Obesity and nonalcoholic fatty liver disease: current perspectives

Abstract

Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the most common cause of chronic liver disease due to an increase in the prevalence of obesity. The development of NASH leads to an increase in morbidity and mortality. While the first line of treatment is lifestyle modifications, including dietary changes and increased physical activity, there are no approved pharmacological treatment agents for NAFLD and NASH currently. Due to its complex pathophysiology, different pathways are under investigation for drug development with the focus on metabolic pathways, inflammation, and slowing or reversing fibrosis. There are several agents advancing in clinical trials, and promising results have been seen with drugs that affect hepatic steatosis, inflammation, and fibrosis. This review will provide an overview on NAFLD and some of the mechanisms of disease that are being targeted with pharmacologic agents.

Keywords: antifibrotics; clinical trials; nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; pharmacotherapy.

Figure 1

Mechanism of action of pharmacotherapies for NASH. Abbreviations: ACC, acetyl-CoA carboxylase; AP1, activator protein 1; ASK, apoptosis signal-regulating kinase; CCR2/5, C-C chemokine receptor type 2/5; CYP7A1, cytochrome P450 7A1; ER, endoplasmic reticulum; FFA, free fatty acids; FGF, fibroblast growth factor; FGFR, fibroblast growth factor receptor; FXR, Farnesoid X receptor; JNK, Jun N-terminal kinases; NASH, nonalcoholic steatohepatitis; ROS, reactive oxygen species; SCD, stearoyl-CoA desaturase; TRβ, thyroid receptor β.