Genome-Wide DNA Methylation Changes of Perirenal Adipose Tissue in Rabbits Fed a High-Fat Diet

SIMPLE SUMMARY: Obesity is spreading rapidly in most countries and regions, becoming a considerable public health concern because it is associated with type II diabetes mellitus, fatty liver disease, hypertension, and even certain cancers. The biological effects of caloric restriction are closely related to epigenetic mechanisms, including DNA methylation. Here, rabbits were used as a model to study the effect of a high-fat diet on the DNA methylation profile of perirenal adipose tissue. The results indicate that 2906 genes associated with differentially methylated regions were obtained and were involved in the PI3K-AKT signaling pathway (KO04151), linoleic acid metabolism (KO00591), DNA replication (KO03030), and MAPK signaling pathway (KO04010). In conclusion, high-fat diet may cause changes in the DNA methylation profile of adipose tissue and lead to obesity. ABSTRACT: DNA methylation is an epigenetic mechanism that plays an important role in gene regulation without an altered DNA sequence. Previous studies have demonstrated that diet affects obesity by partially mediating DNA methylation. Our study investigated the genome-wide DNA methylation of perirenal adipose tissue in rabbits to identify the epigenetic changes of high-fat diet-mediated obesity. Two libraries were constructed pooling DNA of rabbits fed a standard normal diet (SND) and DNA of rabbits fed a high-fat diet (HFD). Differentially methylated regions (DMRs) were identified using the option of the sliding window method, and online software DAVID Bioinformatics Resources 6.7 was used to perform Gene Ontology (GO) terms and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis of DMRs-associated genes. A total of 12,230 DMRs were obtained, of which 2305 (1207 up-regulated, 1098 down-regulated) and 601 (368 up-regulated, 233 down-regulated) of identified DMRs were observed in the gene body and promoter regions, respectively. GO analysis revealed that the DMRs-associated genes were involved in developmental process (GO:0032502), cell differentiation (GO:0030154), and lipid binding (GO:0008289), and KEGG pathway enrichment analysis revealed the DMRs-associated genes were enriched in linoleic acid metabolism (KO00591), DNA replication (KO03030), and MAPK signaling pathway (KO04010). Our study further elucidates the possible functions of DMRs-associated genes in rabbit adipogenesis, contributing to the understanding of HFD-mediated obesity.