Neonatal exposure to parathion alters lipid metabolism in adulthood: Interactions with dietary fat intake and implications for neurodevelopmental deficits.
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.
Lassiter
T Leon
TL
Department of Pharmacology, Box 3813 DUMC, Duke University Medical Center, Durham, NC 27710, USA.
Ryde
Ian T
IT
Levin
Edward D
ED
Seidler
Frederic J
FJ
Slotkin
Theodore A
TA
D052242:Adiponectin / Q000097:blood; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D004032:Diet; D004041:Dietary Fats; D004435:Eating / Q000187:drug effects*; D005260:Female; D020738:Leptin / Q000097:blood; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D010278:Parathion / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D052242:Adiponectin; D002800:Cholinesterase Inhibitors; D004041:Dietary Fats; D020738:Leptin; D017392:Thiobarbituric Acid Reactive Substances; D014409:Tumor Necrosis Factor-alpha; D010278:Parathion