Viral Infections May Be Linked To Obesity

ScienceDaily (Oct. 24, 2007) - Experts don't dispute the important
role that diet and activity play in maintaining a healthy weight. But
can poor eating habits and a less active lifestyle fully explain the
prevalence of obesity in the United States today? That question has
led some researchers to ask whether there might be other causes for
this serious problem.

 Researcher Richard Atkinson, M.D., asserts that there is a growing
body of evidence demonstrating that viruses may play a role in causing
obesity in humans.

"The cause of obesity is not a secret -- if you consume more calories
than you burn in daily activity, you gain weight. What is interesting
is that much of the obesity epidemic cannot be explained just by
Americans eating more and exercising less. There are other factors at
play, and viruses causing obesity may be one of them," say Dr.
Atkinson.

Dr. Atkinson, director of Obetech Obesity Research Center in Richmond,
Va., reviewed multiple published articles that demonstrate a
connection between viral infections and obesity. His article in Mayo
Clinic Proceedings* discusses five animal viruses and three human
viruses that have been shown to cause obesity in laboratory studies.

According to Dr. Atkinson, several studies offer ample evidence that
animals infected with certain human viruses experience excess weight
gain and fat storage. When researchers infected animal subjects with a
human virus known as Human Ad-36, they reported measurable increases
in the infected animals' body fat and the visceral fat that surrounds
the organs deep within the belly. In addition, studies also
demonstrated that infection with Ad-36 and the resulting weight gain
could be transmitted from infected animals to uninfected animals.

Information on virus-induced obesity in human subjects is much more
limited. Citing his own study conducted in 2005, Dr. Atkinson also
showed a connection between obesity and exposure to the Ad-36 virus in
humans. Dr. Atkinson's study screened for antibodies to Ad-36 (a sign
of exposure to this virus) in 502 people of varying body weights, both
obese and non-obese, from three cities in the United States. Ad-36
antibodies were found in 30 percent of obese individuals and 11
percent of lean individuals. Study results also showed highly
significant differences in body mass index (BMI) between antibody-
positive and antibody-negative individuals.

Dr. Atkinson also highlighted a study that looked at 89 sets of
American adult twins and screened them for Ad-36. Because twins tend
to be similar in many characteristics, including body weight, the
researchers looked at twin pairs where one twin tested positively for
Ad-36 and the other did not.

"Antibody-positive twins were slightly, but significantly, heavier and
fatter than their antibody negative co-twins," says Dr. Atkinson. "The
infected twins had a higher BMI and a greater percent of body fat than
the uninfected co-twins."

In the mid-1970s, a virus called SMAM-1 was believed responsible for
an increased death rate among commercially raised chickens in India.
SMAM-1 is associated with decreased immune function and an increased
accumulation of body fat in infected chickens. Dr. Atkinson reports
that one study tested 52 obese humans for antibodies to SMAM-1. About
20 percent had SMAM-1 antibodies, indicating exposure to this virus.
The study participants who had these antibodies were heavier and had a
higher body mass index compared with the antibody-negative group.

Dr. Atkinson's article also explores what current research has to say
about the possible mechanisms underlying virus-induced obesity. Some
research suggests that viral infections have a direct effect on
adipocytes, cells that manufacture and store fat, turning on the
enzymes of fat accumulation and recruitment of new adipocytes.

What's the next step for this research? According to Dr. Atkinson,
"the body of evidence linking adenoviruses to obesity in humans is now
sufficient to think about the next step. Ideally, we could prevent
infection and virus-induced obesity with a vaccine for the obesity
viruses. Development of a human vaccine will take several years."

*This work is published in the October issue of Mayo Clinic
Proceedings.

Adapted from materials provided by Mayo Clinic.

Mayo Clin Proc. 2007;82:1192-1198 © 2007 Mayo Foundation for Medical
Education and Research

REVIEW
Viruses as an Etiology of Obesity
RICHARD L. ATKINSON, MD

Individual reprints of this article are not available. Address
correspondence to Richard L. Atkinson, MD, Director, Obetech Obesity
Research Center, 800 E Leigh St, Suite 50, Richmond, VA 23219
(ratkinson2@vcu.edu).

Obesity is a serious chronic disease that has numerous etiologies. The
prevalence of obesity has increased dramatically since about 1980 in
the United States and worldwide in both developed and developing
countries. This rapid spread is compatible with an infectious origin.
This review discusses the 5 animal viruses and 3 human viruses that
have been shown to cause obesity and examines the evidence to date for
virus-induced obesity. The obesogenic animal viruses include canine
distemper virus, Rous-associated virus type 7, Borna disease virus,
scrapie agent, and SMAM-1. The first 4 viruses attack the central
nervous system to produce obesity. SMAM-1, an avian adenovirus from
India, acts directly on adipocytes and is the only animal virus that
is associated with human obesity. The 3 human adenoviruses, adenovirus
(Ad) 36, Ad-37, and Ad-5, that are associated with obesity also affect
adipocytes directly. These viruses stimulate enzymes and transcription
factors that cause accumulation of triglycerides and differentiation
of preadipocytes into mature adipocytes. Ad-5 and Ad-37 have been
shown to cause obesity in animals. Ad-36 has been studied the most and
is the only human adenovirus to date that has been linked with human
obesity. Ad-36 causes obesity in chickens, mice, rats, and monkeys and
was present in 30% of obese humans and 11% of nonobese humans. In
twins discordant for infection with Ad-36, the infected twins were
heavier and fatter than their cotwins. The growing body of evidence
demonstrating that viruses produce human obesity supports the concept
that at least some of the worldwide epidemic of obesity in the past 25
years is due to viral infections.

Mayo Clin Proc. 2007;82(10):1192-1198