(Beyond Pesticides, November 11, 2008) Researchers at the Duke University School of Medicine have linked organophosphate pesticides to the epidemics of obesity and type 2 diabetes. The researchers specifically link neonatal low-dose parathion exposure in rats to disruption of glucose and fat homeostasis. The study, â€śExposure of Neonatal Rats to Parathion Elicits Sex-Selective Reprogramming of Metabolism and Alters the Response to a High-Fat Diet in Adulthood,â€ť was published in the November 2008 issue of Environmental Health Perspectives. It follows research by the National Institutes of Health (NIH) that links pesticide exposure to type 2 diabetes using epidemiological data from the Agricultural Health Study.
Although most studies of organophosphates focus on their neurotoxicity, there is increasing evidence that these agents may also have a lasting impact on metabolic function. According to authors, obesity and consequent type II diabetes are rising at epidemic rates in the U.S. and many other countries around the world. Two of three U.S. adults are now classified as overweight. There are epidemiologic links between pesticide exposure and diabetes, and the same subpopulations that have the highest rates of obesityâ€”inner-city, low-socioeconomic-status, agricultural populationsâ€”are also those that have greater exposure to organophosphates and other pesticides.
The researchers chose parathion as a representative organophosphate. Neonatal rats were given the insecticide parathion on postnatal days 1â€“4 using doses (0.1 or 0.2 mg/kg/day) that straddle the threshold for barely detectable cholinesterase inhibition and the first signs of systemic toxicity. In adulthood, animals were either maintained on standard lab diet or switched to a high-fat diet for 7 weeks.
While both doses affected the rats’ metabolism, the researchers observed different effects in the males and females throughout the study. Male rats exposed to the low-dose of parathion outweighed contol rats on the same diet and also evoked signs of a prediabetic state, with elevated fasting serum glucose and impaired fat metabolism. The males exposed to the higher dose of parathion weighed similar to the control, but ate less.
Exposed females, on the other hand, weighed less than the control group with higher food consumption in the low dose group and normal food consumption in the high-dose group. This indicates a â€śwastingâ€ť condition, which was confirmed by the disruption of both glucose and lipid metabolism at both doses.
After reaching adulthood, half the rats were switched to a high-fat diet. While the change in diet did not impact males, the females showed dramatically different results, based on the exposure dose. The low dose group gained significantly more weight than the control after switching to the high-fat diet, whereas the high dose group reduced the dietary effect. Food consumption also showed major sex differences. High dose males showed less of a decrease in food consumption on the high-fat diet than did controls. In contrast, high dose females showed exactly the same pattern of decreased food intake as controls when placed on a high-fat diet.
The researchers believe that early-life exposure to organophosphates or other environmental chemicals may play a role in the increased incidence of obesity and diabetes in humans. They also caution that the effects of chemical exposure must be evaluated more broadly. â€śOur most important findings center on the tendency to categorize environmental toxicants by allocating them to preconceived classes. Organophosphates are usually thought of as developmental neurotoxicants, but they obviously have other important targets that contribute to morbidity, including metabolic effects that can have a potential impact on obesity and diabetes.â€ť The study continues, â€śIt is increasingly evident that adverse events in fetal or neonatal life, including chemical exposures like those studied here, can lead to misprogramming of metabolism, appetite, and endocrine status contributing ultimately to morbidities such as obesity and diabetes. Clearly, we need to focus further research on the specific contributions of environmental chemical exposures that might be contributing to the epidemic of these and other metabolic disorders.â€ť