Stages Of Metabolic Syndrome Research Articles

Plasma visfatin and apelin levels in adolescents with polycystic ovary syndrome

Background Polycystic ovary syndrome (PCOS) is a common endocrine disorder that usually begins during adolescence. Patients may have severe metabolic disorders. Objective To investigate the levels of visfatin and apelin in adolescent girls with PCOS and to explore the importance of visfatin and apelin in glucose and lipid metabolism. Methods A total of 88 girls (aged 12–20 years) were prospectively and consecutively recruited during two years for the PCOS group (n = 44) and the control group (n = 44). Serum visfatin, apelin and other metabolic parameters were measured. Receiver operator characteristics (ROC) curve analysis was performed to reveal the diagnostic potential. Results Visfatin, apelin and indicators of glucose and lipid-metabolism were not different for PCOS patients compared to control. However, insulin resistance (IR) in the PCOS-group was more frequent (p < 0.05). Visfatin in non-IR patients was higher than in IR-patients in the PCOS-group (p < 0.05). However, there was no difference in apelin levels between IR and non-IR patients in the PCOS-group (p > 0.05). ROC-curve analyses demonstrated that the optimal value of visfatin for predicting IR in PCOS-patients was 7.14 ng/mL, with 78.1% sensitivity and 68.7% specificity. In the PCOS-group, visfatin was positively correlated with high density lipoprotein cholesterol (HDL-C), and negatively correlated with HOMA-IR, apolipoprotein B (Apo-B), cholesterol (CHO), low density lipoprotein cholesterol (LDL-C) and CHO/HDL-C ratio (p < 0.05). Apelin had no correlation with all indices (p > 0.05). Conclusions Higher visfatin levels may prevent IR in adolescent PCOS patients, showing a positive predictive value for IR and also reflecting a beneficial effect on lipids. It is a possible protective factor at certain stages of metabolic syndrome.

A Novel Sesquiterpene Lactone Xanthatin-13-(pyrrolidine-2-carboxylic acid) Isolated from Burdock Leaf Up-Regulates Cells' Oxidative Stress Defense Pathway.

The aim of our study was to identify novel molecules able to induce an adaptative response against oxidative stress during the first stages of metabolic syndrome. A cellular survival in vitro test against H2O2-based test was applied after pretreatment with various natural bitter Asteraceae extracts. This screening revealed potent protection from burdock leaf extract. Using chromatography and LC-MS—RMN, we then isolated and identified an original sesquiterpene lactone bioactive molecule: the Xanthatin-13-(pyrrolidine-2-carboxylic acid) (XPc). A real-time RT-qPCR experiment was carried out on three essential genes involved in oxidative stress protection: GPx, SOD, and G6PD. In presence of XPc, an over-expression of the G6PD gene was recorded, whereas no modification of the two others genes could be observed. A biochemical docking approach demonstrated that XPc had a high probability to directly interact with G6PD at different positions. One of the most probable docking sites corresponds precisely to the binding site of AG1, known to stabilize the G6PD dimeric form and enhance its activity. In conclusion, this novel sesquiterpene lactone XPc might be a promising prophylactic bioactive agent against oxidative stress and inflammation in chronic diseases such as metabolic syndrome or type 2 diabetes.

Differences in Several Factors in the Development of Erosive Esophagitis Among Patients at Various Stages of Metabolic Syndrome: A Cross-Sectional Study.

BackgroundErosive esophagitis (EE) is strongly associated with metabolic syndrome (MS), but is not always recognized in individuals with MS and the prevalence of EE in individuals with non-MS is not low.AimTo examine the differences in clinical factors associated with EE at various stages of MS, as well as the differences in metabolites between subjects with MS, with and without EE.MethodsA total of 7,097 persons who underwent health checkups including esophagogastroduodenoscopy were analyzed. We examined the differences in clinical factors for EE among subjects with non-MS, pre-MS, and MS and compared metabolites between 34 subjects with MS, with and without EE.ResultsEE prevalence was significantly higher in the MS and pre-MS groups than in the non-MS group (p < 0.001). EE severity was higher in the MS group than in the pre-MS and non-MS groups (p < 0.001). In the non-MS group, there were significant differences between subjects with and without EE with respect to Helicobacter pylori (H. pylori) and smoking. In the pre-MS and MS groups, there were significant differences in H. pylori, hiatal hernia, and drinking in those with and without EE. The levels of glutamine, hypoxanthine, and lactic acid metabolites were significantly different between subjects with MS, with and without EE (all p < 0.05).ConclusionAlthough H. pylori and lifestyle factors such as smoking and drinking are important for EE, differences in these factors should be considered at various stages of MS. Additionally, several metabolites may be involved in the development of EE in MS.

Differences among patients with and without nonalcoholic fatty liver disease having elevated alanine aminotransferase levels at various stages of metabolic syndrome.

BackgroundThe prevalence of nonalcoholic fatty liver disease (NAFLD) in the non-obese population has increased and NAFLD is not always recognized in individuals with metabolic syndrome (MS). The risk of cirrhosis is higher in patients having NAFLD with elevated alanine aminotransferase (ALT) levels than in those having NAFLD with normal ALT levels.ObjectiveTo measure the differences in clinical factors associated with NAFLD having elevation of ALT among subjects with Non-MS, Pre-MS, and MS, and to measure differences in metabolites between MS subjects with and without NAFLD having elevation of ALT.MethodsAmong 7,054 persons undergoing health check-ups, we included 3,025 subjects who met the selection criteria. We measured differences in clinical factors for NAFLD having elevation of ALT among subjects with Non-MS, Pre-MS, and MS, and compared metabolites between subjects with and without NAFLD having elevation of ALT in 32 subjects with MS.ResultsThe prevalence of NAFLD and NAFLD having elevation of ALT was significantly progressively greater in subjects with Non-MS, Pre-MS, and MS (p <0.001, respectively). In the Non-MS group, there were significant differences between subjects with and without NAFLD having elevation of ALT with respect to body mass index (BMI), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, hemoglobin A1c, uric acid, aspartate aminotransferase (AST); In the Pre-MS group, there were significant differences in BMI, hypertension, AST, and gamma-glutamyl transpeptidase (GGT); In the MS group, there were significant differences in HDL-C, impaired glucose tolerance, AST, and GGT. There were significant differences in levels of metabolites of nicotinamide, inosine, and acetyl-L-carnitine between MS subjects with and without NAFLD having elevation of ALT (all p <0.05).ConclusionsAlthough NAFLD having elevation of ALT is important for development of NAFLD, differences in factors associated with NAFLD having elevation of ALT at various stages of MS should be considered. Additionally, several metabolites may play roles in the identification of risk for NAFLD in individuals with MS.

Study on the Relevance of Metabolic Syndrome and Incidence of Gastric Cancer in Korea

(1) Background: This study aimed to determine the relevance between stages of metabolic syndrome (MS) progression and the incidence of gastric cancer utilizing a big data cohort for the national health checkup. (2) Methods: There were 7,785,098 study subjects, and three stages of metabolic syndrome were categorized using the health checkup results from 2009. Incidence of gastric cancer was traced and observed from the date of the health insurance benefit claim in 2009 until 31 December, 2016, and Cox hazard-proportional regression was performed to determine the risk of gastric cancer incidence based on the stage of progression for metabolic syndrome. (3) Results: Hazard ratio (HR) incidence rate for the MS group was 2.31 times higher than the normal group (95% CI 2.22–2.40) after adjustment (Model 4). The HR incidence rate of gastric cancer for the pre-MS group was 1.08 times higher (95% CI 1.04–1.12) than the normal group, while the HR incidence rate of gastric cancer for the MS group was 1.26 times higher (95% CI 1.2–1.32). (4) Conclusions: Causal relevance observed in this study between metabolic syndrome and incidence of gastric cancer was high. Promotion and education for active responses in the general population and establishment of appropriate metabolic syndrome management systems to prevent gastric cancer are needed.

Abstract P463: Deterioration of Vasomotor Regulation of Perivascular Adipose Tissue at Later Stage of Metabolic Syndrome

Obesity is a critical risk factor for metabolic syndrome, which increases development of cardiovascular complications. Perivascular adipose tissue (PVAT) is known to modulate vascular tone. We reported that PVAT increases vasodilation via enhancing endothelial nitric oxide production in mesenteric arteries of SHRSP.Z- Lepr fa /IzmDmcr rats (SHRSP.ZF) with metabolic syndrome (at 20 weeks of age; wks). However, the enhancing effects disappear at later stage (30 wks). We therefore investigated mechanisms underlying deterioration of the compensatory effects of PVAT in metabolic syndrome. Mesenteric arteries were isolated from male 20 and 30-week-old SHRSP.ZF, and vasodilation in response to nitroprusside was examined using bath bioassay techniques. Coexistence of PVAT from SHRSP.ZF at 20 wks increased vasodilation in arteries without PVAT from SHRSP.ZF at 20 wks, but the effects of PVAT were not substituted by replacement with PVAT from rats at 30 wks. Cyclic GMP levels in response to nitroprusside in arteries were increased by the presence of PVAT at 20 wks, but it was not altered by the presence of PVAT at 30 wks. In the presence or absence of vaspin, visfatin omentin, and apelin, vasodilation in response to nitroprusside was unchanged in SHRSP.ZF arteries at 20 wks. These results indicated that the production/release of diffusible vasodilator(s) from PVAT decreases with ageing. Vaspin, visfatin omentin, and apelin could be excluded from potential candidates of vasodilator(s). The deterioration of PVAT’s compensatory effects under the conditions of impaired vasodilations may induce cardiovascular complications at later stages of metabolic syndrome.

Progression of Time-Dependent Changes to the Mechanisms of Vasodilation by Protease-Activated Receptor 2 in Metabolic Syndrome.

Protease-activated receptor 2 (PAR2) is a G protein-coupled receptor activated by serine proteases released from tissues or by synthetic peptide ligands administered pharmacologically. Its wide expression in the cardiovascular system, particularly within the endothelium, vasodilation activity, and link to increased expression of inflammatory cytokines positions PAR2 as a potentially important regulator of vascular pathology under conditions of tissue inflammation, and injury; and thus, a pharmaceutical target for new therapeutics. Obesity is considered a chronic low-grade systemic inflammatory condition as inflammatory cytokines released from adipocytes are closely related to development of metabolic syndrome and related disorders. Our work over the past five-years has focused on the changes in vasomotor functions of PAR2 in metabolic syndrome, using an animal model known as the SHRSP.Z-Leprfa/IzmDmcr rats (SHRSP.ZF). In young SHRSP.ZF that had already developed impaired responses to nitric oxide, we reported that PAR2-induced endothelium-dependent vasodilation is preserved. However, this PAR2 vasodilation decreased with increasing age and further chronic exposure to the conditions of metabolism disorder. These findings raise the possibility that PAR2 regulates tissue perfusion and can protect organs from injury, which is an increasing clinical concern at later stages of metabolic syndrome. Here we present our studies on the time-dependent changes in vasoreactivity to PAR2 in metabolic syndrome and the underlying mechanisms. Furthermore, we discuss the implications of these age-related changes in PAR2 for the cardiovascular system in metabolic syndrome.

Age-related changes to vascular protease-activated receptor 2 in metabolic syndrome: a relationship between oxidative stress, receptor expression, and endothelium-dependent vasodilation.

Protease-activated receptor 2 (PAR2) is expressed in vascular endothelium. Nitric oxide (NO) - cyclic GMP-mediated vasodilation in response to 2-furoyl-LIGRLO-amide (2fLIGRLO), a PAR2-activating peptide, is impaired in aortas from aged SHRSP.Z-Leprfa/IzmDmcr (SHRSP.ZF) rats with metabolic syndrome. Here we investigated mechanisms linking PAR2's vascular effects to phenotypic characteristics of male SHRSP.ZF rats at 10, 20, and 30 weeks of age. We found vasodilation responses to either 2fLIGRLO or enzyme-mediated PAR2 activation by trypsin were sustained until 20 weeks and lessened at 30 weeks. PAR2 protein and mRNA levels were lower in aortas at 30 weeks than at 10 and 20 weeks. PAR2-mediated responses positively correlated with PAR2 protein and mRNA levels. Decreased cGMP accumulation in the presence of 2fLIGRLO paralleled the decreased relaxations elicited by nitroprusside and the cGMP analog 8-pCPT-cGMP, and the less soluble guanylyl cyclase protein at 30 weeks. 2fLIGRLO-induced relaxation was negatively correlated with serum thiobarbituric acid reactive substances, an index of oxidative stress, which increased with age. Forward stepwise data regression supported a model of age-related decreases in PAR2 function resulting from decreased PAR2 mRNA and increased oxidative stress. We conclude that decreased responsiveness of aortic smooth muscle to NO and downregulation of receptor expression impair PAR2 functions at later stages of metabolic syndrome in SHRSP.ZF rats.

Abstract 036: Mitoprotection Preserves the Cytoskeleton and Alleviates Myocardial Injury in Early Swine Metabolic Syndrome

Background: The mechanisms responsible for cardiac injury in the early stage of metabolic syndrome (MetS) remain unknown. Mitochondria are intimately associated with myofibrils, where the cytoskeleton functions as a linkage coordinator. We hypothesized that early MetS is characterized by cytoskeletal-mitochondrial disorganization, and that mitoprotection with mitochondria-targeted peptides (MTP) would preserve cytoskeletal-mitochondrial structure and attenuate myocardial injury in early swine MetS. Methods: Pigs were studied after 16wks of diet-induced MetS, MetS treated for the last 4wks with the MTP Elamipretide (0.1mg/kg SC q.d), and Lean controls (n=6 each). Cardiac function (multidetector CT) was assessed in-vivo, and mitochondrial structure (electron microscopy), the mitochondrial inner membrane phospholipid cardiolipin (mass spectrometry), cytoskeletal proteins, oxidative stress, and apoptosis ex-vivo. Results: MetS pigs developed hypertension and insulin resistance, yet cardiac function was preserved. MetS induced loss of desmin and tubulin that was paralleled by mitochondrial disorganization, decreased 18:2 cardiolipin, and increased oxidative stress and apoptosis. MTP slightly improved cardiolipin species profile, restored mitochondrial organization, and upregulated cytoskeletal proteins, attenuating apoptosis and oxidative stress. Conclusion: Early MetS leads to disorganization of the cardiomyocyte cytoskeletal- mitochondrial architecture and cardiac injury. MTP may provide a novel therapeutic potential for improving cardiac injury in early MetS, and potentially preventing future deterioration in cardiac function.

Submandibular glands in the metabolic syndrome

In addition to their stimulatory action on neuronal differentiation and survival, a variety of neurotrophic factors, such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and ciliary neurotrophic factor, exert metabotrophic effects, including improvement of glucose, lipid and energy homeostasis. It was recently reported that plasma levels of both NGF and BDNF are reduced in patients with advanced metabolic syndrome and with acute coronary syndromes, and that NGF tissue content is decreased in human atherosclerotic coronary arteries. Since NGF and BDNF are synthesized, stored, and released by submandibular salivary glands, we investigated the structure and function of these glands. Here we present our scintigraphic and echographic results of submandibular glands of patients with advanced stage of metabolic syndrome: (i) scintigraphic analysis using the radiotracer (99m)Tc-pertechnetate showed an inhibition of salivary gland excretory activity, and (ii) echographic evaluation revealed a parenchymal destruction and a prominent fibrosis of the glands. Both suggestive for the involvement of submandibular glands in decreased secretion of NGF and BDNF as implicated in the pathogenesis of metabolic syndrome. Biomedical Reviews 2007; 18: 65-67.