Obesity has recently become a major healthy concern in developed countries. This leads to intensive interest in the mechanism study of adipogenesis, in which epigenetic mechanisms are speculated to play an essential role. To explore the function of Dnmt1, its expression was first profiled during the course of adipocyte differentiation of 3T3-L1 cells. The results revealed a dynamic regulation of its expression at the initiation stage. Knockdown of Dnmt1 compromised the differentiation process and decreased lipid production within the cells. To the aspect of epigenetic regulation, promoter methylation of Cdkn1a was significantly increased at the initiation stage of the differentiation, accompanied by decreased Cdkn1a expression. Furthermore, knockdown of Dnmt1 led to an increased Cdkn1a expression, indicating that Dnmt1 inhibits Cdkn1a expression by promoter methylation. Furthermore, we found that knockdown of Cdkn1a up-regulated the expression of PPARγ and resulted in enhanced adipocyte differentiation. In summary, our results demonstrated that Dnmt1 regulated the process of adipogenesis by methylation of Cdkn1a promoter, suggesting that Cdkn1a played a fundamental role in the prevention of adipocyte hyperplasia.
Taking advantage of high-throughput sequencing technology, a large number of long noncoding RNAs （lncRNAs） have been recently characterized. Emerging evidence suggests that they play critical roles in diverse biological processes, including the differentiation of skeletal muscle cells. As previous studies have focused mainly on the polyadenylated lncRNAs, the involvement of polyA-rninus IncRNAs in myocyte differentiation remains largely unexplored. To this aspect, their expression and regulation were examined in the present study. During the course of myocyte differentiation of C2C12 cells, polyA-minus RNAs were isolated and analyzed by RNA-seq. In addition to identifying 904 novel polyA-minus lncRNAs, their temporal expression was further characterized in this process. For many lncRNAs, differentiation-specific profiles were revealed. Based on their unique expression profiles, these lncRNAs were grouped into nine regulation categories. Taken together, our study greatly contributed to the identification of a dynamic regulation ofpolyA-minus lncRNAs, and clarified their potential roles in myocyte differentiation.
Environmental and lifestyle factors together account for the dramatic increase of type 2 diabetes in the past decades, in which defective insulin secretion emerges as the major culprit. Glucagon-like peptide l （GLP-1） is a peptide secreted from the intestine in response to nutrient ingestion, and plays an essential role in the regulation of blood glucose level by stimulating glucoses-dependent insulin secretion. Recently, GLP-1 develops to be a viable therapeutic target for the treatment of type 2 diabetes, by means of GLP-1 receptor agonists and dipeptidyl peptidase-4 inhibitors. Stemmed fi^om its potent physiological activities, GLP-1-based therapies are clinically efficient and safe for both early and late stages of the disease, with low risk of adverse events. In this review, a comprehensive understanding of GLP-1 biology and the recent development of GLP-1-based antidiabetic therapy are summarized.
