title: Fibroblast growth factor-21 protects human skeletal muscle myotubes from palmitate-induced insulin resistance by inhibiting stress kinase and NF-κB.
abstract: We investigated the effects of fibroblast growth factor-21 (FGF-21) on palmitate-induced insulin resistance in skeletal muscle myotubes. First, to determine the effect of FGF-21 on palmitate-induced insulin resistance, we measured 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose uptake and levels of proteins involved in insulin signaling pathways (IRS-1 and Akt) in human skeletal muscle myotubes (HSMMs) exposed to palmitate for 24h, and compared HSMMs exposed to palmitate and different doses of recombinant FGF-21. Second, to determine the mechanisms underlying the contribution of FGF-21 to palmitate-induced insulin resistance, we compared levels of proteins linked to palmitate-induced insulin resistance (PKC-θ, IKKα/β, JNK, p38, IκBα, and NF-κB) in HSMMs exposed to palmitate and different doses of recombinant FGF-21 for 24h. Palmitate-reduced glucose uptake was restored by FGF-21. Palmitate inhibited phosphorylation of Akt and thereby impaired insulin signaling in HSMMs. FGF-21 prevented palmitate from inhibiting the phosphorylation of Akt. These results indicate that FGF-21 prevented palmitate-induced insulin resistance in HSMMs. Palmitate activated NF-κB in HSMMs, thereby impairing the action of insulin and initiating chronic inflammation. FGF-21 inhibited palmitate-induced NF-κB activation in HSMMs. The results of the present study suggest that FGF-21 prevents palmitate-induced insulin resistance in HSMMs by inhibiting the activation of stress kinase and NF-κB.
authors.affiliation: Department of Endocrinology and Metabolism, Ajou University, School of Medicine, Suwon, Republic of Korea.
authors.forename: Min Suk
authors.initials: MS
authors.lastname: Lee
authors.forename: Sung-E
authors.initials: SE
authors.lastname: Choi
authors.forename: Eun Suk
authors.initials: ES
authors.lastname: Ha
authors.forename: So-Yeon
authors.initials: SY
authors.lastname: An
authors.forename: Tae Ho
authors.initials: TH
authors.lastname: Kim
authors.forename: Seung Jin
authors.initials: SJ
authors.lastname: Han
authors.forename: Hae Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Dae Jung
authors.initials: DJ
authors.lastname: Kim
authors.forename: Yup
authors.initials: Y
authors.lastname: Kang
authors.forename: Kwan-Woo
authors.initials: KW
authors.lastname: Lee
mesh_terms: D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives / Q000378:metabolism; D015153:Blotting, Western; D003847:Deoxyglucose / Q000031:analogs & derivatives / Q000378:metabolism; D004789:Enzyme Activation; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit / Q000037:antagonists & inhibitors*; D019308:Palmitic Acid; D010766:Phosphorylation; D016133:Polymerase Chain Reaction / Q000379:methods; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D007328:Insulin; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D034741:RNA, Small Interfering; C495677:SLC2A1 protein, human; C495692:SLC2A4 protein, human; C414620:fibroblast growth factor 21; D019308:Palmitic Acid; D005346:Fibroblast Growth Factors; D003847:Deoxyglucose; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D051550:I-kappa B Kinase; D048670:MAP Kinase Kinase 4; D009327:4-Chloro-7-nitrobenzofurazan; C098340:2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose