Myostatin and the Heart.

Myostatin (growth differentiation factor 8) is a member of the transforming growth factor-β superfamily. It is secreted mostly by skeletal muscles, although small amounts of myostatin are produced by the myocardium and the adipose tissue as well. Myostatin binds to activin IIB membrane receptors to activate the downstream intracellular canonical Smad2/Smad3 pathway, and additionally acts on non-Smad (non-canonical) pathways.

Endogenous and Exogenous Antioxidants in Skeletal Muscle Fatigue Development during Exercise.

Muscle fatigue is defined as a decrease in maximal force or power generated in response to contractile activity, and it is a risk factor for the development of musculoskeletal injuries. One of the many stressors imposed on skeletal muscle through exercise is the increased production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), which intensifies as a function of exercise intensity and duration. Exposure to ROS/RNS can affect Na/K-ATPase activity, intramyofibrillar calcium turnover and sensitivity, and actin-myosin kinetics to reduce muscle force production.

Treadmill Running Changes Endothelial Lipase Expression: Insights from Gene and Protein Analysis in Various Striated Muscle Tissues and Serum.

Endothelial lipase (EL) is an enzyme capable of HDL phospholipids hydrolysis. Its action leads to a reduction in the serum high-density lipoprotein concentration, and thus, it exerts a pro-atherogenic effect. This study examines the impact of a single bout exercise on the gene and protein expression of the EL in skeletal muscles composed of different fiber types (the soleus-mainly type I, the red gastrocnemius-mostly IIA, and the white gastrocnemius-predominantly IIX fibers), as well as the diaphragm, and the heart.

Blood Profile of Cytokines, Chemokines, Growth Factors, and Redox Biomarkers in Response to Different Protocols of Treadmill Running in Rats.

Both positive and negative aspects of sport performance are currently considered. The aim of our study was to determine time- and intensity-dependent effects of a single exercise bout on redox and inflammatory status. The experiment was performed on 40 male Wistar rats subjected to treadmill running for 30 min with the speed of 18 m/min (M30) or 28 m/min (F30), or for 2 h with the speed of 18 m/min (M120).

The Gene and Protein Expression of the Main Components of the Lipolytic System in Human Myocardium and Heart Perivascular Adipose Tissue. Effect of Coronary Atherosclerosis.

The aim of our study was to examine the regulation of triacylglycerols (TG) metabolism in myocardium and heart perivascular adipose tissue in coronary atherosclerosis. Adipose triglyceride lipase (ATGL) is the major TG-hydrolase. The enzyme is activated by a protein called comparative gene identification 58 (CGI-58) and inhibited by a protein called G0/G1 switch protein 2 (G0S2).

Plasma concentration and expression of adipokines in epicardial and subcutaneous adipose tissue are associated with impaired left ventricular filling pattern.

Background: Adipokines in serum derive mainly from subcutaneous and visceral adipose tissues. Epicardial adipose tissue (EAT), being a relatively small but unique fat depot, probably does not make an important contribution to systemic concentrations of adipokines. However, proximity of EAT to cardiac muscle and coronary arteries allows cells and proteins to penetrate between tissues.

Assessment of the Main Compounds of the Lipolytic System in Treadmill Running Rats: Different Response Patterns between the Right and Left Ventricle.

The aim of the present study was to investigate the time and intensity dependent effects of exercise on the heart components of the lipolytic complex. Wistar rats ran on a treadmill with the speed of 18 m/min for 30 min (M30) or 120 min (M120) or with the speed of 28 m/min for 30 min (F30). The mRNA and protein expressions of the compounds adipose triglyceride lipase (ATGL), comparative gene identification-58 (CGI-58), G0/G1 switch gene 2 (G0S2), hormone sensitive lipase (HSL) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) were examined by real-time PCR and Western blot, respectively.

Metformin treatment affects adipocytokine secretion and lipid composition in adipose tissues of diet-induced insulin-resistant rats.

Objectives: Adipose tissue plays a central role in the pathogenesis of insulin resistance (IR) and type 2 diabetes. However, the molecular changes that promote these diseases are not completely understood. Several studies demonstrated that ceramide (Cer) and diacylglycerol (DAG) accumulation in muscle is associated with IR.

Inhibition of Ceramide De Novo Synthesis Affects Adipocytokine Secretion and Improves Systemic and Adipose Tissue Insulin Sensitivity.

Ceramide accumulation in muscle and in liver is implicated in the induction of insulin resistance. Much less in known about the role of ceramide in adipose tissue. The aim of the present study was to elucidate the role of ceramide in adipose tissue and to clarify whether lipids participate in the regulation of adipocytokine secretion.

The effect of high-fat diet and inhibition of ceramide production on insulin action in liver.

Liver, as one of the most important organs involved in lipids and glucose metabolism, is perceived as a key tissue for pharmacotherapy of insulin resistance (IRes) and type 2 diabetes. Ceramides (Cer) are biologically active lipids, which accumulation is associated with the induction of muscle IRes. We sought to determine the role of intrahepatic bioactive lipids production on insulin action in liver of insulin-resistant rats and after myriocin administration.

Ceramide Transporter CERT Is Involved in Muscle Insulin Signaling Defects Under Lipotoxic Conditions.

One main mechanism of insulin resistance (IR), a key feature of type 2 diabetes, is the accumulation of saturated fatty acids (FAs) in the muscles of obese patients with type 2 diabetes. Understanding the mechanism that underlies lipid-induced IR is an important challenge. Saturated FAs are metabolized into lipid derivatives called ceramides, and their accumulation plays a central role in the development of muscle IR.

The effect of high fat diet and metformin treatment on liver lipids accumulation and their impact on insulin action.

We sought to determine whether metformin treatment reverses a high-fat diet (HFD)-induced hepatic insulin resistance (IRes) and to identify lipid intermediates involved in induction of liver IRes. The experiments were conducted on male Wistar rats divided into three groups: 1. Control, 2.

Changes in the Diaphragm Lipid Content after Administration of Streptozotocin and High-Fat Diet Regime.

The diaphragm is a dome-shaped skeletal muscle indispensable for breathing. Its activity contributes up to 70% of the total ventilatory function at rest. In comparison to other skeletal muscles, it is distinguished by an oxidative phenotype and uninterrupted cyclic contraction pattern.

Effect of plasma free fatty acid supply on the rate of ceramide synthesis in different muscle types in the rat.

Ceramide is a key compound in sphingolipid metabolism. Dynamics of ceramide synthesis is important in the several biological processes, such as induction of apoptosis or insulin resistance. So far, its de novo synthesis rate was evaluated indirectly, based on the content of the compound, its intermediates and the activity of respective enzymes.

Effect of metformin on bioactive lipid metabolism in insulin-resistant muscle.

Intramuscular accumulation of bioactive lipids leads to insulin resistance and type 2 diabetes (T2D). There is lack of consensus concerning which of the lipid mediators has the greatest impact on muscle insulin action Our aim was to elucidate the effects of high-fat diet (HFD) and metformin (Met) on skeletal muscle bioactive lipid accumulation and insulin resistance (IR) in rats. We employed a [U-C]palmitate isotope tracer and mass spectrometry to measure the content and fractional synthesis rate (FSR) of intramuscular long-chain acyl-CoA (LCACoA), diacylglycerols (DAG) and ceramide (Cer).

Myriocin treatment affects lipid metabolism in skeletal muscles of rats with streptozotocin-induced type 1 diabetes.

Purpose: The aim of this work was to assess the effect(s) of de novo ceramide synthesis inhibition on lipid metabolism in skeletal muscle tissue of type 1 diabetic rats. The latter seems to be of vital importance, since previous works have shown its positive influence on lipid metabolism and glucose homeostasis in the case of its counterpart - type 2 diabetes.

Materials/methods: The animals were randomly assigned to one of the following groups: C - control, M - myriocin (ceramide de novo synthesis inhibitor), D - diabetes (induced by streptozotocin injections); D+M - diabetes+myriocin.

Liver X Receptor Agonist TO901317 Prevents Diacylglycerols Accumulation in the Heart of Streptozotocin-Diabetic Rats.

Background/aims: Liver X receptors (LXRα and LXRβ) are ligand-activated transcription factors that regulate expression of genes involved in lipid and cholesterol metabolism. LXR expression has been identified in the heart, and enhanced LXR activity in the streptozotocin (STZ) diabetic myocardium was reported recently. The aim of this study was to investigate effect of in vivo LXR activation on myocardial lipid metabolism under conditions of STZ-induced diabetes.

Expression of the energy substrate transporters in uterine fibroids.

Proliferating cells exhibit accelerated rates of substrate utilization, favoring glucose over fatty acids (FA's) oxidation. Protein-mediated transport is thought to play a predominant role in facilitating either glucose or FA routing into the cells. In the present study, we examined the expression of glucose transporters (GLUT-1, GLUT-4) and fatty acids transporters (FAT/CD36, FATP-1, FATP-4) at transcript and protein levels as well as cytosolic fatty acid binding proteins (H-FABP, ACBP) in human fibroids (n=74, size up to 3cm diameter) and compared with pair-matched healthy myometrium.

Sustained Action of Ceramide on the Insulin Signaling Pathway in Muscle Cells: IMPLICATION OF THE DOUBLE-STRANDED RNA-ACTIVATED PROTEIN KINASE.

In vivo, ectopic accumulation of fatty acids in muscles leads to alterations in insulin signaling at both the IRS1 and Akt steps. However, in vitro treatments with saturated fatty acids or their derivative ceramide demonstrate an effect only at the Akt step. In this study, we adapted our experimental procedures to mimic the in vivo situation and show that the double-stranded RNA-dependent protein kinase (PKR) is involved in the long-term effects of saturated fatty acids on IRS1.

Reduction of ceramide de novo synthesis in solid tissues changes sphingolipid levels in rat plasma, erythrocytes and platelets.

Purpose: De novo sphingolipid synthesis does not occur in plasma, erythrocytes and platelets. The purpose of the study was to examine the effect of inhibition of sphingolipid synthesis in solid tissues on the level of the following bioactive sphingolipids: sphinganine, ceramide, sphingosine and sphingosine 1-phosphate in plasma, erythrocytes and platelets.

Material/methods: The experiments were carried out on male Wistar rats.

Myocardial lipid profiling during time course of high fat diet and its relationship to the expression of fatty acid transporters.

Background/aims: It is well documented that increased fatty acids (FA) supply causes lipid accumulation and insulin resistance in skeletal muscles. Whether the same mechanism is present in the heart is still unclear. Therefore, the goal of our study was to determine the content of specific myocardial lipid fractions during feeding rats a high fat diet (HFD) for 5 weeks.

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 in skeletal muscle. Recently, scientists have focused their scrutiny on myriocin, a potent chemical compound that inhibits ceramide (i.

Modest decrease in PGC1α results in TAG accumulation but not in insulin resistance in L6 myotubes.

Background/aims: PGC-1α is an important cellular protein (coactivator) regulating myocyte mitochondria number and function, and therefore whole cellular energy status. The aim of this work was to investigate the effects of modest, temporary PGC-1α knock-down on L6 myotubes insulin resistance in a light of cellular lipid metabolism.

Methods: Gas liquid chromatography was applied for assessing FAs content and composition.

LXR agonist T0901317-Induced hyperlipidemia does not lead to lipid accumulation in the rat heart.

Background/aims: Liver X receptors (LXRα and LXRβ) are ligand-activated transcription factors that regulate expression of genes involved in lipid and cholesterol metabolism. LXR expression has been identified in human and rodent cardiac tissue, however, its role in this tissue remains unclear. The aim of this study was to investigate effects of in vivo LXR activation on lipid metabolism in the rat myocardium under the conditions of low and high lipid intake.