Studies dating back to the 1970s have shown that low dose chemical exposures were associated with weight gain in experimental animals (1). Since then, a growing number of studies show links between toxins and weight gain, obesity and diabetes. Known or suspected culprits behind negative epigenetic changes include toxins such as heavy metals, pesticides, plastic compounds including BPA, diesel exhaust, tobacco smoke, polycyclic aromatic hydrocarbons, hormones, radioactivity, viruses, bacteria and endocrine-disrupting chemicals.
The main role of fat cells is to store energy and release it when needed. Scientists now know that fat tissue acts as an endocrine organ, releasing hormones related to appetite and metabolism. Research to date suggests that different obesogenic compounds may have different mechanisms of action, some affecting the number of fat cells, others the size of fat cells, and still others the hormones that affect appetite, satiety, food preferences, and energy metabolism. Another mechanism through which these chemical obesogens can contribute to weight gain is through their impact on the gut microbiome, linking gut ecology and environmental chemicals to obesity and diabetes (2).
Role of BPA
BPA, or bisphenol A, a chemical found in everything from plastic bottles to metal food containers, may be partly to blame for excess weight. BPA has been shown to alter the body's metabolism, increasing weight gain and making it difficult to lose weight. A number of studies have reported elevated levels of BPA in obese and overweight individuals (3). BPA levels have been related to obesity in US studies (4,5) and in the Chinese population (6). In both American and Chinese schoolchildren, urinary BPA levels were associated with BMI (7-11).
In a study of 1,326 children, girls between ages nine and 12 with high BPA levels had double the risk of being obese compared to girls with low BPA levels, validating previous animal and human studies. The chemical can alter the body's metabolism and make it harder to lose weight. Girls with high levels of BPA - two micrograms per litre or more - were two times more likely to be obese than girls with lower levels of BPA in the same age group. Girls with very high levels of BPA, more than 10 micrograms per litre, were five times more likely to be obese, the study shows (12). Urinary BPA in pregnant women was related to BMI in their offspring at four years of age (13). Similar results were found in girls aged nine years (14). The oestrogenic properties of bisphenol A (BPA) have been known since 1936 (15).
BPA has been shown to induce obesity in rodents in experimental settings (16,17). In animal experiments, mothers' exposure to BPA is producing the same outcomes that we see in humans born light at birth: an increase in abdominal fat and glucose intolerance. BPA was seen to affect rodent fat cells at very low doses - 1,000 times below the dose that regulatory agencies presume causes no effect in humans, whereas at higher doses researchers saw no effect. Hormone receptors typically respond to very low levels of hormone, so it makes sense that they may be activated by low levels of an endocrine mimic, whereas high levels of a chemical may actually cause receptors to shut down altogether, preventing any further response (18).
Weight link to POPS
Children exposed to certain chemicals, POPs (Persistent Organic Pollutants), in the womb have a higher risk of being overweight. POPs include a wide variety of long lasting chemicals that collect in fat and accumulate in wildlife and people. Some were made as pesticides, such as DDT, and others as electrical insulators including polychlorinated biphenyls (PCBs). POPs can also act as endocrine disruptors and disrupt hormone function. The developing foetus is exposed to POPs passed from the mother through the placenta.
Several longitudinal birth cohort studies have examined how prenatal exposure to DDT (now banned in most countries) and DDE affects child growth. Positive associations between prenatal DDT and DDE exposure and body mass index and overweight status have been reported in birth cohorts in Europe 19 and in the United States (20,21).
In a study of 344 children, both PCB and DDE exposure led to an increased risk of weight gain in children. The link between being overweight and PCB and DDE levels in cord blood was stronger in girls than boys. DDT was associated with weight gain only in boys, especially in children with average or above average fat intakes. In some cases, children with higher POPs exposure were almost twice as likely to be overweight compared to children with lower exposure, depending on the pollutant and gender (20). In a study of 6,770 subjects aged six to 19 years, a dose-dependent increase in obesity was observed in the groups with highest urinary concentrations of 2,5-dichlorophenol (2,5-DCP) and reported a possible relationship between exposure to 2,5-DCP and obesity in children (22).
Diabetes and Organophosphate Pesticides
A growing body of evidence demonstrates that the use of certain organophosphate pesticides may also be associated with weight gain and diabetes risk (23).
Similar results of POPs have been found in animal experiments. Mice fed high fat diets gained about 30% more weight and experienced raised blood sugar, compared to other mice eating the same high fat diets, when they also ingested doses of a brominated flame retardant, hexabromocyclododecane (HBCD), which is used in building materials and insulation. It accumulates in the tissues of animals and humans, and previous animal studies have shown that it may disrupt hormones, metabolism and immune systems.
Some evidence, mostly with lab animals, suggests that prenatal exposure to these obesogens can reprogram metabolism, leading to more fat cells and raising the risk of obesity later in life. The mice, which on average weighed 21 grams, were fed a high fat diet with a high dose of flame retardant and gained an average of 21 grams. Mice fed the same diet without the chemical gained about 16 grams. That means that mice fed the extra flame retardant doubled their weight and put on around 25% more weight than the control group, and also had higher blood sugar and higher insulin levels than the unexposed mice. Their livers also weighed more and their adipose tissues were inflamed. Changes were also noted in the gene expression of their glucose transporters (24). HBCD is still used in large volumes.
Perfluorooctanoic acid (PFOA) is a ubiquitous chemical, used in nonstick cookware, Gore-Tex™ waterproof clothing, Scotchgard™ stain repellent on carpeting and mattresses; it is a potential endocrine disruptor. When pregnant mice were given PFOA during pregnancy, their offspring became obese in adulthood, reaching significantly higher weight levels than controls. Exposed offspring also had elevated levels of leptin, a hormone secreted by adipose tissue that affects appetite and metabolism.
Pre and postnatal exposure to Firemaster®550 (FM550) has been associated with increased anxiety, obesity, and early-onset puberty in rats. Researchers reported further evidence that components of FM550 may act as environmental obesogens, stimulating adipogenesis (fat formation) at the expense of bone health. House dust in the US contains high levels of organophosphate flame retardants, and their metabolites are ubiquitous in human urine. The authors estimated that young children could ingest 120 μg/day TPP from indoor exposure to dust alone.
Phthalates are plasticisers that also have been related to obesity in humans and occur in many PVC items, as well as in scented items such as air fresheners, laundry products, personal care products and many plastics. Studies suggest that phthalates have significant effects on obesity, especially after prenatal exposure at low doses (BMI) in children and adults (25).
In early studies, tributyltin (TBT), commonly found in home antimould and dust mite treatments, was given to pregnant mice and resulted in heavier offspring; even if the offspring eat normal food, they get slightly fatter. Tributyltin can exert toxicity through multiple mechanisms but most recently has been shown to bind, activate, and mediate gene regulation central to lipid metabolism and adipocyte biology. In support of this, long-term obesogenic effects on whole body adipose tissue are also reported (26). In another animal experiment, exposure to TBT for 45 days resulted in obesity and hepatic steatosis and induced the occurrence of insulin and leptin resistance (27).
Arsenic in drinking water has been found to promote a number of diseases that may stem from dysfunctional adipose lipid and glucose metabolism. Arsenic inhibits adipocyte differentiation and promotes insulin resistance; it also alters gene signaling for aberrant lipid storage and metabolism that may contribute to the pathogenesis of metabolic disease caused by environmental arsenic exposures (28). Similarly, a study of environmental contaminants in 114 seven to nine year old Flemish children found a negative association between cadmium and abdominal and subcutaneous fat (29).
In a study of hypertensive rats, researchers found that short-term exposure to air pollution, over a 10 week period, elevates blood pressure in rats already predisposed to the condition (30). Another animal study from the same group found that early exposure to ultrafine particulates led to the accumulation of abdominal fat and insulin resistance in mice even if they ate a normal diet (30). The study compared mice fed a high fat diet with those fed a normal, healthy diet, and exposed some members of both groups daily to ultrafine particulate matter, controlling for all other factors. In the end, all of the mice exposed to air pollution, including those fed a normal diet, had increased abdominal and subcutaneous fat. These findings suggest that fine particulate pollution exposure alone, in the presence of a normal diet, may lead to an increase in fat cell size and number, and also have a pro inflammatory effect.
Experimental results also suggest a high fat diet may exacerbate the health effects of inhaled PM2.5; this means obese people may be at increased risk. Mice breathing PM2.5 and eating a high-fat diet developed IR, systemic inflammation, and increased abdominal fat, compared with mice eating the same diet but breathing filtered air (31). This mechanism directly ties a known inflammatory mechanism in the pathogenesis of type 2 diabetes to exposure to environmental air pollution; the inflammatory damage likely creates a vicious cycle that can also contribute to cardiovascular disease and obesity. In addition, studies have recently reported that small increases in urban ambient PM2.5 can decrease insulin sensitivity in healthy subjects (32), suggesting that PM2.5 may contribute to metabolic syndrome and to the progression from metabolic syndrome to diabetes.
DISCLAIMER: Dr Peter Dingle is a researcher, educator and public health advocate. He has a PhD in the field of environmental toxicology and is not a medical doctor.
ReferencesHoltcamp,. 2012. Snedeker, and Hay. 2011Geens et al. 2015, Lang et al. 2008 Shankar et al. 2012Wang et al. 2012bTrasande et al. 2012; Wang et al. 2012a; Bhandari et al. 2013; Harley et al. 2013; Li et al. 2013 Journal of the American Medical Association.2012,Valvi et al. 2013Harley et al. 2013Dodds 1936Miyawaki et al. 2007; Somm et al. 2009Tang-Peronard et al. 2011Delvaux et al. 2014Valvi, D.et al, 2011Warner et al. 2014. Twum and Wei. Volume 26, Issue 3, Pages 215–219Starling et al. 2014. Yanagisawa et al. Environ Health Perspect. Kim and Park 2014. Grun 2014. Zhenghong Zuo et al. 2011Garciafigueroa et al. 2013. Delvaux et al. 2014Rajagopalan. Arteriosclerosis, Thrombosis, and Vascular Biology. DecemberEnviron Health Perspect. DOI:10.1289/ehp.122-A29, Brook et al. 2013
Dr Peter Dingle (PhD) has spent the past 30 years as a researcher, educator, author and advocate for a common sense approach to health and wellbeing. He has a PhD in the field of environmental toxicology and is not a medical doctor. He is Australia’s leading motivational health speaker and has 14 books in publication.