2,3,7,8-四氯二苯并二噁英染毒或联合高脂饮食致小鼠糖脂代谢紊乱的实验研究

doi:10.3969/j.issn.1004-616x.2019.02.004

Abstract

Abstract: OBJECTIVE:To investigate the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alone or in combination with high fat diet (HFD) on glucose and lipid metabolism in mice.METHODS:60 C57BL/6J mice were randomly divided into 4 control and treatment groups.All mice were evaluated for glucose and lipid metabolic functions through measurement of body weight,weights of liver and adipose tissues,glucose tolerance,and insulin tolerance,determined mitochondrial membrane potential and ROS level using specific probes,and measured the mRNA expression of Nrf2,antioxidant enzymes and inflammatory factors.RESULTS:TCDD or HFD alone could induce significant glucose and lipid metabolic disorders,as evidenced by increased adipose weight,increased blood glucose level,impaired tolerance of glucose and insulin.In addition,TCDD aggravated HFD-induced impairment of glucose and lipid metabolism.In liver,TCDD or HFD alone resulted in hyperpolarization of mitochondrial membrane potential and increased levels of ROS.TCDD and HFD induced a more significant mitochondrial dysfunction and increase in ROS.In adipose tissues,TCDD alone or in combination with HFD increased ROS level and perturbed HFD-induced ROS increase.In addition,TCDD decreased the mRNA expression of Nrf2,GCLc,and SOD2.In combination with HFD,the effect of TCDD on the mRNA expression of Nrf2,GCLc,and SOD2 was significantly enhanced.Either TCDD or HFD increased the mRNA expression of IL-1α,IL-6,and MCP-1.TCDD aggravated the HFD-induced increase of these inflammatory factors.CONSLUSION:TCDD and HFD induced glucose and lipid metabolic disorders in mice.In addition,they functioned cooperatively to affect glucose metabolic parameters,oxidative stress indexes,and expression of inflammatory factors In fact,the effects of TCDD in combination with HFD were stronger than the additive effects from each acting alone.The decrease of Nrf2,the downstream effects on antioxidant enzymes and the increase of inflammatory factors may be a key mechanism responsible for the observed cooperative effects.

Key words: TCDD, obesity, diabetes, glucose and lipid metabolic disorder, oxidative stress, inflammation

CLC Number:

R114

LIAO Nai, LONG Zi, HAI Chunxu, WANG Xin. 2,3,7,8-tetrachlorodibenzo-p-dioxin alone or in combination with high fat diet on glucose and lipid metabolism in mice[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2019, 31(2): 111-118.

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2,3,7,8-tetrachlorodibenzo-p-dioxin alone or in combination with high fat diet on glucose and lipid metabolism in mice

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