Effects of methimazole on Drosophila glucolipid metabolism in vitro and in vivo.
Methimazole (MMI) is an antithyroid agent widely used in the treatment of hyperthyroidism, and metabolized by cytochrome P450 enzymes and flavin-containing monooxygenases in mammals. However, drug overdose and the inadequate detoxification of the metabolite(s) are responsible for hepatocellular damage and organ dysfunction. Depending on the desired properties, Drosophila melanogaster has recently emerged as an ideal model organism for the study of human diseases. Here we investigated the changes in metabolic profiles and mRNA expressions related to glucolipid metabolism in response to treatment with MMI in Drosophila. Remarkable loss of lifespan occurred in fruit flies fed on the diets containing 10 or 30mM MMI compared to unsupplemented controls. To examine whether MMI affects glucolipid metabolism in vitro and in vivo, fruit flies were fed diets containing 30mM MMI for two weeks and Drosophila S2 cells were incubated with 300μM MMI for 48h. Measurements of metabolites showed that triglyceride content dramatically decreased (30.56% in vivo and 18.13% in vitro), and glycogen content significantly increased (10.7% in vivo and 126.8% in vitro). Quantitative analyses indicated that mRNA expression levels of Dmfmo1, s6k, dilp2, acc and dilp5 genes involved in metabolic homeostasis were remarkably down-regulated in vivo and in vitro. Meanwhile, the addition of MMI could significantly reduce the lipid droplet content in S2 cells by approximately 25% compared to control subjects. These data may provide a biological basis for the study of MMI on disease symptoms and complications, and discovery of therapeutic treatments.
Department of Pesticide Sciences, College of Plant Protection, Nanjing Agricultural University, State & Local Joint Engineering Research Center of Green Pesticide Invention and Application, Nanjing, China.
Qi
Q
Wei
Department of Pesticide Sciences, College of Plant Protection, Nanjing Agricultural University, State & Local Joint Engineering Research Center of Green Pesticide Invention and Application, Nanjing, China.
Bo
B
Hu
Department of Pesticide Sciences, College of Plant Protection, Nanjing Agricultural University, State & Local Joint Engineering Research Center of Green Pesticide Invention and Application, Nanjing, China.
Yuan
Y
Xue
Department of Pesticide Sciences, College of Plant Protection, Nanjing Agricultural University, State & Local Joint Engineering Research Center of Green Pesticide Invention and Application, Nanjing, China.
David Kibe
DK
Mburu
Department of Pesticide Sciences, College of Plant Protection, Nanjing Agricultural University, State & Local Joint Engineering Research Center of Green Pesticide Invention and Application, Nanjing, China.
Xian
X
Tao
Department of Pesticide Sciences, College of Plant Protection, Nanjing Agricultural University, State & Local Joint Engineering Research Center of Green Pesticide Invention and Application, Nanjing, China. Electronic address: sjy@njau.edu.cn.
Jianya
J
Su
D000818:Animals; D013956:Antithyroid Agents / Q000633:toxicity*; D050260:Carbohydrate Metabolism / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004331:Drosophila melanogaster / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006003:Glycogen / Q000819:agonists / Q000096:biosynthesis; D019476:Insect Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D007928:Lethal Dose 50; D066292:Lipid Droplets / Q000187:drug effects / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D008136:Longevity / Q000187:drug effects; D008297:Male; D008713:Methimazole / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D016019:Survival Analysis; D023382:Toxicity Tests, Acute; D036401:Toxicity Tests, Chronic; D014280:Triglycerides / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D013956:Antithyroid Agents; D019476:Insect Proteins; D012333:RNA, Messenger; D014280:Triglycerides; D008713:Methimazole; D006003:Glycogen
Drosophila melanogaster; Glucolipid metabolism; Glycogen; Methimazole; Triglyceride