Papers by Agnieszka Dobrzyn
Przegla̧d lekarski, 2008
The aim of the study was assessment of plasma level of ceramides and adhesive molecules in patien... more The aim of the study was assessment of plasma level of ceramides and adhesive molecules in patients with stable ischaemic heart disease (IHD). Ischaemic heart disease was verified by coronary angiography as a 1.2 or 3 vessels disease. The study based on 35 patients (11F, 24 M,aged 40-74 yrs). The control group consisted of 16 healthy persons (5F, 11M, aged 43-66 yrs). Fasting plasma was drown to asses levels of ceramides, the soluble forms of E-selectin and intercellular adhesive molecule-1 (ICAM-1) and total cholesterol, chol-HDL, chol-LDL and triglicerides. Decreased concentrations of ceramides with mono- and polyunsaturated fatty acids were observed in patients with stable IHD. In 3 vessels disease the total level of ceramides was higher than in 1 vessel disease (p < 0.05). The plasma concentration of sE-selectin, ssICAM-1 were elevated in patients compared to control group (p < 0.02 and p < 0.05, respectively). The plasma levels of sICAM-1 were significantly higher in 3 vessels disease than in 1 vessel disease (p < 0.01). Ceramides concentration with saturated fatty acids correlated with adhesive molecules (p < 0.05). A negative correlation was observed between sICAM-1 concentration and ceramides with palmitoleic acid or docosahexaenoic acid (p < 0.05).
PubMed, Sep 1, 2002
Ceramide signalling has been implicated in the mechanism of myocardial ischemia/reperfusion injur... more 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.
Experimental Physiology, Dec 17, 2003
In rat skeletal muscle prolonged exercise affects the content and composition of ceramides, but i... more In rat skeletal muscle prolonged exercise affects the content and composition of ceramides, but in human skeletal muscle no data are available on this compound. Our aim was to examine the content of ceramide- and sphingomyelin fatty acids and neutral, Mg(2+)-dependent sphingomyelinase activity in skeletal muscle in untrained and trained subjects before and after prolonged exercise. Healthy male subjects were recruited into an untrained (n = 8, VO2,max 3.8 +/- 0.2 1 min1) and a trained (n = 8, Vo2,max 5.1 +/- 0.1 1 min2) group. Before and after a 3-h exercise bout (58 +/- 1% VO2,max) a muscle biopsy was excised from the vastus lateralis. Ceramide and sphingomyelin were isolated using thin-layer chromatography. The content of individual ceramide fatty acids and sphingomyelin fatty acids was measured by means of gas-liquid chromatography. The activity of neutral, Mg(2+)-dependent sphingomyelinase was measured using N-[14CH3]-sphingomyelin as a substrate. Prior to exercise, the muscle total ceramide fatty acid content in both groups was similar (201 +/- 18 and 197 +/- 9 nmol g(-1) in the untrained and trained group, respectively) and after exercise a 25% increase in the content was observed in each group. At rest, the muscle total sphingomyelin fatty acid content was higher in untrained than in trained subjects (456 +/- 10, 407 +/- 7 nmol g(-1), respectively; P < 0.05). After exercise a 20% increase (P < 0.05) in total sphingomyelin was observed only in the trained subjects. The muscle neutral, Mg(2+)-dependent sphingomyelinase activity was similar in the two groups at rest and a similar reduction was observed after exercise in both groups (untrained from 2.19 +/- 0.08 to 1.78 +/- 0.08 and trained from 2.31 +/- 0.12 to 1.80 +/- 0.09 nmol (mg protein) (-1) h(-1); P < 0.05 in each case). In conclusion, we have reported, for the first time, the values for ceramide fatty acid content and neutral, Mg2(+)-dependent sphingomyelinase activity in human skeletal muscle. The results indicate that acute prolonged exercise affects ceramide metabolism in human skeletal muscle both in untrained and in trained subjects and this may influence muscle cell adaptation and metabolism.
Acta Physiologica Scandinavica, Jul 1, 2004
The sphingomyelin signalling pathway operates in the heart muscle. There are no data on the effec... more The sphingomyelin signalling pathway operates in the heart muscle. There are no data on the effect of exercise on the functioning of this pathway in the myocardium and it was the aim of the present study to examine this question. Methods: The experiments were carried out on male Wistar rats, 300-320 g of body weight. They were divided into three groups: (1) control, (2) run 3 h on a treadmill moving with a speed of 1200 m h)1 and set at +10°incline, and (3) trained on a treadmill for 6 weeks. The rats were anaesthetized and samples of the left ventricle were taken. They were immediately frozen in liquid nitrogen. Thereafter, lipids were extracted and ceramide and sphingomyelin were isolated by means of thin layer chromatography. Their fatty acids were identified and quantified by means of gas-liquid chromatography. In separate heart samples the activity of neutral, Mg 2+-dependent sphingomyelinase and acid sphingomyelinase was determined using labelled sphingomyelin as a substrate. Results: Thirteen different ceramides and sphingomyelins were identified based on their fatty acid residue. Exercise markedly reduced the total content of ceramide-fatty acids and had no effect on the total content of sphingomyelin-fatty acids. Training did not affect the total content either of ceramide-, or sphingomyelin-fatty acids. The activity of both neutral Mg 2+-sphingomyelinase and acid sphingomyelinase was reduced after exercise. Training did not affect the activity of neutral sphingomyelinase and reduced the activity of acid sphingomyelinase. Conclusion: It is concluded that acute, prolonged exercise, but not training, markedly affects the operation of the sphingomyelin-signalling pathway in the heart.
Antioxidants, Oct 15, 2020
Nonalcoholic fatty liver disease (NAFLD) is characterized by the development of steatosis, which ... more Nonalcoholic fatty liver disease (NAFLD) is characterized by the development of steatosis, which can ultimately compromise liver function. Mitochondria are key players in obesity-induced metabolic disorders; however, the distinct role of hypercaloric diet constituents in hepatic cellular oxidative stress and metabolism is unknown. Male mice were fed either a high-fat (HF) diet, a high-sucrose (HS) diet or a combined HF plus HS (HFHS) diet for 16 weeks. This study shows that hypercaloric diets caused steatosis; however, the HFHS diet induced severe fibrotic phenotype. At the mitochondrial level, lipidomic analysis showed an increased cardiolipin content for all tested diets. Despite this, no alterations were found in the coupling efficiency of oxidative phosphorylation and neither in mitochondrial fatty acid oxidation (FAO). Consistent with unchanged mitochondrial function, no alterations in mitochondrial-induced reactive oxygen species (ROS) and antioxidant capacity were found. In contrast, the HF and HS diets caused lipid peroxidation and provoked altered antioxidant enzyme levels/activities in liver tissue. Our work provides evidence that hepatic oxidative damage may be caused by augmented levels of peroxisomes and consequently higher peroxisomal FAO-induced ROS in the early NAFLD stage. Hepatic damage is also associated with autophagic flux impairment, which was demonstrated to be diet-type dependent. The HS diet induced a reduction in autophagosomal formation, while the HF diet reduced levels of cathepsins. The accumulation of damaged organelles could instigate hepatocyte injuries and NAFLD progression.
Annals of the New York Academy of Sciences, Jan 24, 2006
Sphingomyelin has been shown to be a source of bioactive compounds. This sphingolipid is located ... more Sphingomyelin has been shown to be a source of bioactive compounds. This sphingolipid is located mostly in the outer layer of the plasma membrane and in the membranes of organelles. Sphingomyelin located in the plasma membrane is hydrolyzed into ceramide and phosphorylcholine. Ceramide is the principal second messenger in the sphingomyelin transmembrane signaling pathway. Products of ceramide metabolism, namely, sphingosine, sphingosine-1-phosphate, and ceramide-1-phosphate, also exert broad biological effects. The major effects of ceramide are induction of differentiation, inhibition of proliferation, regulation of inflammatory processes, and induction of apoptosis. There is also convincing evidence that ceramide counteracts insulinstimulated glucose uptake. Ceramides are also present in skeletal muscles. We investigated ceramide metabolism in different skeletal muscle types of the rat at rest and after prolonged exercise of moderate intensity. Exercise reduced the total content of ceramide fatty acids and changed their composition in each muscle type. These data indicate that the sphingomyelin-signaling pathway functions in skeletal muscles and that its activity is downregulated during prolonged exercise. The content of ceramide in the muscles was inversely related to 2-deoxyglucose uptake by the muscles. This indicates that ceramide may be involved in regulation of glucose uptake by skeletal muscles in vivo.
Hormone and Metabolic Research, Sep 1, 2002
It has previously been shown that prolonged exercise of moderate intensity reduces the content of... more It has previously been shown that prolonged exercise of moderate intensity reduces the content of ceramide in each type of skeletal muscle. This was accompanied by a reduction in the activity of neutral, Mg++-dependent sphingomyelinase (the major enzyme responsible for ceramide formation from sphingomyelin) in the soleus and red gastrocnemius, but not in the white gastrocnemius (A. Dobrzyń and J. Górski, Am. J. Physiol.: Endorcinol. Metab. 282: E277 - E285, 2002). No other data on regulation of ceramide metabolism in contracting muscles are available. The aim of the present study was to examine the content of sphinganine (a key precursor of ceramide on the de novo synthesis route) and the content of sphingosine (the main product of ceramide catabolism) in different skeletal muscle types after two kinds of acute exercise. The experiments were carried out on 30 male Wistar rats, 250 - 280 g of body weight. The rats were divided equally into three groups: 1 - control, 2 - run until exhaustion (1200 m/h, +10 degree incline), 3 - a group in which the sciatic nerve was stimulated 10 min with tetanic pulses (60 pulses/min). Samples were taken of the soleus and of the red and white section of the gastrocnemius. These muscles are composed mostly of the slow-twitch oxidative, fast-twitch oxidative-glycolytic and fast-twitch glycolytic fibers, respectively. Lipids were extracted with chloroform/methanol. Sphinganine and sphingosine were quantified by high-performance liquid chromatography. At rest, the content of sphinganine in the soleus was higher than in the red gastrocnemius (p < 0.05), and in the latter, it was higher than in the white gastrocnemius (p < 0.01). Prolonged exercise increased the content of sphinganine approximately 6-fold in each muscle. The resting content of sphingosine in the soleus and in the red gastrocnemius was similar--higher than in the white gastrocnemius (p < 0.001 and p < 0.01, respectively). The content of sphingosine increased over 3-fold in the soleus and nearly 2-fold in the red and white sections of the gastrocnemius. Stimulation of the sciatic nerve increased the content of both compounds approximately 2-fold in each muscle. We conclude that acute exercise increases both de novo synthesis and catabolism of ceramide in skeletal muscles. Accumulation of sphingosine in contracting muscles may contribute to the development of fatigue.
Hormone and Metabolic Research, 2004
Ceramide is the main second messenger in the sphingomyelin-transmembrane signalling pathway. The ... more Ceramide is the main second messenger in the sphingomyelin-transmembrane signalling pathway. The compound is likely to play a role in the induction of insulin resistance. The aim of the present study was to examine the effect of streptozotocin diabetes on the content and composition of ceramides and sphingomyelins and the activity of neutral Mg (2+)-dependent sphingomyelinase and acid sphingomyelinase in different types of skeletal muscle of the rat. The experiments were carried out on two groups of male Wistar rats weighing 250-280 g: controls and those treated with streptozotocin at a dose of 60 mg/kg. Determinations were performed on three types of skeletal muscle: the slow-twitch oxidative (soleus), fast-twitch oxidative-glycolytic (red section of the gastrocnemius) and fast-twitch glycolytic (white section of the same muscle). The content and composition of ceramide- and sphingomyelin-fatty acids were determined using gas-liquid chromatography. The activity of the enzymes was measured using N-[(14)CH (3)]-sphingomyelin as the substrate. Twelve different ceramides and sphingomyelins were identified and quantified in each muscle with regard to the fatty acid residue. The ratio of total content of ceramide-saturated fatty acids to the total content of ceramide-unsaturated fatty acids was more than two. In the case of sphingomyelin, the ratio was similar to ceramide in the soleus and much higher in both sections of the gastrocnemius. Treatment with streptozotocin increased the total content of ceramide-fatty acids by 78% (p < 0.001) in the soleus, 27.5% (p < 0.01) in the red and 36.9% (p < 0.001) in the white section of the gastrocnemius. Concomitantly, the total content of sphingomyelin-fatty acids decreased by 43.8%, 31.2%, 24.8% (p < 0.001 in each case) in the respective muscles. The activity of neutral Mg (2+)-dependent sphingomyelinase was elevated by 69.5%, 105.9% and 62.3% in the soleus and red and white gastrocnemius, respectively (p < 0.001 for each muscle). The activity of acid sphingomyelinase was stable in the soleus and white gastrocnemius and decreased by 15.7% (p < 0.01) in the red gastrocnemius. The results obtained show that insulin deficiency results in elevation in the content of ceramide in skeletal muscles. This indicates that the hormone is involved in regulation of the activity of the sphingomyelin-signalling pathway in the muscles.
American Journal of Physiology-endocrinology and Metabolism, Feb 1, 2002
The sphingomyelin-signaling pathway has been described in many tissues. Ceramide is the main seco... more The sphingomyelin-signaling pathway has been described in many tissues. Ceramide is the main second messenger in this pathway. Ceramide has also been shown to be present in skeletal muscles; however, there are few data on the regulation of the content of ceramide in muscle tissue. Moreover, there are no data on the content of particular ceramides or their composition in the muscles. The aim of the present study was to examine the content and composition of fatty acids (FA) in ceramide and sphingomyelin moieties and the activity of neutral Mg 2ϩ-dependent sphingomyelinase in different skeletal muscle types of the rat at rest and after exhausting exercise of moderate intensity. The experiments were carried out on male Wistar rats, divided into two groups: 1) control and 2) exercised until exhaustion on a treadmill. Soleus and red and white gastrocnemius muscles were taken. Ceramide and sphingomyelin were separated by TLC. The content of individual FA in the two compounds was determined by gas-liquid chromatography. Twelve different ceramides and sphingomyelins were identified and quantified in each muscle type according to the FA residues. Saturated FA consisted of 68, 67, and 66% of total ceramide-FA and 75, 77, and 78% of total sphingomyelin-FA in soleus and red and white gastrocnemius, respectively. The total content of ceramide-and sphingomyelin-FA and the activity of sphingomyelinase were highest in the soleus and lowest in the white gastrocnemius. Exercise resulted in a reduction in the total content of ceramide-and sphingomyelin-FA in each muscle. This was accounted for mostly by a reduction in content in the amount of saturated FA. Exercise reduced the activity of neutral Mg 2ϩ-dependent sphingomyelinase in the soleus and red gastrocnemius and did not affect its activity in the white gastrocnemius. We conclude that the sphingomyelin-signaling pathway is present in skeletal muscles and that it is influenced by prolonged exercise. sphingomyelin-signaling pathway A NOVEL TRANSMEMBRANE SIGNALING PATHWAY, called the sphingomyelin-signaling pathway, has been described and characterized in recent years. Sphingolipid sphingomyelin, which is located mostly in the outer layer of the plasma membrane, is hydrolyzed by the enzyme neutral Mg 2ϩ-dependent sphingomyelinase to phosphorylcholine and ceramide. Ceramide may be further
Journal of Physiology and Pharmacology. Supplement, 2001
Antioxidants, 2020
Nonalcoholic fatty liver disease (NAFLD) is characterized by the development of steatosis, which ... more Nonalcoholic fatty liver disease (NAFLD) is characterized by the development of steatosis, which can ultimately compromise liver function. Mitochondria are key players in obesity-induced metabolic disorders; however, the distinct role of hypercaloric diet constituents in hepatic cellular oxidative stress and metabolism is unknown. Male mice were fed either a high-fat (HF) diet, a high-sucrose (HS) diet or a combined HF plus HS (HFHS) diet for 16 weeks. This study shows that hypercaloric diets caused steatosis; however, the HFHS diet induced severe fibrotic phenotype. At the mitochondrial level, lipidomic analysis showed an increased cardiolipin content for all tested diets. Despite this, no alterations were found in the coupling efficiency of oxidative phosphorylation and neither in mitochondrial fatty acid oxidation (FAO). Consistent with unchanged mitochondrial function, no alterations in mitochondrial-induced reactive oxygen species (ROS) and antioxidant capacity were found. In c...
Scientific Reports, 2018
Obesity and related metabolic pathologies represent a significant public health concern. Obesity ... more Obesity and related metabolic pathologies represent a significant public health concern. Obesity is associated with increased oxidative stress that damages genomic and mitochondrial DNA. Oxidatively-induced lesions in both DNA pools are repaired via the base-excision repair pathway, initiated by DNA glycosylases such as 8-oxoguanine DNA glycosylase (OGG1). Global deletion of OGG1 and common OGG1 polymorphisms render mice and humans susceptible to metabolic disease. However, the relative contribution of mitochondrial OGG1 to this metabolic phenotype is unknown. Here, we demonstrate that transgenic targeting of OGG1 to mitochondria confers significant protection from diet-induced obesity, insulin resistance, and adipose tissue inflammation. These favorable metabolic phenotypes are mediated by an increase in whole body energy expenditure driven by specific metabolic adaptations, including increased mitochondrial respiration in white adipose tissue of OGG1 transgenic (Ogg1Tg) animals. T...
Przegla̧d lekarski, 2008
The aim of the study was assessment of plasma level of ceramides and adhesive molecules in patien... more The aim of the study was assessment of plasma level of ceramides and adhesive molecules in patients with stable ischaemic heart disease (IHD). Ischaemic heart disease was verified by coronary angiography as a 1.2 or 3 vessels disease. The study based on 35 patients (11F, 24 M,aged 40-74 yrs). The control group consisted of 16 healthy persons (5F, 11M, aged 43-66 yrs). Fasting plasma was drown to asses levels of ceramides, the soluble forms of E-selectin and intercellular adhesive molecule-1 (ICAM-1) and total cholesterol, chol-HDL, chol-LDL and triglicerides. Decreased concentrations of ceramides with mono- and polyunsaturated fatty acids were observed in patients with stable IHD. In 3 vessels disease the total level of ceramides was higher than in 1 vessel disease (p < 0.05). The plasma concentration of sE-selectin, ssICAM-1 were elevated in patients compared to control group (p < 0.02 and p < 0.05, respectively). The plasma levels of sICAM-1 were significantly higher in 3...
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 2003
Ceramide is the second messenger in the sphingomyelin signalling pathway. A number of extracellul... more 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. ...
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 2002
Ceramide signalling has been implicated in the mechanism of myocardial ischemia/reperfusion injur... more 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 cera...
American Journal of Physiology-Endocrinology and Metabolism, 2002
The sphingomyelin-signaling pathway has been described in many tissues. Ceramide is the main seco... more The sphingomyelin-signaling pathway has been described in many tissues. Ceramide is the main second messenger in this pathway. Ceramide has also been shown to be present in skeletal muscles; however, there are few data on the regulation of the content of ceramide in muscle tissue. Moreover, there are no data on the content of particular ceramides or their composition in the muscles. The aim of the present study was to examine the content and composition of fatty acids (FA) in ceramide and sphingomyelin moieties and the activity of neutral Mg2+-dependent sphingomyelinase in different skeletal muscle types of the rat at rest and after exhausting exercise of moderate intensity. The experiments were carried out on male Wistar rats, divided into two groups: 1) control and 2) exercised until exhaustion on a treadmill. Soleus and red and white gastrocnemius muscles were taken. Ceramide and sphingomyelin were separated by TLC. The content of individual FA in the two compounds was determined...
Proceedings of the National Academy of Sciences, 2005
There are four known stearoyl-CoA desaturase (SCD) enzyme isoforms in mouse and two in humans tha... more There are four known stearoyl-CoA desaturase (SCD) enzyme isoforms in mouse and two in humans that are required for the biosynthesis of monounsaturated fatty acids, mainly oleate. SCD1 isoform plays a role in the regulation of energy metabolism and lipid synthesis, but the roles of the other SCD isoforms have not been investigated. Here we show that the SCD2 isoform is important in lipid synthesis in early development and is required for survival. SCD2-deficient ( Scd2 -/- ) neonatal mice have a skin permeability barrier defect and a specific repartitioning of linoleic acid from epidermal acylceramide species into phospholipids. SCD2 expression is high in liver of wild-type mouse embryos and neonates between embryonic day 18.5 and 21 days of age and is decreased in adult mice. SCD1 expression, on the other hand, is induced after weaning. The liver, skin, and plasma triglyceride contents are decreased in the neonates but are not altered in the adult Scd2 -/- mice. These results indic...
Journal of Lipid Research, 2004
Stearoyl-CoA desaturase (SCD) is a microsomal enzyme involved in the biosynthesis of oleate and p... more Stearoyl-CoA desaturase (SCD) is a microsomal enzyme involved in the biosynthesis of oleate and palmitoleate. Mice with a targeted disruption of the SCD1 isoform (SCD1 ؊ / ؊) exhibit reduced adiposity and increased energy expenditure. To address whether the energy expenditure is attributable to increased thermogenesis, we investigated the effect of SCD1 deficiency on basal and coldinduced thermogenesis. SCD1 ؊ / ؊ mice have increased expression of uncoupling proteins in brown adipose tissue (BAT) relative to controls. The  3-adrenergic receptor ( 3-AR) expression was increased and the phosphorylation of cAMP response element binding protein and the protein level of peroxisome proliferator-activated receptor-␥ coactivator-1 ␣ were increased in the SCD1 ؊ / ؊ mice. Both lipolysis and fatty acid oxidation were increased in the SCD1 ؊ / ؊ mice. When exposed to 4 Њ C, SCD1 ؊ / ؊ mice showed hypothermia, hypoglycemia, and depleted liver glycogen. High levels of dietary oleate partially compensated for the hypothermia and rescued plasma glucose and liver glycogen. These results suggest that SCD1 deficiency stimulates basal thermogenesis through the upregulation of the  3-ARmediated pathway and a subsequent increase in lipolysis and fatty acid oxidation in BAT. The hypothermia and hypoglycemia in cold-exposed SCD1 ؊ / ؊ mice and the compensatory recovery by oleate indicate an important role of SCD1 gene expression in thermoregulation.-Lee, S-H., A.
Journal of Lipid Research, 2010
Journal of Applied Physiology, 2010
Stearoyl-CoA desaturase (SCD), a rate-limiting enzyme in the biosynthesis of monounsaturated fatt... more Stearoyl-CoA desaturase (SCD), a rate-limiting enzyme in the biosynthesis of monounsaturated fatty acids, has recently been shown to be a critical control point in regulation of liver and skeletal muscle metabolism. Herein, we demonstrate that endurance training significantly increases both SCD1 mRNA and protein levels in the soleus muscle, whereas it does not affect SCD1 expression in the EDL muscle and liver. Desaturation index (18:1Δ9/18:0 ratio), an indirect indicator of SCD1 activity, was also significantly higher (3.6-fold) in soleus of trained rats compared with untrained animals. Consistent with greater SCD1 expression/activity, the contents of free fatty acids, diacylglycerol, and triglyceride were elevated in soleus of trained rats. However, training did not affect lipid concentration in EDL and liver. Additionally, endurance training activated the AMP-activated protein kinase pathway as well as increased peroxisome proliferator-activated receptor (PPAR)-δ and PPARα gene e...
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Papers by Agnieszka Dobrzyn