Identification of Circular RNA Expression Profiles in White Adipocytes and Their Roles in Adipogenesis

Abstract

Obesity and its related metabolic diseases have become great public health threats worldwide. Although accumulated evidence suggests that circRNA is a new type of non-coding RNAs regulating various physiological and pathological processes, little attention has been paid to the expression profiles and functions of circRNAs in white adipose tissue. In this study, 3,771 circRNAs were detected in three stages of white adipogenesis (preadipocyte, differentiating preadipocyte, and mature adipocyte) by RNA-seq. Experimental validation suggested that the RNA-seq results are highly reliable. We found that nearly 10% of genes which expressed linear RNAs in adipocytes could also generate circRNAs. In addition, 40% of them produced multiple circRNA isoforms. We performed correlation analysis and found that a great deal of circRNAs (nearly 50%) and their parental genes were highly correlated in expression levels. A total of 41 differential expression circRNAs (DECs) were detected during adipogenesis and an extremely high ratio of them (80%) were correlated with their parental genes, indicating these circRNAs may potentially play roles in regulating the expression of their parental genes. KEGG enrichment and GO annotation of the parental genes suggesting that the DECs may participate in several adipogenesis-related pathways. Following rigorous selection, we found that many up-regulated circRNAs contain multiple miRNAs binding sites, such as miR17, miR-30c, and miR-130, indicating they may potentially facilitate their regulatory functions by acting as miRNA sponges. These results suggest that plenty of circRNAs are expressed in white adipogenesis and the DECs may serve as new candidates for future adipogenesis regulation.

CircRNA Profiling Reveals an Abundant circBDP1 that Regulates Bovine Fat Development by Sponging miR-181b/miR-204 Targeting Sirt1/TRARG1

“…A RNA-Seq study has identified 3771 circRNAs in the three stages of white fat formation. Statistical analysis showed that nearly 10% of the genes expressing linear RNA in adipocytes could generate circRNAs, and 40% of the cells produced multiple circRNA isoforms . In this study, 8165 circRNAs overlapped in 3282 genes.…”

“…Statistical analysis showed that nearly 10% of the genes expressing linear RNA in adipocytes could generate circRNAs, and 40% of the cells produced multiple circRNA isoforms. 37 In this study, 8165 circRNAs overlapped in 3282 genes. Among the circRNA host genes, 46.44% could produce a single circRNA, and the rest could produce two or more circRNAs.…”

“…A total of 41 differentially expressed circRNAs were detected during adipogenesis, among which the proportion of circRNAs related to host genes reached 80%, suggesting that circRNAs may play an essential role in regulating host gene expression. 37 Therefore, in this study, it was reasonable to predict the function of circRNAs by analyzing the function of the circRNA host genes. The distribution of circRNAs in cells (nucleus/cytoplasm) is closely related to their function.…”

“…Zhang et al revealed that nearly 50% circRNAs were highly correlated with host gene expression levels. A total of 41 differentially expressed circRNAs were detected during adipogenesis, among which the proportion of circRNAs related to host genes reached 80%, suggesting that circRNAs may play an essential role in regulating host gene expression . Therefore, in this study, it was reasonable to predict the function of circRNAs by analyzing the function of the circRNA host genes.…”

Epigenetic modifications in obesity‐associated diseases

“…A recent study identified circRNAs profiles in white and brown AT, which provided circRNA candidates for regulating adipose formation. 186,187 Studies suggested that circ-SAMD4A increased preadipocyte differentiation, 188 and circArhgap5-2 played an essential role in adipogenesis and lipid metabolism. 189 Evidence suggests that downregulated hsa_circ_000839 in patients with BC exhibits a negative correlation with BMI, but the underlying mechanism is still unclear.…”