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TM-25659-Induced Activation of FGF21 Level Decreases Insulin Resistance and Inflammation in Skeletal Muscle via GCN2 Pathways.
DC Field | Value | Language |
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dc.contributor.author | Jung, JG | - |
dc.contributor.author | Yi, SA | - |
dc.contributor.author | Choi, SE | - |
dc.contributor.author | Kang, Y | - |
dc.contributor.author | Kim, TH | - |
dc.contributor.author | Jeon, JY | - |
dc.contributor.author | Bae, MA | - |
dc.contributor.author | Ahn, JH | - |
dc.contributor.author | Jeong, H | - |
dc.contributor.author | Hwang, ES | - |
dc.contributor.author | Lee, KW | - |
dc.date.accessioned | 2017-02-01T05:59:47Z | - |
dc.date.available | 2017-02-01T05:59:47Z | - |
dc.date.issued | 2015 | - |
dc.identifier.issn | 1016-8478 | - |
dc.identifier.uri | http://repository.ajou.ac.kr/handle/201003/13445 | - |
dc.description.abstract | The TAZ activator 2-butyl-5-methyl-6-(pyridine-3-yl)-3-[2'-(1H-tetrazole-5-yl)-biphenyl-4-ylmethyl]-3H-imidazo[4,5-b]pyridine] (TM-25659) inhibits adipocyte differentiation by interacting with peroxisome proliferator-activated receptor gamma. TM-25659 was previously shown to decrease weight gain in a high fat (HF) diet-induced obesity (DIO) mouse model. However, the fundamental mechanisms underlying the effects of TM-25659 remain unknown. Therefore, we investigated the effects of TM-25659 on skeletal muscle functions in C2 myotubes and C57BL/6J mice. We studied the molecular mechanisms underlying the contribution of TM-25659 to palmitate (PA)-induced insulin resistance in C2 myotubes. TM-25659 improved PA-induced insulin resistance and inflammation in C2 myotubes. In addition, TM-25659 increased FGF21 mRNA expression, protein levels, and FGF21 secretion in C2 myotubes via activation of GCN2 pathways (GCN2-phosphoeIF2α-ATF4 and FGF21). This beneficial effect of TM-25659 was diminished by FGF21 siRNA. C57BL/6J mice were fed a HF diet for 30 weeks. The HF-diet group was randomly divided into two groups for the next 14 days: the HF-diet and HF-diet + TM-25659 groups. The HF diet + TM-25659-treated mice showed improvements in their fasting blood glucose levels, insulin sensitivity, insulin-stimulated Akt phosphorylation, and inflammation, but neither body weight nor food intake was affected. The HF diet + TM-25659-treated mice also exhibited increased expression of both FGF21 mRNA and protein. These data indicate that TM-25659 may be beneficial for treating insulin resistance by inducing FGF21 in models of PA-induced insulin resistance and HF diet-induced insulin resistance. | - |
dc.language.iso | en | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Anti-Inflammatory Agents | - |
dc.subject.MESH | Bridged Bicyclo Compounds, Heterocyclic | - |
dc.subject.MESH | Cells, Cultured | - |
dc.subject.MESH | Diet, High-Fat | - |
dc.subject.MESH | Fibroblast Growth Factors | - |
dc.subject.MESH | Gene Expression Regulation | - |
dc.subject.MESH | Inflammation | - |
dc.subject.MESH | Insulin Resistance | - |
dc.subject.MESH | Male | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Muscle, Skeletal | - |
dc.subject.MESH | Myoblasts, Skeletal | - |
dc.subject.MESH | Palmitates | - |
dc.subject.MESH | Protein-Serine-Threonine Kinases | - |
dc.subject.MESH | Signal Transduction | - |
dc.subject.MESH | Tetrazoles | - |
dc.title | TM-25659-Induced Activation of FGF21 Level Decreases Insulin Resistance and Inflammation in Skeletal Muscle via GCN2 Pathways. | - |
dc.type | Article | - |
dc.identifier.pmid | 26537193 | - |
dc.identifier.url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4696994/ | - |
dc.contributor.affiliatedAuthor | 최, 성이 | - |
dc.contributor.affiliatedAuthor | 강, 엽 | - |
dc.contributor.affiliatedAuthor | 전, 자영 | - |
dc.contributor.affiliatedAuthor | 이, 관우 | - |
dc.type.local | Journal Papers | - |
dc.identifier.doi | 10.14348/molcells.2015.0100 | - |
dc.citation.title | Molecules and cells | - |
dc.citation.volume | 38 | - |
dc.citation.number | 12 | - |
dc.citation.date | 2015 | - |
dc.citation.startPage | 1037 | - |
dc.citation.endPage | 1043 | - |
dc.identifier.bibliographicCitation | Molecules and cells, 38(12). : 1037-1043, 2015 | - |
dc.identifier.eissn | 0219-1032 | - |
dc.relation.journalid | J010168478 | - |
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