Identification of Genes Related to Fat Deposition as Candidates for ER Stress Based on Combined RNA-ATAC Sequencing Analysis

Abstract

Endoplasmic reticulum (ER) stress is associated with obesity as this state challenges lipid and carbohydrate metabolisms, resulting in glucolipotoxicity and endoplasmic reticulum dysfunction. It can be induced by excessive ectopic fat accumulation, rising blood glucose levels or meta-inflammatory factors, which disturb the liver’s numerous pathways favoring hepatic lipogenesis. In the present study, it was attempted to identify liver molecular processes associated with fat deposition in pigs based on combined RNA-ATAC-seq analysis. The pig groups used in the present study were significantly different in terms of subcutaneous and visceral fat deposition; they belonged to a native Polish breed and were not under selection pressure. Based on RNA-ATAC-seq combined analysis, identification was made of 45 significant differentially expressed genes (DEGs) in liver tissue dependent on fat deposition, for which open chromatin regions in transcription start sites were found. The functional analysis pinpointed that 5 of them are involved in the ER stress process (MANF, SELENOS, HYOU1, PIK3R1, and HSPA5). These five proposed genes expressed in the liver as candidates associated with fat deposition in pigs because ER stress plays a significant role in this organ in molecular process associated with the determination of fat level in the organism, which was previously broadly described in humans.