title: Comprehensive insights into microcystin-LR effects on hepatic lipid metabolism using cross-omics technologies.
abstract: Microcystin-LR (MC-LR) can induce hepatic tissue damages and molecular toxicities, but its effects on lipid metabolism remain unknown. This study investigated the effects of MC-LR exposure on mice lipid metabolism and uncovered the underlying mechanism through metabonomic, transcriptomic and metagenomic analyses after administration of mice with MC-LR by gavage for 28 d. Increased liver weight and abdominal fat weight, and evident hepatic lipid vacuoles accumulation were observed in the mice fed with 0.2mg/kg/d MC-LR. Serum nuclear magnetic resonance analysis showed that MC-LR treatment altered the levels of serum metabolites including triglyceride, unsaturated fatty acid (UFA) and very low density lipoprotein. Digital Gene Expression technology was used to reveal differential expression of hepatic transcriptomes, demonstrating that MC-LR treatment disturbed hepatic UFA biosynthesis and activated peroxisome proliferator-activated receptor (PPAR) signaling pathways via Pparγ, Fabp1 and Fabp2 over-expression. Metagenomic analyses of gut microbiota revealed that MC-LR exposure also increased abundant ratio of Firmicutes vs. Bacteroidetes in gut and altered biosynthetic pathways of various microbial metabolic and pro-inflammatory molecules. In conclusion, oral MC-LR exposure can induce hepatic lipid metabolism disorder mediated by UFA biosynthesis and PPAR activation, and gut microbial community shift may play an important role in the metabolic disturbance.
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China; Center for Environmental Health Research, South China Institute of Environmental Sciences, The Ministry of Environmental Protection of PRC, Guangzhou 510655, China.
authors.forename: Zongyao
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China. Electronic address: zhangxx@nju.edu.cn.
authors.forename: Xu-Xiang
authors.initials: XX
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China.
authors.forename: Jinbao
authors.initials: J
authors.lastname: Yin
authors.affiliation: Center for Environmental Health Research, South China Institute of Environmental Sciences, The Ministry of Environmental Protection of PRC, Guangzhou 510655, China.
authors.forename: Yunjiang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China. Electronic address: yangly@nju.edu.cn.
authors.forename: Liuyan
authors.initials: L
authors.lastname: Yang
mesh_terms: D000818:Animals; D041963:Bacteroidetes / Q000187:drug effects; D005243:Feces / Q000382:microbiology; D000068536:Bacillota / Q000187:drug effects; D000069196:Gastrointestinal Microbiome / Q000187:drug effects; D023281:Genomics; D050356:Lipid Metabolism / Q000187:drug effects* / Q000235:genetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008387:Marine Toxins; D055432:Metabolomics; D008810:Mice, Inbred C57BL; D052998:Microcystins / Q000633:toxicity*; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D059467:Transcriptome
chemical_list: D008387:Marine Toxins; D052998:Microcystins; D012336:RNA, Ribosomal, 16S; C057862:cyanoginosin LR
keywords: Lipid metabolism; Metabonomics; Metagenomics; Microcystin-LR; Transcriptomics