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.

MiRNAs in Alcohol-Related Liver Diseases and Hepatocellular Carcinoma: A Step toward New Therapeutic Approaches?

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Bioconversion, Pharmacokinetics, and Therapeutic Mechanisms of Ginsenoside Compound K and Its Analogues for Treating Metabolic Diseases

“…Additionally, PPARγ influences lipid metabolism, which enhances sensitivity to insulin and glucose metabolism [ 16 ]. AMPK and PPARγ are the fundamental targets in metabolic disorders, including NAFLD, diabetes, osteoporosis, and obesity [ 17 , 18 ]. In addition, CK downregulates PPAR , leptin , aP2 , and C/EBP adipogenic markers, which cause obesity, diabetes, and other metabolic diseases [ 19 ].…”

Aerobic training with moderate or high doses of vitamin D improve liver enzymes, LXRα and PGC-1α levels in rats with T2DM

“…The proper liver function and the levels of several enzymes are regulated by the activation of lipogenic transcriptional factors such as Liver X Receptors (LXRs) and peroxisome proliferator-activated receptor (PPAR) γ coactivator 1α (PGC1α) 4 , 5 . The ligand-activated transcription factors, LXRs, belong to the superfamily of nuclear receptor which is activated in the presence of excess cholesterol accumulation with two main subtypes, LXRβ and LXRα that is highly expressed in the liver 6 , 7 .…”