{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:35:47Z","timestamp":1785198947627,"version":"3.55.0"},"reference-count":60,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,23]],"date-time":"2020-06-23T00:00:00Z","timestamp":1592870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AA026723"],"award-info":[{"award-number":["R01 AA026723"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["Merit Review grant BX004053"],"award-info":[{"award-number":["Merit Review grant BX004053"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: The earliest manifestation of alcohol-related liver disease (ALD) is steatosis, characterized by the accumulation of lipid droplets (LDs) in hepatocytes. Findings from our laboratory have indicated that many pathological changes, including steatosis, correlate with the alcohol-induced hepatocellular increases in S-adenosylhomocysteine (SAH). Based on these considerations, we hypothesized that an experimental increase in intracellular SAH alone will result in similar steatotic changes to those seen after alcohol exposure. Methods: Freshly isolated rat hepatocytes grown on collagen-coated plates were exposed to serum-free medium containing 50 \u00b5mol\/L oleic acid and varying concentrations of 3-deazaadenosine (DZA) to experimentally elevate intracellular SAH levels. Results: Overnight exposure to DZA treatment dose-dependently increased hepatocellular triglyceride accumulation, which was also evident by morphological visualization of larger-sized LDs. The rise in triglycerides and LDs accompanied increases in mRNA and protein levels of several LD-associated proteins known to regulate LD number and size. Furthermore, DZA treatment caused a decline in the levels of lipases that prevent fat accumulation as well as increased the expression of factors involved in lipogenesis and fatty acid mobilization. Collectively, our results indicate that the elevation of intracellular SAH is sufficient to promote fat accumulation in hepatocytes, which is similar to that seen after alcohol exposure.<\/jats:p>","DOI":"10.3390\/cells9061526","type":"journal-article","created":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T07:14:19Z","timestamp":1592982859000},"page":"1526","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Role of Elevated Intracellular S-Adenosylhomocysteine in the Pathogenesis of Alcohol-Related Liver Disease"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0567-7857","authenticated-orcid":false,"given":"Madan Kumar","family":"Arumugam","sequence":"first","affiliation":[{"name":"Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA"},{"name":"Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharanappa","family":"Talawar","sequence":"additional","affiliation":[{"name":"Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA"},{"name":"Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Listenberger","sequence":"additional","affiliation":[{"name":"Departments of Biology and Chemistry, St. Olaf College, Northfield, MN 55057, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Terrence M.","family":"Donohue","sequence":"additional","affiliation":[{"name":"Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA"},{"name":"Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA"},{"name":"Department of Biochemistry &amp; Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7498-0556","authenticated-orcid":false,"given":"Natalia A.","family":"Osna","sequence":"additional","affiliation":[{"name":"Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA"},{"name":"Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7759-8889","authenticated-orcid":false,"given":"Kusum K.","family":"Kharbanda","sequence":"additional","affiliation":[{"name":"Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA"},{"name":"Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA"},{"name":"Department of Biochemistry &amp; Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"962183","DOI":"10.1155\/2012\/962183","article-title":"Betaine treatment attenuates chronic ethanol-induced hepatic steatosis and alterations to the mitochondrial respiratory chain proteome","volume":"2012","author":"Kharbanda","year":"2012","journal-title":"Int. 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