POPs lead to insulin resistance in rats.

Jan 14, 2010

Ruzzin J, R Petersen, E Meugnier, L Madsen, EJ Lock, H Lillefosse, T Ma, S Pesenti, SB Sonne, TT Marstrand, MK Malde, ZY Du, C Chavey, L Fajas, AK Lundebye, CL Brand, H Vidal, K Kristiansen and L Froyland. 2009. Persistent organic pollutant exposure leads to insulin resistance syndrome. Environmental Health Perspectives doi:10.1289/ehp.0901321.

A new study in rats shows that persistent organic pollutants (POPs) – at levels found in food – cause insulin resistance and associated obesity and liver disease in the animals. The study is the first to show this experimentally. Insulin resistance can lead to type 2 diabetes, which is becoming a global epidemic. The association between high levels of POPs in people and increased chance of developing diabetes has been known since 2006. Until now, scientists could not positively conclude that POPs influenced the onset of diabetes.



Persistent organic pollutants (POPs) are a diverse group of toxic chemicals that resist degradation and can remain in the environment for decades. The compounds are known to adversely affect health in people and wildlife.

POPs include organochlorine pesticides, polychlorinated biphenyls (PCBs), dioxins and furans. Many of the synthetic chemicals were created for use in agriculture and construction. Others were used in, or are byproducts of, industry. Some – such as dioxins – also occur naturally as a result of burning and combustion.

The US and Europe banned the production and use of certain POPs more than 30 years ago. This ban was expanded globally during this century. Yet, due to their chemical nature, they can remain intact, persist in the environment and accumulate in wildlife and people. They build up in farmland soils and waterways, contaminating wildlife and making their way up the food chain. People are exposed through eating contaminated fish, poultry, meat and dairy products.

The hormone insulin helps in the uptake and storage of the sugar glucose – a basic regulator of metabolism. Insulin resistence occurs when cells do not respond to the hormone. This allows glucose levels to build up in the blood and leads to more serious health problems. Additionally, insulin and the uptake of glucose regulate the formation of fat.

In the U.S., one out of four adults have metabolic abnormalities that are associated with insulin resistance. Typical symptoms of insulin resistance are fatigue, obesity, accumulation of fat around the belly and difficulty regulating the blood levels of fat and sugar. Insulin resistance is the underlying cause of type 2 diabetes, cardiovascular problems and liver disease.

These drastic increases in metabolic disorders cannot be totally explained by current known risk factors – high fat diets and lack of exercise. Based on animal and human research findings, some scientists suspect that POPs have the potential to contribute to the diabetes epidemic that threatens people around the globe. Human studies have found associations between an increased chance of developing type 2 diabetes and higher levels of POPs in the body (Lee et al. 2006). Animal research has pointed in the same direction.

What did they do?

Adult male rats were fed for 28 days either crude or refined fish oil obtained from farmed Atlantic salmon carcasses.

The crude fish oil contained the levels of POPs that people are typically exposed to after eating the fish. The refined fish oil contained no POPs and was fed to the control rats. The levels of fat in both diets were the same.

After exposure, the researchers measured body weight, whole-body insulin sensitivity and levels of POPs in each group. They compared the levels of fat, triacylglycerol, diacylglycerol and cholesterol in the rat livers.

They also determined how well rats could regulate sugars and fats and measured the expression of several key genes that are thought to be involved in the metabolic process.

In a parallel study, fat cells were exposed to the types of POPs that were stored in the fish fat cells at similar levels found in the salmon oil. The effects on sugar uptake by the cells were measured.

What did they find?

Adult rats exposed to the crude fish oil – which contained the POPs mixture – put on belly fat and developed insulin resistance and liver disease. The rats could not regulate fat properly. They had higher levels of cholesterol and the fatty acids triacylglycerol and diacylglycerol in their livers.

In contrast, none of these changes were seen in the rats that ate fish oil without the POPs.

Although blood levels of insulin and sugar were similar among rats with either diet, the rats exposed to POPs had impaired insulin action. The POPs also altered the expression of number of genes involved in metabolism, which could explain the changes in fat and sugar regulation.

Similar results on insulin and gene expression were seen in the cultured fat cells that were exposed to a POPs mixture similar to that found in the fish oil. The POPs – especially the organochlorine pesticides – drastically inhibited insulin's action and the cells' ability to take up glucose, a first step in insulin resistence.The cells expressed fewer of the genes that regulate fat and sugar levels.

Further analysis showed the liver and fat tissue differed in the components they predominantly store. PCBs and organochlorine pesticides were measured in both liver and fat tissue while certain types of dioxins and furans were more abundant in the liver.

Based on this study, daily exposure to POPs mixtures in food at levels found naturally in the environment leads to insulin resistance and an impaired ability to metabolize fat and sugar in adult male rats. The levels measured in the rats' fat tissues were relevant to humans, as they were similar to those previously reported for middle-aged Europeans.

This rodent study is the first to find that POPs can cause abnormal insulin action and adds an important missing piece to the growing body of human research that has found associations between POPs levels and insulin resistance that could cause such serious health problems as type 2 diabetes, obesity and liver disease.

Generally, animal studies provide a way to ask and answer health-related questions that cannot be studied directly in people. Humans and rats share similar hormones that work in the same general way to guide metabolism and reproduction. Because of these similarities, rats and mice are used to assess both potential drug therapies and potential effects from environmental toxicants. Results from animal studies supply insights into what might be occurring with respect to health and disease in people.

Animals and people accumulate these long-lived compounds from food and store them in fat. Most of us carry at least some types of the chemicals in our bodies. The authors say their results indicate that POPs – as with some other indicted environmental chemicals found in air pollution and plastics – "provide additional evidence that global environmental pollution contributes to the epidemic of insulin resistance-associated metabolic diseases."

The World Health Organization estimates that more than 300 million people will die from disease associated with insulin resistance and metabolic disorders by 2015. The current strategies for prevention include limiting dietary intake and increasing physical activity. This study suggests that considering the role of POPs may be warranted in prevention strategies.

Current methods of risk assessment may also fall short in protecting health, since different types of POPs mixtures impaired insulin action differently. Some did, while others did not. The dioxin and dioxin-like PCB levels that changed insulin action did not fall within the standard measure of toxicity – called the total toxic equivalent (TEQ) concentration – that is currently used to regulate safe exposures to environmental chemicals. The findings "demonstrate that risk assessment based on TEQ assigned to dioxins and dioxins-like PCBs" does not include the risk of insulin resistance, according to the study's authors.

POPs production and use are regulated worldwide. For example, in the U.S., regulations imposed by the Environmental Protection Agency have significantly reduced the release of dioxins and furans. Globally, a number of international laws limit or ban their use.

The chemicals classified as POPs do not degrade easily, so even limited production will still have an additive effect over the years. Because of this, POPs will continue to impact the environment – and possibly human health – into the future.


Insulin resistence and pre-diabetes. The National Diabetes Information Clearinghouse, The National Institute of Diabetes and Digestive and Kidney Diseases.

Lee, DH, IK Lee, K Song, M Steffes, W Toscano, BA Baker and DR Jacobs. 2006. A strong dose response relation between serum concentrations of persistent organic pollutants and diabetes: Results from the National Health and Examination Survey 1999-2002. Diabetes Care 29(7):1638-1644.

Persistant organic pollutants. United Nations Environment Programme.

Stockholm Convention on Persistent Organic Pollutants. Stockholm Convention.



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