{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:20:39Z","timestamp":1792804839988,"version":"4.5.0"},"reference-count":73,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T00:00:00Z","timestamp":1695686400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["R01-GM137656"],"award-info":[{"award-number":["R01-GM137656"]}]},{"name":"National Institutes of Health","award":["I01BX004177"],"award-info":[{"award-number":["I01BX004177"]}]},{"name":"Veterans Administration","award":["R01-GM137656"],"award-info":[{"award-number":["R01-GM137656"]}],"id":[{"id":"https:\/\/ror.org\/006ym5897","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Veterans Administration","award":["I01BX004177"],"award-info":[{"award-number":["I01BX004177"]}],"id":[{"id":"https:\/\/ror.org\/006ym5897","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>MicroRNA-29a (miR-29a) is a well characterized fibro-inflammatory molecule and its aberrant expression is linked to a variety of pathological liver conditions. The long-term effects of a high-fat diet (HFD) in combination with different levels of EtOH consumption on miR-29a expression and liver pathobiology are unknown. Mice at 8 weeks of age were divided into five groups (calorie-matched diet plus water (CMD) as a control group, HFD plus water (HFD) as a liver disease group, HFD plus 2% EtOH (HFD + 2% E), HFD + 10% E, and HFD + 20% E as intervention groups) and fed for 4, 13, 26, or 39 weeks. At each time point, analyses were performed for liver weight\/body weight (BW) ratio, AST\/ALT ratio, as well as liver histology assessments, which included inflammation, estimated fat deposition, lipid area, and fibrosis. Hepatic miR-29a was measured and correlations with phenotypic traits were determined. Four-week feeding produced no differences between the groups on all collected phenotypic traits or miR-29a expression, while significant effects were observed after 13 weeks, with EtOH concentration-specific induction of miR-29a. A turning point for most of the collected traits was apparent at 26 weeks, and miR-29a was significantly down-regulated with increasing liver injury. Overall, miR-29a up-regulation was associated with a lower liver\/BW ratio, fat deposition, inflammation, and fibrosis, suggesting a protective role of miR-29a against liver disease progression. A HFD plus increasing concentrations of EtOH produces progressive adverse effects on the liver, with no evidence of beneficial effects of low-dose EtOH consumption. Moreover, miR-29a up-regulation is associated with less severe liver injury.<\/jats:p>","DOI":"10.3390\/ijms241914564","type":"journal-article","created":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T08:55:01Z","timestamp":1695718501000},"page":"14564","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Dynamic Alterations to Hepatic MicroRNA-29a in Response to Long-Term High-Fat Diet and EtOH Feeding"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8445-3765","authenticated-orcid":false,"given":"Tiebing","family":"Liang","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janaiah","family":"Kota","sequence":"additional","affiliation":[{"name":"Ultragenyx Pharmaceuticals, Novato, CA 94949, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kent E.","family":"Williams","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romil","family":"Saxena","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samer","family":"Gawrieh","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7872-0540","authenticated-orcid":false,"given":"Teresa A.","family":"Zimmers","sequence":"additional","affiliation":[{"name":"Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Indiana Center for Musculoskeletal Health, Indianapolis, IN 46202, USA"},{"name":"Richard L. Roudebush Veterans Administration Medical Center, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naga","family":"Chalasani","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1001\/jama.291.10.1238","article-title":"Actual causes of death in the United States, 2000","volume":"291","author":"Mokdad","year":"2004","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1111\/acer.12011","article-title":"Binge ethanol and liver: New molecular developments","volume":"37","author":"Shukla","year":"2013","journal-title":"Alcohol Clin. Exp. 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