Peroxisome Proliferator-Activated Receptor-γ as a Target and Regulator of Epigenetic Mechanisms in Nonalcoholic Fatty Liver Disease
Abstract
1. Introduction
2. The Role of Epigenetic Mechanisms in Regulating PPARγ Regulatory Function in NAFLD
2.1. DNA Methylation
2.2. Histone Modifications
2.2.1. Histone Methylation/Demethylation
2.2.2. Histone Acetylation/Deacetylation
2.3. Noncoding RNAs
2.3.1. miRNAs-PPARγ Axis
2.3.2. lncRNAs-PPARγ Axis
2.3.3. circRNAs-PPARγ Axis
3. Limitations and Future Perspectives
4. Conclusions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Epigenetic Change | Biological Effect | Reference |
---|---|---|
Pparα/Pparγ/ methylation | DNA methylation of Pparα and Pparγ can distinguish between mild and severe NAFLD-associated fibrosis | [45] |
Pparγ promoter methylation | HFD and palmitic acid alter global and Pparγ promoter DNA methylation, resulting in Pparγ expression and enhanced lipid retention in the liver, which leads to the development of NAFLD | [47] |
Pparγ promoter methylation | Pparγ promoter hypermethylation levels in plasma-free DNA could be used as a non-invasive method to differentiate between NAFLD patients with mild and severe fibrosis | [48] |
Pparγ promoter methylation | Methylation levels of Pparγ correlate with liver fibrosis in rat model as well as in NAFLD patients | [44,48] |
Epigenetic Effector | Biological Effect | Reference |
---|---|---|
MLL4 | Murine steatosis caused by excessive feeding is regulated by the histone H3 lysine 4 methyltransferase MLL4/KMT2D via PPARγ2 | [56] |
Suv39h2 | SUV39H2 expression in hepatocytes, mice, and human livers is induced by pro-NASH stimuli, and thus contributes to NASH pathogenesis by suppressing Pparγ and Sirt1 expression. | [58] |
JMJD1A | JMJD1A promotes PPARγ expression by regulating the demethylation of Pparγ gene and thus inhibit HSCs activation and fibrosis | [60] |
JMJD2B | JMJD2B promotes the development of hepatic steatosis by upregulating PPARγ2 and steatosis target genes. | [61] |
miRNA | Target or Pathway | Pathophysiological Processes | References |
---|---|---|---|
miR-21 | PPARγ/SFR5 | PPARγ prevents inflammation and oxidative stress in mouse models and human tissue samples from NASH patients by modulating the miR21-5p/SFRP5 pathway | [101] |
miR-27 | PPARγ | Disrupting endogenous miR-27b activity in Zebrafish causes lipid accumulation and increased PPARγ expression in the liver, resulting in the early onset of NAFLD and NASH | [110] |
miR-34 | PPARγ | By targeting PPARγ, miR-34a/c activation may be associated with liver fibrosis | [122] |
miR-132 | PPARγ/MeCP/EZH2 | miR132/MeCP2/EZH2 axis is involved in the regulation of liver fibrosis | [125] |
miR-155 | PPARγ | miR-155 contained in obese ATM-exosomes, contributes to insulin resistance and glucose intolerance via a mechanism that is most likely related to direct suppression of its target gene Pparγ | [131] |
miR-3666 | PPARγ | miR-3666 inhibits the development of hepatic steatosis by negatively regulating PPARγ | [134] |
LncRNA | Targeted or Pathway | Pathophysiological Processes | References |
---|---|---|---|
Lnc-HC | miR-130-3p/PPARγ | LncRNA regulates hepatic lipid droplets accumulation via miR-130-3p/PPARγ pathway, which may help to prevent NAFLD | [138] |
H19 | miR-130a/PPARγ | H19 promotes hepatic lipogenesis and the progression of NAFLD via miR-130a/PPARγ axis | [140] |
LncRNA-SRA | PPARγ | LncRNA-SRA promotes hepatic steatosis by repressing the expression of adipose triglyceride lipase | [141] |
Hilnc | IGF22BP2/PPARγ | The loss of Hilnc prevents diet-induced hepatic steatosis by inhibiting PPARγ | [148] |
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Zaiou, M. Peroxisome Proliferator-Activated Receptor-γ as a Target and Regulator of Epigenetic Mechanisms in Nonalcoholic Fatty Liver Disease. Cells 2023, 12, 1205. https://doi.org/10.3390/cells12081205
Zaiou M. Peroxisome Proliferator-Activated Receptor-γ as a Target and Regulator of Epigenetic Mechanisms in Nonalcoholic Fatty Liver Disease. Cells. 2023; 12(8):1205. https://doi.org/10.3390/cells12081205
Chicago/Turabian StyleZaiou, Mohamed. 2023. "Peroxisome Proliferator-Activated Receptor-γ as a Target and Regulator of Epigenetic Mechanisms in Nonalcoholic Fatty Liver Disease" Cells 12, no. 8: 1205. https://doi.org/10.3390/cells12081205
APA StyleZaiou, M. (2023). Peroxisome Proliferator-Activated Receptor-γ as a Target and Regulator of Epigenetic Mechanisms in Nonalcoholic Fatty Liver Disease. Cells, 12(8), 1205. https://doi.org/10.3390/cells12081205