title: Pentamethylquercetin generates beneficial effects in monosodium glutamate-induced obese mice and C2C12 myotubes by activating AMP-activated protein kinase.
abstract: OBJECTIVE
  Pentamethylquercetin (PMQ) has recently been shown to have glucose-lowering properties. Here, we aimed to characterise the effectiveness and underlying mechanisms of PMQ for ameliorating metabolic disorders in vivo and vitro.
  
  
  METHODS
  We generated a mouse model of obesity by neonatal administration of monosodium glutamate (MSG) and used it to assess the properties of PMQ as a treatment for metabolic disorders. We also investigated the possible underlying mechanisms of PMQ in the prevention of metabolic disorders.
  
  
  RESULTS
  Compared with normal mice, MSG mice had metabolic disorders, including central obesity, hyperinsulinaemia, insulin resistance, hyperglycaemia, hyperlipidaemia, decreased phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), and downregulated levels of GLUT4 in gastrocnemius muscles. In MSG mice, PMQ treatment (5, 10, 20 mg/kg daily) reduced body weight gain, waist circumference, adipose tissue mass, serum glucose, triacylglycerol and total cholesterol, while improving insulin resistance, activating AMPK and increasing ACC phosphorylation and GLUT4 abundance. In C2C12 myotubes, PMQ (10 μmol/l) increased glucose consumption by ∼65%. PMQ treatment (1-10 μmol/l) also activated AMPK, increased ACC phosphorylation and GLUT4 abundance, and upregulated the expression of some key genes involved in fatty acid oxidation.
  
  
  CONCLUSIONS
  These findings suggest that PMQ can ameliorate metabolic disorders at least in part via stimulation of AMPK activity.
authors.affiliation: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, Hubei 430030, China.
authors.forename: J Z
authors.initials: JZ
authors.lastname: Shen
authors.forename: L N
authors.initials: LN
authors.lastname: Ma
authors.forename: Y
authors.initials: Y
authors.lastname: Han
authors.forename: J X
authors.initials: JX
authors.lastname: Liu
authors.forename: W Q
authors.initials: WQ
authors.lastname: Yang
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: Y
authors.initials: Y
authors.lastname: Hu
authors.forename: M W
authors.initials: MW
authors.lastname: Jin
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000103:Acetyl-CoA Carboxylase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival; D002784:Cholesterol / Q000097:blood; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism*; D011794:Quercetin / Q000737:chemistry / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012970:Sodium Glutamate / Q000009:adverse effects*; D014280:Triglycerides; D055105:Waist Circumference / Q000187:drug effects; D015430:Weight Gain / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D051275:Glucose Transporter Type 4; C495693:Slc2a4 protein, mouse; D014280:Triglycerides; D002784:Cholesterol; D011794:Quercetin; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase; D012970:Sodium Glutamate