# Tissue-specific epigenetic regulation of fat metabolism in pigs through integrated analysis of DNA methylation and gene expression networks

## TL;DR

This study explores how DNA methylation and gene expression work together in different pig tissues to regulate fat metabolism, which could help improve pork quality.

## Contribution

The study integrates DNA methylation and gene expression data to identify tissue-specific epigenetic regulation of fat metabolism in pigs.

## Key findings

- DNA methylation changes are subtle but aligned with key functional pathways like lipid metabolism and extracellular matrix remodeling.
- Gene expression shows clearer tissue separation than methylation, with the liver having more differentially expressed genes.
- Epigenetic regulation is tissue-dependent and influences transcriptional networks related to lipid handling and muscle function.

## Abstract

Fat metabolism in pigs is controlled by tissue-specific molecular mechanisms that ultimately affect growth performance and meat quality. Understanding how epigenetic modifications interact with gene expression across key metabolic and fat-depositing tissues is essential for identifying regulatory processes and potential biomarkers to improve pork quality traits. Therefore, this study aimed to elucidate tissue specific epigenetic regulation of fat metabolism by integrating DNA methylation and gene expression profiles from liver, backfat, and loin (longissimus dorsi) tissues at two physiologically developmental stages (10 and 26 weeks), representing the early post-weaning growth phase and near-market weight, respectively. By explicitly comparing these ages and tissues, the study was designed to capture the transition from muscle-dominated growth to increased lipid deposition and to identify tissue- and stage-specific regulatory signatures that may serve as biomarkers for pork quality.

Genome-wide DNA methylation exhibited weak clustering by tissue, whereas gene expression showed clear tissue separation. The liver harbored fewer genes with differential methylation across stage and tissue but a greater number of genes with differential expression than backfat and loin, suggesting distinct regulatory modes. Integrative analysis of the overlap genes between methylation and expression signals highlighted epigenetically mediated regulation of extracellular matrix organization, lipid metabolism, and muscle development pathways. Furthermore, weighted gene co-expression network analysis revealed distinct tissue-specific correlations between co-methylated and co-expressed modules, with enrichment in cholesterol biosynthesis, muscle contractility, and extracellular matrix remodeling. Together, these findings suggest that methylation changes are more subtle than transcriptional shifts, yet they are aligned with key functional pathways, consistent with a role for methylation as a fine-tuning mechanism that shapes tissue-specific transcriptional networks during growth.

Across liver, backfat, and loin, DNA methylation modulates transcriptional programs in a tissue-dependent manner, prioritizing pathways central to lipid handling, extracellular matrix remodeling, and muscle function. This integrated multi-omics framework highlights candidate epigenetic markers and regulatory modules with potential utility for improving pork quality traits through selection or management strategies.

The online version contains supplementary material available at 10.1186/s40104-025-01347-x.