Adipocyte Long-Noncoding RNA Transcriptome Analysis of Obese Mice Identified Lnc-Leptin, Which Regulates Leptin

Obesity induces profound transcriptome changes in adipocytes, and recent evidence suggests that long-noncoding RNAs (lncRNAs) play key roles in this process. We performed a comprehensive transcriptome study by RNA sequencing in adipocytes isolated from interscapular brown, inguinal, and epididymal white adipose tissue in diet-induced obese mice. The analysis revealed a set of obesity-dysregulated lncRNAs, many of which exhibit dynamic changes in the fed versus fasted state, potentially serving as novel molecular markers of adipose energy status. Among the most prominent lncRNAs is Lnc-leptin, which is transcribed from an enhancer region upstream of leptin (Lep). Expression of Lnc-leptin is sensitive to insulin and closely correlates to Lep expression across diverse pathophysiological conditions. Functionally, induction of Lnc-leptin is essential for adipogenesis, and its presence is required for the maintenance of Lep expression in vitro and in vivo. Direct interaction was detected between DNA loci of Lnc-leptin and Lep in mature adipocytes, which diminished upon Lnc-leptin knockdown. Our study establishes Lnc-leptin as a new regulator of Lep.