title: Sub-chronically exposing mice to a polycyclic aromatic hydrocarbon increases lipid accumulation in their livers.
abstract: The potential for exposing humans and wildlife to environmental polycyclic aromatic hydrocarbons (PAHs) has increased. Risk assessments describing how PAHs disturb lipid metabolism and induce hepatotoxicity have only received limited attention. In the present study, seven-week-old male ICR mice received intraperitoneal injections of 0, 0.01, 0.1 or 1mg/kg body weight 3-methylcholanthrene (3MC) per week for 10 weeks. A high-fat diet was provided during the exposure. Histopathological lipid accumulation and lipid metabolism-related genes were measured. We observed that sub-chronic 3MC exposure significantly increased lipid droplet and triacylglycerol (TG) levels in the livers. A low dose of 3MC activated the aryl hydrocarbon receptor, which negatively regulated lipid synthesis in the livers. The primary genes including acetyl-CoA carboxylase (Acc), fatty acid synthase (Fas) and stearoyl-CoA desaturase 1 (Scd1) decreased significantly when compared with those in the control group, indicating that de novo fatty acid synthesis in the hepatocytes was significantly inhibited by the sub-chronic 3MC exposure. However, the free fatty acid (FFA) synthesis in the adipose tissue was greatly enhanced by up-regulating the expression of peroxisome proliferator-activated receptor γ (PPARγ) and sterol regulatory element binding protein-1c (SREBP1C) and target genes including Acc, Fas and Scd1. The synthesized FFA was released into the blood and then transported into the liver by the up-regulation of Fat and Fatp2, which resulted in the gradual accumulation of lipids in the liver. In conclusion, histological examinations and molecular level analyses highlighted the development of lipid accumulation and confirmed that 3MC significantly impaired lipid metabolism in mice.
authors.affiliation: College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Yuanxiang
authors.initials: Y
authors.lastname: Jin
authors.affiliation: College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Wenyu
authors.initials: W
authors.lastname: Miao
authors.affiliation: College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Lin
authors.affiliation: College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wu
authors.affiliation: College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Hangjie
authors.initials: H
authors.lastname: Shen
authors.affiliation: College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Chen
authors.affiliation: College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Li
authors.affiliation: College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Qiaoqiao
authors.initials: Q
authors.lastname: Pan
authors.affiliation: College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address: azwfu@zjut.edu.cn.
authors.forename: Zhengwei
authors.initials: Z
authors.lastname: Fu
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D059305:Diet, High-Fat; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008748:Methylcholanthrene / Q000008:administration & dosage* / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR
chemical_list: D005230:Fatty Acids, Nonesterified; D008748:Methylcholanthrene
keywords: Gene transcription; Lipid metabolism; Mice; Polycyclic aromatic hydrocarbon; Sub-chronic exposure