Comparative analysis of circRNA expression profile and circRNA-miRNA-mRNA regulatory network between palmitic and stearic acid-induced lipotoxicity to pancreatic β cells

Chronic exposure to high concentrations of circulating palmitic acid and stearic acid leads to impaired β cell function, which accelerates the development of type 2 diabetes. However, differences in the mechanisms underlying this process between these two saturated fatty acids remain largely unknown. In this study, we screened for potential circular RNAs (circRNAs) and their associated regulatory pathways in palmitic acid- and stearic acid-induced mouse β-TC6 cell dysfunction. CircRNA high-throughput sequencing, gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes analysis were performed and co-expression and competing endogenous RNAs (ceRNA) networks were constructed. We identified that four circRNAs that were differentially expressed specifically in β cells exposed to palmitic acid, whereas four circRNAs were differentially expressed specifically in β cells exposed to stearic acid. Seven circRNAs were differentially co-expressed in palmitic acid- and stearic acid-treated β cells. In pathway exploration, we identified the core protein Solute carrier family 2 member 2 (SLc2a2), which is mainly involved in insulin resistance, maturity onset diabetes of the young and type 2 diabetes. The expressions of key circRNAs in β-TC6 cells were validated by Real time quantitative PCR, with a consistent result in high-throughput sequencing. The findings aid our understanding of the mechanisms governing the difference between palmitic acid- and stearic acid-induced β cell dysfunction and provide potential therapeutic targets for developing treatments against long-term high fat diet-induced β cell injury. Abbreviations: Acvr1c: Activin A receptor, type 1C; CeRNA, Competing endogenous RNAs; circRNA, circular RNA; DEcircRNA: Differentially Expressed circular RNA; DEmiRNA: Differentially Expressed microRNA; DEmRNA: Differentially Expressed mRNA; GO: Gene Ontology; HPDHigh Palmitic acid Diet; HSD: High Stearic acid Diet; KEGG: Kyoto Encyclopedia of Genes and Genomes; miRNA: microRNA; ncRNAs: non-coding RNAs; qPCR: Real time quantitative PCRS; FAs: Saturated Fatty Acids; SLc2a2: Solute carrier family 2 member 2; T2D: Type 2 Diabetes