Vitamin K2 as a New Modulator of the Ceramide De Novo Synthesis Pathway
The aim of the study was to evaluate the influence of vitamin K2 (VK2) supplementation on the sphingolipid metabolism pathway in palmitate-induced insulin resistant hepatocytes. The study was carried out on human hepatocellular carcinoma cells (HepG2) incubated with VK2 and/or palmitic acid (PA). Th...
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| Format: | Article |
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MDPI AG
2021-06-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/11/3377 |
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| author | Adrian Kołakowski Piotr F. Kurzyna Hubert Żywno Wiktor Bzdęga Ewa Harasim-Symbor Adrian Chabowski Karolina Konstantynowicz-Nowicka |
| author_facet | Adrian Kołakowski Piotr F. Kurzyna Hubert Żywno Wiktor Bzdęga Ewa Harasim-Symbor Adrian Chabowski Karolina Konstantynowicz-Nowicka |
| author_sort | Adrian Kołakowski |
| collection | DOAJ |
| description | The aim of the study was to evaluate the influence of vitamin K2 (VK2) supplementation on the sphingolipid metabolism pathway in palmitate-induced insulin resistant hepatocytes. The study was carried out on human hepatocellular carcinoma cells (HepG2) incubated with VK2 and/or palmitic acid (PA). The concentrations of sphingolipids were measured by high-performance liquid chromatography. The expression of enzymes from the sphingolipid pathway was assessed by Western blotting. The same technique was used in order to determine changes in the expression of the proteins from the insulin signaling pathway in the cells. Simultaneous incubation of HepG2 cells with palmitate and VK2 elevated accumulation of sphinganine and ceramide with increased expression of enzymes from the ceramide de novo synthesis pathway. HepG2 treatment with palmitate and VK2 significantly decreased the insulin-stimulated expression ratio of insulin signaling proteins. Moreover, we observed that the presence of PA w VK2 increased fatty acid transport protein 2 expression. Our study showed that VK2 activated the ceramide de novo synthesis pathway, which was confirmed by the increase in enzymes expression. VK2 also intensified fatty acid uptake, ensuring substrates for sphingolipid synthesis through the de novo pathway. Furthermore, increased concentration of sphingolipids, mainly sphinganine, inhibited insulin pathway proteins phosphorylation, increasing insulin resistance development. |
| first_indexed | 2024-03-10T10:44:46Z |
| format | Article |
| id | doaj.art-4e1fd5ef858a44d5b9fceebeebc02a5d |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T10:44:46Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-4e1fd5ef858a44d5b9fceebeebc02a5d2023-11-21T22:38:22ZengMDPI AGMolecules1420-30492021-06-012611337710.3390/molecules26113377Vitamin K2 as a New Modulator of the Ceramide De Novo Synthesis PathwayAdrian Kołakowski0Piotr F. Kurzyna1Hubert Żywno2Wiktor Bzdęga3Ewa Harasim-Symbor4Adrian Chabowski5Karolina Konstantynowicz-Nowicka6Department of Physiology, Medical University of Bialystok, 15-089 Bialystok, PolandDepartment of Physiology, Medical University of Bialystok, 15-089 Bialystok, PolandDepartment of Physiology, Medical University of Bialystok, 15-089 Bialystok, PolandDepartment of Physiology, Medical University of Bialystok, 15-089 Bialystok, PolandDepartment of Physiology, Medical University of Bialystok, 15-089 Bialystok, PolandDepartment of Physiology, Medical University of Bialystok, 15-089 Bialystok, PolandDepartment of Physiology, Medical University of Bialystok, 15-089 Bialystok, PolandThe aim of the study was to evaluate the influence of vitamin K2 (VK2) supplementation on the sphingolipid metabolism pathway in palmitate-induced insulin resistant hepatocytes. The study was carried out on human hepatocellular carcinoma cells (HepG2) incubated with VK2 and/or palmitic acid (PA). The concentrations of sphingolipids were measured by high-performance liquid chromatography. The expression of enzymes from the sphingolipid pathway was assessed by Western blotting. The same technique was used in order to determine changes in the expression of the proteins from the insulin signaling pathway in the cells. Simultaneous incubation of HepG2 cells with palmitate and VK2 elevated accumulation of sphinganine and ceramide with increased expression of enzymes from the ceramide de novo synthesis pathway. HepG2 treatment with palmitate and VK2 significantly decreased the insulin-stimulated expression ratio of insulin signaling proteins. Moreover, we observed that the presence of PA w VK2 increased fatty acid transport protein 2 expression. Our study showed that VK2 activated the ceramide de novo synthesis pathway, which was confirmed by the increase in enzymes expression. VK2 also intensified fatty acid uptake, ensuring substrates for sphingolipid synthesis through the de novo pathway. Furthermore, increased concentration of sphingolipids, mainly sphinganine, inhibited insulin pathway proteins phosphorylation, increasing insulin resistance development.https://www.mdpi.com/1420-3049/26/11/3377sphingolipidsvitamin K2ceramideinsulin resistanceceramidehepatocytes |
| spellingShingle | Adrian Kołakowski Piotr F. Kurzyna Hubert Żywno Wiktor Bzdęga Ewa Harasim-Symbor Adrian Chabowski Karolina Konstantynowicz-Nowicka Vitamin K2 as a New Modulator of the Ceramide De Novo Synthesis Pathway Molecules sphingolipids vitamin K2 ceramide insulin resistance ceramide hepatocytes |
| title | Vitamin K2 as a New Modulator of the Ceramide De Novo Synthesis Pathway |
| title_full | Vitamin K2 as a New Modulator of the Ceramide De Novo Synthesis Pathway |
| title_fullStr | Vitamin K2 as a New Modulator of the Ceramide De Novo Synthesis Pathway |
| title_full_unstemmed | Vitamin K2 as a New Modulator of the Ceramide De Novo Synthesis Pathway |
| title_short | Vitamin K2 as a New Modulator of the Ceramide De Novo Synthesis Pathway |
| title_sort | vitamin k2 as a new modulator of the ceramide de novo synthesis pathway |
| topic | sphingolipids vitamin K2 ceramide insulin resistance ceramide hepatocytes |
| url | https://www.mdpi.com/1420-3049/26/11/3377 |
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