Inhibition of cholinergic and non-cholinergic targets following subacute exposure to chlorpyrifos in normal and high fat fed male C57BL/6J mice

Abstract

The effects of obesity on organophosphate pesticide-mediated toxicities, including both cholinergic and non-cholinergic targets, have not been fully elucidated. Therefore, the present study was designed to determine if high fat diet intake alters the effects of repeated exposure to chlorpyrifos (CPS) on the activities of both cholinergic and noncholinergic serine hydrolase targets. Male C57BL/6J mice were placed on either standard rodent chow or high fat diet for four weeks with CPS exposure (2.0 mg/kg) for the last 10 days of diet intake. Exposure to CPS did not alter acetylcholinesterase in the central nervous system, but it did significantly inhibit circulating cholinesterase activities in both diet groups. CPS significantly inhibited hepatic carboxylesterase and fatty acid amide hydrolase and this inhibition was significantly greater in high fat fed animals. Additionally, CPS exposure and high fat diet intake downregulated genes involved in hepatic de novo lipogenesis as well as cytochrome P450 enzymes involved in hepatic xenobiotic metabolism. In summary, the present study demonstrates that high fat diet intake potentiates CPS mediated inhibition of both carboxylesterase and fatty acid amide hydrolase in the liver of obese animals following subacute exposure and suggests obesity may be a risk factor for increased non-cholinergic hepatic CPS toxicity.

Effects of Lactobacillus plantarum FZU3013-Fermented Laminaria japonica on Lipid Metabolism and Gut Microbiota in Hyperlipidaemic Rats

“…Among them, SREBP-1c plays a significant role in adjusting the expression of adipogenic genes involved in liver fatty acid synthesis ( 52 ). CD36 plays an important role in transmembrane transport and energy metabolism of long-chain fatty acids ( 53 ). Previous experiments have indicated that ACAT2 inhibits TG synthesis by decreasing the transition of esterified cholesterol to cholesterol ester, which is consistent with the results of the current study that dietary supplementation with LPLJ notably reduced the level of ACAT2 in the liver ( 54 ).…”

Oxidative Stress in NAFLD: Role of Nutrients and Food Contaminants

“…Of interest, pesticide exposure and a high-fat diet (HFD) ( Table 2 ) [ 136 ] interact to modify their effect on metabolic homeostasis [ 194 ]. In fact, various chemical families of insecticides seem to be involved, i.e., organochlorine, pyrethroid, neonicotinoid, and organophosphorus compounds ( Table 2 [ 148 , 184 , 185 , 195 , 196 , 197 , 198 , 199 , 200 , 201 , 202 , 203 , 204 , 205 , 206 , 207 , 208 , 209 , 210 ]). Moreover, HFD components may act as a vehicle for pesticides, allowing them to reach target organs more easily, as proposed in [ 136 , 211 ].…”

Programming of intestinal homeostasis in male rat offspring after maternal exposure to chlorpyrifos and/or to a high fat diet

“…The observed impacts might only be predictive of more severe alterations later in life considering that 8 weeks old was a probably too early experimental timing to observe such effects. We could then suggest that may inhibit the bioactivation of CPF into its metabolites by decreasing cytochrome P450 (CYP450) isoforms 26 , 34 . Moreover, since at birth, the bioactivation of CPF, catalyzed by CYP, is much higher than the detoxification 35 , this may indicate a role for a downregulating effect of HFD on CPF toxic effects 36 .…”