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 hepatocytes. Metabolic nuclear receptors (MNRs) 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 (TG) 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 at both the mRNA and protein levels and suppresses hepatocytic lipid droplet formation. Importantly, the function of lnc-HC in regulating PPARγ expression depends on modulating miR-130b-3p expression from the transcriptional to the post-transcriptional level, not through lncRNA's critical modulating patterns. In vivo, the reduction of lnc-HC expression significantly decreases miR-130b-3p expression, induces PPARγ expression, and increases TG concentration in rat livers with hyperlipidemia. These findings further help in understanding the regulatory pattern of lnc-HC in hepatic lipid metabolism and might present a possible therapeutic target for improving lipid homeostasis.

• Authors: Xi Lan, Litao Wu, Nan Wu, Qian Chen, Yue Li, Xiaojuan Du, Chenxi Wei, Lina Feng, Yazhao Li, Ezra Kombo Osoro, Mengyao Sun, Qilan Ning, Xiaofei Yan, Xudong Yang, Dongmin Li, Shemin Lu
• Journal: Molecular therapy. Nucleic acids (Mol Ther Nucleic Acids) Vol. 18 Pg. 954-965 (Dec 06 2019) ISSN: 2162-2531 [Print] United States
• PMID: 31770672 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.