Permethrin Aggravated Adipogenesis:the Involvement Of AMPK?ER Stress And Intestinal Microbiota

Permethrin is a I pyrethroid insecticide that has previously been reported to promote fat accumulation and insulin resistance in vitro.In this study,we explore the potential molecular mechanism of permethrin-induced lipid accumulation in vivo and vitro.In this study,3T3-L1 cell model was used to investigate the potential molecular mechanism.The animal model investigated that permethrin may cause the disorder of glucose and lipid metabolism and lipogenesis by altering the gut microorganism in adult.Finally,the offspring model showed that permethrin could promote the lipid accumulation of the offspring mice.(1)Permethrin increased the accumulation of TG(Total triglycerides)and the expression of adipogenesis-related factors in adipocytes,decreased the expression of pAMPK(Phosphorylated AMP-activated protein kinase),and enhanced the expression of ER Stress(Endoplasmic reticulum stress)-related proteins.Meanwhile,permethrinimproved TG accumulation and the expression of adipogenesis related factors in 3T3-L1 were inhibited by IRE1?(Inositol requiring enzyme1?)knockdown with si RNA,suggesting that permethrin may promote adipogenesis in 3T3-L1 adipocytes through endoplasmic reticulum stress pathway.Transcriptomics analysis revealed that permethrin may also promote fat accumulation by AMPK-PI3K(Phosphatidylinositol-3 kinase)-AKT(Protein kinase B)pathway.(2)Permethrin exposure promoted obesity in male C57BL/6J mice fed with highfat diet.The results showed that permethrin significantly increased body weight in the high-fat diet group(G2),but not the low-fat diet group(G1).Permethrin treatment significantly increased fat mass,serum levels of TG,TC(Total cholesterol)and LDLC(Low-density lipoprotein cholesterol),and liver TG and TC levels in high-fat dietfed male mice.Permethrin treatment increased the expression of endoplasmic reticulum stress-related proteins,at the same time,which decreased the expression of AMPKPI3K-AKT pathway proteins and genes;Permethrin treatment reduced intestinal content of SCFAs(Short-chain fatty acids),?-diversity,but increased the ?-diversity,heterogeneity and F/B(Firmicutes/Bacteroidetes)ratio.Further study showed that permethrin may lead to glucose and lipid metabolism disorders by disrupting the intestinal microbial structure(G3).(3)Parental exposure to permethrin significantly increased the body weight,epididymal adipose tissue,serum TG and LDL-C levels of the pups(G5)that have just left the lactation period;After independent growth period,the offspring female mice continued to be exposed to permethrin(G6),which resulted in significant increase of the organ load.The female progeny(G7)which stopped permethrin exposure after parental exposure to permethrin have increased fat content,serum TG,TC,and fasting insulin levels,but the effects were lower than that of the G6 group.The results indicated that parental exposure to permethrin,may disturb the progeny glucose and lipid metabolism,resulting in increased fat accumulation.