title: The Monascus metabolite monascin against TNF-α-induced insulin resistance via suppressing PPAR-γ phosphorylation in C2C12 myotubes.
abstract: Chronic inflammation in muscle tissue causes insulin resistance and type-2 diabetes. Peroxisome proliferator-activated receptor (PPAR) ligands are reported to activate the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, including pioglitazone, which belong to the thiazolidinedione (TZD). Monascin (MS), a Monascus metabolite, has been reported to exert anti-inflammatory activity in our recent study. Therefore, the alleviating mechanism of MS on tumor necrosis factor-α (TNF-α; 20ng/mL) induced insulin resistance in C2C12 cells was investigated in this study. Results showed that MS increased the uptake of 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-d-glucose (2-NBDG) in C2C12 myotubes. This result was associated with both PPAR-γ activity and PI3K/Akt pathway caused by MS inhibited p-JNK activity and prevented PPAR-γ phosphorylation. Moreover, we found that MS may act a PPAR-γ agonist to improve insulin sensitivity, and this issue was further confirmed by PPAR-γ antagonist (GW9662). Briefly, MS as pioglitazone, stabilized PPAR-γ structure and diminished PPAR-γ phosphorylation thereby improving insulin resistance.
authors.affiliation: Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan.
authors.forename: Bao-Hong
authors.initials: BH
authors.lastname: Lee
authors.forename: Wei-Hsuan
authors.initials: WH
authors.lastname: Hsu
authors.forename: Te-Han
authors.initials: TH
authors.lastname: Liao
authors.forename: Tzu-Ming
authors.initials: TM
authors.lastname: Pan
mesh_terms: D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D003847:Deoxyglucose / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology*; D007333:Insulin Resistance; D051379:Mice; D032741:Monascus / Q000737:chemistry*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D009327:4-Chloro-7-nitrobenzofurazan; D003847:Deoxyglucose; D006575:Heterocyclic Compounds, 3-Ring; D047495:PPAR gamma; D019869:Phosphatidylinositol 3-Kinases; D014409:Tumor Necrosis Factor-alpha; C098340:2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose; C517880:monascin