Title:Acute Injury in Natural Diet-Induced Fatty Livers - A Model for Therapy Development
Volume: 5
Issue: 2
Author(s): Brian Huang, Nicholas A. E. Abbott, Linai Dacon, Siobhan McCormack, Ping Zhou, Liming Zhang, Bin Duan, Jingsong Li, Bo Zhang, Michael Yamin, Latha Paka, Itzhak D. Goldberg and Prakash Narayan
Affiliation:
Keywords:
Acetaminophen, acute, alcohol, fibrosis, injury, liver, steatosis.
Abstract: Given the diabesity and metabolic syndrome epidemics, fatty liver disease is reaching epidemic
proportions. Relatively indolent, this disease is often asymptomatic and the patient is often
made aware of its presence only during a routine physical exam. Nevertheless, fatty livers are more
susceptible to insult compared to their non-fatty counterparts and persons with fatty livers are at increased
risk for morbidity and mortality following consumption of commonly used substances such as
alcohol (EtOH) and acetaminophen (APAP). We have developed a rat model of natural diet-induced
fatty liver disease and evaluated the effects of two commonly used substances viz. EtOH and APAP in this phenotype.
High fat diet (HFD) fed animals exhibited steatosis, liver inflammation and liver fibrosis with an increase in serum aspartate
aminotransferase. Bolus administration of EtOH, which was without effect on the livers from standard diet fed animals,
had a profound and adverse impact on the HFD fatty liver. Similarly, APAP administration which was without effect
on liver function tests in control animals, also provoked an increase in liver enzymes in HFD animals. Treatment with
the poly(ADP-ribose) polymerase-1 inhibitor (PARP-1), veliparib, reduced the increase in liver function tests secondary to
EtOH and APAP. This model forms the framework for identification of fatty liver disease biomarkers given that this disease
is relatively asymptomatic but fraught with risk for acute injury. This model also forms the framework for evaluation of novel
drugs for acute injury in fatty livers especially given that current strategies for management of acute liver failure in non-fatty
livers are inadequate. Also, relevant patents related to the use of liver biomarkers as diagnostic are discussed.
