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The Influence of Coumestrol on Sphingolipid Signaling Pathway and Insulin Resistance Development in Primary Rat Hepatocytes

Coumestrol is a phytoestrogen widely known for its anti-diabetic, anti-oxidant, and anti-inflammatory properties. Thus, it gets a lot of attention as a potential agent in the nutritional therapy of diseases such as obesity and type 2 diabetes. In our study, we evaluated whether coumestrol affects in...

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Autores principales: Zywno, Hubert, Bzdega, Wiktor, Kolakowski, Adrian, Kurzyna, Piotr, Harasim-Symbor, Ewa, Sztolsztener, Klaudia, Chabowski, Adrian, Konstantynowicz-Nowicka, Karolina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918648/
https://www.ncbi.nlm.nih.gov/pubmed/33673122
http://dx.doi.org/10.3390/biom11020268
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author Zywno, Hubert
Bzdega, Wiktor
Kolakowski, Adrian
Kurzyna, Piotr
Harasim-Symbor, Ewa
Sztolsztener, Klaudia
Chabowski, Adrian
Konstantynowicz-Nowicka, Karolina
author_facet Zywno, Hubert
Bzdega, Wiktor
Kolakowski, Adrian
Kurzyna, Piotr
Harasim-Symbor, Ewa
Sztolsztener, Klaudia
Chabowski, Adrian
Konstantynowicz-Nowicka, Karolina
author_sort Zywno, Hubert
collection PubMed
description Coumestrol is a phytoestrogen widely known for its anti-diabetic, anti-oxidant, and anti-inflammatory properties. Thus, it gets a lot of attention as a potential agent in the nutritional therapy of diseases such as obesity and type 2 diabetes. In our study, we evaluated whether coumestrol affects insulin resistance development via the sphingolipid signaling pathway in primary rat hepatocytes. The cells were isolated from the male Wistar rat’s liver with the use of collagenase perfusion. Next, we incubated the cells with the presence or absence of palmitic acid and/or coumestrol. Additionally, some groups were incubated with insulin. The sphingolipid concentrations were assessed by HPLC whereas the expression of all the proteins was evaluated by Western blot. Coumestrol markedly reduced the accumulation of sphingolipids, namely, ceramide and sphinganine through noticeable inhibition of the ceramide de novo synthesis pathway in insulin-resistant hepatocytes. Moreover, coumestrol augmented the expression of fatty acid transport proteins, especially FATP5 and FAT/CD36, which also were responsible for excessive sphingolipid accumulation. Furthermore, coumestrol altered the sphingolipid salvage pathway, which was observed as the excessive deposition of the sphingosine-1-phosphate and sphingosine. Our study clearly showed that coumestrol ameliorated hepatic insulin resistance in primary rat hepatocytes. Thus, we believe that our study may contribute to the discovery of novel preventive and therapeutic methods for metabolic disorders.
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spelling pubmed-79186482021-03-02 The Influence of Coumestrol on Sphingolipid Signaling Pathway and Insulin Resistance Development in Primary Rat Hepatocytes Zywno, Hubert Bzdega, Wiktor Kolakowski, Adrian Kurzyna, Piotr Harasim-Symbor, Ewa Sztolsztener, Klaudia Chabowski, Adrian Konstantynowicz-Nowicka, Karolina Biomolecules Article Coumestrol is a phytoestrogen widely known for its anti-diabetic, anti-oxidant, and anti-inflammatory properties. Thus, it gets a lot of attention as a potential agent in the nutritional therapy of diseases such as obesity and type 2 diabetes. In our study, we evaluated whether coumestrol affects insulin resistance development via the sphingolipid signaling pathway in primary rat hepatocytes. The cells were isolated from the male Wistar rat’s liver with the use of collagenase perfusion. Next, we incubated the cells with the presence or absence of palmitic acid and/or coumestrol. Additionally, some groups were incubated with insulin. The sphingolipid concentrations were assessed by HPLC whereas the expression of all the proteins was evaluated by Western blot. Coumestrol markedly reduced the accumulation of sphingolipids, namely, ceramide and sphinganine through noticeable inhibition of the ceramide de novo synthesis pathway in insulin-resistant hepatocytes. Moreover, coumestrol augmented the expression of fatty acid transport proteins, especially FATP5 and FAT/CD36, which also were responsible for excessive sphingolipid accumulation. Furthermore, coumestrol altered the sphingolipid salvage pathway, which was observed as the excessive deposition of the sphingosine-1-phosphate and sphingosine. Our study clearly showed that coumestrol ameliorated hepatic insulin resistance in primary rat hepatocytes. Thus, we believe that our study may contribute to the discovery of novel preventive and therapeutic methods for metabolic disorders. MDPI 2021-02-12 /pmc/articles/PMC7918648/ /pubmed/33673122 http://dx.doi.org/10.3390/biom11020268 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
Zywno, Hubert
Bzdega, Wiktor
Kolakowski, Adrian
Kurzyna, Piotr
Harasim-Symbor, Ewa
Sztolsztener, Klaudia
Chabowski, Adrian
Konstantynowicz-Nowicka, Karolina
The Influence of Coumestrol on Sphingolipid Signaling Pathway and Insulin Resistance Development in Primary Rat Hepatocytes
title The Influence of Coumestrol on Sphingolipid Signaling Pathway and Insulin Resistance Development in Primary Rat Hepatocytes
title_full The Influence of Coumestrol on Sphingolipid Signaling Pathway and Insulin Resistance Development in Primary Rat Hepatocytes
title_fullStr The Influence of Coumestrol on Sphingolipid Signaling Pathway and Insulin Resistance Development in Primary Rat Hepatocytes
title_full_unstemmed The Influence of Coumestrol on Sphingolipid Signaling Pathway and Insulin Resistance Development in Primary Rat Hepatocytes
title_short The Influence of Coumestrol on Sphingolipid Signaling Pathway and Insulin Resistance Development in Primary Rat Hepatocytes
title_sort influence of coumestrol on sphingolipid signaling pathway and insulin resistance development in primary rat hepatocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918648/
https://www.ncbi.nlm.nih.gov/pubmed/33673122
http://dx.doi.org/10.3390/biom11020268
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