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Long Noncoding RNA lnc-HC Regulates PPAR?-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 PPAR?. Further studies revealed that lnc-HC negatively regulates PPAR? at both the mRNA and protein levels and suppresses hepatocytic lipid droplet formation. Importantly, the function of lnc-HC in regulating PPAR? 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 PPAR? 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.

SUBMITTER: Lan X 

PROVIDER: S-EPMC6881655 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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

Lan Xi X   Wu Litao L   Wu Nan N   Chen Qian Q   Li Yue Y   Du Xiaojuan X   Wei Chenxi C   Feng Lina L   Li Yazhao Y   Osoro Ezra Kombo EK   Sun Mengyao M   Ning Qilan Q   Yan Xiaofei X   Yang Xudong X   Li Dongmin D   Lu Shemin S   Lu Shemin S  

Molecular therapy. Nucleic acids 20191025


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 targe  ...[more]

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