title: Microcystin-LR induced thyroid dysfunction and metabolic disorders in mice.
abstract: There is growing evidence that microcystins (MCs) act as hazardous materials and can disrupt the endocrine systems of animals. However, the response of thyroid function and the related energy metabolism following MCs exposure is still unknown. In the present study, mice were injected intraperitoneally (i.p.) with doses of either 5 or 20 μg/kg MC-LR for 4 weeks. We report, for the first time, that mice exposed to 20 μg/kg MC-LR showed disrupted glucose, triglyceride and cholesterol metabolism with obvious symptoms of hyperphagia, polydipsia, and weight loss. The circulating thyroid hormone (TH) levels in mice following MC-LR exposure were detected. Significantly increased free triiodothyronine (FT3) and decreased free thyroxin (FT4) were largely responsible for the physiological aberrations and metabolic disorders observed in mice after the 20 μg/kg MC-LR exposure. Increased expression of TH receptor (Trα) and mTOR expression in the brain after the 20 μg/kg MC-LR exposure suggests that the increased FT3 enhanced mTOR signaling subsequently led to hyperphagia and elevated energy expenditure in mice. Furthermore, several genes involved in glucose homeostasis and lipid metabolism, which have been identified affected by TH, were also differentially expressed after MC-LR exposure. The above results clearly showed that mice exposed to MC-LR experienced thyroid dysfunction and its downstream functional changes, and are useful to better understand the endocrine toxicity of MC-LR to mammals or even humans.
authors.affiliation: State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, 73 East Beijing Road, Nanjing 210008, PR China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, 73 East Beijing Road, Nanjing 210008, PR China.
authors.forename: Qingju
authors.initials: Q
authors.lastname: Xue
authors.affiliation: State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, 73 East Beijing Road, Nanjing 210008, PR China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Su
authors.affiliation: State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, 73 East Beijing Road, Nanjing 210008, PR China. Electronic address: lqxie@niglas.ac.cn.
authors.forename: Liqiang
authors.initials: L
authors.lastname: Xie
authors.affiliation: College of Life Science and Technology, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, PR China. Electronic address: yanyunjun@hust.edu.cn.
authors.forename: Yunjun
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Annis Water Resources Institute, Grand Valley State University, 740 West Shoreline Drive, Muskegon, MI 49441 USA.
authors.forename: Alan D
authors.initials: AD
authors.lastname: Steinman
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D052244:Endocrine Disruptors / Q000633:toxicity*; D004734:Energy Metabolism / Q000187:drug effects* / Q000235:genetics; D005247:Feeding Behavior / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006963:Hyperphagia / Q000097:blood / Q000139:chemically induced / Q000523:psychology; D008055:Lipids / Q000097:blood; D008297:Male; D008387:Marine Toxins; D008659:Metabolic Diseases / Q000097:blood / Q000139:chemically induced* / Q000235:genetics / Q000503:physiopathology / Q000523:psychology; D051379:Mice; D008807:Mice, Inbred BALB C; D052998:Microcystins / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D013959:Thyroid Diseases / Q000097:blood / Q000139:chemically induced* / Q000235:genetics / Q000503:physiopathology / Q000523:psychology; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D013974:Thyroxine / Q000097:blood; D013997:Time Factors; D014284:Triiodothyronine / Q000097:blood; D015431:Weight Loss / Q000187:drug effects
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D052244:Endocrine Disruptors; D008055:Lipids; D008387:Marine Toxins; D052998:Microcystins; D012333:RNA, Messenger; D014284:Triiodothyronine; C057862:cyanoginosin LR; D013974:Thyroxine
keywords: Hyperphagia; Metabolic disorders; Microcystin-LR; Molecular mechanism; Thyroid hormone