Cardiac energy metabolism disorder mediated by energy substrate imbalance and mitochondrial damage upon tebuconazole exposure

作     者：Tingting Ku Jindong Hu Mengmeng Zhou Yuanyuan Xie Yutong Liu Xin Tan Lin Guo Guangke Li Nan Sang Tingting Ku;Jindong Hu;Mengmeng Zhou;Yuanyuan Xie;Yutong Liu;Xin Tan;Lin Guo;Guangke Li;Nan Sang

作者机构：College of Environmental Science and ResourcesResearch Center of Environment and HealthShanxi UniversityTaiyuan 030006China 

出 版 物：《Journal of Environmental Sciences》 (环境科学学报（英文版）)

年 卷 期：2024年第136卷第2期

页      面：270-278页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 07[理学] 1001[医学-基础医学(可授医学、理学学位)] 0703[理学-化学] 10[医学] 0713[理学-生态学] 

基　　金：supported by the National Science Foundation of China (Nos.21806094,22036005,22176119,22076108 and 21906098) the Natural Science Foundation of Shanxi Province (No.201901D211123)。 

主　　题：Tebuconazole Cardiotoxicity Energy metabolic disorders Energy substrate Mitochondrial damage 

摘      要：Tebuconazole exposure has been described as an increasing hazard to human health.An increasing number of recent studies have shown a positive association between tebuconazole exposure and cardiovascular disease risk,which is characterized by the reduction of adenosine triphosphate(ATP)synthesis.However,researches on the damage of tebuconazole exposure to energy metabolism and the related molecular mechanisms are limited.In the present study,male C57BL/6 mice were treated with tebuconazole at different low concentrations for 4 weeks.The results indicated that tebuconazole could accumulate in the heart and further induce the decrease of ATP content in the mouse heart.Importantly,tebuconazole induced an obvious shift in substrate utilization of fatty acid and glucose by disrupting their corresponding transporters(GLUT1,GLUT4,CD36,FABP3 and FATP1)expression,and significantly repressed the expression of mitochondrial biogenesis(Gabpa and Tfam)and oxidative phosphorylation(CS,Ndufa4,Sdhb,Cox5a and Atp5b)related genes in a dosedependent manner.Further investigation revealed that these alterations were related to the IRS1/AKT and PPARγ/RXRαpathways.These findings contribute to a better understanding of triazole fungicide-induced cardiovascular disease by revealing the key indicators associated with this phenomenon.