Metabolic syndrome represents one of the major health, social and economic issues nowadays, and affects more than 25% people worldwide. Being a multifactorial health problem, metabolic syndrome clusters various features, such as obesity, dyslipidemia, hyperglycemia and hypertension. Each of these disturbances represents a risk factor for developing cardiovascular disease. Moreover, patients with metabolic syndrome are more likely to suffer from depression, thus treatment with antidepressants (e.g. venlafaxine) is often neccessary. However, many of the antidepressants themselves may contribute to worsening or even development of the metabolic syndrome, thus creating a “vicious circle”. The aim of this work was to investigate on the animal model of metabolic syndrome, i.e. on hypertriacylglycerolemic rats fed high-fat-fructose diet (HFFD): 1) the effect of a change in diet from HFFD to a standard diet (SD) and the effect of venlafaxine treatment, 2) during HFFD, 3) as well as during a changed diet to SD. We focused on biometric parameters, blood pressure and selected ECG parameters. We observed the reversibility of the present metabolic and cardiovascular changes by switching the HFFD to SD in the last 3 weeks of the experiment. Switch to the standard diet led to decrease of body weight, even in the presence of venlafaxine. Administration of venlafaxine caused the decrease of heart weight/body weight index in rats fed with HFFD compared to the untreated group fed with HFFD for 8 weeks. Blood pressure, which was increased in the HFFD group showed a tendency to decrease to control values after switching to the standard diet. Administration of venlafaxine led to significant increase in all parameters of blood pressure when rats were fed with HFFD throughout the whole experiment. In untreated rats fed with HFFD for 8 weeks, we observed a shorter PQ interval and prolonged QRS complex as well as QTc interval compared to untreated rats with diet switched to SD. This effect was potentiated by venlafaxine administered not only during HFFD but even after switch to SD. Our results point to the fact that metabolic syndrome is clearly affecting the function of the cardiovascular system by modifying blood pressure and electrical activity of the heart. Moreover, administration of venlafaxine may lead to worsening of the observed changes, especially in the presence of high-fat-fructose diet.

Fat-rich diet (FRD) triggers health complications like hypertension, dyslipidemia, hyperglycemia, insulin resistance and non-alcoholic fatty liver disease, known as the risk factors of metabolic syndrome (MetS), which may result in neurological deficits. The impact of MetS on neuronal functions and brain morphology are poorly understood. We induced MetS-like conditions by exposing hypertriacylglycerolemic (HTG) rats to FRD for eight weeks with the aim to study possible neurological dysfunctions. HTG-FRD rats were compared to HTG rats and Wistar rats on standard diet. The physiological status of the animals was monitored by body, liver and kidney weight (wt). Morphology of the liver, vessel wall and hippocampus were investigated. Basal neurotransmission and synaptic plasticity were measured in the hippocampus ex-vivo. A marked increase of liver weight with marks of steatosis was found in the HTG-FRD group. FRD induced an increase of aortic intima-media thickness. Extracellular recording revealed FRD-induced impairment of long-term potentiation (LTP) at Cornu Ammonis (CA)3-CA1 synapse, contrary to increased presynaptic fiber volley (pV). Reduced thickness of pyramidal cell layer at the CA1 area was found morphometrically. LTP was directly associated with kidney weight and inversely associated with liver weight, pV directly correlated with liver weight, liver wt/body wt ratio and aortic intima-media thickness. Our results suggest correlations between altered physiological status due to MetS-like conditions and neurological deficits, which may be related with consecutive development of socalled metabolic cognitive syndrome.

BackgroundMetabolic syndrome is a cluster of metabolic risk factors. The clear causes of its development are not known yet and there is no comprehensive treatment of this disease. There is a trend to use natural substances in the treatment of various diseases, but their effects need to be well explored. We decided to test effect of rutin compared to the effect of the standard drug atorvastatin.MethodsAs a model of metabolic syndrome we used males of hypertriacylglycerolemic rats in combination with high-fat-high-fructose diet. Rutin (100 mg/kg) and atorvastatin (50 mg/kg) were administered orally daily for 5 weeks.ResultsWe determined biochemical parameters from blood: HDL-cholesterol, LDL-cholesterol, total cholesterol, triacylglycerols. Relaxation and contraction response of aorta was measured to determine vessel dysfunctions and possible predisposition to cardiovascular disease. The negative influence on cognitive functions could be associated with the development of metabolic cognitive syndrome. Therefore we aimed to monitor spatial memory by Morris water maze test. Both rutin and atorvastatin had a tendency to decrease levels of serum triacylglycerols, but only atorvastatin significantly reduced levels od LDL-cholesterol and increased HDL-cholesterol levels. Both compounds significantly reduced the phenylephrine-induced contractile response of the aorta and improved the relaxation response. Further, treated animals learned better compared to untreated rats in the Morris water maze.ConclusionBased on our results we can assume that atorvastatin and rutin had positive effect on spatial memory and vessel reactivity. Atorvastatin optimized lipid profile of blood serum.

Decreasing high fat and high carbohydrate intake, together with the administration of natural bioactive drugs is assumed to have a protective effect in the prevention and amelioration of metabolic syndrome (MetS). The aim of the study was to evaluate effects of diet improvement and/or a phenolic compound - rosmarinic acid (RA) administration (100 mg/kg/day) on metabolic as well as functional changes of vessels and hippocampus caused by MetS-like conditions. MetS-like conditions were induced by high-fat-fructose diet (HFFD) in Prague hereditary hypertriacylglycerolemic rats. The effect of diet improvement and RA administration was studied using biochemical and functional measurements. Consumption of HFFD by hypertriacylglycerolemic rats resulted in the development of conditions like MetS. The fat and fructose restriction from the diet led to amelioration of basic indicators of metabolic state in rats fed HFFD and to amendment parameters of glucose-tolerance test and reduction of the IL-1β serum levels. Moreover, aortic endothelial function was improved with an impact on blood pressure. The functional measurement of electrophysiology of the hippocampus showed that long-term potentiation of neuronal transmission course deteriorated after HFFD was improved by caloric restriction. Oral administration of RA had a supporting effect not only on lipid and glucose metabolism but also on the vascular endothelium. Combination of both types of therapy induced beneficial effect on glucose tolerance and lipid peroxidation. Thus, combined improvement of diet habits and treatment with natural bioactive drugs is assumed to have protective effect in prevention and amelioration of MetS.

The aim of this study was to determine pharmacological possibilities of influencing the risk factors of metabolic syndrome (MetS). Hypertriacylglycerolemic (HTG) rats fed with high-fat-fructose diet (HFFD) were used as a model of the MetS. Wistar rats fed with standard diet were used as negative control group. HTG rats fed with HFFD for 8 weeks were used as positive control group. The effects of atorvastatin and SMe1EC2 were tested. The compounds were administered to the HTG rats after 5 weeks of HFFD, once a day for 3 weeks. After 8 weeks, the blood serum lipid profile and electrophysiology of neurotransmission in hippocampal sections were evaluated in vitro. SMe1EC2 and atorvastatin had a significant effect on total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-cholesterol) and atorvastatin had a significant effect on triacylglycerols (TGs). SMe1EC2 improved the long-term potentiation (LTP) course in the hippocampus.

The aim of our study was to evaluate the possibility of influencing the risk factors of metabolic syndrome (MetS) and metabolic cognitive syndrome. As a model of MetS, we used high-fat-fructose diet (HFFD) fed hypertriacylglycerolemic (HTG) rats. Control group included HTG rats fed with HFFD during 8 weeks (HFFD8). Furthermore, we tested the effect of pharmacological and non-pharmacological therapies. Non-pharmacological therapy, which we chose, was a change in diet from HFFD (5 weeks) to standard one (3 weeks) and thus caloric restriction (HFFD5+3). The drug we used was rosmarinic acid (RA; 100mg/kg), which we administered to rats after 5 weeks of HFFD once a day for consecutive 3 weeks with current change in diet to standard one (HFFD5+3+RA) or during lasting last 3 weeks of HFFD (HFFD8+RA). After 8 weeks of experiment, lipid peroxidation markers, lipid profile of blood serum, and neuronal transmission and synaptic plasticity (long-term potentiation [LTP]) in hippocampal sections were evaluated in vitro. We observed a significant effect of dietary change in lipid profile (decreased total cholesterol and low-density lipoprotein cholesterol [LDL-cholesterol] and increased high-density lipoprotein cholesterol [HDL-cholesterol]). The combination of pharmacological and non-pharmacological treatments caused a decrease in total cholesterol, LDL-cholesterol, and lipid peroxidation in blood serum. Change in HFFD to standard diet without treatment resulted in slight improvement in neuronal transmission in the hippocampus and caloric restriction alone also had positive effect on LTP maintenance. Our results suggest that combination of pharmacological and non-pharmacological approaches had better impact on the biochemical parameters of MetS in blood serum, but weak impact on neuronal functions in the hippocampus, where the expected positive effect was achieved only by caloric restriction.

Previously it was shown that for reduction of anxiety and stress of experimental animals, preventive handling seems to be one of the most effective methods. The present study was oriented on Na,K-ATPase, a key enzyme for maintaining proper concentrations of intracellular sodium and potassium ions. Malfunction of this enzyme has an essential role in the development of neurodegenerative diseases. It is known that this enzyme requires approximately 50% of the energy available to the brain. Therefore in the present study utilization of the energy source ATP by Na,K-ATPase in the frontal cerebral cortex, using the method of enzyme kinetics was investigated. As a model of neurodegeneration treatment with Trimethyltin (TMT) was applied. Daily handling (10 min/day) of healthy rats and rats suffering neurodegeneration induced by administration of TMT in a dose of (7.5 mg/kg), at postnatal days 60-102 altered the expression of catalytic subunits of Na,K-ATPase as well as kinetic properties of this enzyme in frontal cerebral cortex of adult male Wistar rats. Everyday handling of rats, beside the previously published beneficial effect on spatial memory was accompanied by improwed maintenance of sodium homeeostasis in frontal cortex of brains. The key system responsible for this proces, the Na,K-ATPase was able to utilize better the energy substrate ATP. In rats with TMT-induced neurodegeneration handling promoted the expresion of α2 isoform of the enzyme which is typical for glial cells. In healthy rats the handling was followed by increased expression α3 subunit which is typical for neurons.

Previously it was shown that for reduction of anxiety and stress of experimental animals, preventive handling seems to be one of the most effective methods. The present study was oriented on Na,K-ATPase, a key enzyme for maintaining proper concentrations of intracellular sodium and potassium ions. Malfunction of this enzyme has an essential role in the development of neurodegenerative diseases. It is known that this enzyme requires approximately 50% of the energy available to the brain. Therefore in the present study utilization of the energy source ATP by Na,K-ATPase in the frontal cerebral cortex, using the method of enzyme kinetics was investigated. As a model of neurodegeneration treatment with Trimethyltin (TMT) was applied. Daily handling (10 min/day) of healthy rats and rats suffering neurodegeneration induced by administration of TMT in a dose of (7.5 mg/kg), at postnatal days 60-102 altered the expression of catalytic subunits of Na,K-ATPase as well as kinetic properties of this enzyme in frontal cerebral cortex of adult male Wistar rats. Everyday handling of rats, beside the previously published bene cial effect on spatial memory was accompanied by improwed maintenance of sodium homeeostasis in frontal cortex of brains. The key system responsible for this proces, the Na,K-ATPase was able to utilize better the energy substrate ATP. In rats with TMT-induced neurodegeneration handling promoted the expresion of α2 isoform of the enzyme which is typical for glial cells. In healthy rats the handling was followed by increased expression α3 subunit which is typical for neurons.