Date of Award

12-16-2015

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Biology

First Advisor

Dr. Hang Shi

Second Advisor

Dr. Bingzhong Xue

Third Advisor

Dr. Andrew Gewirtz

Abstract

Nonalcoholic steatohepatitis (NASH) is a highly prevalent liver disease in the world. About 15% to 25% of patients with NASH may progress to cirrhosis and hepatocellular carcinoma. However, there remains no U.S. Food and Drug Administration (FDA)-approved therapy for NASH. Our previous studies indicate that the combination of leucine and metformin or leucine and icariin, a phosphodiesterase type 5 inhibitor (PDE5i), improved nonalcoholic fatty liver disease (NAFLD) in Diet-induced Obesity (DIO) mice. Here we aim to evaluate the synergistic effect of leucine, metformin and sildenafil combination (Leu-Met-Sil) on NASH in Atherosclerosis diet-induced mouse model. Our data show that the Leu-Met-Sil combination significantly suppressed hepatic steatosis and fibrosis. This was associated with reduced alanine aminotransferase (ALT) levels in circulation. The Leu-Met-Sil combination also decreased inflammation and increased fatty acid oxidation in liver, which may contribute to the beneficial effects of the treatment on the NASH phenotype. We conclude that Leu-Met-Sil combination could be a novel therapy for the treatment of NASH.

Share

COinS