Abstract

Background Increasing evidence has shown that fatty acid synthase (Fasn) is associated with diabetes mellitus (DM) and insulin resistance, however, it remains unclear how Fasn upregulation leads to dysregulation of energy homeostasis in islet cells. Consequently, uncovering the function of Fasn in islet cells. Consequently, uncovering the function of FASN in islet cells is immensely important for finding a treatment target. Aim In this study, we elucidated the biological function of Fasn on the target genes in a rat insulinoma INS-1 cell line. Methods We created a Fasn overexpressing rat insulinoma cell line ( Fasn-OE ), and performed bulk RNA-sequencing (RNA-seq) experiments on Fasn-OE and INS-1 (control) cells. We first identified differentially expressed genes (DEGs) using Bioconductor package edgeR, and then discovered enriched gene ontology terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways using the KEGG Orthology Based Annotation System (KOBAS) 2.0 web server. Furthermore, we identified alternative splicing events (ASEs) and regulated alternative splicing events (RASEs) by applying the ABLas pipeline. The reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used for validation of selected differentially expressed genes (DEGs) and Fasn-regulated alternative splicing genes (RASGs). Results In this study we found that Fasn overexpression led to significant changes of gene expression profiles, including downregulations of mRNA levels of immune related genes, including Bst2 , Ddit3 , Isg15 , Mx2 , Oas1a , Oasl , and RT1-S3 in INS-1 cell line. Furthermore, Fasn positively regulated the expression of transcription factors such as Fat1 and Ncl diabetes-related genes. Importantly, Fasn overexpression to result in alternative splicing events including in a metabolism-associated ATP binding protein mRNA Abcc5 . In Gene Ontology analysis, the downregulated genes in Fasn -OE cells were mainly enriched in inflammatory r