Animal Model Of Metabolic Syndrome Research Articles

Decaffeinated light-roasted green coffee and green tea extract combination improved metabolic parameters and modulated inflammatory genes in metabolic syndrome rats

Background: Individually, green tea and green coffee have been extensively studied for mitigation of metabolic syndrome (MS) in both rats and humans; however, their combined effect requires further investigation. Thus, we compared the metabolic effect of combining green tea and decaffeinated light roasted green coffee on MS in rats. Methods: An MS animal model was constructed by feeding Sprague-Dawley rats with a high-fat-high-sucrose (HFHS) diet for eight weeks and a low dose of streptozotocin (STZ) injection at week 2. Rats fed with HFHS diets and injected with STZ successfully developed MS phenotypes, indicated by higher body weight, systolic blood pressure, plasma triglyceride level, plasma fasting blood glucose level, and lower plasma HDL-C level, compared to those fed with a normal chow diet. Subsequently, MS rats were continuously fed with HFHS and divided into four groups: MS rats, MS with 300 mg/bw.t green tea extract (GT), MS with 200 mg/bw.t green coffee extract (GC), and MS with combined green tea and green coffee extract (CM) for nine weeks. Results: Combining green tea and green coffee have synergistic effects on reducing plasma fasting blood glucose and triglyceride level. Inflammatory markers both in plasma and liver tissue robustly decreased in CM group rats. However, the reduction of systolic blood pressure was observed only in GT and CM groups. Moreover, all treatment resulted in an increase in plasma HDL-C level in MS rats. Conclusions: Our data highlighted that, in MS animal models, combined green tea and decaffeinated light roasted green coffee augment their several individual beneficial effects of improved metabolic parameters and modulated inflammatory genes.

Effect of Allopregnanolone on Spatial Memory and Synaptic Proteins in Animal Model of Metabolic Syndrome.

Metabolic Syndrome (MetS) is considered a common disorder, especially with a sedentary lifestyle and unhealthy food consumption. Cognitive impairment is one of the MetS consequences that worsens the quality of life of the patients. The study aimed to assess the therapeutic effect of the neurosteroid Allopregnalonone on spatial memory and, therefore, the expression of two synaptic plasticity markers in the hippocampus. Thirty-two male rats were divided into four groups: control groups, MetS, and MetS + Allopregnalone. Spatial memory has been evaluated by the Y-maze task and blood pressure measured by the rat tail method. Biochemical evaluation of serum glucose, insulin, lipid profile, and hippocampal expression of Synaptophysin and Associated Protein 43 (GAP-43) were performed for assessing Allopregnanolone on serum and hippocampal markers. Allopregnanolone therapy improved working spatial memory, hypertension, and biochemical markers measured in the serum and hippocampus.

Neuroprotective Effects of Testosterone in the Hypothalamus of an Animal Model of Metabolic Syndrome

Metabolic syndrome (MetS) is known to be associated to inflammation and alteration in the hypothalamus, a brain region implicated in the control of several physiological functions, including energy homeostasis and reproduction. Previous studies demonstrated the beneficial effects of testosterone treatment (TTh) in counteracting some MetS symptoms in both animal models and clinical studies. This study investigated the effect of TTh (30 mg/kg/week for 12 weeks) on the hypothalamus in a high-fat diet (HFD)-induced animal model of MetS, utilizing quantitative RT-PCR and immunohistochemical analyses. The animal model recapitulates the human MetS features, including low testosterone/gonadotropin plasma levels. TTh significantly improved MetS-induced hypertension, visceral adipose tissue accumulation, and glucose homeostasis derangements. Within hypothalamus, TTh significantly counteracted HFD-induced inflammation, as detected in terms of expression of inflammatory markers and microglial activation. Moreover, TTh remarkably reverted the HFD-associated alterations in the expression of important regulators of energy status and reproduction, such as the melanocortin and the GnRH-controlling network. Our results suggest that TTh may exert neuroprotective effects on the HFD-related hypothalamic alterations, with positive outcomes on the circuits implicated in the control of energy metabolism and reproductive tasks, thus supporting a possible role of TTh in the clinical management of MetS.

N-acetyl cysteine can blunt metabolic and cardiovascular effects via down-regulation of cardiotrophin-1 in rat model of fructose-induced metabolic syndrome

In this study, we investigated the ability of N-acetyl cysteine (NAC) to alleviate the metabolic disorders in fructose-induced metabolic syndrome (MS) in male rats and to examine its protective effect on aortic and cardiac tissues via its influence on cardiotrophin-1 (CT-1) expression. NAC (20 mg/kg b.w./day) was administered to fructose induced MS animals for 12 weeks. Chronic fructose consumption (20% w/v) increased body weight gain, relative heart weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), insulin resistance (IR), and associated with metabolic alterations. Histological and immunohistochemical examination revealed aortic stiffness and myocardial degeneration and fibrosis together with increased CT-1 expression. Treatment with NAC improved IR, SBP, DBP, and mitigated dyslipidaemia and oxidative stress. Additionally, NAC down-regulated CT-1 expression in the heart and aorta. These findings demonstrated the protective effect of NAC against aortic and myocardial degeneration and fibrosis through down-regulation of CT-1 in fructose induced MS animal model.

Surgical ablation of whitened interscapular brown fat ameliorates cardiac pathology in salt-loaded metabolic syndrome rats.

Brown adipose tissue (BAT) is an endocrine organ that contributes to thermogenesis and energy consumption. We investigated the effects of salt loading and surgical removal of whitened interscapular BAT (iBAT) on cardiac and adipose tissue pathology in DahlS.Z-Leprfa /Leprfa (DS/obese) rats, an animal model of metabolic syndrome (MetS). DS/obese rats were subjected to surgical removal of iBAT or sham surgery at 8 weeks of age and were provided with drinking water containing or not containing 0.3% NaCl for 4 weeks beginning at 9 weeks of age. Removal of iBAT suppressed the salt-induced exacerbation of left ventricular inflammation, fibrosis, and diastolic dysfunction, but not that of hypertension development, in DS/obese rats. Salt loading attenuated adipocyte hypertrophy but enhanced inflammation in both visceral white adipose tissue (WAT) and iBAT. Although iBAT removal did not affect visceral WAT pathology in salt-loaded DS/obese rats, it attenuated the elevation of circulating interleukin-6 levels in these animals. Downregulation of uncoupling protein-1 expression in iBAT of DS/obese rats was not affected by salt loading. Our results suggest that the conversion of iBAT to WAT-like tissue contributes to a salt-induced elevation of circulating proinflammatory cytokine levels that leads to exacerbation of cardiac pathology in this model of MetS.

FABP4 inhibitor attenuates inflammation and endoplasmic reticulum stress of islet in leptin receptor knockout rats.

Metabolic syndrome is characterized by abdominal obesity, hypertriglyceridemia and hyperglycemia. Fatty acid binding protein 4 (FABP4), as a member of intracellular lipid chaperones, is not only engaged in lipid transport but involved in inflammation and insulin resistance. The present study was to investigate the effects of BMS309403, a specific FABP4 inhibitor, on metabolic syndrome and its possible molecular mechanisms in islets. Leptin receptor knockout (Lepr-/-) rat, a novel and representative animal model of metabolic syndrome, was adopted in this study. Lepr-/- male rats and their wild littermates were grouped and intragastrically administered with BMS309403. Glucose Tolerance Test (GTT) and Insulin Tolerance Test (ITT) were performed on all rats. Serum insulin was detected by ELISA. The metabolic characters, as well as liver and kidney functions, were evaluated by serum biochemical assay. Immunohistochemistry and Western blot were adopted to detect the expression levels of FABP4, CD68, GRP78, ATF6, p-IRE1a, and Cleaved caspase-3. Lepr-/- rats showed prominent characteristics of metabolic syndrome with increased FABP4, inflammatory infiltration, ER stress and apoptosis in islets. BMS309403 administration attenuated inflammation, ER stress and apoptosis in Lepr-/- rat islets while stimulating insulin secretion as well as improving manifestation of metabolic syndrome without hepatic and renal toxicity. FABP4 increased in Lepr-/- rat islets and might be involved in the regulation of islet inflammation and apoptosis via ER stress. FABP4 inhibitor BMS309403 could ameliorate islet inflammation and apoptosis in metabolic syndrome through suppressing ER stress.

The prebiotic fiber inulin ameliorates cardiac, adipose tissue, and hepatic pathology, but exacerbates hypertriglyceridemia in rats with metabolic syndrome.

Prebiotics ameliorate dysbiosis and influence metabolism and the immune system, but their effects on cardiovascular complications in metabolic disorders remain largely unknown. We here investigated the effects of the soluble fiber inulin on cardiac, adipose tissue, and hepatic pathology as well as on metabolic disorders in DahlS.Z-Leprfa/Leprfa (DS/obese) rats, an animal model of metabolic syndrome (MetS). DS/obese rats and their homozygous lean (DahlS.Z-Lepr+/Lepr+, or DS/lean) littermate controls were fed a purified diet containing 5% or 20% inulin from 9 to 13 wk of age. The high-fiber diet ameliorated hypertension, left ventricular inflammation, fibrosis and diastolic dysfunction; attenuated adipose tissue inflammation and fibrosis; and alleviated the elevation of interleukin-6 levels, without affecting insulin resistance, in DS/obese rats. In addition, high fiber intake ameliorated lipid accumulation, inflammation, and fibrosis; attenuated the reduction in AMPK activity; upregulated sterol regulatory element-binding protein-1c gene expression; and increased the expression of microsomal triglyceride transfer protein gene in the liver of DS/obese rats. It also mitigated increases in total and non-high-density lipoprotein cholesterol levels but increased the triglyceride concentration in serum in these rats. None of these parameters were affected by high dietary fiber in DS/lean rats. The proportion of regulatory T cells in adipose tissue was influenced by dietary fiber but not by genotype. Our results indicate that inulin exacerbates hypertriglyceridemia but alleviates hypertension and cardiac injury as well as adipose tissue and hepatic pathology in MetS rats.NEW & NOTEWORTHY Prebiotics ameliorate dysbiosis and influence metabolism and the immune system, but their effects on cardiovascular complications in metabolic disorders remain largely unknown. Inulin ameliorated hypertension, cardiac injury, and diastolic dysfunction without affecting obesity or insulin resistance in a rat model of metabolic syndrome. The favorable cardiac effects of inulin may be related to inhibition of systemic inflammation associated with a reduction in circulating interleukin-6 levels. Additionally, inulin exacerbated hypertriglyceridemia but alleviates adipose tissue and hepatic pathology in these animals, as well as increased the number of regulatory T cells in adipose tissue.

Use of the ZDF rat to model dietary fat induced hypercoagulability is limited by progressive and fatal nephropathy

Introduction: Zucker diabetic fatty (ZDF) rats are used widely as an animal model of metabolic syndrome and insulin resistance. Our study focused on the effects of high versus low dietary fat on the development of Type 2 diabetes in obese male ZDF rats (fa/fa), including biomarkers to detect early signs of hypercoagulability and vascular injury in the absence of overt thrombosis. Methods: In this study, male (5/group) 10-week-old CRL:ZDF370(obese) rats were fed low (LFD, 16.7% fat) or high fat (HFD, 60% fat) diet for 12 or 15 weeks. Cohorts of 5 rats within diet groups were scheduled for sample collection after weeks 12 and 15. Results: HFD–fed ZDF rats had oily coats, lower rates of food consumption, more accelerated weight gain and increased serum cholesterol (+15%) and triglyceride concentrations (+75%) vs. LFD–fed ZDF rats. Urinary ketones were observed only in HFD–fed ZDF rats and greater urine glucose and protein concentrations in HFD–fed ZDF vs. LFD–fed ZDF rats were seen. Hemostasis testing showed ~2-fold greater fibrinogen concentration, increased von Willebrand factor concentration, and high thrombin generation in HFD–fed ZDF vs LFD–fed ZDF rats. Increased mortality in the HFD–fed ZDF rat was attributed to exacerbations of altered carbohydrate metabolism as evidenced by ketonuria and nephropathy leading to renal failure. Discussion: This characterization shows that the ZDF rat at the age, sex and weight used in this study is highly sensitive to dietary fat content that can exacerbate prothrombotic, metabolic and renal disturbances and increase mortality.

Aqueous extract from Pepino (Solanum muricatum Ait.) leaves ameliorated insulin resistance, hyperlipidemia, and hyperglycemia in mice with metabolic syndrome.

Solanum muricatum Ait. (Pepino) is a plant food commonly cultivated in the Penghu Island, Taiwan. This present study aimed to investigate the protective effects of aqueous extract of Pepino leaves (AEPL) in mice with metabolic syndrome. Metabolic syndrome animal model was induced by continuous high-fat diet feeding and low-dose streptozotocin (40mg/ml) for 5days. A 1% AEPL or metformin were given for 6weeks after streptozotocin injection. The results revealed that 1% AEPL effectively reduced fasting blood glucose, insulin resistance, and hyperlipidemia in metabolic syndrome mice. Histologic examination revealed lipid accumulation in liver decreased by 1% AEPL treatment. Further, western blot analysis revealed 1% AEPL treatment managed enzymes related to lipid synthesis and oxidation pathways and hepatic glucose production. Besides, 1% AEPL treatment increased liver antioxidant activities to against oxidative stress. These results concluded that AEPL treatment attenuated insulin resistance, hyperlipidemia, and hyperglycemia of metabolic syndrome. PRACTICAL APPLICATIONS: Metabolic syndrome (MS) is a multifactorial chronic disease which is characterized by dyslipidemia, insulin resistance, and hyperglycemia. However, there is no single drug or defined medication for MS so far. The present study revealed that AEPL treatment was able to regulate lipid metabolism and glycemic control at the molecular level to alleviate MS. AEPL has the potential to be a novo complementary medication for metabolic syndrome.

Pulmonary vascular smooth muscle contraction in the rat model of metabolic syndrome

Metabolic syndrome is defined as a constellation of many metabolic disorders such as hypertension, impaired glucose tolerance, dyslipidemia and obesity, being this last disorder a key factor in the etiology of the syndrome. Animal model of metabolic syndrome allows us to study the phenomenology of disorders of cooperative interactions of effector cells responsible for regulating of the blood vessels tone. Here, we have characterized the metabolic, vascular changes in male Wistar rats fed on a high-fat, high-carbohydrate diet including lard (17%), fructose (17%) together with 20% fructose in drinking water, control rats were fed a standard rat chow. During 12 weeks on this diet, rats showed a change in body weight with impaired glucose tolerance. Vascular disorders included endothelial dysfunction in pulmonary artery.

Brazilian native fruit extracts act as preventive agents modulating the purinergic and cholinergic signalling in blood cells and serum in a rat model of metabolic syndrome

In this study, we evaluated the effects of native fruit extracts on inflammatory and thromboregulatory parameters in animal model of metabolic syndrome (MetS) induced by highly palatable diet (HPD). Rats were divided into 4 experimental groups: standard chow, HPD, HPD and Psidium cattleianum extract, and HPD and Eugenia uniflora extract. HPD increased serum interleukin-6 (IL-6) levels. On the other hand, this change was prevented by extracts. HPD decreased NTPDase activity in lymphocytes and platelets and 5′-nucleotidase in platelets. Treatment with extracts prevented these changes. An increase in adenosine deaminase (ADA) activity was prevented by E. uniflora in lymphocytes and serum of rats. Fruit extracts prevented the increase in the activity of acetylcholinesterase (AChE) in lymphocytes and butyrylcholinesterase (BuChE) in serum induced by the HPD. Brazilian native fruit extracts have anti-inflammatory and antithrombotic effects, demonstrating therapeutic potential in the prevention of complications associated with MetS.

Spirulina reduces diet-induced obesity through downregulation of lipogenic genes expression in Psammomys obesus

The present study evaluates the protective effect of spirulina against diet-induced obesity and metabolic disorders in Psammomys obesus, an animal model of metabolic syndrome. Psammomys obesus lives on a low-energy diet, in order to remain healthy. However, under a standard laboratory chow diet (SLCD), this animal exhibits insulin resistance, which occurs as a result of obesity. Psammomys obesus was maintained on SLCD, in order to evaluate the effect of spirulina on obesity development with a particular focus on glucose and lipid metabolism, as well as the mRNA expression of some pro-inflammatory cytokines. After 12 weeks of treatment with spirulina, there was a significant reduction in body weight gain, plasma glucose, insulin and triglyceride levels. There was also a significant reduction in the mRNA expression of genes involved in lipogenesis and inflammation. Spirulina improved insulin sensitivity, glucose and lipid metabolism. These findings highlight the positive effect of spirulina on weight maintenance.

High fructose diet-induced metabolic syndrome and the functional abnormalities in the liver and kidney of Wistar albino rats

Background: Metabolic syndrome is the combination of several medical conditions that increase the risk of developing heart diseases, stroke, cancer, non-alcoholic fatty liver, and diabetes mellitus. Different varieties of animal models have been used for the therapeutic studies of diabetes, hyperlipidemia, and kidney diseases. The establishment of appropriate experimental animal models of metabolic syndrome is very important for evaluating the pathophysiology of the disease in humans. Aim and Objective: The aim of the study was to assess the functional abnormalities associated with high fructose diet (HFrD)-induced metabolic syndrome in Wistar albino rats. Materials and Methods: Metabolic syndrome is induced in adult male Wistar albino rats by feeding a combination of HFrD (55%) and fructose enriched water (15%) for 75 days and kept as Group 2 or HFrD group. Normal male Wistar albino rats were kept as normal control. During the entire course of study, weight gain was monitored once a week in both groups. Biochemical investigations such as lipid profile, liver function test, and renal function test were carried out using standard methods. The obtained data were statistically analyzed by students “t-test” and the values were considered statistically significant at p < 0.05. Results: Chronic administration of HFrD resulted in obesity, abnormal hepatic, and renal functions in Wistar rats. Conclusion: Chronic consumption of HFrD produces functional abnormalities in liver and kidney of Wistar rats.

Protective Effects of Bergamot (Citrus bergamia Risso & Poiteau) Juice in Rats Fed with High-Fat Diet.

The bergamot (Citrus bergamia Risso & Poiteau), a small tree cultivated along the Ionian coast of the Calabria region in Southern Italy, is an ancient plant used for the production of essential oil from fruit peel, but recently evaluated also for the high content of phenolics in the fruit pulp. Indeed, the juice is rich in glycosylated flavone and flavanones, showing a wide range of pharmacological activities. Noteworthy preclinical and clinical studies reported that bergamot juice is effective in reducing plasma lipids. The aim of this study was to evaluate the beneficial effects of a C. bergamia juice using an experimental animal model of metabolic syndrome and cardiovascular risk in vivo. A significant reduction of both triglyceride levels and cardiovascular risk was observed in animals fed with a high-fat diet and bergamot juice. Daily oral treatment with bergamot juice significantly limits a high-fat-induced increase in body, visceral adipose tissue, liver, and heart weight. In addition, C. bergamia juice showed protective effects on hepatic steatosis, probably due to the reduction of oxidative stress and inflammation. Chemical constituents of administered bergamot juice, investigated by means of liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) analyses were represented by a wide range of flavonoids, with neohesperidin, neoeriocitrin, and naringin being the most abundant flavonoids according to previous studies. Furthermore, a considerable amount of brutieridin, a flavanone O-glycoside having a 3-hydroxy-3-methyl-glutaryl residue, was observed.

The effect of venlafaxine on blood pressure and ECG in rats fed with high-fat-fructose diet.

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.

GLYPROLINE PEPTIDE PHARMACODYNAMICS IN RATS IN THE SETTING OF METABOLIC SYNDROME BY THE PARAMETERS OF LIPID METABOLISM AND TROMBOELASTOGRAMMA

In this study, experimental data on the biological action of glyproline peptides — Pro-Gly-Pro, Pro-ArgPro, Arg-Pro-Gly-Pro and Pro-Gly-Pro-Leu — on the processes of blood coagulation and lipid metabolism were obtained using animal models of metabolic syndrome. Under the conditions of increased blood clotting and hypercholesterolemia, the regulatory peptides under study were administered intranasally for 7 days once every 24 hours. 20 hours after the last peptide administration, thromboelastogram parameters confi rmed the restoration of the functional state of the coagulating and anticoagulant systems. In addition, a simultaneous positive shift in the parameters of lipid metabolism was observed. These changes lasted for 7 days following the withdrawal of the drugs. It is found that the biological action of the peptides under study consists in their simultaneous regulatory impact on the processes of hemostasis and lipid metabolism.

Antimetabolic Syndrome Effect of Phytosome Containing the Combined Extracts of Mulberry and Ginger in an Animal Model of Metabolic Syndrome.

Due to the antimetabolic syndrome effect of mulberry and ginger together with the advantages of the synergistic effect and phytosome encapsulation technique, we hypothesized that phytosome containing the combined extracts of mulberry and ginger (PMG) should be able to manage MetS. PMG was developed and assessed the phenolic content and biological activities associated with the pathophysiology of MetS. The antimetabolic syndrome effect and the possible underlying mechanisms in the animal model of MetS were also assessed. Male Wistar rats induced MetS by subjecting to a 16-week high-carbohydrate high-fat diet. MetS rats were orally given PMG at doses of 50, 100, and 200 mg/kg for 21 days. They were determined metabolic parameter changes in serum, histomorphology changes of adipose tissue, the inflammatory cytokines such as IL-6 and TNF-α, oxidative stress status, PPAR-γ, and HDAC3 in adipose tissue. Our in vitro data showed that PMG increased phenolic contents and biological activities. PMG significantly improved MetS parameters including body weight gain, lipid profiles, plasma glucose, HOMA-IR, and ACE. In addition, the density and size of adipocyte, adiposity index, and weights of adipose tissues were also improved. Moreover, the decrease in TNF-α and IL-6, oxidative stress status, and HDAC3 expression together with the increase in PPAR-γ expression in adipose tissue was also observed. These data suggest that PMG exhibit antimetabolic syndrome and the possible underlying mechanism may be associated partly with the modulation effect on HDAC3, PPAR-γ, and adipose tissue. In addition, PMG also improves oxidative stress and inflammation in MetS. Therefore, PMG can be served as the potential supplement to manage MetS. However, a clinical trial study is essential to confirm this health benefit.

Cerebroprotective Effect against Cerebral Ischemia of the Combined Extract of Oryza sativa and Anethum graveolens in Metabolic Syndrome Rats.

The novel strategy against ischemic stroke in metabolic syndrome (MetS) targeting at oxidative stress and inflammation has gained attention due to the limitation of the current therapy. Due to the antioxidant and anti-inflammation of the combined extract of Oryza sativa and Anethum graveolens, the cerebroprotective effect against cerebral ischemia in MetS condition has been focused. Since no data were available, this study was set up to determine the effects of the combined extract of Oryza sativa L. and Anethum graveolens Linn. against ischemic stroke in the animal model of metabolic syndrome. The possible underlying mechanism was also further investigated. Male Wistar rats (180-220 g) were fed with high-carbohydrate high-fat diet (HCHF diet) to induce metabolic syndrome-like condition. Then, MetS rats were subjected to reperfusion injury at the right middle cerebral artery. The combined extract of O. sativa and A. graveolens (OA extract) at doses of 0.5, 5, and 50 mg/kg BW was fed once daily for 21 days. Neurological assessment was performed every 7 days throughout the experimental period. At the end of study, brain infarction volume, neuron and glial fibrillary acidic protein- (GFAP-) positive cell density, the oxidative stress status, the expressions of proinflammatory cytokines (NF-κB, IL-6), and eNOS in the cortical area together with the expression of VCAM-1 and the histological changes of common carotid artery were determined. It was found that OA extract decreased brain infarction, neurological score, oxidative stress status, and inflammatory mediators but increased eNOS expression in the cortical area; the increased VCAM-1 and intima-media thickness together with the reduction of lumen diameter of common carotid artery of MetS eats with MCAO were also mitigated by OA extract. These data suggest the cerebroprotective effect of OA, and the underlying mechanism may occur partly via the improvement of oxidative stress status, inflammation, and brain blood supply.

High-fat diet-induced kidney alterations in rats with metabolic syndrome: endothelial dysfunction and decreased antioxidant defense.

IntroductionThis study aimed to investigate changes in renal function and the AGE-RAGE axis in the kidney of a non-genetic animal model of metabolic syndrome (MetS) induced by high-fat diet (HFD). Additionally, we evaluated the protective effect of pyridoxamine (PM), a vitamin B6 analog with anti-AGE effects, in the context of diet-related renal endothelial dysfunction.MethodologyIn Wistar rats, the MetS animal model was induced by 20 or 28 weeks of HFD feeding. When indicated, a subgroup of animals was treated daily with PM (60 mg/kg) for 2 months. Tissue perfusion in renal microcirculation was examined by laser speckle contrast imaging. Oxidative stress was analyzed by thiobarbituric acid reactive species and the inflammatory markers by ELISA (TNF-α and IL-1β). Reverse transcription polymerase chain reaction was used to analyze eNOs, IL-6, vascular cell adhesion molecule (VCAM), NADPH oxidase subunit 47 (N47), catalase, and receptor for AGE (RAGE) gene expression.ResultsWistar rats fed a HFD showed negligible alteration in renal function, decrease in catalase mRNA transcripts and catalase enzyme activity compared to control (CTL) animals. Increased levels of IL-1β were observed in the kidney of MetS-induced rats. HFD-fed rats exhibited kidney endothelial dysfunction, with no significant differences in basal microvascular blood flow. PM significantly improved kidney vasorelaxation in HFD-fed rats. eNOS, VCAM, and RAGE gene expression and AGE content were not altered in kidneys of HFD-induced MetS rats in comparison to CTLs.ConclusionsOur findings suggest that HFD-induced microvascular dysfunction precedes the decline in renal function, and could be related to antioxidant machinery defects and inflammation activation in the kidney. PM showed a vasoprotective effect, and thus, could be an important contributory factor in ameliorating diet-induced renal damage.

Abstract 931: Compensatory Response of Perivascular Adipose Tissue to Vascular Dysfunction in Metabolic Syndrome Rats Involves Apelin

Perivascular adipose tissue (PVAT) regulates vascular homeostasis including vascular tone via release of adipokines. Using SHRSP.Z- Lepr fa /IzmDmcr (SHRSP.ZF) rats, an animal model of metabolic syndrome (MetS), we have demonstrated that mesenteric PVAT enhances vasodilation under impaired vasodilation, in response to nitric oxide. We have also shown that the compensatory effect of PVAT disappears later in the course of MetS. Apelin is an adipokine that is produced at high levels in obesity and acts as a vasorelaxing factor. In this study, we evaluated the role of apelin in the enhancing effect of mesenteric PVAT on relaxations in SHRSP.ZF rats, by examining whether apelin canenhance vasorelaxation in the mesenteric arteries of SHRSP.ZF rats without PVAT, as it does in those with PVAT. Furthermore, we investigated whether apelin expression changes with increasing age. SHRSP.ZF rats at 17, 20, 23, and 30 weeks old were used. The mesenteric artery and surrounding adipose tissue were isolated from each rat; PVAT samples were isolated from surrounding adipose tissue; and the mRNA transcript level of apelin was examined by quantitative real-time PCR assays. Mesenteric arterial ring preparations with and without PVAT were made, and after a stable contraction was obtained by adding phenylephrine, relaxation was elicited using acetylcholine in the presence or absence of apelin (100 ng/mL, 20 min). There was no significant difference in apelin mRNA levels between 17 and 20 weeks, but there was a decrease at 23 and 30 weeks of age, which was when the enhancing effect of PVAT on vasodilation in SHRSP.ZF rats was impaired. In the presence of apelin, acetylcholine-induced relaxation in arteries without PVAT was significantly increased to the level of the response in arteries with PVAT in SHRSP.ZF rats at 20 weeks. These findings suggest that apelin is involved in the enhancing effect of PVAT in MetS rat mesenteric artery, and decreases in the level is associated with deterioration of PVAT function. Further study to investigate the mechanisms underlying the decrease in apelin production with increasing age in metabolic syndrome is needed, butthe apelin level could be one of the predictors for development of cardiovascular complications in patients with MetS.