Organochloride pesticides impaired mitochondrial function in hepatocytes and aggravated disorders of fatty acid metabolism.
Organochloride pesticides impaired mitochondrial function in hepatocytes and aggravated disorders of fatty acid metabolism.
复制标题
有机氯化物农药损害肝细胞线粒体功能并加剧脂肪酸代谢紊乱。
DOI：
10.1038/srep46339
复制
发表时间：
2017-04-11
影响因子：
4.6
通讯作者：
Gu A
中科院分区：
文献类型：
--
作者：
Liu Q;Wang Q;Xu C;Shao W;Zhang C;Liu H;Jiang Z;Gu A
对，对'-二氯二苯基二氯乙烯（p, p’-DDE）和β-六氯环己烷（β-HCH）是人体中两种主要的有机氯农药（OCPs）代谢产物，与脂肪酸代谢紊乱相关。然而，其潜在机制尚未完全阐明。在本研究中，成年雄性C57BL/6小鼠连续8周暴露于低剂量的p, p’-DDE和β-HCH。分析了有机氯农药在各器官中的蓄积情况、肝脏脂肪酸组成、三羧酸循环（TCA）代谢物及其他代谢物谱。检测了参与肝脏脂肪生成和β-氧化的基因表达水平。评估了暴露于有机氯农药的HepG2细胞的线粒体功能。在肝脏中发现p, p’-DDE和β-HCH大量蓄积，并且在电子显微镜下观察到线粒体受损。在有机氯农药处理组中，脂肪酸合成相关基因的表达增加，而线粒体脂肪酸β-氧化相关基因的表达减少。有机氯农药改变了肝脏组织的代谢物谱、肝脏脂肪酸组成以及几种三羧酸循环代谢物的水平。此外，暴露于有机氯农药的HepG2细胞中，线粒体示踪绿荧光、三磷酸腺苷（ATP）水平、线粒体膜电位和耗氧率均下降。总之，长期暴露于与人体内部暴露剂量相当的有机氯农药会损害线粒体功能，降低脂肪酸β-氧化，加剧脂肪酸代谢紊乱。
p,p’-dichlorodiphenyldichloroethylene (p, p’-DDE) and β-hexachlorocyclohexane (β-HCH) were two predominant organochlorine pesticides (OCPs) metabolites in human body associated with disorders of fatty acid metabolism. However, the underlying mechanisms have not been fully clarified. In this study, adult male C57BL/6 mice were exposed to low dose of p, p’-DDE and β-HCH for 8 wk. OCPs accumulation in organs, hepatic fatty acid composition, tricarboxylic acid cycle (TCA) metabolites and other metabolite profiles were analyzed. Expression levels of genes involved in hepatic lipogenesis and β-oxidation were measured. Mitochondrial function was evaluated in HepG2 cells exposed to OCPs. High accumulation of p, p’-DDE and β-HCH was found in liver and damaged mitochondria was observed under electron microscopy. Expression of genes in fatty acid synthesis increased and that in mitochondrial fatty acid β-oxidation decreased in OCPs treatment groups. OCPs changed metabolite profiles in liver tissues, varied hepatic fatty acid compositions and levels of several TCA cycle metabolites. Furthermore, MitoTracker Green fluorescence, ATP levels, mitochondrial membrane potential and OCR decreased in HepG2 cells exposed to OCPs. In conclusion, chronic exposure to OCPs at doses equivalent to internal exposures in humans impaired mitochondrial function, decreased fatty acid β-oxidation and aggravated disorders of fatty acid metabolism.