Table 1.
Relevant DNA methylation alterations associated with gene expression in nonalcoholic fatty liver disease.
| Gene | Stage | Associated Disease Mechanisms | References |
|---|---|---|---|
| Srebf2 | Hepatic steatosis | Supplementation with methyl donors containing folic acid, choline, betaine, and Vitamin B12 improved liver steatosis by reversing the methylation status in the promoter region of sterol regulatory element binding transcription factor 2 (Srebf2) | [68,73] |
| Mttp | Hepatic steatosis | Betaine supplementation decreased DNA methylation of the microsomal triglyceride transfer protein (Mttp) gene promoter in mice and improved HFD-induced hepatic steatosis | [75] |
| Pparγ | NAFLD | HFD and palmitic acid alter Pparγ promoter DNA methylation leading to a significant induction of PPARγ expression and enhanced fat accumulation in mice liver, which may lead to NAFLD | [38] |
| Nrf2 | NAFLD | Treatment of HepG2 cells with high glucose enhanced methylation level of the Nrf2 promoter whereas Resveratrol reversed the effect, which led to a reduction in TG levels and the expression of lipogenesis-related genes | [78] |
| Gnmt | HCC | Reduced Gnmt expression caused by promoter cytosine DNA hypermethylation is one of the key molecular events in the development of NAFLD-derived HCC | [80] |
| Pparγ | NAFLD | Hypermethylation at the Pparγ promoter of plasma DNA correlated with with fibrosis severity in patients with NAFLD | [89] |
| PGC1-α | NAFLD | Hepatic DNA methylation of of PPARγ coactivator 1- α (PGC1-α) promoter significantly correlates with peripheral insulin resistance and is associated with decreased PGC1-α mRNA expression | [85] |
| Pparα, Pparγ, TGFβ1, Collagen 1A1, PDGFα | NAFLDfibrosis | DNA methylation at specific CpGs within PPARα, PPARγ, TGFβ1, Collagen 1A1, and PDGFα genes can distinguish mild from severe fibrosis in NAFLD patients | [83] |
| IGFBP2 | NASH | The IGFBP2 (insulin-like growth factor binding protein 2) locuswas hypermethylated and its mRNA downregulated in NASH | [82] |
| MT-ND6 | NAFLD | Hepatic methylation and transcriptional activity of the MT-ND6 gene are significantly associated with the histological severity of NAFLD | [86] |
| Sirt1, Pparγ | NAFLD | Suv39h2 is significantly elevated in diet-induced obese mice and NAFLD patients, and it increases the methylation levels at histone H3 lysine 9 of both Sirt1 and Pparγ to suppress the gene expression | [94] |
COL1A1, Collagen type I α1; Gnmt, Glycine N-methyltransferase; HFD, high-fat diet; IGFBP2, insulin-like growth factor binding protein 2; MT-ND6, mitochondrial gene NADH dehydrogenase 6; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; Nrf2, Nuclear factor-erythroid 2-related factor-2; PDGFα, Platelet-derived growth factor alpha; PGC1-α, PPARγ coactivator 1- α; PPARα, peroxisome proliferator-activated receptor α; PPARγ, peroxisome proliferator-activated receptor γ; Srebf2, sterol regulatory element binding transcription factor 2; Suv39h2, the methylation transferase suppressor of variegation 3-9 homologue 2; TGFβ1, transforming growth.