Epigenetic Mechanisms in Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum from simple steatosis to steatohepatitis, fibrosis and cirrhosis, driven by the interplay of genetic predisposition, metabolic stress and environmental factors. Epigenetic mechanisms—heritable and reversible modifications that regulate gene expression without altering nucleotide sequences—have emerged as critical mediators linking diet, lifestyle and metabolic cues to hepatic lipid homeostasis. Key processes include DNA methylation at CpG islands, post-translational histone modifications that alter chromatin accessibility, non-coding RNA interference and emerging layers of epitranscriptomic regulation. These modifications can be dynamically written, read and erased by specialised enzyme complexes, coupling metabolic inputs such as high-fat feeding to transcriptional programmes governing fatty acid uptake, synthesis and oxidative disposal. Aberrant epigenetic patterns have been detected in liver tissue and circulating cell-free nucleic acids, offering both mechanistic insights and potential non-invasive biomarkers for disease stratification. Furthermore, targeted manipulation of epigenetic marks holds promise for novel therapies that restore balanced lipid metabolism, attenuate inflammation and impede fibrotic progression. Understanding the precise orchestration of epigenetic networks in NAFLD is therefore essential for the development of precision-medicine approaches in metabolic liver disease.

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Epigenetic Mechanisms in Non-Alcoholic Fatty Liver Disease publication trend

The graph below shows the total number of articles in epigenetic mechanisms in non-alcoholic fatty liver disease across all publications each year (not limited to Nature Index journals).

Technical terms

DNA methylation: Addition of methyl groups to cytosine bases in DNA, often leading to transcriptional repression.

Histone modifications: Covalent post-translational alterations (e.g. acetylation, methylation) of histone proteins that influence chromatin structure and gene accessibility.

Non-coding RNA: RNA molecules (e.g. microRNAs, long non-coding RNAs) that regulate gene expression post-transcriptionally or by chromatin remodelling.

Epitranscriptomics: Study of chemical modifications on RNA molecules that affect their processing, stability and translation without changing the sequence.

N6-methyladenosine (m6A): A reversible methylation mark on adenosine residues of RNA, regulating mRNA fate through specialised ‘writer’, ‘eraser’ and ‘reader’ proteins.

References

1. Dnmt1/Tet2-mediated changes in Cmip methylation regulate the development of nonalcoholic fatty liver disease by controlling the Gbp2-Pparγ-CD36 axis. Experimental & Molecular Medicine (2023).
2. Epigenetic Regulation of Hepatic Lipid Metabolism by DNA Methylation. Advanced Science (2023).
3. Roles of N6‐methyladenosine epitranscriptome in non‐alcoholic fatty liver disease and hepatocellular carcinoma. Smart Medicine (2023).
4. Plasma DNA methylation: a potential biomarker for stratification of liver fibrosis in non-alcoholic fatty liver disease. Gut (2016).
5. Post-translational histone modifications associated with the development of metabolic dysfunction-associated fatty liver disease. Part 1. General provisions. Gastroenterology (2024).