Time-Dependent Changes in Hepatic Sphingolipid Accumulation and PI3K/Akt/mTOR Signaling Pathway in a Rat Model of NAFLD
Increased lipid bioavailability in a diet favors lipid accumulation, enhancing hepatic lipotoxicity and contributing to insulin resistance (IR) development. The aim of our study was to examine time-dependent alterations in the intrahepatic content of sphingolipids and insulin signaling pathway in ra...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/22/12478 |
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| author | Klaudia Sztolsztener Karolina Konstantynowicz-Nowicka Ewa Harasim-Symbor Adrian Chabowski |
| author_facet | Klaudia Sztolsztener Karolina Konstantynowicz-Nowicka Ewa Harasim-Symbor Adrian Chabowski |
| author_sort | Klaudia Sztolsztener |
| collection | DOAJ |
| description | Increased lipid bioavailability in a diet favors lipid accumulation, enhancing hepatic lipotoxicity and contributing to insulin resistance (IR) development. The aim of our study was to examine time-dependent alterations in the intrahepatic content of sphingolipids and insulin signaling pathway in rats fed a high-fat diet (HFD). The experiment was conducted on male Wistar rats receiving a standard diet or HFD for five weeks. At the end of each experimental feeding week, liver sphingolipids were determined using high-performance liquid chromatography. The expression of proteins from the sphingolipid pathway and glucose transporter expression were assessed by Western blot. The content of phosphorylated form of proteins from the insulin pathway was detected by a multiplex assay kit. Our results revealed that HFD enhanced hepatic ceramide deposition by increasing the expression of selected proteins from sphingomyelin and salvage pathways in the last two weeks. Importantly, we observed a significant inhibition of Akt phosphorylation in the first week of HFD and stimulation of PTEN and mTOR phosphorylation at the end of HFD. These changes worsened the PI3K/Akt/mTOR signaling pathway. We may postulate that HFD-induced reduction in the insulin action in the time-dependent matter was exerted by excessive accumulation of sphingosine and sphinganine rather than ceramide. |
| first_indexed | 2024-03-10T05:25:13Z |
| format | Article |
| id | doaj.art-02b4a795e98c41b29d31c6be982f3a36 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T05:25:13Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-02b4a795e98c41b29d31c6be982f3a362023-11-22T23:43:00ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-11-0122221247810.3390/ijms222212478Time-Dependent Changes in Hepatic Sphingolipid Accumulation and PI3K/Akt/mTOR Signaling Pathway in a Rat Model of NAFLDKlaudia Sztolsztener0Karolina Konstantynowicz-Nowicka1Ewa Harasim-Symbor2Adrian Chabowski3Department 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, PolandIncreased lipid bioavailability in a diet favors lipid accumulation, enhancing hepatic lipotoxicity and contributing to insulin resistance (IR) development. The aim of our study was to examine time-dependent alterations in the intrahepatic content of sphingolipids and insulin signaling pathway in rats fed a high-fat diet (HFD). The experiment was conducted on male Wistar rats receiving a standard diet or HFD for five weeks. At the end of each experimental feeding week, liver sphingolipids were determined using high-performance liquid chromatography. The expression of proteins from the sphingolipid pathway and glucose transporter expression were assessed by Western blot. The content of phosphorylated form of proteins from the insulin pathway was detected by a multiplex assay kit. Our results revealed that HFD enhanced hepatic ceramide deposition by increasing the expression of selected proteins from sphingomyelin and salvage pathways in the last two weeks. Importantly, we observed a significant inhibition of Akt phosphorylation in the first week of HFD and stimulation of PTEN and mTOR phosphorylation at the end of HFD. These changes worsened the PI3K/Akt/mTOR signaling pathway. We may postulate that HFD-induced reduction in the insulin action in the time-dependent matter was exerted by excessive accumulation of sphingosine and sphinganine rather than ceramide.https://www.mdpi.com/1422-0067/22/22/12478insulin signalinginsulin resistancesphingolipidlipid accumulationhigh-fat diet |
| spellingShingle | Klaudia Sztolsztener Karolina Konstantynowicz-Nowicka Ewa Harasim-Symbor Adrian Chabowski Time-Dependent Changes in Hepatic Sphingolipid Accumulation and PI3K/Akt/mTOR Signaling Pathway in a Rat Model of NAFLD International Journal of Molecular Sciences insulin signaling insulin resistance sphingolipid lipid accumulation high-fat diet |
| title | Time-Dependent Changes in Hepatic Sphingolipid Accumulation and PI3K/Akt/mTOR Signaling Pathway in a Rat Model of NAFLD |
| title_full | Time-Dependent Changes in Hepatic Sphingolipid Accumulation and PI3K/Akt/mTOR Signaling Pathway in a Rat Model of NAFLD |
| title_fullStr | Time-Dependent Changes in Hepatic Sphingolipid Accumulation and PI3K/Akt/mTOR Signaling Pathway in a Rat Model of NAFLD |
| title_full_unstemmed | Time-Dependent Changes in Hepatic Sphingolipid Accumulation and PI3K/Akt/mTOR Signaling Pathway in a Rat Model of NAFLD |
| title_short | Time-Dependent Changes in Hepatic Sphingolipid Accumulation and PI3K/Akt/mTOR Signaling Pathway in a Rat Model of NAFLD |
| title_sort | time dependent changes in hepatic sphingolipid accumulation and pi3k akt mtor signaling pathway in a rat model of nafld |
| topic | insulin signaling insulin resistance sphingolipid lipid accumulation high-fat diet |
| url | https://www.mdpi.com/1422-0067/22/22/12478 |
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