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1

Molecular mechanism of lipid-induced insulin resistance — the role of stearoyl-CoA desaturase

100%
Dobrzyn A.
Acta Biochimica Polonica
|
2007
|
tom 54
|
nr Supplement 4
2

The role of stearoyl- CoA desaturase in the control of lipid metabolism

75%
Dobrzyn A.
Acta Biochimica Polonica
|
2006
|
tom 53
|
nr Supplement 1
3

Układ endokanabinoidowy i jego rola w regulacji metabolizmu tkanek obwodowych

63%
Ruminska A., Dobrzyn A.
Postępy Biochemii
|
2012
|
tom 58
|
nr 2
4
Content available remote

Stearoyl-CoA desaturase - a new player in skeletal muscle metabolism regulation

63%
Dobrzyn A., Dobrzyn P.
Journal of Physiology and Pharmacology. Supplement
|
2006
|
tom 57
|
nr 10
31-42
Stearoyl-CoA desaturase (SCD) is a rate-limiting enzyme catalyzing the synthesis of monounsaturated fatty acids, mainly oleate (18:1) and palmitoleate (16:1), which are a major component of tissue lipids. SCD1 deficient mice reveal increased energy expenditure and decreased body adiposity due to the upregulation of genes of fatty acid oxidation and the downregulation of genes of lipid synthesis in liver. In this review, we examine data showing that SCD is an important component in the regulation of skeletal muscle metabolism, which affects insulin sensitivity, mitochondrial fatty acid oxidation and ceramide de novo synthesis in oxidative myofibers. The lack of SCD1 gene increases the rate of fatty acid ß-oxidation through activation of the AMP-activated protein kinase (AMPK) pathway and by upregulating genes of fatty acid oxidation in soleus and red gastrocnemius muscles. Consistent with increased ß-oxidation, the contents of free fatty acids and long-chain acyl-CoAs are significantly decreased, which together with reduced mRNA level and activity of serine palmitoyltransferase led to reduced ceramide synthesis in oxidative muscles of SCD1-/- mice. Thus, reduced contents of free fatty acids, acyl-CoAs and ceramides as well as increased AMPK phosphorylation, might contribute to increased insulin sensitivity observed in muscle of SCD1-/- mice. SCD1 deficiency also results in downregulation of the expression of the protein-tyrosine phosphatase 1B, which is responsible for the sustained insulin receptor autophosphorylation despite reduced levels of plasma insulin in the SCD1-/- mice. SCD1 deficiency reduced ceramide synthesis, increased AMPK phosphorylation and carnitine palmitoyltransferase 1 activity also in soleus and red gastrocnemius muscles of leptin deficient ob/ob mice. These findings raise the possibility that SCD1 may be a downstream component of the leptin signaling pathway in skeletal muscle.
5

The role of stearoyl-CoA disaturase 1 in cardiac lipid accumulation

51%
Dobrzyn P., Dobrzyn A., Ntambi J. M.
Acta Biochimica Polonica
|
2006
|
tom 53
|
nr Supplement 1
6

Regulacja transkrypcji genów przez długołańcuchowe kwasy tłuszczowe

51%
Jazurek M., Dobrzyn P., Dobrzyn A.
Postępy Biochemii
|
2008
|
tom 54
|
nr 3
7

Stearoyl-CoA desaturase 1 deficiency decreases fatty acid oxidation in the heart

51%
Dobrzyn P., Dobrzyn A., Ntambi J.-M.
Acta Biochimica Polonica
|
2007
|
tom 54
|
nr Supplement 4
8
Content available remote

Accumulation of specific ceramides in ischemic-reperfused rat heart; effect of ischemic preconditioning

51%
Beresewicz A., Dobrzyn A., Gorski J.
Journal of Physiology and Pharmacology
|
2002
|
tom 53
|
nr 3
Ceramide signalling has been implicated in the mechanism of myocardial ischemia/reperfusion injury (IR). This study tested the hypothesis that ceramides containing a specific amino-linked acyl residue mediate the injury, and that ischemic preconditioning (IPC) affords myocardial protection because it prevents increased ceramide accumulation in IR myocardium. Perfused rat hearts were subjected either to the sham perfusion or to 30 min global ischemia, 30 min ischemia/30 min reperfusion (IR) or were preconditioned prior to the standard IR. The ventricles were harvested for biochemical assay that involved transmethylation of ceramide amino-linked acyl residues, and gas liquid chromatography measurement of acyl methyl esters. Fourteen ceramides containing myrystic, palmitic, palmitoleic, stearic, oleic, linoleic, linolenic, arachidic, arachidonic, eicosapentaenoic, behenic, docosapentaenoic, docosahexaenoic or nervonic acid were identified in the myocardium of rats. The total basal ceramide concentration in the myocardium was 135 nmol/g tissue, and it was increased by 14.1% and 48.4% in the ischemia and IR group, respectively. However, in fact, IR increased the accumulation of only 7 out of 14 ceramides identified in the heart (i.e., those containing palmitic, stearic, oleic, linoleic, and arachidonic acid), and the relative magnitude of these increases varied between the particular ceramides and was independent from their basal tissue concentration. IPC improved postischemic hemodynamic recovery and partially prevented the reperfusion-induced increases in these 7 ceramides, while the other ceramides were unaffected by IPC. These results support the role of the specific ceramide signalling in the mechanism of myocardial IR injury. We speculate that by preventing tissue accumulation of certain ceramides, IPC attenuates this signalling, that adds to the mechanism of myocardial protection afforded by IPC.
9

The composition and content of ceramides and sphingomyelins in gastrointestinal epithelium

51%
Marcinkiewicz M., Dobrzyn A., Gorski J.
Journal of Physiology and Pharmacology. Supplement
|
2001
|
tom 52
|
nr 2
10
Content available remote

Effect of hypothyreosis on the content of ceramides in rat tissues

51%
Gorska M., Dobrzyn A., Langfort J., Gorski J.
Journal of Physiology and Pharmacology
|
2003
|
tom 54
|
nr 1
Ceramide is the second messenger in the sphingomyelin signalling pathway. A number of extracellular stimuli increase the content of ceramide in the cell. There are some data indicating that the content of ceramide may also be regulated by hormones. The aim of the present study was to examine the effect of hypothyreosis on the content and composition of ceramide in rat tissues. The rats were thyroidectomized and thereafter they received propylthiouracyl in drinking water. The control rats were sham operated. 30 days after thyroidectomy or sham operation the rats were anaesthetized and samples of the liver, white and red vastus lateralis and left ventricle were taken. One set of samples was frozen in liquid nitrogen for analysis of ceramide. Another set of samples was freshly homogenized in chloroform/methanol for further determination of the content of sphingomyelin phosphorous. The content and composition of ceramide-fatty acids was determined by means of gas-liquid chromatography. Twelve ceramides containing different fatty acid residues were identified in both groups. Hypothyreosis reduced the total content of ceramide in each tissue studied: in the heart by 50.9%, in the red vastus by 28.6%, in the white vastus by 29.4% and in the liver by 22%. Concomitantly, the content of individual ceramides was either reduced, stable or even elevated, depending on the tissue. The content of sphingomyelin was elevated in both sections of the vastus lateralis and remained stable in the heart and the liver. The ratio: total content of sphingomyelin to total content of ceramide was elevated in the muscles and remained stable in the liver. This indicates that the reduction in the content of ceramide in the tissues of hypothyroid rats may be a consequence either of a reduction in the formation of ceramide from sphingomyelin, its increased hydrolysis or both. It is concluded that normal thyroid function is needed to maintain the content and composition of ceramide in the tissues.
11
Content available remote

Effect of endurance training on the sphingomyelin-signalling pathway activity in the skeletal muscles of the rat

51%
Dobrzyn A., Zendzian-Piotrowska M., Gorski J.
Journal of Physiology and Pharmacology
|
2004
|
tom 55
|
nr 2
The sphingomyelin signalling pathway has been shown to function in different skeletal muscle types. The aim of the present study was to examine the effect of endurance training on the functioning of the pathway in the muscles. The experiments were carried out on two groups of male Wistar rats: sedentary and trained for six weeks. 24h after cessation of the training rats were anaesthetized and samples of the soleus, red and white section of the gastrocnemius were taken. The content and composition of sphingomyelin-fatty acids and ceramide - fatty acids was determined by means of gas-liquid chromatography. The content of sphingosine and sphinganine was determined by means of high-pressure liquid chromatography. The activity of neutral Mg++-dependent sphingomyelinase was determined spectophotometrically using trinitrophenylaminolauroyl-sphingomyelin as the substrate. It has been found that training reduces the total content of sphingomyelin- and ceramide-fatty acids, increases the content of sphinganine and does not affect the content of sphingosine in individual muscle types. The activity of the enzyme in the muscles is also elevated. It is concluded that training affects functioning of the sphingomyelin -signalling pathway in skeletal muscles. The reduction in the content of ceramide may contribute to elevation in glucose uptake in skeletal muscles observed after training.
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