Peroxisome Proliferator-Activated Receptor-γ as a Target and Regulator of Epigenetic Mechanisms in Nonalcoholic Fatty Liver Disease

Abstract

Peroxisome proliferator-activated receptor-γ (PPARγ) belongs to the superfamily of nuclear receptors that control the transcription of multiple genes. Although it is found in many cells and tissues, PPARγ is mostly expressed in the liver and adipose tissue. Preclinical and clinical studies show that PPARγ targets several genes implicated in various forms of chronic liver disease, including nonalcoholic fatty liver disease (NAFLD). Clinical trials are currently underway to investigate the beneficial effects of PPARγ agonists on NAFLD/nonalcoholic steatohepatitis. Understanding PPARγ regulators may therefore aid in unraveling the mechanisms governing the development and progression of NAFLD. Recent advances in high-throughput biology and genome sequencing have greatly facilitated the identification of epigenetic modifiers, including DNA methylation, histone modifiers, and non-coding RNAs as key factors that regulate PPARγ in NAFLD. In contrast, little is still known about the particular molecular mechanisms underlying the intricate relationships between these events. The paper that follows outlines our current understanding of the crosstalk between PPARγ and epigenetic regulators in NAFLD. Advances in this field are likely to aid in the development of early noninvasive diagnostics and future NAFLD treatment strategies based on PPARγ epigenetic circuit modification.