{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:39:24Z","timestamp":1760150364403,"version":"build-2065373602"},"reference-count":14,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T00:00:00Z","timestamp":1699488000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073419","32171532"],"award-info":[{"award-number":["82073419","32171532"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Non-alcoholic fatty liver disease (NAFLD) is the leading chronic liver disease, with a worldwide prevalence of more than 25%, and there is no approved drug for NAFLD specifically. In our previous study, the synthetic peptide AWRK6 was found to ameliorate NAFLD in mice. However, the mechanisms involved are still largely unknown. Here, AWRK6 treatment presented an alleviative effect on lipid accumulation induced by oleic acid in hepatocytes. Meanwhile, miR-5100 and miR-505 were found to be elevated by oleic acid induction and reversed by AWRK6 incubation. Further, the miR-5100 inhibitor inhibited oleic acid-induced lipid accumulation, and the alleviation effect of AWRK6 was partially counteracted by miR-5100 mimics. The screening of potential target genes revealed that a catalytic subunit of G6Pase G6PC was significantly inhibited by miR-5100 mimics transfection in both mRNA and protein levels. The direct targeting of miR-5100 on G6PC was verified by a Dual-Luciferase Reporter Assay. Moreover, the mRNA and protein levels of G6PC were found to be significantly increased by AWRK6 treatment. These results suggested that the peptide AWRK6 could alleviate lipid accumulation in hepatocytes, partly through reducing miR-5100 to restore one of its targets: G6PC. Thus, AWRK6 has the potential to treat NAFLD. Additionally, miR-5100 is a mediator of lipid accumulation in hepatocytes, which could be targeted by AWRK6.<\/jats:p>","DOI":"10.3390\/ijms242216141","type":"journal-article","created":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T10:19:27Z","timestamp":1699525167000},"page":"16141","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Peptide AWRK6 Alleviates Lipid Accumulation in Hepatocytes by Inhibiting miR-5100 Targeting G6PC"],"prefix":"10.3390","volume":"24","author":[{"given":"Jiaxin","family":"Liu","sequence":"first","affiliation":[{"name":"School of Life Sciences, Liaoning University, Shenyang 110036, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Stem Cells and Regenerative Medicine, Key Laboratory of Cell Biology, National Health Commission of China, and Key Laboratory of Medical Cell Biology, Ministry of Education of China, China Medical University, Shenyang 110122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiuyu","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Liaoning University, Shenyang 110036, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lili","family":"Jin","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Liaoning University, Shenyang 110036, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7063-7742","authenticated-orcid":false,"given":"Dianbao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Stem Cells and Regenerative Medicine, Key Laboratory of Cell Biology, National Health Commission of China, and Key Laboratory of Medical Cell Biology, Ministry of Education of China, China Medical University, Shenyang 110122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/S2468-1253(22)00165-0","article-title":"The prevalence and incidence of NAFLD worldwide: A systematic review and meta-analysis","volume":"7","author":"Riazi","year":"2022","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1038\/s41575-021-00523-4","article-title":"Advancing the global public health agenda for NAFLD: A consensus statement","volume":"19","author":"Lazarus","year":"2022","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1053\/j.gastro.2020.01.051","article-title":"Therapeutic Landscape for NAFLD in 2020","volume":"158","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/s41574-021-00507-z","article-title":"Emerging therapeutic approaches for the treatment of NAFLD and type 2 diabetes mellitus","volume":"17","author":"Ferguson","year":"2021","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1136\/gutjnl-2018-318146","article-title":"miRNAs and NAFLD: From pathophysiology to therapy","volume":"68","author":"Gjorgjieva","year":"2019","journal-title":"Gut"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"101581","DOI":"10.1016\/j.molmet.2022.101581","article-title":"MicroRNAs in non-alcoholic fatty liver disease: Progress and perspectives","volume":"65","author":"Hochreuter","year":"2022","journal-title":"Mol. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"170597","DOI":"10.1016\/j.peptides.2021.170597","article-title":"A synthetic peptide AWRK6 ameliorates metabolic associated fatty liver disease: Involvement of lipid and glucose homeostasis","volume":"143","author":"Jin","year":"2021","journal-title":"Peptides"},{"key":"ref_8","unstructured":"Liu, J. (2022). 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