On the infectious etiology of obesity.
“I remember giving a talk at a conference where I presented 15 different studies in which Ad-36 either caused or was correlated to fatness. At the end of it, a good friend said to me, ‘I just don’t believe it.’ He didn’t give a reason; he just didn’t believe it. People are really stuck on eating and exercise as the only contributors to fatness. But there is more to it,” Richard Atkinson, M.D., emeritus professor of medicine and nutrition at the University of Wisconsin at Madison, said in 2016.
By 2050, it is projected that 50% of the global population will be obese if the current trends continue. Obesity is a multifactorial chronic disease. Genetic, environmental, and lifestyle risk factors exist for obesity, including viruses in the environment.
The Adv36 and Obesity Link
In January of 2009, there was hype on the possibility of viruses responsible for obesity over the internet news, Twitter, and blogs. As usual, it soon subsided but research on it continues.
Adenovirus serotype 36 (Adv36 or Ad-36) is one of the 52 adenoviruses that causes the common cold in humans. A review of 36 epidemiological studies found that the prevalence of Adv36 differs between countries, it ranges from 65% in Italy to 6% in Belgium and Holland. Obese individuals are more than twice as likely to be seropositive for Adv36. In the United States, for example, 30% of obese and 11% of non-obese carry Adv36 infection.
In January 2020, Jihye Kim and colleagues from Korea published in the Nature Internal Journal of Obesity a review of the existing literature on obesogenic effects of Adv36 from 1982 to 2019, providing up-to-date information on this topic.
What Animal Studies Show
Inject canine distemper virus into mice and they became obese 6 weeks later. Those mice continued to gain weight until the 16th week wherein their weight doubled from the initial weight. This finding was published in Science in 1982, which is the first scientific evidence for “virally-induced obesity.”
Since then, scientists began to test this theory with other viruses. Over the years, Adv36 has become the most consistent microbial agent linked to obesity. Laboratories in many parts of the world can make lean mice, rats, chickens, marmosets, or rhesus monkeys obese by infecting them with Adv36. Importantly, these studies are published in reputed peer-reviewed academic journals.
What Human Studies Show
Ethics would not allow such experiments of causality to be performed on humans. Scientists instead study association and what they found is also remarkable. Atkinson, Dhurandhar, and colleagues recruited 28 pairs of twins, with each pair having one infected with Adv36 and the other uninfected. They discovered that co-twins with Adv36 infection had a higher fat percentage and were heavier than their uninfected counterparts.
“This is the closest you can come to showing the role of the virus in humans, short of infecting them,” Dhyrandhar explains.
On a larger scale, a 2014 meta-analysis combining 11 case-control studies calculated that Adv36 infection (seropositivity) increases the risk of obesity by 60%, with greater risk in children at 95%. A more comprehensive meta-analysis update in the following year also found that Adv36 infection increased the risk of obesity by 77% and 126% in adults and children, respectively. The numbers got worse with just one year of data.
At a 2018 conference in the American Society for Microbiology in Atlanta, Georgia, Wilmore Webley and colleagues — who initially sought to investigate breast cancer — discovered that 81% of overweight women carry Adv36 in their breast tissue, compared to 19% of non-overweight women.
How Adv36 initiate or contribute to obesity
Adv36 rapidly inserts its genetic element into adipose tissues and induces metabolic dysregulation therein. Adv36 increases the expression of 35 genes involved in human adipogenesis — the generation of new fat cells from the existing stem cells. These genes then become cross-regulated and sustain their upregulation, even in the absence of Adv36.
Adipogenesis, hence, ensues despite that our immune system may have eradicated Adv36. Interestingly, Adv36 also enhances angiogenesis (formation of blood vessels), glucose uptake, and mitochondrial function SELECTIVELY in fat cells — promotes “metabolic robustness” in fat cells.
This may explain why hunger remains despite consuming sufficient calories for the day. Adv36 may be allocating those energy resources to the adipose tissues, depriving other tissues or cells of energy. When Adv36 infection is coupled with the easily accessible, hyper-palatable, caloric-dense, high-fat, high-carb foods, obesity might as well be a pandemic that is hardly reversible long-term.
“It’s reasonable that this virus is a contributing factor. Virtually everyone who gets this virus gains weight. It’s a pretty robust phenomenon,” explains Richard Atkinson, one of the pioneers on obesity-Adv36 research.
Atkinson also said that no company is interested in investing in an Adv36 vaccine. “The government and insurance companies do not want to admit that obesity is a disease because then they would have to cover treatment as they do for other diseases.” writes Atkinson.
Would an Adv36 vaccine lower the prevalence of obesity?
Maybe we will know in the future. In mice, however, vaccination against Adv36 prevented weight gain, fat accumulation, and inflammation after being infected with Adv36. “These results provide proof-of-concept for prophylactic vaccination against virus-induced adiposity,” the Korean researchers wrote.
Direct vs. reverse causality
Nonetheless, it could be that obesity renders one more susceptible to Adv36 infection — a reverse causality, critics Dr. Keith Godfrey from the University Hospital Southampton in the UK. I think there’s some truth to this as the minority who have Adv36 infection retain a healthy weight.
But animal studies that showed causality cannot be discounted, and there are established mechanisms of action underlying the obesogenic effects of Adv36. Mitra and Clarke from the University of Southern Mississippi, Hattiesburg, said it well in their 2010 publication in Obesity Reviews:
“Viral infection could probably be considered as another component cause, although not a necessary cause of obesity in humans.”