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

Abstract

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 <i>Lnc-leptin</i>, which is transcribed from an enhancer region upstream of leptin (<i>Lep</i>). Expression of <i>Lnc-leptin</i> is sensitive to insulin and closely correlates to <i>Lep</i> expression across diverse pathophysiological conditions. Functionally, induction of <i>Lnc-leptin</i> is essential for adipogenesis, and its presence is required for the maintenance of <i>Lep</i> expression in vitro and in vivo. Direct interaction was detected between DNA loci of <i>Lnc-leptin</i> and <i>Lep</i> in mature adipocytes, which diminished upon <i>Lnc-leptin</i> knockdown. Our study establishes <i>Lnc-leptin</i> as a new regulator of <i>Lep</i>.