Exposure of Neonatal Rats to Parathion Elicits Sex-Selective Reprogramming of Metabolism and Alters the Response to a High-Fat Diet in Adulthood

Abstract

BackgroundDevelopmental exposures to organophosphate pesticides are virtually ubiquitous. These agents are neurotoxicants, but recent evidence also points to lasting effects on metabolism.ObjectivesWe administered parathion to neonatal rats. In adulthood, we assessed the impact on weight gain, food consumption, and glucose and lipid homeostasis, as well as the interaction with the effects of a high-fat diet.MethodsNeonatal rats were given parathion on postnatal days 1–4 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 chow or switched to a high-fat diet for 7 weeks.ResultsIn male rats on a normal diet, the low-dose parathion exposure caused increased weight gain but also evoked signs of a prediabetic state, with elevated fasting serum glucose and impaired fat metabolism. The higher dose of parathion reversed the weight gain and caused further metabolic defects. Females showed greater sensitivity to metabolic disruption, with weight loss at either parathion dose, and greater imbalances in glucose and lipid metabolism. At 0.1 mg/kg/day parathion, females showed enhanced weight gain on the high-fat diet; This effect was reversed in the 0.2-mg/kg/day parathion group, and was accompanied by even greater deficits in glucose and fat metabolism.ConclusionsNeonatal low-dose parathion exposure disrupts glucose and fat homeostasis in a persistent and sex-selective manner. Early-life toxicant exposure to organophosphates or other environmental chemicals may play a role in the increased incidence of obesity and diabetes.

Preference of laboratory rats for food based on wheat grown under organic versus conventional production conditions

“…Investigations of crop protection agents (organophosphates) have shown metabolic effects in neonatal rats that can have a potential impact on obesity and diabetes [9]. Such possible interactions should be further investigated in topically specified tests.…”

Working to eat: Vulnerability, food insecurity, and obesity among migrant and seasonal farmworker families

“…Organophosphate exposure, known to affect neurological function, has recently been confirmed as interfering with metabolism leading to obesity and diabetes in rat models [Lassiter et al, 2008]. Because farmworkers have a high risk of exposure to organophosphates in the workplace and home [Quandt et al, 2004a;Arcury et al, 2001;Bradman et al, 2007], farmworker complaints of increased obesity and the development of diabetes warrants investigation.…”

Imidacloprid, a neonicotinoid insecticide, induces insulin resistance

“…There is currently limited knowledge on the underlying biochemical mechanisms by which insecticides alter glucose homeostasis. Those include Slotkin et al (2005) and Lassiter et al (2008) reporting exposure to organophosphorus insecticides (parathion and chlorpyrifos) during the developmental period disrupted glucose homeostasis in rats (Slotkin et al, 2005;Lassiter et al, 2008). However, other insecticides have not been tested for their potential contribution with regard to glucose homeostasis.…”