title: Exposure of neonatal rats to parathion elicits sex-selective reprogramming of metabolism and alters the response to a high-fat diet in adulthood.
abstract: BACKGROUND
  Developmental exposures to organophosphate pesticides are virtually ubiquitous. These agents are neurotoxicants, but recent evidence also points to lasting effects on metabolism.
  
  
  OBJECTIVE
  We 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.
  
  
  METHODS
  Neonatal 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.
  
  
  RESULTS
  In 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.
  
  
  CONCLUSIONS
  Neonatal 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.
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: T Leon
authors.initials: TL
authors.lastname: Lassiter
authors.forename: Ian T
authors.initials: IT
authors.lastname: Ryde
authors.forename: Emiko A
authors.initials: EA
authors.lastname: Mackillop
authors.forename: Kathleen K
authors.initials: KK
authors.lastname: Brown
authors.forename: Edward D
authors.initials: ED
authors.lastname: Levin
authors.forename: Frederic J
authors.initials: FJ
authors.lastname: Seidler
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Slotkin
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D004041:Dietary Fats / Q000008:administration & dosage*; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D007306:Insecticides / Q000494:pharmacology*; D008297:Male; D010278:Parathion / Q000494:pharmacology*; D051381:Rats; D012737:Sex Factors
chemical_list: D004041:Dietary Fats; D007306:Insecticides; D010278:Parathion