Long Noncoding RNA lnc-HC Regulates PPARγ-Mediated Hepatic Lipid Metabolism through miR-130b-3p

• Published in: Molecular therapy. Nucleic acids Vol. 18; pp. 954 - 965
• Main Authors: Lan, Xi, Wu, Litao, Wu, Nan, Chen, Qian, Li, Yue, Du, Xiaojuan, Wei, Chenxi, Feng, Lina, Li, Yazhao, Osoro, Ezra Kombo, Sun, Mengyao, Ning, Qilan, Yan, Xiaofei, Yang, Xudong, Li, Dongmin, Lu, Shemin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06-12-2019; Elsevier Limited; American Society of Gene & Cell Therapy; Elsevier
• Subjects: ABCA1 protein; Adipocytes; Alcohol; Atherosclerosis; ATP-binding protein; Cholesterol; Diabetes; Fatty acids; Fatty liver; Gene expression; hepatocyte; Hepatocytes; Homeostasis; Hyperlipidemia; Lipid metabolism; Lipids; lipogenesis; liver; Liver diseases; lnc-HC; Metabolism; molecular mechanism; Nuclear receptors; Phenols; Post-transcription; Proteins; RNA polymerase; Statistical analysis; Studies; Therapeutic applications; United States > US; China; lnc-HC; molecular mechanism; lipogenesis; hepatocyte; liver
• ISSN: 2162-2531; 2162-2531
• DOI: 10.1016/j.omtn.2019.10.018

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.
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