The Expression And Potential Role Of CircRNA In Beige Adipose Tissue

Background: Obesity,one of the most concerning public health problem,is more than ungainly figure,but also a major cause of metabolismassociated disease,cardiovascular disease and some kinds of cancers.Therefore,it is very meaningful to find a safe and effective way to combat obesity and its related diseases.Circular RNAs(circ RNAs)participate in many physiological and pathological process,but their roles in white adipose tissue(WAT)browning remain unclear.Objective: In this paper,we detected the circ RNAs expression profiles in 3 pairs of WAT and browning WAT samples by RNA-seq to discover the key circ RNAs,which may regulate white adipose tissue browning,alleviate obesity and related diseases.Method: we kept mice in room temperature(25 ℃)and 4℃ for 24 h,which could activate browning process of WAT,quantitative reverse transcription polymerase chain reaction(q RT-PCR),Western Blot(WB),hematoxylin and eosin(H&E)staining and immunohistochemistry(IHC)were used to confirm the generation of beige adipose tissue.Then the inguinal white adipose tissue(i WAT)was isolated for circ RNAs expression profiles construction by RNA-seq,q RT-PCR was applied to validate these RNA-seq results.Results: We identified 2,865 distinct circ RNA candidates,there were336 differentially expressed circ RNAs between WAT and beige adipose tissue,including 167 upregulated and 169 downregulated circ RNAs,which may regulate white adipose tissue browning.Besides,Gene Ontology(GO)and Kyoto Encyclopedia Genes and Genomes(KEGG)pathway enrichment analysis of parental genes of differentially expressed circ RNAs indicated that most parental genes were associated with lipid metabolism process and metabolic pathways.Additionally,we further detected the expression of one significantly upregulated circ RNA,circ Npr3,in i WAT of diet induced obese mice and ob/ob mice,q RT-PCR results indicate that circ Npr3 was increased in obese animals.Overexpression of circ Npr3 in mice inguinal WAT or differentiated 3T3-L1 inhibits the upregulation of UCP1 induced by cold or ISO respectively.Conclusion: Here,for the first time,we detected the expression profiles of circ RNAs in beige adipose tissue,which may provide a shred of reliable circ RNA resource for further research on white adipose tissue browning and provide potential therapeutic targets for obesity-related diseases.