbation is still being investigated. In a paper published last year in The International Journal of Obesity, Atkinson and Dhurandhar, along with five of their colleagues, presented evidence for how Ad-36 might affect fat cells directly, “leading to an increased fat-cell number and increased fat-cell size.”

As for the other pathogens implicated in infectobesity — nine in all — certain viruses are known to impair the brain’s appetite-control mechanism in the hypothalamus, as happens in some cases of people becoming grossly obese after meningitis. Scientists also point to a commonality between fat cells and immune-system cells, although the exact significance of the connection is unclear. Immature fat cells, for instance, have been shown to behave like macrophages, the immune cells that engulf and destroy invading pathogens. Mature fat cells secrete hormones that stimulate the production of macrophages as well as another kind of immune-system cell, T-lymphocytes.

Another line of investigation in the field of infectobesity concerns inflammation, a corollary of infection. Obese people have higher levels of two proteins related to inflammation, C-reactive protein and interleukin-6. This may suggest that an infectious agent has set off some sort of derangement in the body’s system of fat regulation, making the infected person fat. A different interpretation is not about obesity causation but about its associated risks. Some scientists, including Jeffrey Gordon’s colleagues at Washington University, are trying to see whether the ailments of obesity (especially diabetes and high blood pressure) might be caused not by the added weight per se, but by the associated inflammation.

Infectobesity has its critics, among them Stephen Bloom, a researcher at Imperial College London. Bloom said that if he were working at a research agency, he’d give money for studies into the viral causes of obesity, just in case there’s something there. But he said he wouldn’t put the theory into a medical-school textbook just yet. His main objection, he said, is that “I don’t think we need that explanation, since we have a perfectly good other explanation.” Like Dhurandhar and Atkinson, Bloom suspects that obesity has a biological cause — but rather than turning to gut microflora or adenovirus infection for an explanation, he is partial to what he calls “the lazy-greedy gene” hypothesis, his slightly disparaging shorthand for what is more generally known as the thrifty genotype.