Adipocyte long noncoding RNA transcriptome analysis of obese mice identified Lnc-leptin which regulates Leptin

Obesity induces profound transcriptome changes in adipocytes; recent evidence suggests that lncRNAs play key roles in this process. Here, we performed a comprehensive transcriptome study by RNA-Seq in adipocytes isolated from interscapular brown, inguinal and epididymal white adipose tissues in diet-induced obese mice. Our analysis reveals a set of obesity-dysregulated lncRNAs, many of which exhibit dynamic changes in fed vs. fasted state, potentially serving as novel molecular markers reflecting adipose energy status. Among the most prominent ones is Lnc-leptin, an lncRNA transcribed from an enhancer region upstream of Leptin. Expression of Lnc-leptin is sensitive to insulin and closely correlates to Leptin expression across diverse pathophysiological conditions. Functionally, induction of Lnc-leptin is essential for adipogenesis, and its presence is required for a loop formation between exon2 of Lnc-leptin and promoter of Leptin in mature adipocytes and the maintenance of Leptin expression in vitro and in vivo. Our study establishes Lnc-leptin as a new regulator of Leptin. For inguinal and epididymal adipocytes, RNA-Seq experiments on biological triplicates were performed per diet per type of adipocyte. For interscapular brown adipocytes, only one biological sample was collected per diet. In order to collect a substantial floating adipocyte layer, each biological sample consists of tissues from 3-5 mice.