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.