Chronic exposure to parabens promotes non-alcoholic fatty liver disease in association with the changes of the gut microbiota and lipid metabolism

肠道菌群 脂质代谢 新陈代谢 尼泊金甲酯 油酸 花生四烯酸 代谢物 化学 脂肪肝 生物 生物化学 内分泌学 疾病 医学 内科学 食品科学 防腐剂
作者
Yilin Ren,Xinyi Shi,Jing Mu,Shenyin Liu,Qian Xin,Wenlong Pei,Shanhong Ni,Zhengduo Zhang,Lei Li,Zhan Zhang
出处
期刊:Food & Function [The Royal Society of Chemistry]
卷期号:15 (3): 1562-1574 被引量:8
标识
DOI:10.1039/d3fo04347a
摘要

Non-alcoholic fatty liver disease (NAFLD) has become a serious public health issue due to changing dietary patterns and composition. However, the relationship between NAFLD occurrence and food additives, such as preservatives, remains unknown. This study aimed to evaluate the toxicity of parabens, namely methylparaben (MeP) and ethylparaben (EtP), in relation to NAFLD occurrence in mice under different dietary conditions. Exposure to MeP and EtP exacerbated high-fat diet (HFD)-induced obesity, glucose intolerance, higher serum lipid concentrations, and fat accumulation by upregulating genes involved in lipid metabolism. Untargeted metabolomics revealed that arachidonic acid (AA) metabolism was the top enriched pathway upon MeP and EtP exposure in the presence of HFD. 11,12-Epoxyeicosatrienoic acid (11,12-EET) was the most abundant AA metabolite and was significantly reduced upon exposure to MeP or EtP. Moreover, an integrative analysis of differential fecal taxa at the genus level and serum AA metabolites revealed significant associations. In addition, MeP and EtP enhanced lipid accumulation in AML12 cells and HepG2 cells cultured with oleic acid. 11,12-EET supplementation could significantly alleviate lipid accumulation by suppressing the expression of lipid metabolism-related genes and proteins. The present study suggests that chronic exposure to MeP and EtP promoted NAFLD
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