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Influence of Genistein on Hepatic Lipid Metabolism in an In Vitro Model of Hepatic Steatosis

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 PPARα and SREBP-1c signaling pathways, which are central transcription factors associated with lipid degradation and de novo li...

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Autores principales: Seidemann, Lena, Krüger, Anne, Kegel-Hübner, Victoria, Seehofer, Daniel, Damm, Georg
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926972/
https://www.ncbi.nlm.nih.gov/pubmed/33671486
http://dx.doi.org/10.3390/molecules26041156
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author Seidemann, Lena
Krüger, Anne
Kegel-Hübner, Victoria
Seehofer, Daniel
Damm, Georg
author_facet Seidemann, Lena
Krüger, Anne
Kegel-Hübner, Victoria
Seehofer, Daniel
Damm, Georg
author_sort Seidemann, Lena
collection PubMed
description 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 PPARα 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. PPARα protein expression was induced in steatotic PHHs, accompanied by an increase in CPT1L and ACSL1 mRNA. Genistein treatment increased PPARα protein expression only in control PHHs, while CPTL1 and ACSL1 were unchanged and PPARα 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 PPARα were abolished by high hepatic lipid levels.
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spelling pubmed-79269722021-03-04 Influence of Genistein on Hepatic Lipid Metabolism in an In Vitro Model of Hepatic Steatosis Seidemann, Lena Krüger, Anne Kegel-Hübner, Victoria Seehofer, Daniel Damm, Georg Molecules Article 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 PPARα 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. PPARα protein expression was induced in steatotic PHHs, accompanied by an increase in CPT1L and ACSL1 mRNA. Genistein treatment increased PPARα protein expression only in control PHHs, while CPTL1 and ACSL1 were unchanged and PPARα 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 PPARα were abolished by high hepatic lipid levels. MDPI 2021-02-22 /pmc/articles/PMC7926972/ /pubmed/33671486 http://dx.doi.org/10.3390/molecules26041156 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Seidemann, Lena
Krüger, Anne
Kegel-Hübner, Victoria
Seehofer, Daniel
Damm, Georg
Influence of Genistein on Hepatic Lipid Metabolism in an In Vitro Model of Hepatic Steatosis
title Influence of Genistein on Hepatic Lipid Metabolism in an In Vitro Model of Hepatic Steatosis
title_full Influence of Genistein on Hepatic Lipid Metabolism in an In Vitro Model of Hepatic Steatosis
title_fullStr Influence of Genistein on Hepatic Lipid Metabolism in an In Vitro Model of Hepatic Steatosis
title_full_unstemmed Influence of Genistein on Hepatic Lipid Metabolism in an In Vitro Model of Hepatic Steatosis
title_short Influence of Genistein on Hepatic Lipid Metabolism in an In Vitro Model of Hepatic Steatosis
title_sort influence of genistein on hepatic lipid metabolism in an in vitro model of hepatic steatosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926972/
https://www.ncbi.nlm.nih.gov/pubmed/33671486
http://dx.doi.org/10.3390/molecules26041156
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