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

Jiahao Shao,Songjia Lai,Xianbo Jia,Xue Bai,Yanhong Li,Ting Pan,Jie Wang

doi:10.3390/ani10122213

Abstract

Simple SummaryObesity 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.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.

Highlights

From the last 5 decades, the incidence of obesity has sharply increased, becoming one of the most considerable threats to human health because it is associated with the risk of type II diabetes mellitus, fatty liver disease, hypertension, and even certain cancers [1]
To further understand the epigenetic mechanisms influencing fat metabolism in obese rabbits, we investigated the role of DNA methylation in perirenal adipose tissue by sequencing and analyzing
A total of 24 female Tianfu black rabbits from a strain breed at the Sichuan Agricultural University in China were randomly divided into two groups and fed either a standard normal diet (SND) or a high-fat diet (HFD; 10% lard was added to the standard normal diet) for four weeks

Summary

Introduction

From the last 5 decades, the incidence of obesity has sharply increased, becoming one of the most considerable threats to human health because it is associated with the risk of type II diabetes mellitus, fatty liver disease, hypertension, and even certain cancers [1]. Fat deposition is characterized by an increase in the number and size of adipocytes, and its process is closely related to physiological homeostasis, far beyond simple fat storage [4]. As part of abdominal visceral fat, is often used to elucidate the molecular and pathophysiological mechanisms of metabolic disorders associated with obesity or adipose development, because it is closely related to kidney injury, metabolism of triacylglycerol, and other metabolic regulation [8]. Detailed studies have shown that the perirenal fat thickness in obese patients could be a valuable marker to define the risk of developing hypertension and kidney dysfunction [9,10]. The expression profile of perirenal fat microRNA was changed during different growth stages of rabbits, and the differential microRNA expression was enriched for the MAPK signaling pathway, Wnt signaling pathway, aldosterone synthesis, and secretion pathways [11]

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Results

Conclusion