Flame retardants found to cause metabolic, liver problems
Chemicals used as synthetic flame retardants that are found in common household items such as couches, carpet padding, and electronics have been found to cause metabolic and liver problems that can lead to insulin resistance, which is a major cause of obesity, according to new research from the University of New Hampshire.
“Being obese or overweight increases one’s risk of many diseases including Type 2 diabetes, high blood pressure, coronary heart disease, stroke, gall bladder disease, osteoarthritis, sleep apnea and certain cancers,” said Gale Carey, professor of nutrition and the lead researcher.
Carey and her team of researchers found that laboratory rats exposed to polybrominated diphenyl ethers, or PBDEs, experienced a disruption in their metabolism that resulted in the development of metabolic obesity and enlarged livers.
“Despite the plethora of resources devoted to understanding the roles of diet and exercise in the obesity epidemic, this epidemic continues to escalate, suggesting that other environmental factors may be involved.
At the biochemical level there is a growing body of experimental evidence suggesting certain environmental chemicals, or ‘obesogens’, could disrupt the body’s metabolism and contribute to the obesity epidemic,” she said.
In Carey’s research, fat cells isolated from rats dosed with high levels of flame retardants daily for one month developed a sensitivity to hormones that was similar to the sensitivity experienced by people who are overweight: the fat cells became more sensitive to epinephrine and less sensitive to insulin.
Complications of obesity include the following:
Metabolic syndrome
Diabetes mellitus
Cardiovascular disorders
Liver disorders (nonalcoholic steatohepatitis [fatty liver] and cirrhosis)
Gallbladder disease
Gastroesophageal reflux
Obstructive sleep apnea
Reproductive system disorders, including infertility
Many cancers
Osteoarthritis
Social and psychologic problems
Insulin resistance, dyslipidemias, and hypertension (metabolic syndrome) can develop, often leading to diabetes mellitus and coronary artery disease. These complications are more likely in patients with fat that is concentrated abdominally, a high serum triglyceride level, a family history of type 2 diabetes mellitus or premature cardiovascular disease, or a combination of these risk factors.
Obesity is also a risk factor for nonalcoholic steatohepatitis (which may lead to cirrhosis) and for reproductive system disorders, such as a low serum testosterone level in men and polycystic ovary syndrome in women.
Obstructive sleep apnea can result if excess fat in the neck compresses the airway during sleep. Breathing stops for moments, as often as hundreds of times a night. This disorder, often undiagnosed, can cause loud snoring and excessive daytime sleepiness and increases the risk of hypertension, cardiac arrhythmias, and metabolic syndrome.
Obesity may cause the obesity-hypoventilation syndrome (Pickwickian syndrome). Impaired breathing leads to hypercapnia, reduced sensitivity to CO2 in stimulating respiration, hypoxia, cor pulmonale, and risk of premature death. This syndrome may occur alone or secondary to obstructive sleep apnea.
Osteoarthritis and tendon and fascial disorders may result from obesity. Skin disorders are common; increased sweat and skin secretions, trapped in thick folds of skin, are conducive to fungal and bacterial growth, making intertriginous infections especially common. Being overweight probably predisposes to cholelithiasis, gout, Deep venous thrombosis and Pulmonary embolism, and some cancers (especially colon and breast cancers).
Obesity leads to social, economic, and psychologic problems as a result of prejudice, discrimination, poor body image, and low self-esteem. For example, people may be underemployed or unemployed.
“One of the hallmarks of somebody who is becoming diabetic - and often this accompanies weight gain - is that their fat cells become sluggish in their response to insulin. With epinephrine, the fat cells more easily release the fatty acids into the blood stream and if those fatty acids are not used, they promote insulin resistance,” Carey said.
“Those two features - insulin resistance and epinephrine sensitivity - are two features of fat cells from people who are above normal weight. And that’s what we were seeing in our rats. Even though our rats had not gained weight, they were experiencing ‘metabolic obesity’,” she said.
The cause of the flame retardant-induced insulin resistance is unknown but one possibility is the suppression of a key metabolic enzyme - phosphoenolpyruvate carboxykinase, or PEPCK - in the liver. Carey and her students found that the activity of PEPCK, which is responsible for sugar and fat metabolism, dropped by nearly 50 percent in livers of rats exposed to flame retardants for just one month, compared to controls.
Metabolic obesity: the paradox between visceral and subcutaneous fat.
In contrast to the accumulation of fat in the gluteo-femoral region, the accumulation of fat around abdominal viscera and inside intraabdominal solid organs is strongly associated with obesity-related complications like Type 2 diabetes and coronary artery disease. The association between visceral adiposity and accelerated atherosclerosis was shown to be independent of age, overall obesity or the amount of subcutaneous fat.
Recent evidence revealed several biological and genetic differences between intraabdominal visceral-fat and peripheral subcutaneous-fat. Such differences are also reflected in their contrasting roles in the pathogenesis of obesity-related cardiometabolic problems, in either lean or obese individuals. The functional differences between visceral and the subcutaneous adipocytes may be related to their anatomical location. Visceral adipose tissue and its adipose-tissue resident macrophages produce more proinflamatory cytokines like tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) and less adiponectin. These cytokines changes induce insulin resistance and play a major role in the pathogenesis of endothelial dysfunction and subsequent atherosclerosis. The rate of visceral fat accumulation is also different according to the individual’s gender and ethnic background; being more prominent in white men, African American women and Asian Indian and Japanese men and women. Such differences may explain the variation in the cardiometabolic risk at different waist measurements between different populations. However, it is unclear how much visceral fat reduction is needed to induce favorable metabolic changes.
On the other hand, peripheral fat mass is negatively correlated with atherogenic metabolic risk factors and its selective reduction by liposuction does improve cardiovascular risk profile. The increasing knowledge about body fat distribution and its modifiers may lead to the development of more effective treatment strategies for people with/or at high risk for Type 2 diabetes and coronary artery disease. These accumulating observations also urge our need for a new definition of obesity based on the anatomical location of fat rather than on its volume, especially when cardiometabolic risk is considered. The term “Metabolic Obesity”, in reference to visceral fat accumulation in either lean or obese individuals may identify those at risk for cardiovascular disease better than the currently used definitions of obesity.
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Hamdy O, Porramatikul S, Al-Ozairi E.
PMID: 18220642
“Because PEPCK regulates production of the backbone of the fat molecule, if the backbone isn’t made, the fatty acids that usually attach to this backbone have nothing to attach to. Their levels can rise in the liver and the blood. And it is elevated fatty acids that can lead to insulin resistance,” Carey explained. Indeed, the lab’s most recent findings demonstrated that the ability to create the backbone for the fat molecule was suppressed by 42 percent in liver tissue from rats treated with flame retardants compared to controls. In addition, rats exposed to flame retardants were found to have livers that were significantly larger than livers of rats that had not been exposed.
For more than 10 years, Carey and more than a dozen graduate and undergraduate students have collaborated with researchers from several universities and industries across the nation to examine the persistent organic environmental chemicals that could impact human health. “The average person probably has about 300 chemicals in her body that are manmade,” she said.
In a previous study, Carey and a graduate student examined the amount of flame retardant chemicals in breast milk. They found that the levels of these chemicals in breast milk are about two orders of magnitude greater than in European countries that do not allow the use of flame retardant chemicals.
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These results will be presented at the Experimental Biology annual meeting in Boston March 28-April 1, 2015. The research is funded by the NH Agricultural Experiment Station at the UNH College of Life Sciences and Agriculture.
Founded in 1887, the NH Agricultural Experiment Station at the UNH College of Life Sciences and Agriculture is UNH’s original research center and an elemental component of New Hampshire’s land-grant university heritage and mission. We steward federal and state funding to provide unbiased and objective research concerning diverse aspects of sustainable agriculture and foods, aquaculture, forest management, and related wildlife, natural resources and rural community topics. We maintain the Woodman and Kingman agronomy and horticultural farms, the Macfarlane Greenhouses, the Fairchild Dairy Teaching and Research Center, and the Organic Dairy Research Farm. Additional properties also provide forage, forests and woodlands in direct support to research, teaching, and outreach.
The University of New Hampshire, founded in 1866, is a world-class public research university with the feel of a New England liberal arts college. A land, sea, and space-grant university, UNH is the state’s flagship public institution, enrolling 12,300 undergraduate and 2,200 graduate students.
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Lori Wright
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603-862-1452
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University of New Hampshire
Funder
New Hampshire Agricultural Experiment Station