title: Hypolipidemic effect of oleanolic acid is mediated by the miR-98-5p/PGC-1β axis in high-fat diet-induced hyperlipidemic mice.
abstract: Oleanolic acid (OA) is an active component of the traditional Chinese herbOlea europaea L.and has been found to exhibit a significant lipid-lowering effect; however, its direct molecular target is still unknown, which limits its clinical application and the possible structure modification to improve its beneficial functions. In this regard, we carried out the present study to identify potential hepatic targets of OA to mediate its lipid-lowering effect. We found that both acute and chronic OA treatments reduced serum levels of triglycerides, total cholesterol, and LDL cholesterol, and decreased hepatic expression levels of peroxisome proliferator-activated receptor-γ coactivator-1β (PGC-1β), which is an important regulator in maintaining hepatic lipid homeostasis, and its downstream target genes. Of note, liver-specific knockdown of PGC-1β recapitulated the hypolipidemic effects of OA. At the molecular level, OA accelerated mRNA degradation of PGC-1β. Microarray analysis revealed a host of microRNAs that potentially mediate OA-induced PGC-1β mRNA degradation, among which, miR-98-5p significantly inhibited activity ofPgc-1β3' UTR as well as PGC-1β expression and promoted its mRNA degradation. Conversely, miR-98-5p inhibitors blunted the inhibitory effects of OA on PGC-1β expression. Collectively, our data demonstrated that OA ameliorated hyperlipidemia, likelyviaregulation of the miR-98-5p/PGC-1β axis.-Chen, S., Wen, X., Zhang, W., Wang, C., Liu, J., Liu, C. Hypolipidemic effect of oleanolic acid is mediated by the miR-98-5p/PGC-1β axis in high-fat diet-induced hyperlipidemic mice.
authors.affiliation: Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China; and.|Jiangsu Key Laboratory of Human Functional Genomics, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Siyu
authors.initials: S
authors.lastname: Chen
authors.affiliation: Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China; and.
authors.forename: Xiaoan
authors.initials: X
authors.lastname: Wen
authors.affiliation: School of Life Sciences, China Pharmaceutical University, Nanjing, China; and.
authors.forename: Wenxiang
authors.initials: W
authors.lastname: Zhang
authors.affiliation: School of Life Sciences, China Pharmaceutical University, Nanjing, China; and.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China; and junincpu@yahoo.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China; and changliu@njnu.edu.cn.|School of Life Sciences, China Pharmaceutical University, Nanjing, China; and.|Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006949:Hyperlipidemias / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009828:Oleanolic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D020871:RNA Stability; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood
chemical_list: D020413:3' Untranslated Regions; D000960:Hypolipidemic Agents; C557404:MIRN98 microRNA, mouse; D035683:MicroRNAs; D009687:Nuclear Proteins; C000620215:Ppargc1b protein, mouse; D014157:Transcription Factors; D014280:Triglycerides; D009828:Oleanolic Acid; D002784:Cholesterol
keywords: lipid-lowering function; liver; miRNA; molecular target; triterpenoid compound