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TM-25659-Induced Activation of FGF21 Level Decreases Insulin Resistance and Inflammation in Skeletal Muscle via GCN2 Pathways.

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dc.contributor.authorJung, JG-
dc.contributor.authorYi, SA-
dc.contributor.authorChoi, SE-
dc.contributor.authorKang, Y-
dc.contributor.authorKim, TH-
dc.contributor.authorJeon, JY-
dc.contributor.authorBae, MA-
dc.contributor.authorAhn, JH-
dc.contributor.authorJeong, H-
dc.contributor.authorHwang, ES-
dc.contributor.authorLee, KW-
dc.date.accessioned2017-02-01T05:59:47Z-
dc.date.available2017-02-01T05:59:47Z-
dc.date.issued2015-
dc.identifier.issn1016-8478-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/13445-
dc.description.abstractThe 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.isoen-
dc.subject.MESHAnimals-
dc.subject.MESHAnti-Inflammatory Agents-
dc.subject.MESHBridged Bicyclo Compounds, Heterocyclic-
dc.subject.MESHCells, Cultured-
dc.subject.MESHDiet, High-Fat-
dc.subject.MESHFibroblast Growth Factors-
dc.subject.MESHGene Expression Regulation-
dc.subject.MESHInflammation-
dc.subject.MESHInsulin Resistance-
dc.subject.MESHMale-
dc.subject.MESHMice-
dc.subject.MESHMuscle, Skeletal-
dc.subject.MESHMyoblasts, Skeletal-
dc.subject.MESHPalmitates-
dc.subject.MESHProtein-Serine-Threonine Kinases-
dc.subject.MESHSignal Transduction-
dc.subject.MESHTetrazoles-
dc.titleTM-25659-Induced Activation of FGF21 Level Decreases Insulin Resistance and Inflammation in Skeletal Muscle via GCN2 Pathways.-
dc.typeArticle-
dc.identifier.pmid26537193-
dc.identifier.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4696994/-
dc.contributor.affiliatedAuthor최, 성이-
dc.contributor.affiliatedAuthor강, 엽-
dc.contributor.affiliatedAuthor전, 자영-
dc.contributor.affiliatedAuthor이, 관우-
dc.type.localJournal Papers-
dc.identifier.doi10.14348/molcells.2015.0100-
dc.citation.titleMolecules and cells-
dc.citation.volume38-
dc.citation.number12-
dc.citation.date2015-
dc.citation.startPage1037-
dc.citation.endPage1043-
dc.identifier.bibliographicCitationMolecules and cells, 38(12). : 1037-1043, 2015-
dc.identifier.eissn0219-1032-
dc.relation.journalidJ010168478-
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
Journal Papers > School of Medicine / Graduate School of Medicine > Endocrinology & Metabolism
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