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

Department of Physiology, Medical University of Bialystok, 15-274 Bialystok, Poland
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Academic Editor: Yusuf A. Hannun
Biomolecules 2021, 11(2), 268; https://doi.org/10.3390/biom11020268
Received: 17 December 2020 / Revised: 8 February 2021 / Accepted: 10 February 2021 / Published: 12 February 2021
(This article belongs to the Section Biological Factors)
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. View Full-Text
Keywords: coumestrol; sphingolipids; ceramide; insulin resistance; hepatocytes coumestrol; sphingolipids; ceramide; insulin resistance; hepatocytes
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MDPI and ACS Style

Zywno, H.; Bzdega, W.; Kolakowski, A.; Kurzyna, P.; Harasim-Symbor, E.; Sztolsztener, K.; Chabowski, A.; Konstantynowicz-Nowicka, K. The Influence of Coumestrol on Sphingolipid Signaling Pathway and Insulin Resistance Development in Primary Rat Hepatocytes. Biomolecules 2021, 11, 268. https://doi.org/10.3390/biom11020268

AMA Style

Zywno H, Bzdega W, Kolakowski A, Kurzyna P, Harasim-Symbor E, Sztolsztener K, Chabowski A, Konstantynowicz-Nowicka K. The Influence of Coumestrol on Sphingolipid Signaling Pathway and Insulin Resistance Development in Primary Rat Hepatocytes. Biomolecules. 2021; 11(2):268. https://doi.org/10.3390/biom11020268

Chicago/Turabian Style

Zywno, Hubert, Wiktor Bzdega, Adrian Kolakowski, Piotr Kurzyna, Ewa Harasim-Symbor, Klaudia Sztolsztener, Adrian Chabowski, and Karolina Konstantynowicz-Nowicka. 2021. "The Influence of Coumestrol on Sphingolipid Signaling Pathway and Insulin Resistance Development in Primary Rat Hepatocytes" Biomolecules 11, no. 2: 268. https://doi.org/10.3390/biom11020268

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