The Influence of Epigenetic Mechanisms on the Development of Metabolic Dysfunction Associated Steatotic Liver Disease: A Review

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) occupies a leading place in the structure of modern hepatology. A growing body of literature identifies MASLD as a global epidemic. Accumulated data from studies in the field of hepatology support the idea that MASLD is a hepatic manifestation of a systemic metabolic disease. MASLD is a multifactorial metabolic disease associated with the presence of insulin resistance, abdominal obesity, oxidative stress, endothelial dysfunction and a systemic inflammatory response. Current scientific data demonstrate the existence of a relationship between MASLD and an increased risk of developing cardiovascular disease, regardless of traditional risk factors such as diabetes mellitus, dyslipidemia, obesity and hypertension. The pathogenesis of MASLD includes the development of hepatic steatosis with subsequent progression to metabolic dysfunction-associated steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Epigenetics, a new field of biology that studies the influence of external factors on gene activity without changing in deoxyribonucleic acid (DNA) sequences, offers a new perspective on the pathogenesis of MASLD. This review summarizes current knowledge on the epigenetic determinants of MASLD, such as DNA methylation, histone modifications, noncoding ribonucleic acids (RNAs) and N6-methyladenosine in patients with MASLD which may also contribute to the development of preventive or therapeutic strategies for MASLD-associated complications.