Inhibition of Ceramide De Novo Synthesis Ameliorates Diet Induced Skeletal Muscles Insulin Resistance

Nowadays wrong nutritional habits and lack of physical activity give a rich soil for the development of insulin resistance and obesity. Many researches indicate lipids, especially the one from the sphingolipids class, as the group of molecules heavily implicated in the progress of insulin resistance...

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Main Authors: Krzysztof Kurek, Agnieszka Mikłosz, Bartłomiej Łukaszuk, Adrian Chabowski, Jan Górski, Małgorzata Żendzian-Piotrowska
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2015/154762
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author Krzysztof Kurek
Agnieszka Mikłosz
Bartłomiej Łukaszuk
Adrian Chabowski
Jan Górski
Małgorzata Żendzian-Piotrowska
author_facet Krzysztof Kurek
Agnieszka Mikłosz
Bartłomiej Łukaszuk
Adrian Chabowski
Jan Górski
Małgorzata Żendzian-Piotrowska
author_sort Krzysztof Kurek
collection DOAJ
description Nowadays wrong nutritional habits and lack of physical activity give a rich soil for the development of insulin resistance and obesity. Many researches indicate lipids, especially the one from the sphingolipids class, as the group of molecules heavily implicated in the progress of insulin resistance in skeletal muscle. Recently, scientists have focused their scrutiny on myriocin, a potent chemical compound that inhibits ceramide (i.e., central hub of sphingolipids signaling pathway) de novo synthesis. In the present research we evaluated the effects of myriocin application on type 2 diabetes mellitus in three different types of skeletal muscles: (1) slow-oxidative (red gastrocnemius), (2) oxidative-glycolytic (soleus), and (3) glycolytic (white gastrocnemius). For these reasons the animals were randomly divided into four groups: “control” (C), “myriocin” (M), “high fat diet” (HFD), “high fat diet” (HFD), and “high fat diet + myriocin” (HFD + M). Our in vivo study demonstrated that ceramide synthesis inhibition reduces intramuscular ceramide, its precursor sphinganine, and its derivatives sphingosine and sphingosine-1-phosphate concentrations. Moreover, FFA and TG contents were also decreased after myriocin treatment. Thus, myriocin presents potential therapeutic perspectives with respect to the treatment of insulin resistance and its serious consequences in obese patients.
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spelling doaj-art-ba00e8b2d2a34566be7188e160080c922025-02-03T05:59:46ZengWileyJournal of Diabetes Research2314-67452314-67532015-01-01201510.1155/2015/154762154762Inhibition of Ceramide De Novo Synthesis Ameliorates Diet Induced Skeletal Muscles Insulin ResistanceKrzysztof Kurek0Agnieszka Mikłosz1Bartłomiej Łukaszuk2Adrian Chabowski3Jan Górski4Małgorzata Żendzian-Piotrowska5Department of Physiology, Medical University of Bialystok, 2C Mickiewicza Street, 15-222 Białystok, PolandDepartment of Physiology, Medical University of Bialystok, 2C Mickiewicza Street, 15-222 Białystok, PolandDepartment of Physiology, Medical University of Bialystok, 2C Mickiewicza Street, 15-222 Białystok, PolandDepartment of Physiology, Medical University of Bialystok, 2C Mickiewicza Street, 15-222 Białystok, PolandDepartment of Physiology, Medical University of Bialystok, 2C Mickiewicza Street, 15-222 Białystok, PolandDepartment of Physiology, Medical University of Bialystok, 2C Mickiewicza Street, 15-222 Białystok, PolandNowadays wrong nutritional habits and lack of physical activity give a rich soil for the development of insulin resistance and obesity. Many researches indicate lipids, especially the one from the sphingolipids class, as the group of molecules heavily implicated in the progress of insulin resistance in skeletal muscle. Recently, scientists have focused their scrutiny on myriocin, a potent chemical compound that inhibits ceramide (i.e., central hub of sphingolipids signaling pathway) de novo synthesis. In the present research we evaluated the effects of myriocin application on type 2 diabetes mellitus in three different types of skeletal muscles: (1) slow-oxidative (red gastrocnemius), (2) oxidative-glycolytic (soleus), and (3) glycolytic (white gastrocnemius). For these reasons the animals were randomly divided into four groups: “control” (C), “myriocin” (M), “high fat diet” (HFD), “high fat diet” (HFD), and “high fat diet + myriocin” (HFD + M). Our in vivo study demonstrated that ceramide synthesis inhibition reduces intramuscular ceramide, its precursor sphinganine, and its derivatives sphingosine and sphingosine-1-phosphate concentrations. Moreover, FFA and TG contents were also decreased after myriocin treatment. Thus, myriocin presents potential therapeutic perspectives with respect to the treatment of insulin resistance and its serious consequences in obese patients.http://dx.doi.org/10.1155/2015/154762
spellingShingle Krzysztof Kurek
Agnieszka Mikłosz
Bartłomiej Łukaszuk
Adrian Chabowski
Jan Górski
Małgorzata Żendzian-Piotrowska
Inhibition of Ceramide De Novo Synthesis Ameliorates Diet Induced Skeletal Muscles Insulin Resistance
Journal of Diabetes Research
title Inhibition of Ceramide De Novo Synthesis Ameliorates Diet Induced Skeletal Muscles Insulin Resistance
title_full Inhibition of Ceramide De Novo Synthesis Ameliorates Diet Induced Skeletal Muscles Insulin Resistance
title_fullStr Inhibition of Ceramide De Novo Synthesis Ameliorates Diet Induced Skeletal Muscles Insulin Resistance
title_full_unstemmed Inhibition of Ceramide De Novo Synthesis Ameliorates Diet Induced Skeletal Muscles Insulin Resistance
title_short Inhibition of Ceramide De Novo Synthesis Ameliorates Diet Induced Skeletal Muscles Insulin Resistance
title_sort inhibition of ceramide de novo synthesis ameliorates diet induced skeletal muscles insulin resistance
url http://dx.doi.org/10.1155/2015/154762
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