{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T13:52:03Z","timestamp":1791553923895,"version":"4.3.4"},"reference-count":27,"publisher":"American Chemical Society (ACS)","issue":"10","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP15H02448"],"award-info":[{"award-number":["JP15H02448"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP20H05683"],"award-info":[{"award-number":["JP20H05683"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP20K05960"],"award-info":[{"award-number":["JP20K05960"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP25H00923"],"award-info":[{"award-number":["JP25H00923"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hepatic triglyceride accumulation reflects an imbalance in hepatic lipid metabolism, and pharmacological approaches that enhance fatty acid utilization may provide a strategy for reducing excessive lipid accumulation in the liver. Here, we evaluated the effects of a synthetic osa-miR166g-3p mimic, corresponding to a microRNA sequence originally identified in Oryza sativa L., on hepatic lipid metabolism in mice and hepatic cell models. Systemic administration of the osa-miR166g-3p mimic reduced hepatic triglyceride levels in mice without significant short-term changes in serum aminotransferase activities, body weight, or adipose tissue weight. In HFD-fed mice, the osa-miR166g-3p mimic significantly reduced hepatic triglyceride content and increased hepatic AMP-activated protein kinase (AMPK) phosphorylation compared with NC mimic treatment. In HepG2 cells, the osa-miR166g-3p mimic increased FAOBlue fluorescence, a cellular readout associated with fatty acid \u03b2-oxidation, and increased PPAR\u03b1 and CPT1A expression. These changes were accompanied by increased AMPK phosphorylation. Selected time-dependent transcriptional responses were also observed in NMuLi cells. In addition, target prediction, sequence analysis, and reduced PPP2R5C\/Ppp2r5c mRNA expression in HepG2 and NMuLi cells supported PPP2R5C\/Ppp2r5c as a predicted candidate target requiring direct validation. Collectively, these findings provide short-term pharmacological proof-of-concept that the osa-miR166g-3p mimic modulates hepatic lipid metabolism in association with fatty acid \u03b2-oxidation-related and AMPK-related signaling. Further studies are required to validate its direct molecular target(s), characterize its tissue distribution and pharmacokinetics, and determine its long-term efficacy and safety.<\/jats:p>","DOI":"10.1021\/acsptsci.6c00406","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T01:01:51Z","timestamp":1789520511000},"page":"2928-2938","source":"Crossref","is-referenced-by-count":0,"title":["osa-miR166g-3p\nMimic Reduces Hepatic Triglyceride\nAccumulation in Mice"],"prefix":"10.1021","volume":"9","author":[{"given":"Yun","family":"Lin","sequence":"first","affiliation":[{"name":"Kyushu University , , ,","place":["Fukuoka, Japan, 819-0395"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motofumi","family":"Kumazoe","sequence":"additional","affiliation":[{"name":"Kyushu University , , ,","place":["Fukuoka, Japan, 819-0395"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryouya","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Kyushu University , , ,","place":["Fukuoka, Japan, 819-0395"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chihiro","family":"Inoue","sequence":"additional","affiliation":[{"name":"Kyushu University , , ,","place":["Fukuoka, Japan, 819-0395"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Shimada","sequence":"additional","affiliation":[{"name":"Kyushu University , , ,","place":["Fukuoka, Japan, 819-0395"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0798-0649","authenticated-orcid":true,"given":"Yoshinori","family":"Fujimura","sequence":"additional","affiliation":[{"name":"Kyushu University , , ,","place":["Fukuoka, Japan, 819-0395"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4820-2122","authenticated-orcid":true,"given":"Hirofumi","family":"Tachibana","sequence":"additional","affiliation":[{"name":"Kyushu University , , ,","place":["Fukuoka, Japan, 819-0395"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"2026100909102827800_cit1","doi-asserted-by":"publisher","first-page":"1343","DOI":"10.1172\/JCI23621","article-title":"Sources of Fatty\nAcids Stored in Liver and Secreted\nvia Lipoproteins in Patients with Nonalcoholic Fatty Liver Disease","volume":"115","author":"Donnelly","year":"2005","journal-title":"J. Clin. Invest."},{"key":"2026100909102827800_cit2","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1053\/j.gastro.2007.11.038","article-title":"Alterations in Adipose Tissue and\nHepatic Lipid Kinetics in Obese Men and Women with Nonalcoholic Fatty\nLiver Disease","volume":"134","author":"Fabbrini","year":"2008","journal-title":"Gastroenterology"},{"key":"2026100909102827800_cit3","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1053\/j.gastro.2015.09.003","article-title":"Physiological Mechanisms\nof Weight Gain-Induced Steatosis in People with Obesity","volume":"150","author":"Fabbrini","year":"2016","journal-title":"Gastroenterology"},{"key":"2026100909102827800_cit4","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1038\/nrm.2017.95","article-title":"AMPK: Guardian of Metabolism and Mitochondrial Homeostasis","volume":"19","author":"Herzig","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2026100909102827800_cit5","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.970292","article-title":"The AMPK Pathway in\nFatty Liver Disease","volume":"13","author":"Fang","year":"2022","journal-title":"Front.\nPhysiol."},{"key":"2026100909102827800_cit6","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/j.molmet.2014.02.002","article-title":"Integrated\nPhysiology and Systems Biology of PPAR\u03b1","volume":"3","author":"Kersten","year":"2014","journal-title":"Mol. Metab."},{"key":"2026100909102827800_cit7","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1007\/s10545-010-9061-2","article-title":"A General Introduction to the Biochemistry of Mitochondrial\nFatty Acid \u03b2-Oxidation","volume":"33","author":"Houten","year":"2010","journal-title":"J. Inherited Metab.\nDis."},{"key":"2026100909102827800_cit8","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.cell.2018.03.006","article-title":"Metazoan\nMicroRNAs","volume":"173","author":"Bartel","year":"2018","journal-title":"Cell"},{"key":"2026100909102827800_cit9","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1097\/MOL.0000000000000420","article-title":"MicroRNAs\nand Lipid Metabolism","volume":"28","author":"Aryal","year":"2017","journal-title":"Curr. Opin. Lipidol."},{"key":"2026100909102827800_cit10","doi-asserted-by":"publisher","first-page":"1290","DOI":"10.1038\/nm.3980","article-title":"Genome-Wide Identification\nof MicroRNAs Regulating Cholesterol and Triglyceride Homeostasis","volume":"21","author":"Wagschal","year":"2015","journal-title":"Nat. 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Sci."},{"key":"2026100909102827800_cit14","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1089\/hum.2024.113","article-title":"Advances in MicroRNA Therapeutics:\nFrom Preclinical to Clinical Studies","volume":"35","author":"Brillante","year":"2024","journal-title":"Hum. Gene\nTher."},{"key":"2026100909102827800_cit15","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1038\/cr.2011.158","article-title":"Exogenous Plant MIR168a Specifically Targets\nMammalian LDLRAP1: Evidence of Cross-Kingdom Regulation by MicroRNA","volume":"22","author":"Zhang","year":"2012","journal-title":"Cell Res."},{"key":"2026100909102827800_cit16","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1038\/nbt.2737","article-title":"Lack of Detectable Oral\nBioavailability of Plant MicroRNAs after Feeding in Mice","volume":"31","author":"Dickinson","year":"2013","journal-title":"Nat. Biotechnol."},{"key":"2026100909102827800_cit17","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.4161\/rna.24909","article-title":"Ineffective\nDelivery of Diet-Derived MicroRNAs to Recipient Animal Organisms","volume":"10","author":"Snow","year":"2013","journal-title":"RNA Biol."},{"key":"2026100909102827800_cit18","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2015.09.004","article-title":"Contamination\nor Artifacts May Explain Reports of Plant miRNAs in Humans","volume":"26","author":"Witwer","year":"2015","journal-title":"J. Nutr. 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Invest."},{"key":"2026100909102827800_cit23","doi-asserted-by":"publisher","DOI":"10.3390\/nu11123067","article-title":"Nonalcoholic Fatty Liver Disease\nInduced by High-Fat Diet in C57BL\/6 Models","volume":"11","author":"Aydos","year":"2019","journal-title":"Nutrients"},{"key":"2026100909102827800_cit24","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19092826","article-title":"AMPK Activation\nReduces Hepatic Lipid\nContent by Increasing Fat Oxidation In Vivo","volume":"19","author":"Foretz","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"2026100909102827800_cit25","doi-asserted-by":"publisher","first-page":"3023","DOI":"10.1039\/C9CC09993J","article-title":"Fluorescence Detection of Metabolic\nActivity of the Fatty Acid Beta Oxidation Pathway in Living Cells","volume":"56","author":"Uchinomiya","year":"2020","journal-title":"Chem. Commun."},{"issue":"D1","key":"2026100909102827800_cit26","doi-asserted-by":"publisher","first-page":"D127","DOI":"10.1093\/nar\/gkz757","article-title":"miRDB: An Online Database for Prediction of Functional MicroRNA Targets","volume":"48","author":"Chen","year":"2020","journal-title":"Nucleic Acids Res."},{"issue":"10","key":"2026100909102827800_cit27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005561","article-title":"PPP2R5C Couples\nHepatic Glucose and Lipid Homeostasis","volume":"11","author":"Cheng","year":"2015","journal-title":"PLoS\nGenet."}],"container-title":["ACS Pharmacology &amp; Translational\nScience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsptsci.6c00406","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/aptsfn\/article-pdf\/9\/10\/2928\/68525197\/acsptsci.6c00406.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/aptsfn\/article-pdf\/9\/10\/2928\/68525197\/acsptsci.6c00406.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T13:23:14Z","timestamp":1791552194000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/aptsfn\/article\/9\/10\/2928\/5430865\/osa-miR166g-3p-Mimic-Reduces-Hepatic-Triglyceride"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,15]]},"references-count":27,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,9,15]]},"published-print":{"date-parts":[[2026,10,9]]}},"URL":"https:\/\/doi.org\/10.1021\/acsptsci.6c00406","relation":{},"ISSN":["2575-9108"],"issn-type":[{"value":"2575-9108","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,15]]}}}