Abstract
Obesity is closely associated with numerous adipogenic regulatory factors, including coding and non-coding genes. Long noncoding RNAs (lncRNAs) play a major role in adipogenesis. However, differential expression profiles of lncRNAs in inguinal white adipose tissue (iWAT) between wild-type (WT) and ob/ob mice, as well as their roles in adipogenesis, are not well understood. Here, a total of 2809 lncRNAs were detected in the iWAT of WT and ob/ob mice by RNA-Sequencing (RNA-Seq), including 248 novel lncRNAs. Of them, 46 lncRNAs were expressed differentially in WT and ob/ob mice and were enriched in adipogenesis signaling pathways as determined by KEGG enrichment analysis, including the PI3K/AKT/mTOR and cytokine–cytokine receptor interaction signaling pathways. Furthermore, we focused on one novel lncRNA, which we named lnc-ORA (obesity-related lncRNA), which had a seven-fold higher expression in ob/ob mice than in WT mice. Knockdown of lnc-ORA inhibited preadipocyte proliferation by decreasing the mRNA and protein expression levels of cell cycle markers. Interestingly, lnc-ORA knockdown inhibited adipocyte differentiation by regulating the PI3K/AKT/mTOR signaling pathway. In summary, these findings contribute to a better understanding of adipogenesis in relation to lncRNAs and provide novel potential therapeutic targets for obesity-related metabolic diseases.
Highlights
Obesity has become a public health hazard worldwide and is the main cause of cardiovascular diseases, type 2 diabetes, and obesity-associated metabolic syndrome [1]
We identified a novel Long noncoding RNAs (lncRNAs), obesity-related lncRNA, with a seven-fold change in ob/ob mice compared to WT mice, suggesting it may play an important role in adipogenesis
To illustrate the differential lncRNA profiles in inguinal white adipose tissue (iWAT) between WT and ob/ob mice and to identify obesity-related lncRNAs, we performed RNA-seq of iWAT samples, which were isolated from eight-week-old WT and ob/ob mice kept with identical feeding conditions
Summary
Obesity has become a public health hazard worldwide and is the main cause of cardiovascular diseases, type 2 diabetes, and obesity-associated metabolic syndrome [1]. Adipogenesis is mediated by a series of complex processes, including commitment of mesenchymal stem cells into preadipocytes and the induction of preadipocytes to mature adipocytes [2,3]. The exploration of this process and its regulation mechanism is of great significance for the prevention and therapy of obesity-related diseases. The ob/ob mouse is a genetic obesity mouse with a deficiency of the leptin gene that constitutively develops obesity [4]. It is a good model for investigating the gene regulatory network of obesity. Leptin is a hormone that is primarily made and secreted by mature adipocytes and binds to its receptor in the hypothalamus, with positive effects on energy homeostasis and weight loss [5]
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