Neonatal exposure to parathion alters lipid metabolism in adulthood: Interactions with dietary fat intake and implications for neurodevelopmental deficits

Abstract

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.

Figure 1

Serum adipokines: (A) leptin, (B) adiponectin. Data represent means and standard errors; values for fed and fasted adiponectin were combined because of the absence of a main effect of feeding status or interaction of status with the other variables. ANOVA for each sex appears below the panels. Asterisks denote individual groups that differ from the corresponding control, evaluated only where permitted by the interaction terms; otherwise, only main effects are shown.

Figure 2

TNFα in (A) mesenteric white fad pad, (B) inguinal white fat pad. Data represent means and standard errors. ANOVA for each sex appears below the panels. Asterisks denote individual groups that differ from the corresponding control, evaluated only where permitted by the interaction terms; otherwise, only main effects are shown.

Figure 3

TBARS in (A) mesenteric white fat pad, (B) inguinal white fat pad, (C) temporal/occipital cortex, (D) cerebellum, (E) gastrocnemius muscle. Data represent means and standard errors. ANOVA for each sex appears below the panels. Asterisks denote individual groups that differ from the corresponding control, evaluated only where permitted by the interaction terms; otherwise, only main effects are shown.