A balanced diet plus low dose BPA exposure in womb and while nursing causes fatter, sicker rats.

Jul 05, 2011

 Wei, J, Y Lin, Y Li, C Ying, J Chen, L Song, Z Zhou, Z Lv, W Xia, X Chen, and S Xu. 2011. Perinatal exposure to Bisphenol A at reference dose predisposes offspring to metabolic syndrome in adult rats on a high-fat diet. Endocrinology http://dx.doi.org/doi:10.1210/en.2011-0045.



Synopsis by Renee Gardner

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Prenatal exposure to low levels of BPA caused rats to become obese and unhealthy as adults, finds a new study. Pups exposed to a low dose through their mothers while in the womb and nursing – but fed a balanced diet as they grew – were fatter and had a suite of metabolic problems later in life when compared to unexposed rats.

Worse health effects occurred at a younger age in exposed animals fed a high fat diet. The effects were seen at a low dose currently considered safe by the U.S. Environmental Protection Agency but not at a medium or high dose.

Studies find almost everyone in the United States is exposed to BPA since it is used widely in polycarbonate plastics, dental sealants, resins that line food cans and some store receipt paper.


Context

Bisphenol A (BPA) is a component of polycarbonate plastics used for food and drink containers. It is also found in resins that line food and beverage cans, thermal paper used to print many retail receipts and dental sealants.

Humans are exposed to BPA through eating, drinking and absorbing it through the skin. Eating canned foods and handling retail receipts may increase exposure. Because the chemical is so common, exposure is widespread. Researchers detect BPA in over 90 percent of urine samples tested in the United States. BPA can cross the placenta into the womb during pregnancy and can pass from mother to baby after birth through breast milk.

BPA is an endocrine disrupting chemical, or EDC. These chemicals can interfere with the natural signals of the endocrine system, which uses hormones to relay important biological messages throughout the body. Evidence is increasing that BPA exposure may increase risk of obesity and its complications. Previous studies in animals show that BPA exposure early in life increases body fat and weight gain later in in life. Some studies in humans have shown that exposure to BPA and other endocrine disrupting chemicals is associated with increased risk of obesity, cardiovascular disease and metabolic syndrome.

Metabolic syndrome is a set of medical problems associated with obesity, including increased insulin resistance and blood insulin levels (hyperinsulinemia), increased glucose tolerance and blood sugar levels (hyperglycemia), high blood pressure (hypertension), and high levels of triglycerides and LDL (“bad cholesterol”) in the blood. Individuals with metabolic syndrome are more likely to develop Type II diabetes and cardiovascular disease.

Insulin is a hormone that regulates metabolism in the body. Normally, when blood sugar starts to rise after eating a meal, insulin rises as well so that muscle and fat cells will take up the sugar, keeping the balance of blood sugar levels. As people become overweight and obese, their cells often stop responding to the normal levels of insulin, leading to insulin resistance and potentially dangerous elevated blood sugar levels.

The lowest dose of BPA used in this study was the reference dose – a dose estimated by the U.S. Environmental Protection Agency (EPA) to be the dose that humans can be exposed to on a daily basis for their entire lives without experiencing any negative health effects. This dose was estimated from animal studies in which rats were given high doses of BPA, and was last updated by the EPA in 1993. There is controversy as to whether the current reference dose is low enough to protect human health.

What did they do?

Researchers treated groups of pregnant rats, from the beginning of their pregnancy to the time the pups were weaned, with several different doses of BPA. The lowest was the 'reference dose' – a which the dose the EPA considers safe,  – of 50 micrograms of BPA per kilogram of body weight per day (μg/kg/day). Other groups of rats were given a dose 5 or 250 times the reference dose.

The offspring were divided into two groups: one group was fed a balanced diet  and one group was fed a high fat diet to mimic the fat- and calorie-rich diets increasingly eaten throughout the world. No rats were given any BPA after they were weaned.

Researchers monitored the offspring as they grew to adults. They calculated weight gain and measured markers of metabolic syndrome, including levels of glucose (sugar), insulin and cholesterol in the blood.

What did they find?

There was no apparent size difference between the BPA-exposed and non-exposed rat pups at birth. However, as they grew, the rats treated with the reference dose of BPA but fed a normal diet were heavier, had a higher percentage of body fat and were more insulin resistant and glucose intolerant than rats who were not exposed to BPA.

These problems developed even earlier and were more severe in BPA-treated rats that were fed a high-fat diet. These rats also had higher LDL ("bad cholesterol") and lower HDL ("good cholesterol").

With both the regular diet and the high-fat diet, males were more sensitive than females to the effects of BPA. The effects of BPA exposure compounded with age. 

Interestingly, rats exposed to doses 5 and 25 times higher than the lowest dose did not show any adverse effects in terms of weight gain, fat mass or metabolic function.

What does it mean?

Exposure to a low dose of bisphenol A (BPA) while in the womb and while nursing may increase the risk of obesity and a suite of metabolic problems even if eating a balanced diet into adulthood, finds a study with rats. Similar effects were seen earlier in animals exposed to the same low dose but fed a high-fat diet. These health effects were not seen in the growing rats exposed to medium and high doses.

This study is one of a number of recent studies that suggest that BPA may have adverse health effects at or even below the current reference dose. It also adds more detail to studies that point to BPA affecting weight and metabolism.  

Even though this was an animal study and the results can't be directly applied to people, it's a first step in understanding how environmental chemicals like BPA may influence development in ways that last a lifetime. More research is needed to determine if the results apply to people.

The research shows one example of a chemical for which the health effects observed after a small dose are not just a milder version of the health effects observed after a big dose. Rather, the health effects seem to be completely different at the different dose levels.

This study finds that exposure to BPA while in the womb and from the mother’s milk increases weight gain and a host of health problems associated with obesity later in life. The effects of BPA were magnified in rats that were fed a high fat diet after weaning. BPA exposure at the early stages of development may lead to a “metabolic reprogramming” that sets the exposed offspring on an early path toward an increased risk of obesity and its associated health complications.

Additionally, this research suggests that we may need to rethink the method for testing the toxicity of certain chemicals by evaluating the potentially toxic effects of chemicals at doses that reflect realistic human exposures. Health effects were only observed at the lowest dose in this study – a dose that is supposed to reflect a "safe" exposure to BPA.

The rates of obesity and overweight in adults and especially in children are on the rise, though some recent studies indicate that the rates may be at least leveling off among adults. According to the Centers for Disease Control, 34 percent of adults are obese and a further 34 percent are overweight. Twenty percent of children 6-11 years old are also obese, as are 10 percent of children 2-5 years old.

The risk of obesity is clearly influenced by the increasingly high-fat and calorie-dense diets of most of the world’s population. In addressing the obesity epidemic, less attention has been paid to the potential role of other environmental exposures.

Because the time before and after birth is an especially crucial period for development, changes in the early life environment can have potentially profound impacts later in life. This study showed that the time period surrounding birth may be particularly crucial for the effects of BPA exposure on later metabolism. Researchers are now working to understand whether these sorts of early life exposures in humans may be contributing to the obesity epidemic, especially among children.

Resources

Berenson, GS, M Agirbasli, QM Nguyen, W Chen, and SR Srinivasan. 2011. Glycemic status, metabolic syndrome, and cardiovascular risk in children. Medical Clinics of North America 95(2):409-417.

Calafat, AM, X Ye, LY Wong, JA Reidy, and LL Needham. 2008. Exposure of the U.S. population to bisphenol A and 4-tertiary-octylphenol: 2003–2004. Environmental Health Perspectives 116:39-44.

Flegal, KM, MD Carroll, CL Ogden, and LR Curtin. 2010. Prevalence and trends in obesity among US adults, 1999-2008. Journal of the American Medical Association 303(17):1695-1696.

Lang, IA, TS Galloway, A Scarlett, WE Henley, M Depledge, RB Wallace, and D Melzer. 2008. Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults. Journal of the American Medical Association 300(11):1303-1310.

Somm, E, VM Schwitzgebel, A Toulotte, CR Cederroth, C Combescure, S Nef, ML Aubert, and PS Hüppi. 2009. Perinatal exposure to bisphenol A alters early adipogenesis in the rat. Environmental Health Perspectives 117:1549-1555.

 

 

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