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dc.contributor.authorEsquejo, RM
dc.contributor.authorSalatto, CT
dc.contributor.authorDelmore, J
dc.contributor.authorAlbuquerque, B
dc.contributor.authorReyes, A
dc.contributor.authorShi, Y
dc.contributor.authorMoccia, R
dc.contributor.authorCokorinos, E
dc.contributor.authorPeloquin, M
dc.contributor.authorMonetti, M
dc.contributor.authorBarricklow, J
dc.contributor.authorBollinger, E
dc.contributor.authorSmith, BK
dc.contributor.authorDay, EA
dc.contributor.authorNguyen, C
dc.contributor.authorGeoghegan, KF
dc.contributor.authorKreeger, JM
dc.contributor.authorOpsahl, A
dc.contributor.authorWard, J
dc.contributor.authorKalgutkar, AS
dc.contributor.authorTess, D
dc.contributor.authorButler, L
dc.contributor.authorShirai, N
dc.contributor.authorOsborne, TF
dc.contributor.authorSteinberg, GR
dc.contributor.authorBirnbaum, MJ
dc.contributor.authorCameron, KO
dc.contributor.authorMiller, RA
dc.date.accessioned2020-12-17T03:39:04Z
dc.date.available2020-12-17T03:39:04Z
dc.date.issued2018-05
dc.identifierpii: S2352-3964(18)30137-3
dc.identifier.citationEsquejo, R. M., Salatto, C. T., Delmore, J., Albuquerque, B., Reyes, A., Shi, Y., Moccia, R., Cokorinos, E., Peloquin, M., Monetti, M., Barricklow, J., Bollinger, E., Smith, B. K., Day, E. A., Nguyen, C., Geoghegan, K. F., Kreeger, J. M., Opsahl, A., Ward, J. ,... Miller, R. A. (2018). Activation of Liver AMPK with PF-06409577 Corrects NAFLD and Lowers Cholesterol in Rodent and Primate Preclinical Models.. EBioMedicine, 31, pp.122-132. https://doi.org/10.1016/j.ebiom.2018.04.009.
dc.identifier.issn2352-3964
dc.identifier.urihttp://hdl.handle.net/11343/254973
dc.description.abstractDysregulation of hepatic lipid and cholesterol metabolism is a significant contributor to cardiometabolic health, resulting in excessive liver lipid accumulation and ultimately non-alcoholic steatohepatitis (NASH). Therapeutic activators of the AMP-Activated Protein Kinase (AMPK) have been proposed as a treatment for metabolic diseases; we show that the AMPK β1-biased activator PF-06409577 is capable of lowering hepatic and systemic lipid and cholesterol levels in both rodent and monkey preclinical models. PF-06409577 is able to inhibit de novo lipid and cholesterol synthesis pathways, and causes a reduction in hepatic lipids and mRNA expression of markers of hepatic fibrosis. These effects require AMPK activity in the hepatocytes. Treatment of hyperlipidemic rats or cynomolgus monkeys with PF-06409577 for 6weeks resulted in a reduction in circulating cholesterol. Together these data suggest that activation of AMPK β1 complexes with PF-06409577 is capable of impacting multiple facets of liver disease and represents a promising strategy for the treatment of NAFLD and NASH in humans.
dc.languageeng
dc.publisherElsevier BV
dc.titleActivation of Liver AMPK with PF-06409577 Corrects NAFLD and Lowers Cholesterol in Rodent and Primate Preclinical Models.
dc.typeJournal Article
dc.identifier.doi10.1016/j.ebiom.2018.04.009
melbourne.affiliation.departmentMedicine and Radiology
melbourne.source.titleEBioMedicine
melbourne.source.volume31
melbourne.source.pages122-132
dc.rights.licenseCC BY-NC-ND
melbourne.elementsid1326017
melbourne.openaccess.pmchttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC6014578
melbourne.contributor.authorSteinberg, Gregory
dc.identifier.eissn2352-3964
melbourne.accessrightsOpen Access


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