TY  - JOUR
AU  - Esquejo, RM
AU  - Salatto, CT
AU  - Delmore, J
AU  - Albuquerque, B
AU  - Reyes, A
AU  - Shi, Y
AU  - Moccia, R
AU  - Cokorinos, E
AU  - Peloquin, M
AU  - Monetti, M
AU  - Barricklow, J
AU  - Bollinger, E
AU  - Smith, BK
AU  - Day, EA
AU  - Nguyen, C
AU  - Geoghegan, KF
AU  - Kreeger, JM
AU  - Opsahl, A
AU  - Ward, J
AU  - Kalgutkar, AS
AU  - Tess, D
AU  - Butler, L
AU  - Shirai, N
AU  - Osborne, TF
AU  - Steinberg, GR
AU  - Birnbaum, MJ
AU  - Cameron, KO
AU  - Miller, RA
Y2  - 2020/12/17
Y1  - 2018/05
SN  - 2352-3964
UR  - http://hdl.handle.net/11343/254973
AB  - Dysregulation 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.
LA  - eng
PB  - Elsevier BV
T1  - Activation of Liver AMPK with PF-06409577 Corrects NAFLD and Lowers Cholesterol in Rodent and Primate Preclinical Models.
DO  - 10.1016/j.ebiom.2018.04.009
IS  - EBioMedicine
VL  - 31
SP  - 122-132
L1  - /bitstream/handle/11343/254973/PMC6014578.pdf?sequence=1&isAllowed=y
ER  -