Obesogens: An Environmental Link to Obesity
Obesogens: An Environmental Link to Obesity
Obesity is strongly linked with exposure to risk factors during fetal and infant development. "There are between fifteen and twenty chemicals that have been shown to cause weight gain, mostly from developmental exposure," says Jerry Heindel, who leads the extramural research program in obesity at the National Institute of Environmental Health Sciences (NIEHS). However, some obesogens have been hypothesized to affect adults, with epidemiologic studies linking levels of chemicals in human blood with obesity and studies showing that certain pharmaceuticals activate PPARγ receptors.
Chemical pesticides in food and water, particularly atrazine and DDE (dichlorodiphenyldichloroethylene—a DDT breakdown product), have been linked to increased BMI in children and insulin resistance in rodents. Certain pharmaceuticals, such as the diabetes drug Avandia® (rosiglitazone), have been linked to weight gain in humans and animals, as have a handful of dietary obesogens, including the soy phytoestrogen genistein and monosodium glutamate.
Most known or suspected obesogens are endocrine disruptors. Many are widespread, and exposures are suspected or confirmed to be quite common. In one 2010 study, Kurunthachalam Kannan, a professor of environmental sciences at the University at Albany, State University of New York, documented organotins in a designer handbag, wallpaper, vinyl blinds, tile, and vacuum cleaner dust collected from 24 houses. Phthalates, plasticizers that also have been related to obesity in humans, occur in many PVC items as well as in scented items such as air fresheners, laundry products, and personal care products.
One of the earliest links between human fetal development and obesity arose from studies of exposure to cigarette smoke in utero. Although secondhand-smoke exposure has decreased by more than half over the past 20 years, an estimated 40% of nonsmoking Americans still have nicotine by-products in their blood, suggesting exposure remains widespread. Babies born to smoking mothers are frequently underweight, but these same infants tend to make up for it by putting on more weight during infancy and childhood. "If a baby is born relatively small for its gestational age, it tries to 'play catch-up' as it develops and grows," explains Retha Newbold, a developmental biologist now retired from the NTP.
This pattern of catch-up growth is often observed with developmental exposure to chemicals now thought to be obesogens, including diethylstilbestrol (DES), which Newbold spent the last 30 years studying, using mice as an experimental model. Doctors prescribed DES, a synthetic estrogen, to millions of pregnant women from the late 1930s through the 1970s to prevent miscarriage. The drug caused adverse effects in these women's children, who often experienced reproductive tract abnormalities; "DES daughters" also had a higher risk of reproductive problems, vaginal cancer in adolescence, and breast cancer in adulthood. Newbold discovered that low doses of DES administered to mice pre- or neonatally also were associated with weight gain, altered expression of obesity-related genes, and modified hormone levels.
"What we're seeing is there's not a difference in the number of fat cells, but the cell itself is larger after exposure to DES," Newbold says. "There was also a difference in how [fat cells] were distributed—where they went, how they lined up, and their orientation with each other. The mechanism for fat distribution and making fat cells are set up during fetal and neonatal life."
A Growing List of Potential Obesogens
Obesity is strongly linked with exposure to risk factors during fetal and infant development. "There are between fifteen and twenty chemicals that have been shown to cause weight gain, mostly from developmental exposure," says Jerry Heindel, who leads the extramural research program in obesity at the National Institute of Environmental Health Sciences (NIEHS). However, some obesogens have been hypothesized to affect adults, with epidemiologic studies linking levels of chemicals in human blood with obesity and studies showing that certain pharmaceuticals activate PPARγ receptors.
Chemical pesticides in food and water, particularly atrazine and DDE (dichlorodiphenyldichloroethylene—a DDT breakdown product), have been linked to increased BMI in children and insulin resistance in rodents. Certain pharmaceuticals, such as the diabetes drug Avandia® (rosiglitazone), have been linked to weight gain in humans and animals, as have a handful of dietary obesogens, including the soy phytoestrogen genistein and monosodium glutamate.
Most known or suspected obesogens are endocrine disruptors. Many are widespread, and exposures are suspected or confirmed to be quite common. In one 2010 study, Kurunthachalam Kannan, a professor of environmental sciences at the University at Albany, State University of New York, documented organotins in a designer handbag, wallpaper, vinyl blinds, tile, and vacuum cleaner dust collected from 24 houses. Phthalates, plasticizers that also have been related to obesity in humans, occur in many PVC items as well as in scented items such as air fresheners, laundry products, and personal care products.
One of the earliest links between human fetal development and obesity arose from studies of exposure to cigarette smoke in utero. Although secondhand-smoke exposure has decreased by more than half over the past 20 years, an estimated 40% of nonsmoking Americans still have nicotine by-products in their blood, suggesting exposure remains widespread. Babies born to smoking mothers are frequently underweight, but these same infants tend to make up for it by putting on more weight during infancy and childhood. "If a baby is born relatively small for its gestational age, it tries to 'play catch-up' as it develops and grows," explains Retha Newbold, a developmental biologist now retired from the NTP.
This pattern of catch-up growth is often observed with developmental exposure to chemicals now thought to be obesogens, including diethylstilbestrol (DES), which Newbold spent the last 30 years studying, using mice as an experimental model. Doctors prescribed DES, a synthetic estrogen, to millions of pregnant women from the late 1930s through the 1970s to prevent miscarriage. The drug caused adverse effects in these women's children, who often experienced reproductive tract abnormalities; "DES daughters" also had a higher risk of reproductive problems, vaginal cancer in adolescence, and breast cancer in adulthood. Newbold discovered that low doses of DES administered to mice pre- or neonatally also were associated with weight gain, altered expression of obesity-related genes, and modified hormone levels.
"What we're seeing is there's not a difference in the number of fat cells, but the cell itself is larger after exposure to DES," Newbold says. "There was also a difference in how [fat cells] were distributed—where they went, how they lined up, and their orientation with each other. The mechanism for fat distribution and making fat cells are set up during fetal and neonatal life."