Body fat virus link still unproven

A virus “could make children obese by attacking fat cells”, according to the Daily Mail. It said that the virus causes fat cells to multiply, “triggering a massive gain in weight”.

This news story is based on a small study that compared a group of obese children with children of a healthy weight. It looked for evidence of a previous infection by a virus called AD36. The study found that 22% of the obese children and 7% of the non-obese children had antibodies (substances produced by the body to fight disease) against the virus. However, this study did not follow the children over time, so it cannot determine whether the children were exposed to the virus before gaining weight or if they were infected once they were already obese. As such, it cannot determine whether AD36 causes or increases the likelihood of putting on excessive weight in childhood.

Additionally, the study did not take into account lifestyle factors such as exercise or diet, so it is unclear whether these contributed to the children’s weight gain. For now, eating an appropriate diet and taking regular exercise are the most important ways to maintain a healthy weight.

Where did the story come from?

The study was carried out by researchers from the University of California and was funded by the Rest Haven Foundation and the US National Institutes of Health. The study was published in the peer-reviewed medical journal Pediatrics.

The research was covered well by the BBC, which highlighted that a causal link could not be established by this study. While the Daily Mail suggested biological mechanisms that might explain how AD36 affects fat cells, these have only been examined in the laboratory-based cellular studies cited by the researchers. Research has not yet demonstrated whether an infection with AD36 can affect cells in living humans in this way.

What kind of research was this?

This cross-sectional study looked at whether there was an association between childhood obesity and exposure to a virus called adenovirus36 (AD36).

Obesity is considered to arise from an imbalance between energy intake and energy expenditure, with the body storing excess, unburned calories as fat. The likelihood of putting on weight may be influenced by genetic background. The researchers suggest that exposure to viruses may also lead to obesity. Some animal studies have shown that infections with the AD36 virus have led to increased body fat. While these animal models have suggested there may be a link, the researchers wanted to see whether there was an association between evidence of exposure to this virus in children and childhood obesity.

A cross-sectional study measures factors about its subjects at only a single point in time. Therefore, this study cannot determine whether obesity occurred before or after the children were exposed to the virus. It cannot rule out the possibility that any association seen might be because obese children are more prone to infection. The design of this study can only determine whether exposure to AD36 is associated with obesity in children, but not whether this exposure can cause or contribute to obesity.

What did the research involve?

Children between 8 and 18 years of age were recruited throughout San Diego, California. The children’s body mass index (BMI) was calculated. The researchers used national BMI reference values for age and gender to classify children as obese if their BMI was in the top 5% of these BMI ranges. The researchers enrolled 67 obese children and 57 non-obese children. Of these, 124 children (63%) were of Hispanic origin.

The researchers took blood samples from the children and measured the amount of AD36-specific antibodies, a measure of exposure to AD36.

What were the basic results?

The researchers found that 19 of the 124 children had AD36-specific antibodies. The children who tested positive for AD36 antibodies had an average age of 15 years. This was older than the AD36 antibody-negative children, who were 13 years old on average.

Fifteen out of the 67 obese children (22%) had the AD36 antibody, whereas 4 of the 57 non-obese children (7%) were positive for the antibody (P=0.02).

The researchers found that the average BMI of all the obese children was 32.7kg/m2 (± 5.1kg/m2). Obese children who were positive for the specific AD36 antibody had an average BMI of 36.4kg/m2 (± 5.9kg/m2). This was greater than the average BMI of 31.8kg/m2 (± 4.4kg/m2) of the obese children who tested negative (P<0.05).

How did the researchers interpret the results?

The researchers suggested that their study “supported an association between the presence of AD36 antibodies and obesity in children”.  They say that, “the vast majority of children who were AD36-positive were obese and they were also significantly heavier than the children who were AD36-negative.” The researchers propose that the association they found is either due to “true causality, increased susceptibility to infection in obese children or a predisposition to persistent AD36-specific antibodies after infection”.

Conclusion

The researchers suggest that this small cross sectional study demonstrates an association between exposure to AD36 and childhood obesity. Various limitations to this study mean that it should be interpreted cautiously:

• Firstly, no causal link can be established as measurements were taken at one point in time and it is not possible to determine whether the children put on weight before or after being exposed to the virus.
• The study found that only 22% of the obese children were positive for AD36 antibodies and 7% of the non-obese children had this antibody. This indicates that other factors are likely to contribute to obesity and that the association is not particularly strong.
• The study did not take into account lifestyle factors such as diet and exercise, which may have differed between the obese and non-obese children.
• The study included children over a large age range (8-18 years) and found that older children were more likely to have been exposed to the virus (or at least have the AD36-specific antibodies). It is not clear from the research how the likelihood of being obese changes with age in children. The data was not adjusted for age, despite the fact that the participants’ ages ranged from pre-pubescence to near adulthood.

As the researchers acknowledge, further research is needed to determine whether the susceptibility to viruses differs between obese children and non-obese children and also to understand how long the AD36 antibodies persist after infection in both groups. To assess whether AD36 has any influence on the likelihood of becoming obese, a larger population of non-obese children would have to be followed over time to assess whether exposure to the virus affected their subsequent likelihood of putting on weight.

If future longitudinal studies are designed to investigate this association, they should adjust for the factors already known to influence obesity.