Anti-inflammatory effects of cannabidiol in early stages of neuroinflammation induced by high-fat diet in cerebral cortex of rats.

High-fat diet (HFD) contributes to neuroinflammation forming, hence it is crucial to find safe and effective substances that are able to counteract its progress. The anti-inflammatory properties of phytocannabinoids acquired from the Cannabis plant have been widely acknowledged. We evaluated the effects of cannabidiol (CBD) treatment on induced by applying HFD early stages of neuroinflammation in Wistar rat cerebral cortex. In our 7-week experiment, CBD was injected intraperitoneally over the last 14days at a dose of 10 mg/kg of body weight once a day. The level of arachidonic acid, a precursor to pro-inflammatory eicosanoids, decreased in all analysed lipid classes after CBD administration to the HFD group. Moreover, the extent of diminishing the activity of the omega-6 (n-6) fatty acid pathway by CBD was the greatest in diacylglycerols and phospholipids. Surprisingly, CBD was also capable of downregulating the activity of the omega-3 (n-3) pathway. The expression of enzymes involved in the synthesis of the eicosanoids was significantly increased in the HFD group and subsequently lowered by CBD. Significant changes in various cytokines levels were also discovered. Our results strongly suggest the ability of CBD to reduce the formation of lipid inflammation precursors in rat cerebral cortex, as a primary event in the development of neurodegenerative diseases. This can raise hopes for the future use of this cannabinoid for therapeutic purposes since it is a substance lacking lasting and severe side effects.

The Role of Oxidative Stress and Inflammatory Parameters in Heart Failure.

Heart failure (HF) remains a major medical and social problem. The NT-pro-brain natriuretic peptide (NT-proBNP) and its active form, brain-type natriuretic peptide (BNP), in a simple blood test are the gold-standard biomarkers for HF diagnosis. However, even good biomarkers such as natriuretic peptides fail to predict all the risks associated with HF due to the diversity of the mechanisms involved. The pathophysiology of HF is determined by numerous factors, including oxidative stress, inflammation, neuroendocrine activation, pathological angiogenesis, changes in apoptotic pathways, fibrosis and vascular remodeling. High readmission and mortality rates prompt a search for new markers for the diagnosis, prognosis and treatment of HF. Oxidative-stress-mediated inflammation plays a crucial role in the development of subsequent changes in the failing heart and provides a new insight into this complex mechanism. Oxidative stress and inflammatory biomarkers appear to be a promising diagnostic and prognostic tool in patients with HF. This systematic review provides an overview of the current knowledge about oxidative stress and inflammation parameters as markers of HF.

Therapeutic effect of cannabidiol on myocardial arachidonic acid content in various lipid fractions in a rat model of obesity.

The study explored the potential protective influence of cannabidiol (CBD) on myocardial inflammation state, with a special focus on arachidonic acid (AA), and oxidative balance in lipid overload conditions. The 7-week experiment was conducted on male Wistar rats receiving standard or high-fat diet (HFD) with intraperitoneal CBD injections for the last 14 days. The n-3 and n-6 polyunsaturated fatty acids (PUFAs) activities and AA concentration in selected fractions were evaluated by gas-liquid chromatography (GLC). The expression of proteins was determined by Western blot and the concentration of different parameters by ELISA, colorimetric, or multiplex assay kits. Our results revealed that CBD increased n-3 PUFAs activity in phospholipid and triacylglycerol fractions, and decreased AA content in the HFD group, especially in the phospholipid pool. Simultaneously, CBD decreased the expression of nuclear factor kappa B, cyclooxygenase-1, and - 2, resulting in the reduction of prostaglandin E2 and the increment of prostaglandin I2. CBD appears to be relatively safe for the treatment of obesity-induced heart disease, as it has anti-inflammatory and partially antioxidative properties.

Distinct Effects of Cannabidiol on Sphingolipid Metabolism in Subcutaneous and Visceral Adipose Tissues Derived from High-Fat-Diet-Fed Male Wistar Rats.

Available data suggest that cannabidiol (CBD) may ameliorate symptoms of insulin resistance by modulating the sphingolipid concentrations in particular organs. However, it is not entirely clear whether its beneficial actions also involve adipose tissues in a state of overnutrition. The aim of the study was to evaluate the effect of CBD on sphingolipid metabolism pathways and, as a result, on the development of insulin resistance in subcutaneous (SAT) and visceral (VAT) adipose tissues of an animal model of HFD-induced insulin resistance. Our experiment was performed on Wistar rats that were fed with a high-fat diet and/or received intraperitoneal CBD injections. We showed that CBD significantly lowered the ceramide content in VAT by reducing its de novo synthesis and increasing its catabolism. However, in SAT, CBD decreased the ceramide level through the inhibition of salvage and de novo synthesis pathways. All of these changes restored adipose tissues' sensitivity to insulin. Our study showed that CBD sensitized adipose tissue to insulin by influencing the metabolism of sphingolipids under the conditions of increased availability of fatty acids in the diet. Therefore, we believe that CBD use may be considered as a potential therapeutic strategy for treating or reducing insulin resistance, T2DM, and metabolic syndrome.

Cannabidiol Downregulates Myocardial de Novo Ceramide Synthesis Pathway in a Rat Model of High-Fat Diet-Induced Obesity.

It is known that metabolic disturbances, including obesity, predispose to an increased incidence of cardiovascular diseases. Elevated consumption of dietary fat results in intramyocardial accumulation of lipids and their biologically active derivatives, which can disrupt the contractile function of the heart, its metabolism, and intracellular signaling pathways. Therefore, alternative methods, such as phytocannabinoids, are being sought for the treatment of obesity-related effects. In a model of rodent obesity (seven weeks of high-fat-diet (HFD) regime), we used cannabidiol-CBD therapy (intraperitoneal injections for 14 days; 10 mg/kg). High-performance and gas-liquid chromatographies were applied in order to determine sphingolipids in the heart and plasma as well as Western blotting for protein expression. Two-week CBD administration significantly inhibited the de novo ceramide synthesis pathway in the heart of HFD fed rats by lowering sphinganine and sphinganine-1-phosphate contents. The above reductions were accompanied by markedly diminished expressions of myocardial serine palmitoyltransferase 1 and 2 as well as ceramide synthase 5 and 6 in the HFD group with 2-week CBD treatment. To our knowledge, this research is the first that reveals unknown effects of CBD treatment on the heart, i.e., amelioration of de novo ceramide synthesis pathway in obese rats.

The Endocannabinoid System and Physical Activity-A Robust Duo in the Novel Therapeutic Approach against Metabolic Disorders.

Rapidly increasing worldwide prevalence of obesity and related pathologies encompassing coronary heart disease, hypertension, metabolic syndrome, or type 2 diabetes constitute serious threats to global health and are associated with a significantly elevated risk of premature death. Considering the enormous burden of these pathologies, novel therapeutic and preventive patterns are indispensable. Dysregulation of one of the most complex biological systems in the human body namely, the endocannabinoid system (ECS) may result in metabolic imbalance and development of insulin resistance, type 2 diabetes, or non-alcoholic fatty liver disease. Furthermore, many studies showed that physical exercises, depending on their type, intensity, and frequency, exert various alterations within the ECS. Emerging evidence suggests that targeting the ECS via physical activity may produce robust beneficial effects on the course of metabolic pathologies. However, the data showing a direct correlation between the ECS and physical activity in the aspect of metabolic health are very scarce. Therefore, the aim of this review was to provide the most up-to-date state of knowledge about the interplay between the ECS activity and physical exercises in the novel therapeutic and preventive approach toward metabolic pathologies. We believe that this paper, at least in part, will fulfill the existing gap in knowledge and encourage researchers to further explore this very complex yet interesting link between the ECS, its action in physical activity, and subsequent positive outcomes for metabolic health.

Biomarkers of Glucose Metabolism Alterations and the Onset of Metabolic Syndrome in Survivors of Childhood Acute Lymphoblastic Leukemia.

Owing to advances in treatment modalities and supportive care, overall survival rates have reached up to 90% among children with acute lymphoblastic leukemia (ALL). However, due to the underlying illness and therapy, they are at a greater risk of developing lifestyle diseases. Hence, special attention is paid to early detection of the components of metabolic syndrome (MetS). This study aimed at investigating the association of plasma levels of nine diabetes markers with being overweight and components of MetS in ALL survivors. The study included 56 subjects with mean age of 12.36 ± 5.15 years. The commercially available Bio-Plex Pro Human Diabetes 10-Plex Panel kit was used to evaluate levels of diabetes biomarkers. ALL survivors presented statistically higher concentrations of GIP (p = 0.026), glucagon (p = 0.001), leptin (p = 0.022), and PAI-1 (p = 0.047), whereas the concentration of ghrelin was lower (p < 0.001) compared to the control group. Moreover, subjects within normal BMI range showed higher GIP (p = 0.005) and lower ghrelin concentration (p < 0.001) compared to healthy peers. At least one risk factor of MetS was present in 58.9% of participants, who showed significantly higher levels of C-peptide (p = 0.028), leptin (p = 0.003), and PAI-1 (p = 0.034) than survivors who did not meet any MetS criteria. In conclusion, ALL survivors are at greater risk of disturbances in carbohydrate metabolism. Understanding the pathogenesis and applicability of diabetes markers is crucial for developing strategies to prevent metabolic syndrome in ALL survivors.

Molecular Advances in MAFLD-A Link between Sphingolipids and Extracellular Matrix in Development and Progression to Fibrosis.

Metabolic-Associated Fatty Liver Disease (MAFLD) is a major cause of liver diseases globally and its prevalence is expected to grow in the coming decades. The main cause of MAFLD development is changed in the composition of the extracellular matrix (ECM). Increased production of matrix molecules and inflammatory processes lead to progressive fibrosis, cirrhosis, and ultimately liver failure. In addition, increased accumulation of sphingolipids accompanied by increased expression of pro-inflammatory cytokines in the ECM is closely related to lipogenesis, MAFLD development, and its progression to fibrosis. In our work, we will summarize all information regarding the role of sphingolipids e.g., ceramide and S1P in MAFLD development. These sphingolipids seem to have the most significant effect on macrophages and, consequently, HSCs which trigger the entire cascade of overproduction matrix molecules, especially type I and III collagen, proteoglycans, elastin, and also tissue inhibitors of metalloproteinases, which as a result cause the development of liver fibrosis.

Solanaceae glycoalkaloids: α-solanine and α-chaconine modify the cardioinhibitory activity of verapamil.

CONTEXT: Solanaceae glycoalkaloids (SGAs) possess cardiomodulatory activity. OBJECTIVE: This study investigated the potential interaction between verapamil and glycoalkaloids. MATERIAL AND METHODS: The cardioactivity of verapamil and glycoalkaloids (α-solanine and α-chaconine) was tested in adult beetle (Tenebrio molitor) myocardium in vitro using microdensitometric methods. The myocardium was treated with pure substances and mixtures of verapamil and glycoalkaloids for 9 min with saline as a control. Two experimental variants were used: simultaneous application of verapamil and glycoalkaloids or preincubation of the myocardium with one of the compounds followed by perfusion with a verapamil solution. We used 9 × 10-6-5 × 10-5 M and 10-9-10-5 M concentration for verapamil and glycoalkaloids, respectively. RESULTS: Verapamil, α-solanine and α-chaconine showed cardioinhibitory activity with IC50 values equal to 1.69 × 10-5, 1.88 × 10-7 and 7.48 × 10-7 M, respectively. When the glycoalkaloids were applied simultaneously with verapamil, an antagonistic effect was observed with a decrease in the maximal inhibitory effect and prolongation of t50 and the recovery time characteristic of verapamil. We also confirmed the expression of two transcript forms of the gene that encodes the α1 subunit of L-type calcium channels in the myocardium and brain with equal transcription levels of both forms in the myocardium and significant domination of the shorter form in the brain of the insect species tested. DISCUSSION AND CONCLUSIONS: The results show that attention to the composition of the daily diet during therapy with various drugs is particularly important. In subsequent studies, the nature of interaction between verapamil and SGAs on the molecular level should be checked, and whether this interaction decreases the efficiency of cardiovascular therapy with verapamil in humans.

The influence of dexamethasone on hepatic fatty acids metabolism and transport in human steatotic HepG2 cell line exposed to palmitate.

Dexamethasone (DEX) is a synthetic glucocorticoid with anti-inflammatory properties. We evaluated a potentially protective dexamethasone influence on hepatocellular lipid metabolism and fatty acid (FA) transporters expression. The HepG2 cells were incubated with palmitic acid (PA) and/or dexamethasone in two different time expositions (16 h and 40 h). Intracellular and extracellular lipid and sphingolipid concentrations were estimated by the gas-liquid chromatography and high-performance liquid chromatography, respectively. The protein expression involved in FA uptake and lipid metabolism was determined by immunoblotting. The treatment of HepG2 with dexamethasone and palmitate enhanced lipid transport to the cell via increased especially FABPpm expression and resulted in the increased triacylglycerol (TAG), diacylglycerol (DAG) and ceramide deposition. Dexamethasone with palmitate treatment altered FA composition resulting in the elevated n-3 polyunsaturated fatty acid (PUFA) activity in DAG and TAG and the diminished n-6 PUFA activity in DAG after prolonged exposure. We may speculate that although protective lipid secretion into media and decrease in inflammatory FA precursors dexamethasone treatment exacerbated lipotoxicity in HepG2 cells.

Insects as a New Complex Model in Hormonal Basis of Obesity.

Nowadays, one of the biggest problems in healthcare is an obesity epidemic. Consumption of cheap and low-quality energy-rich diets, low physical activity, and sedentary work favor an increase in the number of obesity cases within many populations/nations. This is a burden on society, public health, and the economy with many deleterious consequences. Thus, studies concerning this disorder are extremely needed, including searching for new, effective, and fitting models. Obesity may be related, among other factors, to disrupting adipocytes activity, disturbance of metabolic homeostasis, dysregulation of hormonal balance, cardiovascular problems, or disorders in nutrition which may lead to death. Because of the high complexity of obesity, it is not easy to find an ideal model for its studies which will be suitable for genetic and physiological analysis including specification of different compounds' (hormones, neuropeptides) functions, as well as for signaling pathways analysis. In recent times, in search of new models for human diseases there has been more and more attention paid to insects, especially in neuro-endocrine regulation. It seems that this group of animals might also be a new model for human obesity. There are many arguments that insects are a good, multidirectional, and complex model for this disease. For example, insect models can have similar conservative signaling pathways (e.g., JAK-STAT signaling pathway), the presence of similar hormonal axis (e.g., brain-gut axis), or occurrence of structural and functional homologues between neuropeptides (e.g., neuropeptide F and human neuropeptide Y, insulin-like peptides, and human insulin) compared to humans. Here we give a hint to use insects as a model for obesity that can be used in multiple ways: as a source of genetic and peptidomic data about etiology and development correlated with obesity occurrence as well as a model for novel hormonal-based drug activity and their impact on mechanism of disease occurrence.

Time-Dependent Changes in Hepatic Sphingolipid Accumulation and PI3K/Akt/mTOR Signaling Pathway in a Rat Model of NAFLD.

Increased lipid bioavailability in a diet favors lipid accumulation, enhancing hepatic lipotoxicity and contributing to insulin resistance (IR) development. The aim of our study was to examine time-dependent alterations in the intrahepatic content of sphingolipids and insulin signaling pathway in rats fed a high-fat diet (HFD). The experiment was conducted on male Wistar rats receiving a standard diet or HFD for five weeks. At the end of each experimental feeding week, liver sphingolipids were determined using high-performance liquid chromatography. The expression of proteins from the sphingolipid pathway and glucose transporter expression were assessed by Western blot. The content of phosphorylated form of proteins from the insulin pathway was detected by a multiplex assay kit. Our results revealed that HFD enhanced hepatic ceramide deposition by increasing the expression of selected proteins from sphingomyelin and salvage pathways in the last two weeks. Importantly, we observed a significant inhibition of Akt phosphorylation in the first week of HFD and stimulation of PTEN and mTOR phosphorylation at the end of HFD. These changes worsened the PI3K/Akt/mTOR signaling pathway. We may postulate that HFD-induced reduction in the insulin action in the time-dependent matter was exerted by excessive accumulation of sphingosine and sphinganine rather than ceramide.

Vitamin K2 as a New Modulator of the Ceramide De Novo Synthesis Pathway.

The aim of the study was to evaluate the influence of vitamin K2 (VK2) supplementation on the sphingolipid metabolism pathway in palmitate-induced insulin resistant hepatocytes. The study was carried out on human hepatocellular carcinoma cells (HepG2) incubated with VK2 and/or palmitic acid (PA). The concentrations of sphingolipids were measured by high-performance liquid chromatography. The expression of enzymes from the sphingolipid pathway was assessed by Western blotting. The same technique was used in order to determine changes in the expression of the proteins from the insulin signaling pathway in the cells. Simultaneous incubation of HepG2 cells with palmitate and VK2 elevated accumulation of sphinganine and ceramide with increased expression of enzymes from the ceramide de novo synthesis pathway. HepG2 treatment with palmitate and VK2 significantly decreased the insulin-stimulated expression ratio of insulin signaling proteins. Moreover, we observed that the presence of PA w VK2 increased fatty acid transport protein 2 expression. Our study showed that VK2 activated the ceramide de novo synthesis pathway, which was confirmed by the increase in enzymes expression. VK2 also intensified fatty acid uptake, ensuring substrates for sphingolipid synthesis through the de novo pathway. Furthermore, increased concentration of sphingolipids, mainly sphinganine, inhibited insulin pathway proteins phosphorylation, increasing insulin resistance development.

Can Physical Activity Support the Endocannabinoid System in the Preventive and Therapeutic Approach to Neurological Disorders?

The worldwide prevalence of neurological and neurodegenerative disorders, such as depression or Alzheimer's disease, has spread extensively throughout the last decades, becoming an enormous health issue. Numerous data indicate a distinct correlation between the altered endocannabinoid signaling and different aspects of brain physiology, such as memory or neurogenesis. Moreover, the endocannabinoid system is widely regarded as a crucial factor in the development of neuropathologies. Thus, targeting those disorders via synthetic cannabinoids, as well as phytocannabinoids, becomes a widespread research issue. Over the last decade, the endocannabinoid system has been extensively studied for its correlation with physical activity. Recent data showed that physical activity correlates with elevated endocannabinoid serum concentrations and increased cannabinoid receptor type 1 (CB1R) expression in the brain, which results in positive neurological effects including antidepressant effect, ameliorated memory, neuroplasticity development, and reduced neuroinflammation. However, none of the prior reviews presented a comprehensive correlation between physical activity, the endocannabinoid system, and neuropathologies. Thus, our review provides a current state of knowledge of the endocannabinoid system, its action in physical activity, as well as neuropathologies and a possible correlation between all those fields. We believe that this might contribute to finding a new preventive and therapeutic approach to both neurological and neurodegenerative disorders.

Experimental Activation of Endocannabinoid System Reveals Antilipotoxic Effects on Cardiac Myocytes.

Hypertension coincides with myocardial alternations in lipid (including sphingolipids) and glucose metabolism. The latest data indicate that accumulation of metabolically active lipids, especially ceramide (CER) and diacylglycerol (DAG) significantly influences intracellular signaling pathways along with inducing insulin resistance. Since, it was demonstrated that the endocannabinoid system (ECS) affects myocardial metabolism it seems to be a relevant tool in alleviating metabolic disturbances within the cardiac muscle due to hypertension. All designed experiments were conducted on the animal model of primary hypertension, i.e., spontaneously hypertensive rat (SHR) with chronic ECS activation by injections of fatty acid amide hydrolase (FAAH) inhibitor-URB597. Lipid analyses were performed using chromatography techniques (gas liquid, thin layer, and high performance liquid chromatography). Colorimetric and immunoenzymatic testes were applied in order to determine plasma concentrations of insulin and glucose. Total myocardial expression of selected proteins was measured by Western blotting and/or immunohistochemistry methods. SHRs exhibited significantly intensified myocardial de novo pathway of CER synthesis as well as DAG accumulation compared to the control Wistar Kyoto rats. Besides, intramyocardial level of potentially cardioprotective sphingolipid, i.e., sphingosine-1-phosphate was considerably decreased in SHRs, whereas URB597 treatment restored the level of this derivative. Unexpectedly, ECS upregulation protected overloaded cardiac muscle against CER and DAG accumulation. Moreover, chronic URB597 treatment improved intramyocardial insulin signaling pathways in both normotensive and hypertensive conditions. It seems that the enhanced ECS triggers protective mechanisms in the heart due to decreasing the level of lipid mediators of insulin resistance.

High-Fat Feeding in Time-Dependent Manner Affects Metabolic Routes Leading to Nervonic Acid Synthesis in NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation in the liver. The disturbances in the fatty acid composition of stored lipids are more important than the lipid species itself, which may influence the overall effect caused by these molecules. Thus, uncovering time-dependent changes in the fatty acid composition of accumulated lipid fractions after a high fat diet seems to be a new marker of NAFLD occurrence. The experiments were conducted on high fat fed Wistar rats. The blood and liver samples were collected at the end of each experimental week and used to assess the content of lipid fractions and their fatty acid composition by gas liquid chromatography. The expression of proteins from lipid metabolism pathways and of fatty acid exporting proteins were detected by Western blotting. In the same high fat feeding period, decreased de novo lipogenesis, increased ß-oxidation and lipid efflux were demonstrated. The observed effects may be the first liver protective mechanisms against lipotoxicity. Nevertheless, such effects were still not sufficient to prevent the liver from proinflammatory lipid accumulation. Moreover, the changes in liver metabolic pathways caused the plasma nervonic acid concentration in sphingomyelin to decrease simultaneously with NAFLD development, which may be a steatosis occurrence prognostic marker.

Heart mechanical and hemodynamic parameters of a beetle, Tenebrio molitor, at selected ages.

The physiological processes that occur during the aging of insects are poorly understood. The aim of this study was to describe the changes in contractile activity and hemodynamic parameters of the heart that take place as the coleopteran beetle, Tenebrio molitor, ages. The frequency of heart contractions in beetles that had just undergone metamorphosis (median 24.7 beats/min) was significantly lower than the frequency of heart contractions in older beetles. In 56% of beetles that were < 1 week of age, a pattern of contractile activity with alternating periods of higher and lower contraction frequency was detected, suggesting that some posteclosion developmental processes occur during the first week of adulthood. All beetles that were 1 week of age showed a regular rhythm of heart contractions (median 72 beats/min). In older beetles, abnormalities such as heart arrhythmias or heart arrest were observed. The incidence of arrhythmia as well as the arrhythmicity index was highest in beetles that were 8-18 weeks old. The calculated stroke volume (SV) was also found to increase from eclosion to 12 weeks of age, and then decreased as adults aged further. Interestingly, cardiac output increased gradually, but the ejection fraction did not change significantly with age.

Plant-Derived Substances Used Against Beetles-Pests of Stored Crops and Food-and Their Mode of Action: A Review.

Plants are sources of numerous active substances that are used to protect crops. Currently, due to the limitations of using synthetic insecticides, plant products have attracted increasing attention as possible pesticides. In this review, we discuss some of the most interesting plant products (for example, Solanaceae, or Asteraceae extracts, Artemisia absinthium or Citrus spp. essential oils, and single compounds like α-chaconine, or α-solanine) that exhibit insecticidal activity against beetles that are pests of stored food products. Next, we describe and discuss the mode of action of these products, including lethal and sublethal effects, such as antifeedant or neurotoxic activity, ultrastructural malformation, and effects on prooxidant/antioxidant balance. Furthermore, the methods of application of plant-derived substances in food storage areas are presented.

Complete genome sequences of two novel autographiviruses infecting a bacterium from the Pseudomonas fluorescens group.

In this paper, we describe two independent isolates of a new member of the subfamily Autographivirinae, Pseudomonas phage KNP. The type strain (KNP) has a linear, 40,491-bp-long genome with GC content of 57.3%, and 50 coding DNA sequences (CDSs). The genome of the second strain (WRT) contains one CDS less, encodes a significantly different tail fiber protein and is shorter (40,214 bp; GC content, 57.4%). Phylogenetic analysis indicates that both KNP and WRT belong to the genus T7virus. Together with genetically similar Pseudomonas phages (gh-1, phiPSA2, phiPsa17, PPPL-1, shl2, phi15, PPpW-4, UNO-SLW4, phiIBB-PF7A, Pf-10, and Phi-S1), they form a divergent yet coherent group that stands apart from the T7-like viruses (sensu lato). Analysis of the diversity of this group and its relatedness to other members of the subfamily Autographivirinae led us to the conclusion that this group might be considered as a candidate for a new genus.

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. Moreover, the relation between changes in myocardial lipid content, whole body insulin resistance and the expression of fatty acid transporters in each week of HFD was established. METHODS: Gas liquid chromatography and high performance liquid chromatography were used to determine the content of lipid fractions in the left ventricle. Expression of selected proteins was estimated by Western blot technique. All measurements were made after each week of HFD. RESULTS: As expected, lipid profile in myocardium was altered by HFD in different weeks of the study with the most intense changes in triacylglycerols, long chain fatty acid-CoA and ceramide. Furthermore, there was a significant elevation of plasmalemmal (the 4th and the 5th week) and mitochondrial expression (from the 3rd to the 5th week) of fatty acid translocase. CONCLUSION: High fat diet affects myocardial lipid profile in each week of its duration and causes alternations in FA metabolism in cardiomyocytes.