Study on the effects and mechanisms of obesity in mice induced by bisphenol A and high-fat diet
Objective To observe the effects of high fat diet and low dose of bisphenol A exposure on lipid metabolism,so as to explore whether bisphenol A and high fat diet have interaction on the occurrence and development of obesity in mice and the mechanism of inducing obesity.Methods C57BL/6J male mice aged 6 to 8 weeks were randomly divided into four groups according to body weight:Control group(non-high-fat group without BPA,C0),high-fat group(high-fat group without BPA,C1),50 μg/kg/d BP A group(non-high-fat group with BPA,C2),and 50 μg/kg/d BPA+high-fat group(high-fat group with BPA,TM).At the same time,in order to understand the dose-effect relationship of BPA in the condition of high fat,two additional groups were added,namely,5 μg/kg/d BPA+high fat group(TL)and 500 μg/kg/d BPA+high fat group(TH).Animals in each group were given corn oil(solvent)or BPA and the corresponding feed by oral gavage,respectively.After 90 days,the animals were anesthetized and killed,and blood and tissue samples were kept for detection.The changes in the expression levels of pathway and autophagy related proteins were detected by automatic biochemical analyzer,aliphatic factor assay(ELISA),immunohistochemistry and Western blot.Results The combined treatment of bisphenol A and high-fat diet could successfully build a mouse obesity model,and the levels of lipid TC and HDL in mice were significantly increased(FTC=4.639,P＜0.05;FHDL=3.335,P＜0.05),the level of adiponectin was decreased(F=22.545,P＜0.05).The result of IHC and Western blot showed that bisphenol A and high-fat diet could significantly up-regulate the expression levels of inflammatory factor IL-6,transcription factor PPARγ,autophagy protein p62 and LC3A/B(FIL-6=35.834,P＜0.05;FPPARγ=7.697,P＜0.05;Fp62=3.954,P＜0.05;FLC3A/B=3.668,P＜0.05),down-regulated the expression level of metabolic enzyme HSL(F=11.077,P＜0.05).Conclusion Bisphenol A and high-fat diet treating together for 90 days can successfully build a mouse obesity model.Bisphenol A and high-fat diet interacted with inflammatory factor IL-6,transcription factor PPARγ,metabolic enzyme HSL,autophagy protein p62,LC3A/B in mice,suggesting that these factors may be involved in the obesity effect mediated by bisphenol A and high-fat diet.
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