Bardoxolone methyl prevents insulin resistance and the development of hepatic steatosis in mice fed a high-fat diet

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dc.contributor.authorCamer, Den_AU
dc.contributor.authorYu, YHen_AU
dc.contributor.authorSzabo, Aen_AU
dc.contributor.authorDinh, CHLen_AU
dc.contributor.authorWang, HQen_AU
dc.contributor.authorCheng, LCen_AU
dc.contributor.authorHuang, XFen_AU
dc.date.accessioned2017-05-15T00:52:51Zen_AU
dc.date.available2017-05-15T00:52:51Zen_AU
dc.date.issued2015-09-05en_AU
dc.date.statistics2017-05-15en_AU
dc.description.abstractHigh-fat (HF) diet-induced obesity is a major risk factor for the development of insulin resistance and hepatic steatosis. We examined the hypothesis that bardoxolone methyl (BM) would prevent the development of insulin resistance and hepatic steatosis in mice fed a HF diet. C57BL/6J male mice were fed a lab chow (LC), HF (40% fat), or HF diet supplemented with 10 mg/kg/day BM orally for 21 weeks. Glucose metabolism was assessed using a glucose tolerance test (GTT) and insulin sensitivity test (IST). Signalling molecules involved in insulin resistance, inflammation, and lipid metabolism were examined in liver tissue via western blotting and RT-PCR. BM prevented HF diet-induced insulin resistance and alterations in the protein levels of protein tyrosine phosphatase 1B (PTP1B), forkhead box protein O1 (FOXO1) and BDNF, and expression of the insulin receptor (IR), IRS-1 and glucose-6-phosphatase (G6Pase) genes. Furthermore, BM prevented fat accumulation in the liver and decreases in the β-oxidation gene, peroxisomal acyl-coenzyme A oxidase 1 (ACOX) in mice fed a HF diet. In the livers of HF fed mice, BM administration prevented HF diet-induced macrophage infiltration, inflammation as indicated by reduced IL-6 and signal transducer and activator of transcription 3 (STAT3) protein levels and TNFα mRNA expression, and increased nuclear factor-like 2 (Nrf2) mRNA expression and nuclear protein levels. These findings suggest that BM prevents HF diet induced insulin resistance and the development of hepatic steatosis in mice fed a chronic HF diet through modulation of molecules involved in insulin signalling, lipid metabolism and inflammation in the liver.© 2015, Elsevier Ireland Ltd.en_AU
dc.identifier.citationCamer, D., Yu, Y., Szabo, A., Dinh, C. H. L., Wang, H., Cheng, L., & Huang, X.-F. (2015). Bardoxolone methyl prevents insulin resistance and the development of hepatic steatosis in mice fed a high-fat diet. Molecular and Cellular Endocrinology, 412, 36-43. doi: http://dx.doi.org/10.1016/j.mce.2015.05.018en_AU
dc.identifier.govdoc8223en_AU
dc.identifier.issn0303-7207en_AU
dc.identifier.journaltitleMolecular and Cellular Endocrinologyen_AU
dc.identifier.pagination36-43en_AU
dc.identifier.urihttp://dx.doi.org/10.1016/j.mce.2015.05.018en_AU
dc.identifier.urihttp://apo.ansto.gov.au/dspace/handle/10238/8699en_AU
dc.identifier.volume412en_AU
dc.language.isoenen_AU
dc.publisherElsevieren_AU
dc.subjectInsulinen_AU
dc.subjectDieten_AU
dc.subjectInflammationen_AU
dc.subjectMiceen_AU
dc.subjectMetabolic diseasesen_AU
dc.subjectLiveren_AU
dc.titleBardoxolone methyl prevents insulin resistance and the development of hepatic steatosis in mice fed a high-fat dieten_AU
dc.typeJournal Articleen_AU
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