Journal article

Activation of Liver AMPK with PF-06409577 Corrects NAFLD and Lowers Cholesterol in Rodent and Primate Preclinical Models.

Ryan M Esquejo, Christopher T Salatto, Jake Delmore, Bina Albuquerque, Allan Reyes, Yuji Shi, Rob Moccia, Emily Cokorinos, Matthew Peloquin, Mara Monetti, Jason Barricklow, Eliza Bollinger, Brennan K Smith, Emily A Day, Chuong Nguyen, Kieran F Geoghegan, John M Kreeger, Alan Opsahl, Jessica Ward, Amit S Kalgutkar Show all

EBioMedicine | Published : 2018

Abstract

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 ..

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