Organophosphates are developmental neurotoxicants but recent evidence also points to metabolic dysfunction. We determined whether neonatal
parathion exposure in rats has long-term effects on regulation of
adipokines and lipid peroxidation. We also assessed the interaction of these effects with increased fat intake. Rats were given
parathion on postnatal days 1-4 using doses (0.1 or 0.2mg/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 chow or switched to a high-fat diet for 7 weeks. We assessed serum
leptin and
adiponectin,
tumor necrosis factor-alpha (
TNFalpha) in adipose tissues, and
thiobarbituric acid reactive species (
TBARS) in peripheral tissues and brain regions. Neonatal
parathion exposure uncoupled serum
leptin levels from their dependence on
body weight, suppressed
adiponectin and elevated
TNFalpha in white adipose tissue. Some of the effects were offset by a high-fat diet.
Parathion reduced
TBARS in the adipose tissues, skeletal muscle and temporal/occipital cortex but not in heart, liver, kidney or frontal/parietal cortex; it elevated
TBARS in the cerebellum; the high-fat diet again reversed many of the effects. Neonatal
parathion exposure disrupts the regulation of
adipokines that communicate metabolic status between adipose tissues and the brain, while also evoking an inflammatory adipose response. Our results are consistent with impaired fat utilization and
prediabetes, as well as exposing a potential relationship between effects on fat metabolism and on synaptic function in the brain.