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Endothelial dysfunction in experimental models of metabolic syndrome − effect of fructose

Abstract

The aim of the work was to find an experimental model suitable for the study of endothelial dysfunction induced by MS. We used hypertriglyceridemic rats (HTG) that were fed a hypercholesterolemic diet of different composition and duration: a 6-week administration of standard diet with an addition of cholesterol and fat (HTGChol) and a three-month administration of the same diet with an addition of fructose (HTGCholF). We investigated the effect of different diets on aortic endothelial function. The standard diet fed Wistar (W) and HTG rats served as controls. Decision for addition of fructose to HTGChol was done based on in vitro experiments evaluating the effect of high concentration of saccharide in the incubation solution on aortic endothelial function. This intervention caused significant deterioration of relaxation induced by acetylcholine (ACh). While in HTGChol, we did not find significant differences in the function of the aorta compared to W or HTG rats, adding of fructose to high fat diet and prolonging its administration resulted in significantly impaired endothelium-dependent relaxation. It seems that such a model is suitable for the study of endothelial dysfunction in MS and the effect of substances that may protect the endothelium.

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Surrogate Measures of Insulin Resistance in Middle-aged Non-diabetic Subjects

Abstract

Objective: Insulin resistance has been shown to be a risk factor for type 2 diabetes and cardiovascular disease. The assessment of insulin sensitivity in the clinical practice, however, faces several difficulties. The study proposes to analyze surrogate measures of insulin resistance based on fasting insulin levels in central Romania, and check whether the diagnosis of the metabolic syndrome is an adequate strategy to identify middle-aged persons with reduced insulin sensitivity. Methods: Anthropometric measurements, metabolic profile, and surrogates measures of insulin sensitivity (GIR, HOMA, QUICKI, FIRI, Belfiore, Bennett, Raynaud, McAuley index) based on fasting insulin levels were assessed in 233 non-diabetic middle aged subjects. Results: Cutoff values, determined as the lowest quartile of insulin sensitivity for fasting insulin, HOMA, IRI (1/QUICKI), FIRI and Belfiore's, Bennett's, Raynaud's and McAuley's insulin sensitivity indices were 10.49 mU/L, 2.1, 3.01, 2.32, and 0.03, 1.34, 3.81, 6.29, 5.82. Components of the metabolic syndrome showed moderate but significant correlations with the surrogate measures of insulin resistance (r = 0.22-0.56, p <0.05). HOMA-IR and McAuley indices were the best predictors of clustered cardiometabolic risk factors (AUC - 0.83, 0.81 and 0.82). The metabolic syndrome diagnosis performed well in identifying patients with reduced insulin sensitivity (McAuley 2: sensitivity - 0.78, specificity - 0.84). Conclusion: Fasting insulin derived insulin sensitivity indices may help the recognittion of insulin resistant states predicting cardiometabolic disorders. Actively looking for insulin resistance by these simple indices, or by diagnosing the metabolic syndrome, those at increased risk can be recognized

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Abnormal lipid metabolism in metabolic syndrome: an epigenetic perspective

Abstract

Metabolic syndrome is a complex pathology including central obesity, impaired glucose tolerance/diabetes, an atherogenic dyslipidemia and a prothrombotic state.

A new perspective on understanding the mechanisms underlying metabolic syndrome is provided by the epigenetic changes (mainly DNA methylation and histone covalent modifications), which influence gene expression without changing of the DNA sequence.

DNA methylation (mainly in carnitine palmitoyltransferase 1A gene) and histone modifications were shown to be associated with VLDL and LDL phenotypes, with hyperglycemia and reduced level of HDL cholesterol, with hypertriglyceridemic waist phenotype and with progression of atherosclerotic occlusion in peripheral arteries. The epigenetic changes can occur in the prenatal period, throughout the life span, and can be transmitted to the offspring. Both poor maternal nutrition and maternal obesity, diabetes and overfeeding can result in epigenetic alterations that amplify the risk of metabolic syndrome for the offspring.

Throughout life span, environmental factors, such as nutrition and exercise can induce epigenetic changes influencing the evolution of the metabolic syndrome (through adipocyte metabolism and insulin signaling pathway). The epigenetic modifications are not completely erased during gametogenesis and embryogensis, resulting in a transgenerational transmission of an epigenetic state up to the fifth generation.

Epigenetic mechanisms are an interface between environmental stimuli and resulting phenotype by inducing a certain transcriptional state, which may be also transmitted to the next generation(s) and which may predispose to an increased risk for developing metabolic syndrome in the context of a mismatched environment.

Elucidating epigenetic modulation might provide additional information about risk evaluation and more targeted therapeutical intervention.

Open access
Specificity of Metabolic Syndrome Model Reproduction at Pubertal and Adult Male Rats

Abstract

Background and Aims: Comparative estimation of metabolic syndrome (MS) mediated changes of blood, cardio-vascular system, liver, pancreas and kidneys morphologic structure in adult and pubertal rats. Materials and Methods: Wistar albino male rats of two age categories (young animals of 21 days age (50-70g) and adults (160-180g)) were divided into 4 groups (8 animals in each): 1 - Control 1 (intact young rats); 2 - Control 2 (intact adult rats); 3 - MS3 (young rats with MS) and 4 - MS4 (adult rats with MS). The metabolic syndrome model was induced by full replacement of drinking water with 20% fructose solution (200g/l). After 60 days of MS modeling, determination of rat hematological and serum biochemical parameters, glucose tolerance, blood pressure, liver rates of lipid peroxydation and chromatin DNA fragmentation, as well as morphological macroscopic and microscopic studies were carried out. Results: In pubertal rats, glucose tolerance, hypertension, blood clotting disturbances, DNAfragmentation and lipid peroxydation rates were affected more profoundly, while mature rats showed greater Pseudo Pelger-Huet anomaly development, serum cholesterol and lipoproteins increases, liver and kidney morphology changes. Conclusions: Our current data combined with previous results of other authors allow us to conclude that an animal model (Wistar rats) of MS is quite easily obtained in a full age range, from juvenile to mature rats.

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Working in Shifts and the Metabolic Syndrome: Epidemiological Evidence and Physiopathological Mechanisms

Abstract

The Metabolic syndrome (MetS) is considered as an association of the abdominal obesity, abnormal metabolism of the lipids and glucose (high level of triglycerides, low level of HDL-cholesterol and high level of glycemia) and high values of blood pressure, determined by an underlying mechanism of insulin resistance. As a result of environmental-gene interaction, MetS is associated with unhealthy nutrition, smoking, alcohol abuse, lack of physical activity, shorter sleep duration and desynchronization of the circadian rhytm caused by working in shifts. The aim of this article is to review the effects of working in shifts on the MetS through the epidemiological evidence and the perspective of the physiopathological mechanisms.

Open access
Perspectives on the Nutritional Management of Metabolic Syndrome in Asia: People, Practice and Programmes

Abstract

Numerous Asian countries have a high prevalence of metabolic syndrome, also associated with cardiovascular disease and diabetes mellitus. Healthcare expenditure varies among Asian countries, and is influenced by poverty factor and large populations. The effect of metabolic syndrome on nutritional management in Asia demonstrates the essential for clinicians to equalize the needs for higher standards of dietetics practice; as they execute optimal care processes with the aim of improving outcomes, alongside setting of workforce limitations, inadequate expertise in metabolic syndrome nutrition practice, as well as ethnic diversity among Asians. This paper presents some aspects of dietetics practice and the possibility that an alteration in practice is mandatory if dietitians are to play an active role in preventing or decelerating the evolution of the metabolic syndrome.

Open access
Age Dependent Effects of Metformin in Wistar Albino Male Rats with Metabolic Syndrome

Abstract

Background and aims: Comparative estimation of metformin treatment effectiveness in adult and young rats with metabolic syndrome (MS).

Materials and methods: A metabolic syndrome model was induced by full replacement of drinking water with 20% fructose solution in Wistar albino male rats of two age categories (young animals of 21 days age (50-70g) and adults (160-180g)). After 60 days of MS modelling and metformin treatment, hematological, biochemical, blood pressure, chromatin DNA fragmentation investigations, as well as morphological macroscopic and microscopic studies were carried out.

Results: In young rats, effects of metformin on blood clotting time, lipid metabolism and DNA fragmentation were more pronounced. Mature rats showed greater susceptibility to this drug as for influence on pancreas and visceral fat relative weights.

Conclusions: In our experiment with young and adult rats with MS and metformin treatment we showed that this preparation effect was age-dependent for lipid metabolism indices, blood clotting time, nuclear DNA fragmentation parameters, as well as for changes of relative organs weights and target organs morphological structure. Metformin treatment allowed a partial normalization of serum levels of lowdensity lipoproteins (LDLP) and ratio high lowdensity lipoproteins / lowdensity lipoproteins (HDLP/LDLP), hemoglobin contents, hematocrit percentage, DNA fragmentation rates, with simultaneous worsening in blood clotting time, blood pressure levels, liver and pancreas relative organs weights (of young rats).

Open access
Serum Level of the Adipokine “Vaspin” in Relation to Metabolic Parameters: Short – Term Effect of Specific Dietary Therapy

Abstract

AIM To investigate the association between the circulating vaspin concentration and both of glucose homeostasis and insulin resistance in metabolic syndrome (MetS) patients, and also to evaluate the metabolic impact of two different dietary therapies on such conditions.

MATERIALS AND METHODS Fifty eight obese female volunteers suffering from MetS, followed a specially designed dietary therapy consists of a low caloric balanced diet, accompanied by either 30% doum biscuits (group A), or whole wheat biscuits (group B) for four weeks (phase 1). During the next four weeks, they were continued on the hypocaloric diet alone (phase 2).

RESULTS The health effects of two dietary therapies were more prominent in improving the biochemical markers of the MetS than in the body weight reduction. The lower levels of serum vaspin were significantly increased at the end of the 1st phase in both groups especially group (A). Sustained negative correlations were detected between vaspin level and both of C-peptide and insulin resistance expressed as modified homeostatic model assessment (M.HOMA).

CONCLUSION The effect of the dietary supplements may play a role in alleviating the impact of the components of the MetS and may also sustain the level of the vaspin in the sensitization of the C-peptide in order to attain glucose homeostasis.

Open access
Flow Cytometry Analysis of Pparα Receptors in Metabolic Syndrome / Studiul Receptorilor Pparα prin Metoda Citometriei în Flux în Sindromul Metabolic

Abstract

Introduction. Metabolic syndrome (MS) is a cluster of distinct metabolic alterations with an increased cardiovascular risk. Peroxisome Proliferator-Activated Receptor - Alpha (PPARα), member of the nuclear receptor superfamily of transcription factors, is critically involved in the management of lipid metabolism during homeostasis or inflammatory stresses in various cell types and represents one of the therapeutic targets in MS. We analysed the PPARα expression in leukocytes of pacients with MS, in order to address PPARα involvement in these group of diseases. Material and method. Our study included 57 adult patients recruited under informed voluntary consent, investigated in order to establish whether they present MS, according to International Diabetes Federation (IDF) European guidelines and grouped in 2 lots: the MS Lot (26 patients) and control group, non-MS Lot (31 subjects). Common clinical and laboratory parameters targeted in MS evaluation were determined for all the studied cases. The expression levels of 2 molecules, PPARα and CD36 were evaluated in various circulating leukocyte populations of these patients by an optimized flow cytometry method. Statistic analysis clarifying the significance of value differences for various parameters measured was performed under SPSS and simple statistical tests (Pearson, t-Student, Chi -test). Results and discussion. The fluorescence staining for PPARα were significantly dimmer when comparing the cellular expression in eosinophils (p<0.05) of MS versus the Control group of subjects. Conclusions: Our study is the first to show that circulating eosinophils display significantly reduced PPARα protein expression in MS patients. The differences in key molecule expression in circulating leukocytes (like PPAR species, CD36, and other) might be evocatory for the endothelial dysfunction and obesity and might be of use in the therapeutic decision.

Open access
Gender Influence on Resting Metabolic Rate and Adipocytokines Levels in Newly Diagnosed Type 2 Diabetic Patients with Metabolic Syndrome

Abstract

Background and Aims: Resting metabolic rate (RMR) is important to estimate energy requirements. Our aim was to investigate the RMR in newly diagnosed type 2 diabetic (T2DM) patients with metabolic syndrome (MS) in relation with obesity, gender, some adipokines and insulin resistance parameters. Material and Methods: 138 newly diagnosed T2DM adults were evaluated for anthropometric, clinical, biochemical parameters, and RMR. The group was subdivided according to body mass index and MS presence. Results: Determined RMR (RMRd), predicted RMR (RMRp), oxygen consumption and carbon dioxide production at rest were significantly lower for subjects with BMI < 30 kg/m2 compared to subjects with BMI ≥ 30 kg/m2 (p<0.001). RMRd positively correlated with fat-free mass (p < 0.001), waist (p < 0.001), BMI (p < 0.001), insulinemia (p = 0.021) and negatively with age (p < 0.001) and adiponectin (p = 0.027). The percent of determined from predicted RMR in subjects with MS was lower than in those without MS, but only for men (p< 0.005). Conclusions: Subjects with T2DM and MS have significantly lower than predicted RMR, compared to those without MS, indicating that they may have an energy sparing metabolism. Gender influences the energy metabolism and may play a particular role in energy the metabolism of people with T2DM and MS.

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