Major Components Of Metabolic Syndrome Research Articles

Targeting the Renin-Angiotensin System in Obesity-Driven Hyperlipidemia and Hypertension

The renin-angiotensin system (RAS) plays a crucial role in the regulation of blood pressure, fluid balance, and lipid metabolism. Dysregulation of the RAS has been implicated in the pathogenesis of obesity-driven hyperlipidemia and hypertension, two major components of metabolic syndrome that significantly increase the risk of cardiovascular disease. In obese individuals, increased adipose tissue promotes local activation of the RAS, leading to heightened angiotensin II (Ang II) activity, oxidative stress, inflammation, and impaired lipid metabolism. These pathological mechanisms contribute to both elevated blood pressure and abnormal lipid profiles. Targeting the RAS through angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), and novel agents offers therapeutic potential in reducing obesity-associated hypertension and hyperlipidemia. This review discusses the molecular mechanisms linking obesity to RAS overactivation, examines current pharmacological strategies, and explores emerging therapeutic options aimed at modulating the RAS in the context of obesity-driven cardiometabolic disorders. Keywords: Renin-angiotensin system, obesity, hyperlipidemia, hypertension, angiotensin II, ACE inhibitors, ARBs, metabolic syndrome, cardiovascular disease.

Altered Autonomic Function in Metabolic Syndrome: Interactive Effects of Multiple Components

Metabolic syndrome (MetS) describes a set of disorders that collectively influence cardiovascular health, and includes hypertension, obesity, insulin resistance, diabetes, and dyslipidemia. All these components (hypertension, obesity, dyslipidemia, and prediabetes/diabetes) have been shown to modify autonomic function. The major autonomic dysfunction that has been documented with each of these components is in the control of sympathetic outflow to the heart and periphery at rest and during exercise through modulation of the arterial baroreflex and the muscle metaboreflex. Many studies have described MetS components in singularity or in combination with the other major components of metabolic syndrome. However, many studies lack the capability to study all the factors of metabolic syndrome in one model or have not focused on studying the effects of how each component as it arises influences overall autonomic function. The goal of this review is to describe the current understanding of major aspects of metabolic syndrome that most likely contribute to the consequent/associated autonomic alterations during exercise and discuss their effects, as well as bring light to alternative mechanisms of study.

The Association between Atherosclerotic Disease Risk Factors and Serum 25-Hydroxyvitamin D Concentration in Japanese Subjects.

Recent studies have described that vitamin D deficiency/insufficiency is associated with hypertension, insulin resistance, and dyslipidemia, which are major components of metabolic syndrome causing atherosclerosis. Therefore, we investigated the relationship between serum 25-hydroxyvitamin D [25(OH)D] concentration and atherosclerotic disease risk factors in healthy Japanese adults. In the present cross-sectional study, 1,177 subjects (348 males and 829 females) aged 20-72 y living in Japan (34.7-35.0ºN) were evaluated for vitamin D status by measuring serum 25(OH)D concentration. Atherosclerotic disease risk factors were defined as the presence of two or more of the following three risk factors: high blood pressure, dyslipidemia, and hyperglycemia. The percentages of vitamin D deficient and insufficient subjects were 33% and 46% in males and 59% and 32% in females, respectively. Subjects with atherosclerotic disease risk factors were significantly older and had higher BMI than those without it in both sexes. Male subjects with atherosclerotic disease risk factors had significantly lower physical activity and serum 25(OH)D concentration than those without it. In a logistic regression analysis adjusted for confounding factors, serum 25(OH)D concentration showed a significant inverse association with risk factors of atherosclerotic disease in males (OR=0.951, 95%CI: 0.906-0.998), but not in females. A covariance structure analysis also suggested that serum 25(OH)D level has a direct association with risk factors of atherosclerotic disease. In conclusion, we have demonstrated that low serum 25(OH)D level is a significant factor for increased atherosclerotic disease risk factors in males.

Meme kanserinde neoadjuvan kemoterapi yanıtlarını öngörmede belirleyici olarak açlık kan şekeri ve vücut kitle indeksi

Aim: Obesity is a well-known modifiable risk factor for breast cancer. Impaired fasting glucose is a component of metabolic syndrome and a significant risk for diabetes. We aimed to research the effect of these two major components of metabolic syndrome on neoadjuvant chemotherapy (NAC) response in breast cancer.Methods: We conducted 161 patients who had received NAC from January 2016 to January 2022. Fasting plasma glucose levels were measured at least two times and BMI was recorded before starting NAC. Impaired fasting glucose is defined as plasma glucose levels of 100 to 125 mg per dL. Analyses were compared into two groups according to FPG levels below or above 100 mg/dl and according to BMI obese (BMI30≥ kg/m2), or non-obese (BMI <30 kg/m2). The pathologic response was evaluated, and patients were divided into five groups according to the Miller-Payne grading system classified from grade V to I, complete pathologic response, loss of more than 90% of tumor cells, reduced 30% and 90% of tumor cells, lost less than 30% of tumor cells, and had no reduction in cellularity and no change malignant cells respectivelyResults: In the pathologic responses, 70.8% of patients with impaired fasting glucose levels were grade 1 non-reduction with NAC. Disease free-survival was shorter in the group that had impaired fasting glucose than in the group that had normal fasting plasma glucose (FPG) (p=0.031). In univariate analysis clinical stage 3 (p <0.001), postmenopausal status (p=0.037), human epidermal growth factor receptor 2 (HER-2) negativity (p<0.001), estrogen receptor (ER) positivity (p <0.001), progesterone receptor (PR) positivity (p <0.001) rate were higher in grade 1 unresponsive patients compared to patients with pathological response grade 2, grade 3 and grade 4. In multivariate analysis showed that fasting plasma glucose, clinical stage, HER-2 status, and ER status were independent predictor factors for pathological complete response (pCR). BMI had no impact on pCR. Our trial showed that the ratio of pCR in patients with impaired fasting glucose was 2.5 times lower than that in patients who had normal FPG levels [HR: 2.5, 95%CI 1.08–5.92, p = 0.03].Conclusion: Fasting plasma glucose significantly impacted both pCR and recurrence.

Musa acuminate seed extract attenuates the risk of obesity and associated inflammation in obese mice via suppression of PPARγ and MCP-1

Obesity is a severe public health burden and a major component of metabolic syndrome. It is critical to identify treatment medicines for obesity and associated inflammation. We examined the anti-obesity and anti-inflammatory properties of Musa acuminate seeds methanol extract in high-fat diet-induced obesity. Changes in body weight, Lee index, fat mass accumulation, serum cholesterol, and serum triglyceride were monitored. Alteration in the expression of PPARγ, GLUT4, and MCP-1 at the transcript level in adipose tissue was also studied. After tabulation of our data, a significant reduction (p < 0.05) was recorded for body weight gain, and fat mass accumulation followed by significant changes (p < 0.05) in serum cholesterol, and serum triglyceride levels by the extract. In agreement with the biochemical data, the extract was capable enough (p < 0.05) to reduce the mRNA expression of PPARγ, and MCP-1, confirming the ability of the extract to ameliorate the risk of obesity and obesity-associated inflammation. Moreover, an in-silico study showed the high binding affinity of the reported compounds from M. acuminate like Delphinidin, Umbelliferon with COX-2, PPARγ, and MCP-1, supporting the notion of the risk-reducing potential of M.acuminate for obesity and obesity mediated inflammatory.

AT1 receptor autoantibodies mediate effects of metabolic syndrome on dopaminergic vulnerability

The metabolic syndrome has been associated to chronic peripheral inflammation and related with neuroinflammation and neurodegeneration, including Parkinson’s disease. However, the responsible mechanisms are unclear. Previous studies have involved the brain renin-angiotensin system in progression of Parkinson’s disease and the angiotensin receptor type 1 (AT1) has been recently revealed as a major marker of dopaminergic vulnerability in humans. Dysregulation of tissue renin-angiotensin system is a key common mechanism for all major components of metabolic syndrome. Circulating AT1 agonistic autoantibodies have been observed in several inflammation-related peripheral processes, and activation of AT1 receptors of endothelial cells, dopaminergic neurons and glial cells have been observed to disrupt endothelial blood -brain barrier and induce neurodegeneration, respectively. Using a rat model, we observed that metabolic syndrome induces overactivity of nigral pro-inflammatory renin-angiotensin system axis, leading to increase in oxidative stress and neuroinflammation and enhancing dopaminergic neurodegeneration, which was inhibited by treatment with AT1 receptor blockers (ARBs). In rats, metabolic syndrome induced the increase in circulating levels of LIGHT and other major pro-inflammatory cytokines, and 27-hydroxycholesterol. Furthermore, the rats showed a significant increase in serum levels of proinflammatory AT1 and angiotensin converting enzyme 2 (ACE2) autoantibodies, which correlated with levels of several metabolic syndrome parameters. We also found AT1 and ACE2 autoantibodies in the CSF of these rats. Effects of circulating autoantibodies were confirmed by chronic infusion of AT1 autoantibodies, which induced blood–brain barrier disruption, an increase in the pro-inflammatory renin-angiotensin system activity in the substantia nigra and a significant enhancement in dopaminergic neuron death in two different rat models of Parkinson’s disease. Observations in the rat models, were analyzed in a cohort of parkinsonian and non-parkinsonian patients with or without metabolic syndrome. Non-parkinsonian patients with metabolic syndrome showed significantly higher levels of AT1 autoantibodies than non-parkinsonian patients without metabolic syndrome. However, there was no significant difference between parkinsonian patients with metabolic syndrome or without metabolic syndrome, which showed higher levels of AT1 autoantibodies than non-parkinsonian controls. This is consistent with our recent studies, showing significant increase of AT1 and ACE2 autoantibodies in parkinsonian patients, which was related to dopaminergic degeneration and neuroinflammation. Altogether may lead to a vicious circle enhancing the progression of the disease that may be inhibited by strategies against production of these autoantibodies or AT1 receptor blockers (ARBs).

Effect of lifestyle modification for two years on obesity and metabolic syndrome components in elementary students: A community- based trial.

Background: Lifestyle modifications, especially improving nutritional patterns and increasing physical activity are the most important factors in preventing obesity and metabolic syndrome in children and adolescents. For this purpose, the following interventional study was designed to investigate the effects of educational programs for students, as well as the changes in diet and physical activity on obesity and components of the metabolic syndrome.Methods:This study is part of an interventional research project (elementary school) conducted on all students of Sama schools in Zanjan and Abhar in three levels;elementary, middle and high school, including 1000 individuals in Zanjan (intervention group) and 1000 individuals (control group) in Abhar in 2011. Interventions were based on educating students, teachers and parents, changes in food services and physical activity. We primarily measured anthropometric indices, fasting blood sugar, lipid profiles and blood pressure and completed standard nutrition and physical activity questionnaires. Also, blood insulin levels were randomly measured in a number of students. Data analysis was done by SPSS software Version 16.0.Results:Overall, 589 individuals (252 males, 337 females) entered the case group and 803 individuals (344 males, 459 females) entered the control group. After two years of intervention, the mean waist circumference (63.8±10.9) and diastolic BP (63.8±10.4) were significantly lower, however, the mean systolic BP (10.1.0±12.5), food score (25.0±5.0) and drinking score (12.1±2.3) were higher in the intervention group (p<0.001). Comparing the components of metabolic syndrome between the second year and at the time of recruitment within the intervention group, showed that although the number of overweight/obese individuals, individuals with hypertriglyceridemia and high LDL increased, while those with abdominal obesity, high BP, hyperglycemia, and insulin resistance decreased (p<0.001). On the other hand, in the control group, the number of individuals with high BP increased significantly.Conclusion:The prevalence of abdominal obesity and hypertension, which are the two major components of metabolic syndrome, are much higher in our study than the other regions of the country. However, interventions for modification of diet and increasing physical activity, are effective in lowering of their prevalence.

Dietary supplementation of L-carnitine ameliorates metabolic syndrome independent of trimethylamine N-oxide produced by gut microbes in high-fat diet-induced obese mice.

Metabolic syndrome (MS) is a collection of risk factors of serious metabolic diseases. L-Carnitine is an essential nutrient for human health, and the precursor of trimethylamine N-oxide (TMAO). Previous studies have shown that the effect of L-carnitine on MS is controversial, and no studies have considered the role of gut microbiota in the regulation of MS by L-carnitine. In the present study, we established a high-fat diet (HFD)-induced obese mice model and systematically explored the effect of a broad range of dietary L-carnitine concentrations (0.2% to 4%) on the major components of MS. The results show that L-carnitine (0.5%-4%) reduced HFD-caused body-weight gain, visceral adipose tissue, glucose intolerance, hyperglycemia, HOMA-IR index, hyperlipemia, hypertension, and hyperuricemia. The elevation in the concentrations of IL-6, IL-1β, and TNF-α and decline in IL-10 in both serum and adipose tissue were also attenuated by L-carnitine. Furthermore, dietary L-carnitine increased the serum levels of TMAO produced by gut microbes. High-dose L-carnitine (2% and 4%), but not low-dose L-carnitine (0.2%-1%), notably modulated the composition of gut microbiota and partially attenuated HFD-induced gut microbiota dysbiosis. These results suggest that the ameliorative effect of L-carnitine on MS was independent of TMAO production and only partially related to the regulation of gut microbiota. This study provides crucial evidence for the utilization of L-carnitine as a safe and effective supplement for MS.

459-P: Liver-Targeted Mitochondrial Uncoupling by CRMP Improves Whole-Body Insulin Sensitivity and Attenuates Atherosclerosis in A LDLR-/- Mouse Model of Metabolic Syndrome

Progress in preventing cardiovascular disease (CVD) has been stalled by the growing epidemic of type 2 diabetes, which increases the relative risk of developing atherosclerosis four-fold compared to nondiabetic individuals. We recently developed an orally available, liver-targeted controlled release mitochondrial protonophore (CRMP) that promotes oxidation of hepatic triglycerides by promoting a subtle sustained increase in hepatic mitochondrial inefficiency and shown that this agent safely reverses dyslipidemia, fatty liver, and insulin resistance in rodents and nonhuman primates. While these studies suggest that CRMP may be a novel therapy for the major components of metabolic syndrome, its therapeutic utility for the treatment of CVD remains unknown. To assess the effect of CRMP on atherogenesis, we performed progression studies in Ldlr-/- mice fed a high-fat cholesterol diet and treated with CRMP (30 mg/kg-day) or vehicle control for 12 weeks. Here, we show that CRMP-treated mice display a 30% reduction in fasting plasma triglycerides (which could be attributed to a 20% decrease in VLDL-production) and a significant improvement in both hepatic and peripheral insulin sensitivity, due to reductions in hepatic and muscle ectopic lipid content. Importantly, CRMP-mediated decreases in hypertriglyceridemia and improvements in whole-body insulin sensitivity were associated with a 30% reduction in aortic root plaque area and neutral lipid accumulation (P&amp;lt;0.05). More detailed analysis of these plaques revealed that CRMP treatment also significantly lowered markers of plaque vulnerability, as evidenced by a 30% reduction in necrotic core area and increase in fibrous cap area (P&amp;lt;0.05). Conclusion: Taken together, these results support an anti-atherogenic role for CRMP and suggest the therapeutic potential of liver-targeted mitochondrial uncouplers for the treatment of cardiometabolic disorders. Disclosure L. Goedeke: None. N. Rotllan: None. K. Toussaint: None. A. Nasiri: Employee; Spouse/Partner; Medtronic. X. Zhang: None. J. Lee: None. X. Zhang: None. C. Fernández-Hernando: None. G.I. Shulman: Advisory Panel; Self; AstraZeneca, Janssen Research &amp; Development, LLC, Merck &amp; Co., Inc. Advisory Panel; Spouse/Partner; Merck &amp; Co., Inc. Consultant; Self; Novo Nordisk A/S. Consultant; Spouse/Partner; Novo Nordisk A/S. Other Relationship; Self; Gilead Sciences, Inc., iMetabolic Biopharma Corporation. Other Relationship; Spouse/Partner; iMetabolic Biopharma Corporation. Other Relationship; Self; Maze Therapeutics. Funding National Institutes of Health (R01DK119968, R01DK116774, P30DK045735 to G.I.S.), (K99 HL150234 to L.G.)

Prevalence of metabolic syndrome and its components among a population-based study in south of Iran, PERSIAN Kharameh cohort study

Objectivesover the past few years, lifestyle modification has increased the prevalence of major components of metabolic syndrome (MetS), leading to increased risk of non-communicable diseases, especially cardiovascular disease. The present study was aimed to determine the prevalence of MetS and its components and present results according to the major demographic characteristics of the participants in a population-based study. MethodsThis cross-sectional study was conducted on a total of 10663 subjects aged 40–70 years who participated in phase one of PERSIAN Kharameh cohort carried out between 2014 and 2017. ResultAccording to IDF, ATP III, and an Iranian definition, the prevalence of MetS were reported as 37.00%(36.08–37.92), 33.82% (32.93–34.73), and 33.13% (32.24–34.03), respectively. The most prevalent component of MetS was abdominal obesity (73.59), followed by reduced HDL cholesterol levels (44.83), elevated triglyceride (28.3), fasting glucose (35.34), and high blood pressure (32.64). In addition, the prevalence of MetS were 50.3, 70.4, 68.2, 65.7, and 60.8 among individuals with abdominal obesity, high triglyceride levels, hypertension, impaired fasting glucose, and low HDL-C levels, respectively. Results showed that 90% of the subjects displayed at least one component of MetS, and all MetS components were associated with major demographic characteristics of the study subjects. ConclusionsThe findings of this study indicate high prevalence of metabolic risk factors among study population. This study with a large sample size would contribute to establishment of efficient interventions and programs aimed at reducing the prevalence of MetS by health staff, supervisors and policymakers.

Effect of spirulina and silicon-enriched spirulina on metabolic syndrome features, oxidative stress and mitochondrial activity in Zucker fatty rats.

The use of Spirulina platensis (Sp) as a functional food was suggested decades ago. Biological incorporation of Silicon (Si) into Sp increases its bioavailability for potential food supplement applications. This work aimed at determining the effects of Sp and Si-enriched Sp (Sp+Si) on metabolic syndrome features in Zucker fatty rats. Thirty Zucker fatty rats were divided into three groups and supplemented with placebo or Sp or Sp+Si croquettes for 12weeks. Food consumption, glucose intolerance, hepatic steatosis, and mitochondrial and oxidative stress were determined. Zucker fatty rats exhibited several hepatic metabolic alterations as well as mitochondrial and oxidative stress perturbations. The intake of Sp increased plasma TG levels and decreased the hepatic NADPH oxidase activity and ameliorated transitorily the glucose intolerance. However, Si-spirulina does not appear to have more beneficial effects than spirulina alone. Other experiments with different species of rats/mice, different diets, or durations of diet intake should be undertakento confirm or infirm these results. PRACTICAL APPLICATIONS: Glucose intolerance and hepatic steatosis,two major components of metabolic syndrome, are increasing and becomes a major public health issue. Use of Spirulina platensis (Sp) as a functional food was suggested as a protein-dense food source. Bioavailable silicon (Si) may be an essential nutrient for higher animals, including humans. Sp but not Sp+Si decreased liver NADPH oxidase activity and improved transitorily glucose tolerance. This is the first study where Sp and Sp+Si effect on glucose intolerance is reported in Zucker rat. Other experiments should be undertaken to confirm or infirminvalidate the beneficial effects of Sp+Si supplement in the metabolic syndrome features.

Akebia Saponin D Regulates the Metabolome and Intestinal Microbiota in High Fat Diet-Induced Hyperlipidemic Rats.

Hyperlipidemia is a major component of metabolic syndrome, and regarded as one of the main risk factors causing metabolic diseases. We have developed a therapeutic drug, akebia saponin D (ASD), and determined its anti-hyperlipidemia activity and the potential mechanism(s) of action by analyzing the metabolome and intestinal microbiota. Male Sprague-Dawley rats were fed a high fat diet to induce hyperlipidemia, and then given ASD orally for 8 weeks. Lipid levels in serum were determined biochemically. Metabolites in serum, urine and feces were analyzed by UPLC-Q/TOF-MS, and the structure of the intestinal microbiota was determined by 16S rRNA sequencing. The ASD treatment significantly decreased the levels of TC, TG and LDL-c and increased the serum level of HDL-c. Metabolomics analysis indicated that the ASD treatment mainly impacted seven differential metabolites in the serum, sixteen differential metabolites in the urine and four differential metabolites in feces compared to the model group. The ASD treatment significantly changed eight bacteria at the genus level compared to the model group. In conclusion, ASD treatment can significantly alleviate HFD-induced hyperlipidemia and the hypolipidemic effect of ASD treatment is certainly associated with a systematic change in the metabolism, as well as dynamic changes in the structure of the intestinal microbiota.

Hyperglycemic and Hypertension are Major Component of Metabolic Syndrome that Caused Circulatory Morbidity in Hajj Pilgrims

Hajj is a community that needs special attention, the series of worship activities during in the holy places in Makkah and Madinah must be supported by physical and mental prime. One of the health problems has related to circulatory disease. This study presents the impact of metabolic syndrome (hyperglycemic, hypertension, and obesity) that caused circulatory morbidity in Indonesian Hajj Pilgrims. The design study is Retrospective Cohort, conducted on 152,429 Indonesian pilgrims departing in the Hajj season 2016/1437H sourced from The Siskohatkes data of the Ministry of Health of the Republic of Indonesia. The prevalence of metabolic syndrome (hyperglycemic, hypertension, and central obesity) on Indonesian pilgrims 1.6% and significant differences were found in all characteristic: sex, age, employment, and education, BMI, istitha’ah, and smoking behaviour. Hyperglycemic had greater HR than hypertension and central obesity with HR of 2.06 (1.63-2.60) adjusted by BMI, smoking, age, and sex as a risk of inpatient care. While, hypertension had greater HR than hyperglycemic and central obesity with HR 2.04 (1.99-2.09) adjusted by smoking, age, and sex as a risk of outpatient care in the holy places in Makkah or Madinah. Regulation for additional history of drugs consumed on screening of pre-existing disease before departure is needed. Keywords: hyperglycemic, hypertension, Mets, hajj, morbidity

Capsaicin in Metabolic Syndrome.

Capsaicin, the major active constituent of chilli, is an agonist on transient receptor potential vanilloid channel 1 (TRPV1). TRPV1 is present on many metabolically active tissues, making it a potentially relevant target for metabolic interventions. Insulin resistance and obesity, being the major components of metabolic syndrome, increase the risk for the development of cardiovascular disease, type 2 diabetes, and non-alcoholic fatty liver disease. In vitro and pre-clinical studies have established the effectiveness of low-dose dietary capsaicin in attenuating metabolic disorders. These responses of capsaicin are mediated through activation of TRPV1, which can then modulate processes such as browning of adipocytes, and activation of metabolic modulators including AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor α (PPARα), uncoupling protein 1 (UCP1), and glucagon-like peptide 1 (GLP-1). Modulation of these pathways by capsaicin can increase fat oxidation, improve insulin sensitivity, decrease body fat, and improve heart and liver function. Identifying suitable ways of administering capsaicin at an effective dose would warrant its clinical use through the activation of TRPV1. This review highlights the mechanistic options to improve metabolic syndrome with capsaicin.

Symptoms of Anxiety and Depression in Obese Singaporeans: a Preliminary Study

Obesity is a major component of metabolic syndrome and an independent risk factor for various chronic diseases. It is also closely associated with mental illness, and the interaction is complex and multifactorial. This study aimed to estimate the prevalence of anxiety and depressive symptoms among obese Singaporeans. Cross-sectional data of 36 male and 47 female obese Singaporeans who had been referred to the weight management clinic of National University Hospital, Singapore, between January 2010 and November 2011 were collected. Obesity was classified according to criteria of the World Health Organization. The extents of anxiety and depressive symptoms were measured using the Hospital Anxiety and Depression Scale. In obese Singaporeans attending the weight management clinic, the prevalence of anxiety symptoms was higher than that of depressive symptoms (28% vs 11%). There was no major socioeconomic difference between obese patients with and without anxiety, or with and without depressive symptoms. In obese Singaporeans, anxiety symptoms may be more common than depressive symptoms. Weight management programmes should incorporate anxiety management as part of standard treatment. Early detection and pharmacological and psychological interventions should be implemented.

Manifestations of Renal Impairment in Fructose-induced Metabolic Syndrome.

IntroductionInternational studies show an increased incidence of chronic kidney disease (CKD) in patients with metabolic syndrome (MS). It is assumed that the major components of MS - obesity, insulin resistance, dyslipidemia, and hypertension - are linked to renal damage through the systemic release of several pro-inflammatory mediators, such as uric acid (UA), C-reactive protein (CRP), and generalized oxidative stress. The aim of the present study was to investigate the extent of kidney impairment and manifestations of dysfunction in rats with fructose-induced MS.MethodsWe used a model of high-fructose diet in male Wistar rats with 35% glucose-fructose corn syrup in drinking water over a duration of 16 weeks. The experimental animals were divided into two groups: control and high-fructose drinking (HFD). Serum samples were obtained from both groups for laboratory study, and the kidneys were extracted for observation via light microscopy examination.ResultsAll HFD rats developed obesity, hyperglycemia, hypertriglyceridemia, increased levels of CRP and UA (when compared to the control group), and oxidative stress with high levels of malondialdehyde and low levels of reduced glutathione. The kidneys of the HFD group revealed a significant increase in kidney weight in the absence of evidence of renal dysfunction and electrolyte disturbances. Under light microscopy, the kidneys of the HFD group revealed amyloid deposits in Kimmelstiel-Wilson-like nodules and the walls of the large caliber blood vessels, early-stage atherosclerosis with visible ruptures and scarring, hydropic change (vacuolar degeneration) in the epithelial cells covering the proximal tubules, and increased eosinophilia in the distant tubules when compared to the control group.ConclusionUnder the conditions of a fructose-induced metabolic syndrome, high serum UA and CRP correlate to the development of early renal disorders without a clinical manifestation of renal dysfunction. These phenomena are of particular importance for assessing the risk of developing future CKD.

Relationship between Sex Hormone-Binding Globulin (SHBG) and Insulin-Like Growth Factor-I (IGF-I) with Metabolic Syndrome

Background: Glucose intolerance, insulin resistance, hypertension, visceral obesity, and ‎dyslipidemia are the major components of metabolic syndrome (MS).‎ Aim: To evaluate the association between serum SHBG and IGF-1 levels and the risk of ‎MS. Furthermore, to determine the correlations between SHBG and IGF-1 and the main ‎components of MS.‎ Subjects and Methods: A total of 402 subjects with and without MS were enrolled in ‎this study (MS=156, Non-MS=246) aged > 18 years. The age, height, weight, BMI, HC, ‎WC, and incidence of diabetes, hypertension and dyslipidemia of all cases were recorded. ‎The collected serum samples were used to assess lipid profile, glucose and insulin levels. ‎The levels of LDL-cholesterol were calculated using Friedewald’s formula. Insulin ‎resistance was measured (as HOMA score). The levels of serum SHBG and IGF-1 were ‎measured using Elisa technique.‎ Results: A positive relationship between SHBG and MS was detected , ‎however no such correlation was observed concerning IGF-1. There were ‎positive correlations between SHBG and main components of MS; with insulin, HOMA-‎index, TC, TG and HDL . Conversely, IGF-1showed negative correlations. Finally, SHGB was ‎more sensitive (63.5%), accurate (61.9%) than IGF-1 (51.9%), accuracy ‎‎(59%) .‎ Conclusion: Our study reveals that lower SHBG is more strongly associated with ‎metabolic syndrome and its main components than lower IGF-1. SHBG could be the ‎essential driver of these relations, conceivably reflecting its association with insulin ‎sensitivity, however, more studies are required to confirm this relationship.‎

The Effect of Anthocyanin-Rich Purple Vegetable Diets on Metabolic Syndrome in Obese Zucker Rats.

Consumption of highly colored fruits and vegetables rich in anthocyanins has been associated with numerous health benefits. Purple carrots (PC) and purple potatoes (PP) have higher anthocyanin concentrations and higher biological activities compared with less pigmented cultivars. We hypothesized that substitution of the majority of carbohydrate in a high fat diet with PP or PC, for 8 weeks, would improve insulin resistance and hypertension, major components of metabolic syndrome, compared with orange carrots (OC), white potatoes (WP) or a control, high fat, sucrose-rich diet (HFD) in obese Zucker rats. After 8 weeks of feeding, intraperitoneal glucose tolerance test, intraperitoneal insulin tolerance test (ipITT), and invasive hemodynamic tests were performed. The PP group had better glucose tolerance compared with the WP and the HFD groups and higher insulin sensitivity as measured by the ipITT and homeostatic model assessment of insulin resistance (P = .018) compared with the HFD without having any effect on blood pressure. The PC reduced left ventricular pressure compared with both the HFD (P = .01) and the OC (P = .049) groups and reduced systolic and diastolic blood pressures compared with the HFD group (P = .01 and <.0001, respectively) without having any effect on glucose homeostasis. The PC animals consumed more and were more obese than other groups, possibly obscuring any benefit of this vegetable on glucose tolerance. The bioactives in the vegetables responsible for blood pressure and glucose homeostasis could be different, and their effects could be independent of each other. The specific bioactives of each vegetable and their molecular targets remain to be identified. Nonetheless, incorporation of purple vegetables in functional food products may provide metabolic/cardiovascular benefits in the background of a high-fat diet that promotes obesity.

Phenolics from Garcinia mangostana alleviate exaggerated vasoconstriction in metabolic syndrome through direct vasodilatation and nitric oxide generation.

BackgroundExaggerated vasoconstriction plays a very important role in the hypertension, a major component of metabolic syndrome (MetS). In the current work, the potential protective effect of methanol extract of fruit hulls of Garcinia mangostana L. on the exaggerated vasoconstriction in MetS has been investigated. In addition, the bioactive fraction and compounds as well as the possible mechanism of action have been illustrated.MethodsThe effect of methanol extract of G. mangostana (GMT) fruit hulls on the vascular reactivity of aorta isolated from animals with MetS was investigated through bioassay-guided fractionation procedures. GMT was partitioned with chloroform (I) and the remaining mother liquor was fractionated on a Diaion HP-20 with H2O, 50 and 100 % methanol to give fractions II, III, and IV, respectively. The effect of total extract (GMT), bioactive fraction and the bioactive compounds on the vasoconstriction were examined in aortae isolated from animals with MetS by incubation for 30 min before exposing aortae to cumulative concentrations of phenylephrine (PE). The direct relaxant effect was also examined by adding cumulative concentrations of the bioactive fraction and its bioactive compounds to PE precontracted vessels. In addition, aortic nitric oxide (NO) and reactive oxygen species (ROS) production was investigated.ResultsBioassay-guided fractionation of GMT revealed isolation of garcimangosone D (1), aromadendrin-8-C-β-D-glucopyranoside (2), 2,4,3′-trihydroxy benzophenone-6-O-β-D-glucopyranoside (3), maclurin-6-O-β-D-glucopyranoside (rhodanthenone) (4), epicatechin (5), and 2,3′,4,5′,6-pentahydroxy benzophenone (6). Only compounds 2, 4, and 5 significantly alleviated the exaggerated vasoconstriction of MetS aortae and in the same time showed significant vasodilation of PE pre-contracted aortae. To further illustrate the mechanism of action, the observed vasodilation was completely blocked by the nitric oxide (NO) synthase inhibitor, Nω-nitro-L-arginine methyl ester hydrochloride and inhibited by guanylate cyclase inhibitor, methylene blue. However, vasodilation was not affected by the potassium channel blocker, tetraethylammonium or the cyclooxygenase inhibitor, indomethacin. In addition, compounds 2, 4, and 5 stimulated NO generation from isolated aortae to levels comparable with acetylcholine. Furthermore, 4 and 5 inhibited reactive oxygen species generation in MetS aortae.ConclusionThe phenolic compounds 2, 4, and 5 ameliorated the exaggerated vasoconstriction in MetS aortae through vasodilatation-NO generation mechanism.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-016-1340-5) contains supplementary material, which is available to authorized users.

PS 06-16 PREVALENCE AND CLINICAL FEATURES OF PREDIABETES IN PATIENTS WITH HYPERTENSION

Objective: Although prediabetes and hypertension are major components of metabolic syndrome, there is no reported data on the prevalence of prediabetes (FBS 100–125 mg/dL or HbA1c 5.7–6,4%) in hypertensive patients. We evaluated the prevalence and characteristics of prediabetes among hypertensive patients treated at primary clinics in Korea. Design and Method: Anthropometric and hemodynamic data and a variety of laboratory tests using serum and urine were obtained for 3109 patients who participated in the Wonder study which is a nation-wide, multi-centered, cross-sectional study. Risk factors and comorbidities according to diabetes status tertiles (normal, prediabetes and diabetes) were identified using multilevel logistic regression models. Results: The overall prevalence of normal, prediabetes and diabetes in patients with hypertension was 21.8%, 48.7and 29.5%, respectively. Smoking is significantly less in prediabetes and diabetic patients compared to normal glucose hypertensive subject. However, risk factors (high waist circumference and serum triglycerides, and low serum high-density lipoprotein), and subclinical organ damages such as LVH and microalbuminuria, and coronary artery disease, CKD and peripheral arterial disease were significantly increased as increasing diabetes status tertiles. Conclusions: The prevalence of prediabetic state in hypertension patients was 48.7%. Epidemiological factors of the prediabetes in hypertension patients showed higher CV risk factors and CV comorbidities, Almost half adults in Korean hypertensive patients was found to have prediabetes. We should have action to prevent prediabetes to be diabetes through better detection, awareness, prevention and treatment.