The period circadian regulator 3 (PER3) has been reported to play a negative role in human immortalized bone marrow-derived Scp-1 cells (iBMSCs) and patient adipose-derived stromal cells (PASCs) or a negative/positive role in mice adipogenesis. However, human PER3 (hPER3) was identified as a positive regulator of human adipose tissue-derived stromal cells (hADSCs) adipogenesis in this study. Silencing or overexpression of hPER3 in hADSCs inhibited and promoted adipogenesis in vitro. In vivo, the overexpression of hPER3 increased high-fat diet-induced inguinal white adipose tissue (iWAT) and epididymal white adipose tissue (eWAT) forms, increasing systemic glucose intolerance and insulin resistance. Molecularly, hPER3 does not interact with hPPARγ, but represses Notch1 signaling pathway to enhance adipogenesis by interacting with hHSP90AA1, which is able to combine with the promoter of hNotch1 and inactivate its expression. Thus, our study revealed hPER3 as a critical positive regulator of hADSCs adipogenesis, which was different from the other types of cells, providing a critical role of it in treating obesity.

Purpose Type 2 diabetes mellitus (T2DM) increases the incidence of diabetic nephropathy (DN) and eventually progresses to end-stage renal disease. Circular RNAs (circRNAs) are a class of non-coding RNAs that are promising as diagnostic biomarkers and therapeutic targets for human diseases. The aim of this study was to analyze the differential expression of circRNAs (DECs) in peripheral blood from patients with early type 2 diabetic nephropathy (ET2DN), T2DM and controls, which will facilitate to discover some new biomarkers for ET2DN. Patients and Methods Twenty ET2DN patients, 20 T2DM patients, and 20 normal controls were included in this study. Blood samples from 3 random subjects of age- and sex-matched patients in each group, respectively, were used to detect circRNA expression profiles by circRNA microarray, and the circRNA expression of remaining subjects was validated by real-time quantitative polymerase chain reaction (qRT-PCR). Further functional assessment was performed by bioinformatic tools. Results There were 586 DECs in ET2DN vs T2DM group (249 circRNAs were upregulated and 337 circRNAs were downregulated); 176 circRNAs were upregulated and 101 circRNAs were downregulated in T2DM vs control group; 57 circRNAs were upregulated and 5 circRNAs were downregulated in ET2DN vs control group. The functional and pathway enrichment of DECs were analyzed by GO and KEGG. qRT-PCR results revealed that hsa_circ_0001831 and hsa_circ_0000867 were significantly upregulated in ET2DN group compared to both of T2DM and control group. The ROC curve demonstrated that hsa_circ_0001831 and hsa_circ_0000867 have high sensitivity and specificity associated with ET2DN. Conclusion Our study showed the expression profiles of circRNAs in ET2DN patients and demonstrated that hsa_circ_0001831 and hsa_circ_0000867 can be used as novel diagnostic biomarkers for ET2DN.

Purpose Brown adipose tissue (BAT) can rapidly generate heat and improve energy metabolism. Circular RNAs (circRNAs) are cellular endogenous non-coding RNAs, which can regulate the development and progress of different diseases. However, the role of circRNAs in human BAT is not fully understood. Here, we analyzed the differentially expressed circRNAs (DECs) in human BAT, as well as in white adipose tissue (WAT), and identified new biomarkers of BAT. Patients and Methods Three human BAT and three human subcutaneous WAT samples were selected, and circRNA microarray was performed. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR) was applied to determine the expression of six circRNAs. Finally, the functional analysis was performed by bioinformatics. Results Compared to WAT, 152 upregulated circRNAs and 201 downregulated circRNAs were identified in BAT. The DECs were further subjected to GO and KEGG enrichment analysis. Several circRNAs, for example, hsa_circ_0006168, hsa_circ_26337 and hsa_circ_0007507 were found upregulated and hsa_circ_0030162 was found downregulated in human BAT compared to WAT. Conclusion This study profiles the circRNA expression in human BAT and WAT, and suggests hsa_circ_0006168, hsa_circ_26337, hsa_circ_0007507, and hsa_circ_0030162 as novel biomarkers for human BAT.