February 14, 2007

obesity risk from prenatal chemical exposure

Scientists commented to findings from mouse studies, published in Science, suggesting that exposure to certain compounds found in plastics and pesticides whilst in the womb raised the risk of obesity later in life.

Prof Keith Frayn, Professor of Human Metabolism, University of Oxford, said:

“The idea that events early in life can affect risk of various conditions, including obesity and type 2 diabetes, later in life is reasonably well established through observational studies in humans and experimental studies in animals. It does seem to be true that rapid ‘catch-up’ growth soon after birth predisposes to later obesity. However, there are some important caveats.

“First, this is not a very strong effect in humans and can only be unmasked with very careful studies of fairly large numbers.

“Secondly, despite what is claimed by Professor vom Saal, there is no evidence for any ‘magic’ alteration of metabolism: the evidence is that like almost all human obesity, this results mainly from over-consumption of energy rather than ‘slow metabolism’.

“One theory is that the body’s response to the appetite-regulating hormone leptin is reset at this early stage, but this would need more work to prove it. The idea that endocrine-disrupting chemicals can affect birthweight and predispose to rapid catch-up growth does not have support from human studies, and it would be very important to know that the doses of chemicals used in the animal studies bear any resemblance to typical human exposures.

“Interestingly, there is good evidence for adverse interactions between obesity in adults and environmental chemicals: many of these chemicals are fat-soluble and they are stored with the body fat in adipose tissue. It has been clearly shown that when obese people lose weight, these chemicals (e.g. organochlorine compounds) are released into the bloodstream. It has been speculated although not proven that this might have some adverse effects.”

Prof Stephen O’Rahilly, Professor of Clinical Biochemistry and Medicine, University of Cambridge, said:

“These studies seem to show that if you give pregnant mice lots some particular chemicals their offspring are small at birth but become obese later.

“These observations seem interesting and worthy of follow up but their relevance to human obesity is entirely uncertain at this stage. In particular the link between being small at birth and obese later in life is not very relevant to humans. Although they do seem to have a somewhat higher risk of later diabetes, babies who are born small don’t have a particularly high risk of becoming obese later in life.

“The “modern obesity epidemic” has actually occurred during a time when the average birth weight of a baby has been increasing. So, things that tend to make babies small at birth are very unlikely to be driving the increased frequency of obesity in populations.

“While new hypotheses are always exciting, they do sometimes carry the risk, particularly when they receive a lot of media coverage, of acting as distractions rather than aiding the progress of real scientific understanding.”

Professor Richard Sharpe, MRC Human Reproductive Sciences Unit, University of Edinburgh, said:

“As far as we understand it, metabolic syndrome arises because of a combination of factors; it’s rarely the case that there’s only one cause.

“In the same way that there is not one cause for heart disease or obesity, it is inherently unlikely that one environmental chemical or group of chemicals will turn out to be the single cause of a wide range of common disorders.

“So, as a scientist, I have an inherent mistrust with the new evidence suggesting that yet another collection of important disorders (those comprising metabolic syndrome) is the result of exposure to bisphenol A or related chemicals.

“From what we know already, metabolic syndrome disorders in humans are related to several factors: initial growth restriction of the fetus (which could occur for multiple reasons) followed by unusually fast catch up growth in the first 6 or so months after birth. This has all the hallmarks of multiple factors interacting – genetic makeup, lifestyle and dietary choices, and unknown factors.

“Chemical exposures could be one such unknown factor, but I have not yet seen evidence that would convince me. But for certain, if chemicals are involved they will be only one of a number of factors and I would expect with confidence that lifestyle and dietary choices of mothers coupled with their genetic makeup and their own growth in the womb would be far more important factors.

“We know that endogenous hormones (the stress hormones, glucocorticoids) probably play a key role in ‘adaptation’ of the growth restricted fetus to its malnourishment, and how this may then predispose that individual to metabolic syndrome disorders. This process can be modelled in laboratory animal studies using glucocorticoids.

“First and foremost with the new research, it must prove to be repeatable if we are to take it seriously. Much of the previous work from Dr Vom Saal has not been repeatable.”