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

Kurek K, Mikłosz A, Łukaszuk B, Chabowski A, Górski J, Żendzian-Piotrowska M - J Diabetes Res (2015)

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Medical University of Bialystok, 2C Mickiewicza Street, 15-222 Białystok, Poland.

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.

No MeSH data available.


Related in: MedlinePlus

Effect of high-fat diet (HFD) feeding (5 weeks) and/or myriocin application (7 days) on sphinganine (SFA) content in skeletal muscles (n (per group) = 8). M+: rats administered with myriocin. M−: untreated group. Results are expressed as means ± SD. ∗p < 0.05 compared with control group. †p < 0.05 compared with HF diet group.
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fig1: Effect of high-fat diet (HFD) feeding (5 weeks) and/or myriocin application (7 days) on sphinganine (SFA) content in skeletal muscles (n (per group) = 8). M+: rats administered with myriocin. M−: untreated group. Results are expressed as means ± SD. ∗p < 0.05 compared with control group. †p < 0.05 compared with HF diet group.

Mentions: Compared with control group rats fed with high-fat diet were characterized by significant increase of SFA content in soleus and red gastrocnemius, but not in white gastrocnemius muscle (Figure 1, p < 0.05 and p < 0.05, resp.). After myriocin treatment a dramatic reduction in SFA level in comparison with control and HFD groups was noted in all three examined sections of skeletal muscle (Figure 1, p < 0.05). Subsequently, we found that high-fat diet feeding resulted in significant elevation of ceramide concentration in both soleus and red gastrocnemius, but not in white gastrocnemius muscle (Figure 2, p < 0.05 and p < 0.05, resp.). Treatment with myriocin significantly decreased ceramide content compared with control and HFD groups in soleus, red gastrocnemius, and white gastrocnemius muscle (Figure 2, p < 0.05). Surprisingly, we observed that sphingomyelin content remained unchanged after high-fat diet feeding as well as after myriocin treatment in all three sections of skeletal muscle (Figure 3). We found that high-fat diet had no influence on sphingosine content in any of the observed groups. However, groups receiving myriocin were characterized by significant reduction of SFO concentration in soleus, red gastrocnemius, and white gastrocnemius muscle (Figure 4, p < 0.05). Finally, we observed significant increment in sphingosine-1-phosphate content after high-fat diet feeding only in soleus muscle. Treatment with myriocin significantly decreased S1P concentrations in both soleus and red gastrocnemius muscles, but not in white gastrocnemius muscle (Figure 5, p < 0.05 and p < 0.05, resp.).


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

Kurek K, Mikłosz A, Łukaszuk B, Chabowski A, Górski J, Żendzian-Piotrowska M - J Diabetes Res (2015)

Effect of high-fat diet (HFD) feeding (5 weeks) and/or myriocin application (7 days) on sphinganine (SFA) content in skeletal muscles (n (per group) = 8). M+: rats administered with myriocin. M−: untreated group. Results are expressed as means ± SD. ∗p < 0.05 compared with control group. †p < 0.05 compared with HF diet group.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4562089&req=5

fig1: Effect of high-fat diet (HFD) feeding (5 weeks) and/or myriocin application (7 days) on sphinganine (SFA) content in skeletal muscles (n (per group) = 8). M+: rats administered with myriocin. M−: untreated group. Results are expressed as means ± SD. ∗p < 0.05 compared with control group. †p < 0.05 compared with HF diet group.
Mentions: Compared with control group rats fed with high-fat diet were characterized by significant increase of SFA content in soleus and red gastrocnemius, but not in white gastrocnemius muscle (Figure 1, p < 0.05 and p < 0.05, resp.). After myriocin treatment a dramatic reduction in SFA level in comparison with control and HFD groups was noted in all three examined sections of skeletal muscle (Figure 1, p < 0.05). Subsequently, we found that high-fat diet feeding resulted in significant elevation of ceramide concentration in both soleus and red gastrocnemius, but not in white gastrocnemius muscle (Figure 2, p < 0.05 and p < 0.05, resp.). Treatment with myriocin significantly decreased ceramide content compared with control and HFD groups in soleus, red gastrocnemius, and white gastrocnemius muscle (Figure 2, p < 0.05). Surprisingly, we observed that sphingomyelin content remained unchanged after high-fat diet feeding as well as after myriocin treatment in all three sections of skeletal muscle (Figure 3). We found that high-fat diet had no influence on sphingosine content in any of the observed groups. However, groups receiving myriocin were characterized by significant reduction of SFO concentration in soleus, red gastrocnemius, and white gastrocnemius muscle (Figure 4, p < 0.05). Finally, we observed significant increment in sphingosine-1-phosphate content after high-fat diet feeding only in soleus muscle. Treatment with myriocin significantly decreased S1P concentrations in both soleus and red gastrocnemius muscles, but not in white gastrocnemius muscle (Figure 5, p < 0.05 and p < 0.05, resp.).

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Medical University of Bialystok, 2C Mickiewicza Street, 15-222 Białystok, Poland.

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.

No MeSH data available.


Related in: MedlinePlus