Keris KrennHrubec, Diana Zuckerman, PhD, and Sarah Miller, RN
Today’s obesity epidemic is also an epidemic of the health problems resulting from excess weight, such as diabetes, heart disease, some types of cancer, and early onset of puberty. The best way to combat obesity is to exercise more and eat less. However, it is not clear that eating more and exercising less are the only reasons for the current increase in obesity in the U.S. and many other countries. Our current obesity epidemic coincides with an increase in industrial chemicals being released into the environment over the past 40 years.
Humans are exposed to so many different chemicals that it is difficult to figure out which are the ones causing harm. This is why studies with animals are important. While researchers can’t experiment on humans, they can experiment on mice by deliberately exposing a group of mice to one particular chemical (at different doses for different periods of time) and comparing that group to a group of mice who have not been exposed. For instance, we know now that exposure to specific chemicals while in the womb can affect the size and weight of mice after they are born.1 This suggests that the chemicals we are exposed to before we are born could potentially increase our likelihood of becoming obese later in life.
Hormones, Environmental Chemicals and Obesity
For any kind of developmental change to happen in the body, cells need signals from hormones telling them what to do. Hormones are involved in almost every process in the human body, including how much fat the body stores, and where in the body it is stored. Usually, hormones help to control how many of our calories to burn right away and how many to store as fat for the body’s energy needs.
Many of the chemicals from industry that are released into the environment resemble hormones. These chemicals can provoke the same response in the body that a natural hormone would.
In addition, some chemicals that we are exposed to through our food, water, and the products that we use can interfere with our natural hormones, including our sex hormones. The chemicals that do this are called “endocrine disruptors” because they change the way our hormones (our endocrine system) operate. Chemicals can cause the body to “think” that it has to store more fat than it actually does, or they can interfere with the processes our bodies use to make fat cells. Babies developing in the womb are especially vulnerable to these kinds of chemicals. There is evidence that babies who are exposed to endocrine disrupting chemicals in the womb may be at higher risk for obesity and other problems as adults.1
DES: A Miscarriage Treatment Gone Wrong
Diethylstilbestrol, or DES, is a synthetic version of the hormone estrogen that was given to pregnant women in the 1940s through the 1970s to prevent miscarriages. It was later learned that DES did not prevent miscarriages but instead harmed the babies, increasing the risk of cancers when those babies were young adults, and even increasing the risks of cancer in the next generation.
If pregnant mice are treated with DES, we see similar cancers in their offspring to those we saw in humans.2 Mice that are exposed to DES in the womb also have higher levels of body fat, even when they eat the exact same diets and do the exact same activities as mice who are not exposed. They are also hungry for more food than they actually need.2
Today, DES is no longer used as a medication because of its deadly risks. Based on what we know about DES, however, scientists are studying the long-term effects of other hormone-disrupting chemicals, because those chemicals may act similarly to DES and “trick” pregnant women’s bodies into reacting as if the chemicals were estrogen. Some chemicals can also bind to receptors and block hormones from getting to the receptors. These chemicals can cause changes in the development of babies, many of which are not obvious until after the babies grow up.
Chemicals that influence our hormones and can lead to obesity are called “obesogens.” These chemicals are not just causing us to gain weight. They are actually modifying our genes and changing which ones get used and which ones don’t. They may turn off genes that we need to keep us trim, or turn on genes that will make us store more fat but still feel hungry. We still don’t know the full extent to which they affect us, but one thing seems likely: obesity may no longer just be influenced by food and exercise.
Bisphenol A (BPA)
Bisphenol A (BPA) was also developed as a synthetic estrogen, although it stopped being used for that purpose when DES was developed, because DES was more similar to estrogen. BPA is now used in many hard plastics, including some food and beverage containers, and until recently was used in plastic baby bottles and sports water bottles. It is still used in the lining of all canned food and beverages. BPA has been linked to heart disease and diabetes in adults, possibly because it increases the risk of obesity.3
Studies of mice exposed to BPA in the womb found that these mice tended to put on more body fat after birth.4,5 However, as adults, the BPA-exposed mice were the same size and weight as mice who were not exposed to BPA in the womb. This finding does not mean that the BPA had no effect on the mice’s development as adults, but no one is quite sure yet what that effect is. For more information on BPA, read “Are Bisphenol A (BPA) Plastic Products Safe?”
Phthalates are another category of hormone-disrupting chemicals. They are used to soften plastic (for soft plastic books and toys) as well as to provide fragrances for many household and personal care products, such as lotions. Although a law passed in 2008 that prevents the riskiest phthalates from being used in baby and toddler toys and plastic products, babies, children, pregnant women, and other adults are still exposed to phthalates every day, in products such as nail polish, creams, shampoo, and air fresheners.
Unlike BPA, phthalates do not act like estrogen, but rather block androgens (male hormones). What BPA and phthalates have in common is that they appear to contribute to a similar imbalance of sex hormones. There is research evidence, for instance, that they could potentially cause abnormal genital development, especially in baby boys, and that exposure may increase the risk of testicular cancer.6
Based on what we know about the effects of phthalates on our cells, it is also possible that exposure to phthalates could increase a person’s risk of becoming overweight or obese.2 A study of 1,443 men in the U.S. found that those who had higher levels of some types of phthalates in their urine samples at the time of the study also had larger waist measurements and were more resistant to insulin, which put them at higher risk for diabetes.7
One study has also linked phthalate exposure to girls developing breasts at an early age.8 It is not clear, though, whether this is because the girls are more likely to be overweight or whether the breast development is more likely regardless of the girls’ weight.8,9
Studies with mice have been more difficult to interpret, in part because mice do not respond to phthalates the same way humans do. For instance, in one study, one group of mice was engineered to have the human type of a gene that is activated by phthalates and the other group was not interfered with genetically. This study found that for the group that kept the mouse version of the gene, the phthalate DEHP was surprisingly protective against obesity, while in the group of mice with the human gene, DEHP was not protective against obesity.10 This research may help explain why some mice studies found no connection between phthalate exposure and adult obesity.11
In July 2013, Denmark urged the European Union to phase phthalates out of medical devices as part of the EU’s new medical devices regulations.12 For more information on phthalates, read “Phthalates and Children’s Products.”
Tributyltin (TBT) is a chemical used to kill fungi (for example, mold). This fungicide disrupts hormones by blocking estrogen from being made in the body.13 This causes higher than normal levels of testosterone. Testosterone is a male hormone and therefore a type of androgen; females have testosterone too, but at lower levels than males.
TBT was formerly in paint used for boats to keep mold and barnacles away, but this use is now prohibited because it was found to be causing abnormalities in fish (including fish that people eat) and even causing some species of female fish to become male.13 It is still in use, however as a fungicide in fruit, vegetable, and grain crops; as a component of PVC pipes (where it can get into our drinking water); and in various other consumer products, including disposable diapers.
A study found that undifferentiated cells from humans and mice that were exposed to TBT were more likely to become fat cells, even though those undifferentiated cells had the potential to become either bone, cartilage, or fat cells.13
Another study, in which one group of adult mice was not fed TBT and three other groups were fed three different amounts of TBT,14 found that the mice who were fed the second-highest amount of TBT had higher levels of body fat even though they ate the same amount and had the same activity levels as the other mice. The mice with the second-highest dose of TBT also had higher levels of insulin in their blood but similar blood sugar levels to the other mice, meaning that they were more resistant to the effects of insulin. All of the mice who ate TBT had higher levels of leptin in their blood than the mice who did not eat TBT, but ate the same amount of food. Leptin is a hormone that is secreted by fat cells, and which turns off the “hunger signal” to our brains, letting us know when we have eaten enough. This could mean either that they were more resistant to the effects of leptin or that they simply had more fat cells, which were releasing more leptin. All the mice that ate TBT had fattier livers than the mice that did not eat TBT.14
The researchers speculate that the reason only the mice who ate the second-highest amount of TBT and not the highest amount had the most significant effects was that the high dose of TBT was toxic to the liver, which interfered with the body’s ability to convert calories into body fat.14 Other researchers have found similar results.15
Many other chemicals also disrupt hormones, including those found in pesticides and in air near manufacturing facilities and trash incinerators. A study of people who were tested for various chemicals by the Centers for Disease Control and Prevention (CDC) found that people who tested positive for endocrine-disrupting chemicals from pesticides and air pollution were more likely to be overweight.16
How Does This Happen?
At very high doses, many of these chemicals cause a person’s body to burn fat rather than storing it.2,17 So, why have several studies shown that people are more likely to be overweight it they were exposed to these chemicals while they were infants or whose mothers were exposed while pregnant?
One theory is that this increased tendency to burn fat may cause a baby’s body to think that it is malnourished and cause the baby to develop a “slow” metabolism for life, which tends to store more fat to prevent starvation.2 This is similar to the paradoxical effect of extreme dieting, which can result in a body conserving calories to prevent starvation, and thereby storing extra fat.
It is possible that people whose metabolisms develop in this way may be less sensitive to certain hormones. One of these hormones is leptin, which as noted earlier, is secreted by fat cells and lets us know when we have eaten enough. People who are less sensitive to leptin are more likely to continue to feel hungry even after they have consumed enough food.
People whose metabolisms have developed in this way may also be less sensitive to insulin, which is a hormone secreted by the pancreas. Insulin brings sugar from our bloodstream into our cells so that we can use it for energy. People who are less sensitive to insulin may develop chronically high blood sugar levels. When these levels become very high, this is what is known as type 2 diabetes.
Research on human cells shows that some hormone-disrupting chemicals can activate hormone receptors in the parts of our cells that house DNA.18 This could be especially harmful to developing babies because some of their cells are “undifferentiated,” meaning they have the potential to become different types of cells. Hormones can turn genes in a cell’s DNA on or off to determine what type of cell it will become. The research suggests that hormone disrupting chemicals may interfere with this process and cause more cells to develop into adipocytes or “fat cells.”18
Is this why I can’t lose weight?
If you are like many people who struggle with weight loss, you may eat the number of calories you are told that you need, but still feel hungry, or eat the same number of calories as thinner people but still gain weight when others stay thin. When you exercise, you may not see results as quickly as expected.
After reading this article, you may wonder whether exposure to hormone-disrupting chemicals is contributing to the difficulties so many people have with weight loss.
There are no human studies that can conclude whether exposure to chemicals in infancy or later in life contributes to these weight control problems. It would be unethical to intentionally expose anyone to these chemicals, and it is difficult to measure all the many factors that might affect weight. However, as shown in this article, there is growing evidence to suggest that reducing exposures to endocrine-disrupting chemicals could help to prevent obesity as well as other health problems.
- Grun, F; & Blumberg, B; Endocrine disruptors as obesogens; Molecular & Cellular Endocrinology,2009, 304(1-2) pp. 19-29. ▲
- Newbold, RR; Padilla-Banks, E; & Jefferson, WN; Environmental estrogens and obesity; Mollecular and Cellular Endocrinology, 2009, 304 (1-2) pp. 84-89. ▲
- Lang, IA; Galloway, TS; Scarlett, A; Henley, WE; Depledge, M; Wallace, RB; & Melzer, D; Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults; JAMA; 2008, 300(11), pp. 1303-9. ▲
- Somm E, Schwitzgebel VM, Toulotte A, Cederroth CR, Combescure C, Nef S, Aubert ML, Hüppi PS. Perinatal exposure to bisphenol a alters early adipogenesis in the rat. Environ Health Perspect. 2009 Oct;117(10):1549-55. ▲
- Ryan KK, Haller AM, Sorrell JE, Woods SC, Jandacek RJ, Seeley RJ; Perinatal exposure to bisphenol-a and the development of metabolic syndrome in CD-1 mice. Endocrinology. 2010, 151(6):2603-12. ▲
- Main, KM; Skakkebaek, NE; Virtanen, HE; & Toppari, J; Genital abnormalities in boys and the environment; Best Practice and Research in Clinical Endocrinology and Metabolism; 2010 24(2), pp. 279-89. ▲
- Stahlhut, RW; Van Wijngaarten, E; Dye, TD; Cook, S; & Swan, SS; Concentrations of urinary phthalate metabolites are associated with increased waist circumference and insulin resistance in adult U.S. males; Environmental Health Perspectives; 2007, 115(6), pp. 876-81. ▲
- Colo´n I, Caro D, Bourdony CJ, Rosario O 2000 Identification of phthalate esters in the serum of young Puerto Rican girls with premature breast development. Environmental Health Perspectives; 108:895-900. ▲
- Diamanti-Kandarakis, E; Bourguinon, JP; Guidice, LC; Hauser, R; Prins, GS; Soto, AM; Zoeller, RT; & Gore, AC; Endocrine-disrupting chemicals: An endocrine society scientific statement; Endocrine Reviews;2009, 30(4) pp. 293-342. ▲
- Feige JN, Gerber A, Casals-Casas C, Yang Q, Winkler C, Bedu E, Bueno M, Gelman L, Auwerx J,Gonzalez FJ, Desvergne B; The pollutant diethylhexyl phthalate regulates hepatic energy metabolism via species-specific PPARalpha-dependent mechanisms. Environ Health Perspect.2010; 118(2):234-41. ▲
- Casals-Casas C, Feige JN, Desvergne B; Interference of pollutants with PPARs: endocrine disruption meets metabolism Int J Obes (Lond). 2008;32 Suppl 6:S53-61. ▲
- EurActiv.com. Danes Want Chemicals out of Medical Devices. Viewed July 10, 2013. http://www.euractiv.com/health/danes-want-phthalate-chemicals-m-news-529149 ▲
- Kirchner S, Kieu T, Chow C, Casey S, Blumberg B. Prenatal exposure to the environmental obesogen tributyltin predisposes multipotent stem cells to become adipocytes. Mol Endocrinol.2010; 24(3):526-39. Epub 2010 Feb 16. ▲
- Zuo Z, Chen S, Wu T, Zhang J, Su Y, Chen Y, Wang C. Tributyltin causes obesity and hepatic steatosis in male mice. Environ Toxicol. 2009. ▲
- Grun F, Blumberg B. Environmental obesogens: Organotins and endocrine disruption via nuclear receptor signaling. Endocrinology 2006 147:S50-S55. ▲
- Elobeid, MA; Brock, DW; Allison, DB; Padilla, MA; & Ruden, DM; Endocrine disruptors and obesity: An examination of persistent organic pollutants in the NHANES 1999-2002 data; International Journal of Environmental Research and Public Health; 2010; 7, pp. 2988-3005. ▲
- Hanson, MA, & Gluckman, PD; Developmental origins of health and disease: New insights; Basic and Clinical Pharmacology and Toxicology; 2008 102(2), pp. 90-3. ▲
- Sargis, RM; Johnson, DN; Choudhury, RA; & Brady, MJ; Environmental Endocrine Disruptors Promote Adipogenesis in the 3T3-L1 Cell Line through Glucocorticoid Receptor Activation; 2010 Obesity, 18(7) pp. 1283-8. ▲