Bisphenol A Induces Fatty Liver by an Endocannabinoid-Mediated Positive Feedback Loop
Bisphenol A Induces Fatty Liver by an Endocannabinoid-Mediated Positive Feedback Loop
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DOI：
10.1210/en.2015-1384
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发表时间：
2016-05-01
期刊：
影响因子：
4.8
通讯作者：
Carnevali, Oliana
中科院分区：
文献类型：
--
作者：
Martella, Andrea;Silvestri, Cristoforo;Carnevali, Oliana
异雌激素双酚A（BPA）是一种广泛存在的增塑剂，在多个生态系统中均可检测到。BPA被认为是一种代谢干扰物，影响不同的器官;然而，人们对其在肝脏中的作用机制知之甚少，它会引发甘油三酯的积累。暴露于BPA的成年斑马鱼（Danio rerio）出现肝脂肪变性，这与致肥胖内源性大麻素2-花生四烯酸甘油和大麻素的肝脏水平增加以及棕榈酰乙醇胺的伴随减少有关。这些变化与关键内源性大麻素分解代谢和代谢酶表达的变化以及内源性大麻素受体cnr 1表达的增加有关。急性和慢性的体外治疗与纳米和微摩尔BPA剂量显示anandamide的水平增加与脂肪酸酰胺水解酶，主要的anandamide水解酶的活性降低，并诱导甘油三酯积累在HHL-5细胞中的CB 1依赖性的方式。我们的结论是，双酚A是能够产生脂肪肝在斑马鱼和人类肝细胞通过上调内源性大麻素系统。
The xenoestrogen bisphenol A (BPA) is a widespread plasticizer detectable within several ecosystems. BPA is considered a metabolic disruptor, affecting different organs; however, little is known about its mechanism of action in the liver, in which it triggers triglyceride accumulation. Adult zebrafish (Danio rerio) exposed to BPA developed hepatosteatosis, which was associated with an increase in the liver levels of the obesogenic endocannabinoids 2-arachidonoylglycerol and anandamide and a concomitant decrease in palmitoylethanolamide. These changes were associated with variations in the expression of key endocannabinoid catabolic and metabolic enzymes and an increase in the expression of the endocannabinoid receptor cnr1. Acute and chronic in vitro treatments with nano-and micromolar BPA doses showed increased anandamide levels in line with decreased activity of fatty acid amide hydrolase, the main anandamide hydrolytic enzyme, and induced triglyceride accumulation in HHL-5 cells in a CB1-dependent manner. We conclude that BPA is able to produce hepatosteatosis in zebrafish and human hepatocytes by up-regulating the endocannabinoid system.