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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Autores principales:	Klaudia Sztolsztener, Karolina Konstantynowicz-Nowicka, Ewa Harasim-Symbor, Adrian Chabowski
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	insulin signaling insulin resistance sphingolipid lipid accumulation high-fat diet Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/02b4a795e98c41b29d31c6be982f3a36
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spelling	oai:doaj.org-article:02b4a795e98c41b29d31c6be982f3a362021-11-25T17:57:01ZTime-Dependent Changes in Hepatic Sphingolipid Accumulation and PI3K/Akt/mTOR Signaling Pathway in a Rat Model of NAFLD10.3390/ijms2222124781422-00671661-6596https://doaj.org/article/02b4a795e98c41b29d31c6be982f3a362021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12478https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Increased 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.Klaudia SztolsztenerKarolina Konstantynowicz-NowickaEwa Harasim-SymborAdrian ChabowskiMDPI AGarticleinsulin signalinginsulin resistancesphingolipidlipid accumulationhigh-fat dietBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12478, p 12478 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	insulin signaling insulin resistance sphingolipid lipid accumulation high-fat diet Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	insulin signaling insulin resistance sphingolipid lipid accumulation high-fat diet Biology (General) QH301-705.5 Chemistry QD1-999 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
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.
format	article
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
title	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_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_sort	time-dependent changes in hepatic sphingolipid accumulation and pi3k/akt/mtor signaling pathway in a rat model of nafld
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/02b4a795e98c41b29d31c6be982f3a36
work_keys_str_mv	AT klaudiasztolsztener timedependentchangesinhepaticsphingolipidaccumulationandpi3kaktmtorsignalingpathwayinaratmodelofnafld AT karolinakonstantynowicznowicka timedependentchangesinhepaticsphingolipidaccumulationandpi3kaktmtorsignalingpathwayinaratmodelofnafld AT ewaharasimsymbor timedependentchangesinhepaticsphingolipidaccumulationandpi3kaktmtorsignalingpathwayinaratmodelofnafld AT adrianchabowski timedependentchangesinhepaticsphingolipidaccumulationandpi3kaktmtorsignalingpathwayinaratmodelofnafld
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Time-Dependent Changes in Hepatic Sphingolipid Accumulation and PI3K/Akt/mTOR Signaling Pathway in a Rat Model of NAFLD

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