(Epi)Genetic Alterations and Their Physiological Consequences in Metabolic Dysfunction-associated Steatotic Liver Disease: A Crucial Step Towards Precision Medicine in MASLD

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as NAFLD, is the most common chronic liver disease and a growing cause of liver-related morbidity and mortality. The increasing global occurrence of MASLD, along with metabolic conditions such as obesity and diabetes, may be partly due to dietary, environmental, and lifestyle-related factors (e.g., lack of physical activity). However (epi)genetic factors including transgenerational epigenetic inheritance also play a crucial role in the differences in MASLD rates among populations.

(Epi)Genetic variation in population is a key determinant in the accessibility of genes to the cellular machinery responsible for gene expression. These alterations in gene expression can significantly influence a range of physiological processes, including cell growth, differentiation, and environmental response. In the context of MASLD, (epi)genetic mechanisms can disrupt cellular pathways, leading to changes in lipid metabolism, increased inflammation, and cell death in liver cells. This underscores the pivotal role of (epi)genetics in the development of MASLD.

(Epi)Genetic changes are heritable and thus modify the offspring's disease risk. Studies on the developmental origins of health and disease (DOHaD) concept have suggested that establishing an (epi)genetic profile reflecting disease status could significantly contribute to precision medicine in MASLD. Understanding the relationship between MASLD and (epi)genetics could lead to new treatment options and preventative measures for these conditions and can be targeted therapeutically to halt the advancement of metabolic diseases.

Therefore, through this Research Topic, we aim to deepen our understanding of the (epi)genetic regulation of MASLD by collecting original research, reviews, mini-reviews, and perspective articles exploring (epi)genetic-based physiological regulation, intervention, and therapy for MASLD. In addition, we welcome articles that investigate how various (epi)genetic modifications influence specific key metabolic pathways in the liver.

Potential areas of interest may include, but are not limited to:
• Impact of (Epi)genetic Changes on Hepatic Glucose Metabolism in MASLD
• How (Epi)genetics Regulate Inflammatory Pathways in MASLD
• Role of (Epi)genetic in Liver Fat Metabolism and MASLD Pathophysiology
• (Epi)Genetic Biomarkers for MASLD
• Novel methodologies to study (epi)genetic changes in MASLD
• Genome-wide (epi)genetic changes including expression-based polygenic risk (ePRS) studies in MASLD
• Genetic variants altering epigenetics related to MASLD
• The role and impact of (epi)genetic mechanisms in MASLD onset and progression
• Influence of transgenerational epigenetic inheritance on MASLD risk
• New treatment approaches targeting or incorporating (epi)genetic markers in MASLD

Keywords: Steatosis, Epigenetic regulation, DNA Methylation, Histone, Genetics, Genetic Variant, Metabolic disease, Precision medicine

Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.