title: Inhibition of Ceramide De Novo Synthesis Ameliorates Diet Induced Skeletal Muscles Insulin Resistance.
abstract: 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.
authors.affiliation: Department of Physiology, Medical University of Bialystok, 2C Mickiewicza Street, 15-222 Białystok, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kurek
authors.affiliation: Department of Physiology, Medical University of Bialystok, 2C Mickiewicza Street, 15-222 Białystok, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Mikłosz
authors.affiliation: Department of Physiology, Medical University of Bialystok, 2C Mickiewicza Street, 15-222 Białystok, Poland.
authors.forename: Bartłomiej
authors.initials: B
authors.lastname: Łukaszuk
authors.affiliation: Department of Physiology, Medical University of Bialystok, 2C Mickiewicza Street, 15-222 Białystok, Poland.
authors.forename: Adrian
authors.initials: A
authors.lastname: Chabowski
authors.affiliation: Department of Physiology, Medical University of Bialystok, 2C Mickiewicza Street, 15-222 Białystok, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Górski
authors.affiliation: Department of Physiology, Medical University of Bialystok, 2C Mickiewicza Street, 15-222 Białystok, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Żendzian-Piotrowska
mesh_terms: D000818:Animals; D002518:Ceramides / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000178:diet therapy / Q000378:metabolism; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D006019:Glycolysis; D007333:Insulin Resistance; D008246:Lysophospholipids / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D013107:Sphingolipids / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D002518:Ceramides; D005229:Fatty Acids, Monounsaturated; D008246:Lysophospholipids; D013107:Sphingolipids; C060506:sphingosine 1-phosphate; D013110:Sphingosine; C005682:safingol; D010100:Oxygen; C001996:thermozymocidin