부산대학교 도서관

Adipose tissue plays a central role in metabolic diseases, and, in particular, abdominal obesity is considered unfavorable due to its tight relationship with development of diabetes and cardiovascular diseases. As both genetic and environmental factors contribute to the development of obesity and its co-morbidities, we aimed to explore how the DNA methylome contributes to an altered transcriptome profile of adipocytes in obesity. The gene expression profile of mature adipocytes isolated from the retroperitoneal fat pad (abdominal fat) was compared between a group of lean and a group of obese pigs. Simultaneously the epigenetic signature was profiled by analyzing the global methylation of the DNA isolated from the same adipocytes. The pigs used in this study were housed in the same farm under the same environmental conditions with free access to food and water. This very stringent and controlled environment suggests that the differences in epigenetic profile detected in the study primarily reflect variations due to obesity. We found a total of 1155 coding genes and 66 non-coding RNAs that were differentially expressed between the lean and obese animals. The methylation analysis revealed a higher degree of DNA hypomethylation in obese animals, and we identified more than 6000 differentially methylated regions. Combining the transcriptome and the methylation analysis revealed a total of 100 genes, which have expression profiles that are directly (cis-acting) influenced by methylation. Gene ontology analyses of these genes show an overrepresentation of genes involved in lipid and fatty acid metabolism and inflammatory response, clearly indicating that the altered methylation profile of the adipocytes is implicated in development of obesity and subsequent inflammation progress in the obese pigs. We are currently validating the most relevant results.