title: Azoxystrobin, a mitochondrial complex III Qo site inhibitor, exerts beneficial metabolic effects in vivo and in vitro.
abstract: BACKGROUND
  Several anti-diabetes drugs exert beneficial effects against metabolic syndrome by inhibiting mitochondrial function. Although much progress has been made toward understanding the role of mitochondrial function inhibitors in treating metabolic diseases, the potential effects of these inhibitors on mitochondrial respiratory chain complex III remain unclear.
  
  
  METHODS
  We investigated the metabolic effects of azoxystrobin (AZOX), a Qo inhibitor of complex III, in a high-fat diet-fed mouse model with insulin resistance in order to elucidate the mechanism by which AZOX improves glucose and lipid metabolism at the metabolic cellular level.
  
  
  RESULTS
  Acute administration of AZOX in mice increased the respiratory exchange ratio. Chronic treatment with AZOX reduced body weight and significantly improved glucose tolerance and insulin sensitivity in high-fat diet-fed mice. AZOX treatment resulted in decreased triacylglycerol accumulation and down-regulated the expression of genes involved in liver lipogenesis. AZOX increased glucose uptake in L6 myotubes and 3T3-L1 adipocytes and inhibited de novo lipogenesis in HepG2 cells. The findings indicate that AZOX-mediated alterations to lipid and glucose metabolism may depend on AMP-activated protein kinase (AMPK) signaling.
  
  
  CONCLUSIONS
  AZOX, a Qo inhibitor of mitochondrial respiratory complex III, exerts whole-body beneficial effects on the regulation of glucose and lipid homeostasis in high-fat diet-fed mice.
  
  
  CONCLUSIONS
  These findings provide evidence that a Qo inhibitor of mitochondrial respiratory complex III could represent a novel approach for the treatment of obesity.
authors.affiliation: Laboratory of Physiology, School of Life Science, East China Normal University, Shanghai 200062, China; National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: An-Hui
authors.initials: AH
authors.lastname: Gao
authors.affiliation: National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yan-Yun
authors.initials: YY
authors.lastname: Fu
authors.affiliation: Laboratory of Physiology, School of Life Science, East China Normal University, Shanghai 200062, China.
authors.forename: Kun-Zhi
authors.initials: KZ
authors.lastname: Zhang
authors.affiliation: National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Laboratory of Physiology, School of Life Science, East China Normal University, Shanghai 200062, China.
authors.forename: Hao-Wen
authors.initials: HW
authors.lastname: Jiang
authors.affiliation: Laboratory of Physiology, School of Life Science, East China Normal University, Shanghai 200062, China.
authors.forename: Li-Xia
authors.initials: LX
authors.lastname: Fan
authors.affiliation: National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Fa-Jun
authors.initials: FJ
authors.lastname: Nan
authors.affiliation: Laboratory of Physiology, School of Life Science, East China Normal University, Shanghai 200062, China. Electronic address: cgyuan@bio.ecnu.edu.cn.
authors.forename: Chong-Gang
authors.initials: CG
authors.lastname: Yuan
authors.affiliation: Laboratory of Physiology, School of Life Science, East China Normal University, Shanghai 200062, China; National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. Electronic address: ybzhou@mail.shcnc.ac.cn.
authors.forename: Yu-Bo
authors.initials: YB
authors.lastname: Zhou
authors.affiliation: National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. Electronic address: jyli@mail.shcnc.ac.cn.
authors.forename: Jing-Ya
authors.initials: JY
authors.lastname: Li
mesh_terms: D050156:Adipogenesis / Q000235:genetics; D000818:Animals; D059305:Diet, High-Fat; D014450:Electron Transport Complex III / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004734:Energy Metabolism / Q000235:genetics; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008689:Methacrylates / Q000008:administration & dosage* / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D011743:Pyrimidines / Q000008:administration & dosage* / Q000378:metabolism; D000073739:Strobilurins; D014280:Triglycerides / Q000378:metabolism
chemical_list: D008689:Methacrylates; D011743:Pyrimidines; D000073739:Strobilurins; D014280:Triglycerides; D014450:Electron Transport Complex III; D005947:Glucose; C087670:azoxystrobin
keywords: AMP-activated protein kinase; Azoxystrobin; Metabolic diseases; Mitochondria complex III