{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T04:30:38Z","timestamp":1780806638203,"version":"3.54.1"},"reference-count":67,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T00:00:00Z","timestamp":1613952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["BMBF 0315741"],"award-info":[{"award-number":["BMBF 0315741"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Nonalcoholic fatty liver disease (NAFLD) is among the leading causes of end-stage liver disease. The impaired hepatic lipid metabolism in NAFLD is exhibited by dysregulated PPAR\u03b1 and SREBP-1c signaling pathways, which are central transcription factors associated with lipid degradation and de novo lipogenesis. Despite the growing prevalence of this disease, current pharmacological treatment options are unsatisfactory. Genistein, a soy isoflavone, has beneficial effects on lipid metabolism and may be a candidate for NAFLD treatment. In an in vitro model of hepatic steatosis, primary human hepatocytes (PHHs) were incubated with free fatty acids (FFAs) and different doses of genistein. Lipid accumulation and the cytotoxic effects of FFAs and genistein treatment were evaluated by colorimetric and enzymatic assays. Changes in lipid homeostasis were examined by RT-qPCR and Western blot analyses. PPAR\u03b1 protein expression was induced in steatotic PHHs, accompanied by an increase in CPT1L and ACSL1 mRNA. Genistein treatment increased PPAR\u03b1 protein expression only in control PHHs, while CPTL1 and ACSL1 were unchanged and PPAR\u03b1 mRNA was reduced. In steatotic PHHs, genistein reversed the increase in activated SREBP-1c protein. The model realistically reflected the molecular changes in hepatic steatosis. Genistein suppressed the activation of SREBP-1c in steatotic hepatocytes, but the genistein-mediated effects on PPAR\u03b1 were abolished by high hepatic lipid levels.<\/jats:p>","DOI":"10.3390\/molecules26041156","type":"journal-article","created":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T03:34:47Z","timestamp":1613964887000},"page":"1156","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Influence of Genistein on Hepatic Lipid Metabolism in an In Vitro Model of Hepatic Steatosis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1531-7735","authenticated-orcid":false,"given":"Lena","family":"Seidemann","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary Surgery and Visceral Transplantation, University Hospital, Leipzig University, 04103 Leipzig, Germany"},{"name":"Saxonian Incubator for Clinical Translation (SIKT), Leipzig University, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Kr\u00fcger","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Transplantation Surgery, Charit\u00e9 University Medicine Berlin, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Kegel-H\u00fcbner","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery and Visceral Transplantation, University Hospital, Leipzig University, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Seehofer","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery and Visceral Transplantation, University Hospital, Leipzig University, 04103 Leipzig, Germany"},{"name":"Department of General, Visceral and Transplantation Surgery, Charit\u00e9 University Medicine Berlin, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2104-8076","authenticated-orcid":false,"given":"Georg","family":"Damm","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery and Visceral Transplantation, University Hospital, Leipzig University, 04103 Leipzig, Germany"},{"name":"Saxonian Incubator for Clinical Translation (SIKT), Leipzig University, 04103 Leipzig, Germany"},{"name":"Department of General, Visceral and Transplantation Surgery, Charit\u00e9 University Medicine Berlin, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2672","DOI":"10.1002\/hep.30251","article-title":"Global Perspectives on Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis","volume":"69","author":"Younossi","year":"2019","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1053\/jhep.2003.50161","article-title":"Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome","volume":"37","author":"Marchesini","year":"2003","journal-title":"Hepatology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1053\/j.gastro.2014.11.039","article-title":"Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States","volume":"148","author":"Wong","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Pais, R., Barritt, A.S., Calmus, Y., Scatton, O., Runge, T., Lebray, P., Poynard, T., Ratziu, V., and Conti, F. 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