Decabromodiphenyl ether causes insulin resistance and glucose and lipid metabolism disorders in mice

摘要

BACKGROUND Decabromodiphenyl ether(BDE-209)is the most commonly used brominated flame retardant.Recently,BDE-209 has been suspected of being an environmental risk factor for metabolic diseases such as obesity,insulin resistance(IR),type 2 diabetes mellitus,and hypertension.AIM To investigate the effects of BDE-209 on IR and glucose and lipid metabolism in C57BL/6 mice.METHODS Adult male C57BL/6 mice were randomly divided into high,medium-high,medium,medium-low,and low dose BDE-209 groups,and a control group(n=6 per group),which received 1000,800,600,450,300,and 0 mg/kg BDE-209,respectively.After BDE-209 exposure for 60 d,the mice were fasted overnight,and then sacrificed to obtain tissues.An automatic biochemical analyzer was used to detect serum triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),and high density lipoprotein cholesterol(HDL-C);enzymelinked immunosorbent assay kits were used to detect fasting serum insulin(FINS),leptin(LEP),and adiponectin(Adp)levels;a blood glucose meter was used to detect fasting blood glucose(FBG).Morphological changes of the liver were observed by hematoxylin and eosin staining.Real-time quantitative polymerase chain reaction and Western blot were used to determine the messenger ribonucleic acid(mRNA)and protein levels,respectively,of LEP,Adp,and peroxisome proliferators activated receptor-γ(PPARγ)in mouse liver and adipose tissues.RESULTS There was a statistically significant difference in the weight of mice in each group after 45 and 60 d of exposure(P<0.05).After 60 d of exposure,the weight of liver and adipose tissues in the exposure groups were greater than that of the control group(P<0.05).The liver tissue structure was disordered and the liver tissues were accompanied by local inflammatory cell infiltration in the high,mediumhigh,and medium dose BDE-209 groups.The levels of FINS,insulin sensitivity index,Adp,and HDL-C were decreased in the BDE-209 group compared with the control group,as were the mRNA and protein levels of Adp in liver and adipose tissues(P<0.05).Serum level of FBG and LEP were higher in the BDE-209 group than in controls.TC,TG,and LDL-C levels as well as the mRNA and protein expression of LEP and PPARγin liver and adipose tissues were higher than those in the control group(P<0.05).Homeostatic assessment model of IR was higher in the medium and medium-low dose BDE-209 groups(P<0.05).CONCLUSION BDE-209 increases the body weight,fat and liver tissue weight,TC,TG,and LDLC,reduces HDL-C,and causes IR in mice,which may be related to activating the PPARγreceptor.