Long noncoding RNA Lnc-HC Regulates PPARγ-mediated Hepatic Lipid Metabolism through MiR-130b-3p

Abstract Nonalcoholic fatty liver disease (NAFLD) is due to the excessive lipid accumulation within hepatocyte. Metabolic nuclear receptors play great roles in lipid homeostasis. We have identified a novel long noncoding RNA (lncRNA) lnc-HC, which regulates hepatocytic cholesterol metabolism through reducing Cyp7a1 and Abca1 expression. Here, we further elucidate its roles in hepatic fatty acid and triglyceride metabolism through a novel lncRNA regulatory mechanism. The most prominent target of lnc-HC identified by in vitro study is PPARγ. Further studies revealed that lnc-HC negatively regulates PPARγ both at mRNA and protein level, and suppresses hepatocytic lipid droplet formation. Importantly, the function of lnc-HC in regulating PPARγ expression depends on modulating miR-130b-3p expression from transcriptional to post-transcriptional level, not through lncRNAs' critical modulating patterns. In vivo, the reduction of lnc-HC expression significantly decreases miR-130b-3p expression, induces PPARγ expression and increases triglyceride concentration in the rat livers with hyperlipidemia. These findings further help understand the regulatory pattern of lnc-HC in hepatic lipid metabolism and might present a possible therapeutic target for improving lipid homeostasis.