Effects Of Pesticide On Metabolic Syndrome And Its Metabolic Mechanism

Pesticide is a double edged sword,which plays very important roles in increasrng crop production and income,but it also causes some negative effects,such as environmental pollutions,cancer and other diseases.Epidemiological studies showed that pesticide exposure might lead to metabolic syndrome.Thus,studies on the mechanism of pesticides-lead-metabohc syndrome are of great importance.In this paper,we investigated the effects of pesticides and emulsifier on metabolic in animal models,lipid metabolites and gut microbiota was analyzed to study the mechanism.Chlorpyrifos is a widely used organophosphorus pesticide with a high detection rate.Epidemiologic studies have shown that the extensive use of the OP pesticides has become an important risk factor for developing metabolic diseases.Thus to investigate the mechanism of chlorpyrifos induced metabolic syndrome,the effects of chlorpyrifos on the insulin resistance and obesity in different diet(high fat diet and normal fat diet),under different genetic backgrounds(inbred strain C57B1/6 mice and outbred strain CD-1(ICR)mice)were investigated.Results showed that long term exposure to chlorpyrifos(1)caused integrity deficiency of the gut barrler;(2)increased lipopolysaccharide-bearing species in gut microbiota;which was expected to cause increased lipopolysaccharide entry into the body.Elevated LPS levels in blood will lead to increased expression of TLR4 receptors,thereby increase the level of pro-inflammatory mediators,thus leading to chronie inflammation and finally resulted in insulin resistance and obesity.During this process,obese mice would have more severe symptoms,while healthy mice fed normal fat diet could develop IR and obesity.Similar results were observed in mice with different genetic background,which indicates that this process is not limited by genetic background.Tween 80 is a widely used pesticide adjuvant.It could affect the composition of gut microbiota,and in turn affects metabolic syndrome.On the other hand,parent could affect their offsprings' gut microbiota.To investigate the effects of Tween 80 on mice and their offsprings,inbred strais C57B1/6 mice were exposed to Tween 80 for 10 weeks before and after pregnancy.Results showed that Tween 80 exposure significantly increased the body weight of female mice and damaged the glucose homeostasis of both male and female mice,changed lipid metabolism and gut microbiota conposition in male and female mice.In addition,changes in the composition of the gut microbiota could lead to obesity.As for the Tween 80 treat miee's offsprings(TMO),although they were not directly exposed to Tween 80,the body weight of male TMO mice were significantly increased at one-month old and returned to no significantly difference until three-month old Both one-month old female and male TMO mice had significantly impaired glucose homeostasis,and male TMO mice still showed signigicantly impaired glucose homeostasis at three-montt old.The metabolites of one-month old TMO mice were different from their control goups,and 5 metabolites were changed same with their parent Tween 80 treated mice.At three-month old,the changed metablites of female TMO mice was no longer the same as that of their parents,while male TMO mice still had common change.Similarly,the changes of gut microbiota composition of the one-month old TMO mice were similar to their parent Tween 80 treated mice.There were no significant differences in the gut microbiota between three-month old female TMO mice and control group,while three-month old male TMO mice still had similar changes to their Tween 80-treated parents.The changed gut microbiota composition and lipid metabolites caused by Tween 80 could lead to obesity.That might be the reason for the obesity and insulin resistance in the TMO mice.DDE is the main metabolite of DDT and could be widely detected in human samples.Studies have shown that exposure to p,p'-DDE could lead to metabolic syndrome.The effects of chronic exposure to p,p'-DDE on obesity and insulin resistance were investigated in Sprague Dawley rats in this study.Lipid metabolites and gut microbiota were also detected to study the mechanism.Results showed that after 21 days exposure of p,p'-DDE,the weight of p,p'-DDE-treated rats were significantly higher than that of the control group,and the weight of the fat pad and the fat pad weight percentage were significantly higher than those of the control group.At the same time,fasting blood glucose,fasting insulin and glucose tolerance showed that p,p'-DDE exposure could lead to the impaired glucose regulation and insulin resistance in rats.Changed hpid metabolites were observed in p,p'-DDE treated mice and some of these have effect on obesity and insulin resistance.p,p'-DDE exposure could lead to the change of gut microbiota composition in rats,causing the content of Bacteroidetes decreased,Firmicutes and Tenericutes increased and increasing Firmicutes/Bacteroidetes ratio,all these changes are related to obesity and might have influence on p,p'-DDE-induced obesity.Quizalofop-ethyl is a widely use chiral herbicide consisting of a pair of enantiomers.Chiral pesticides are composed of two or multiple enantiomers,which have the same physical,chemical properties and affection in achiral environment.However,for the individual enantiomers can interact enantioselectively with enzymes or biological receptors in organisms,the biological and physiological properties of enantiomers are often different.To fully assess the fate of quizalofop-ethyl in animals,the pharmacokinetic and distribution of the enantiomers of quizalofop-ethyl and its metabolite quizalofop-acid were studied in Sprague-Dawley male rats by Intragastric administration.Although the high concentration of quizalofop-acid was found in the blood and tissues,quizalofop-ethyl could not be detected through the whole study which indicated a quick metabolism of quizalofop-ethyl to quizalofop-acid in vivo.In almost all samples,the concentrations of(+)-quizalofop-acid exceeded those of(-)-quizalofop-acid.Protein binding experiments showed that quizalofop-ethyl interacted with pepsin,trypsin and serum albumin without enantioselectivity In plasma,the metabolic process of quizalofop-ethyl was enantioselective with preferential degradation of(+)-quizalofop-ethyl and generation of(+)-quizalofop-acid.However there was no enantioselectivity in the degradation of quizalofop-ethyl or formation of quizalofop-acid in liver microsome.The metabolism of quizalofop-acid was noenantioselective by liver microsome,sulfotransferase,glucuronosyltransferase.In the everted gut sac,quizalofop-ethyl was degraded rapidly to quizalofop-acid without enantioselectivity and the preferential absorption of(+)-quizalofop-acid was observed throughout the gut.It could be inferred that the enantioselective absorption of quizalofop-acid enantiomers by intestine was the main reason for the enantioselectivity observed in rats in vivo.