Deciphering the role of aberrant DNA methylation in NAFLD and NASH

Sex difference in liver diseases: How preclinical models help to dissect the sex-related mechanisms sustaining NAFLD and hepatocellular carcinoma

“…The main epigenetic modification related to the X-linked chromosome is DNA methylation that covers an important role in patients with NAFLD. 201 , 202 , 203 In fact, women presented a higher methylation profile in the X chromosome with respect to men, which results in hepatic gene expression changes and subsequent lower cholesterol and triglycerides levels, in accordance with different metabolic activities. 204 Moreover, treatment with low-dose aspirin reduced body weight and hepatic lipid accumulation in female, but not in male, offspring mice with maternal over-nutrition as a high-risk model of obesity and NAFLD.…”

The relationship between folic acid and nonalcoholic fatty liver disease

“…22 In regulatory sites of genes, CpG islands are mostly unmethylated, whereas those present in non-regulatory regions are typically methylated. 23 Methylation cytosine can modulate cell/tissue-specific gene expression by inhibiting transcription by blocking mRNA binding transcription factors or recruiting methyl-CPG binding domain proteins, such as methyl CpG binding protein 2 (MeCP2). 24 The methylation of DNA is catalysed by DNA methyltransferases (DNMTs), of which DNMT1, DNMT3A and DNMT3B have been identified as having DNA methyltransferase activity.…”

“…CpG islands are primarily located in gene regions associated with transcription initiation or promoters activity 22 . In regulatory sites of genes, CpG islands are mostly unmethylated, whereas those present in non‐regulatory regions are typically methylated 23 . Methylation cytosine can modulate cell/tissue‐specific gene expression by inhibiting transcription by blocking mRNA binding transcription factors or recruiting methyl‐CPG binding domain proteins, such as methyl CpG binding protein 2 (MeCP2) 24 .…”

Short-chain fatty acids in nonalcoholic fatty liver disease: New prospects for short-chain fatty acids as therapeutic targets

“…The change in DNA methylation induced by SCFAs is an important epigenetic modification [ 67 ]. During the occurrence and development of NAFLD, the hypo-and hypermethylation genes such as growth factor-α ( PDGFα ), phospholipase C gamma 1 ( PLCG1 ), caspase 1 ( CASP1 ) are epigenetic regulated and exacerbate the progression of NAFLD by participating in immune response, oxidative stress, and liver lipid degeneration [ 68 ]. It is notably that SCFAs reduce the expression of DNA methyltransferases 1 ( DNMT1 ) and methyl CpG binding structural domain protein 2 ( MBD2 ), inhibiting the binding of these enzymes toadiponectin and resistin promoters.…”