Relationship between Lung Function and Metabolic Syndrome

Although the link between impaired lung function and cardiovascular events and type 2 diabetes mellitus has been recognized, the association between impaired lung function and metabolic syndrome has not been comprehensively assessed in the United States (U.S.) population. The aim of our study was to explore the association between impaired lung function and metabolic syndrome in a nationally representative sample of men and women. This cross-sectional population-based study included 8602 participants aged 20–65 years in the Third National Health and Nutrition Examination Survey (NHANES III). We examined the relationship between the different features of metabolic syndrome and lung function, including forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1). After adjusting for potential confounders such as age, body mass index, inflammatory factors, medical condition, and smoking status, participants with more components of metabolic syndrome had lower predicted values of FVC and FEV1 (p for trend <0.001 for both). Impaired pulmonary function was also associated with individual components of metabolic syndrome, such as abdominal obesity, high blood pressure, high triglycerides, and low high density lipoprotein (HDL) cholesterol (p<0.05 for all parameters). These results from a nationally representative sample of US adults suggest that a greater number of features of metabolic syndrome is strongly associated with poorer FVC and FEV1. In clinical practice, more comprehensive management strategies to address subjects with metabolic syndrome and impaired lung function need to be developed and investigated.     

代谢调衡饮治疗代谢综合征的临床疗效观察

目的:考察代谢调衡饮治疗代谢综合征的临床疗效。方法:将60例代谢综合征患者随机分为试验组和对照组,对照组口服卡托普利和二甲双胍,试验组在此基础上加服代谢调衡饮,疗程3个月,观察两组治疗前后体重指数、血压、血糖、血脂等指标变化。结果:试验组有效率明显高于对照组(P<0.05)。与对照组相比,试验组患者治疗后体重指数、血压、血糖、血脂指标改善更明显(P<0.05 or P<0.01)。结论:代谢调衡饮对代谢综合征患者具有减重降压,降糖调脂功效,是干预代谢调衡饮的有效方剂。     

代谢调衡饮对代谢综合征胰岛素抵抗的影响

目的:初步探讨代谢调衡饮对代谢综合征胰岛素抵抗的影响。方法:将60例代谢综合征患者随机分为试验组和对照组,对照组口服卡托普利和二甲双胍,试验组在此基础上加服代谢调衡饮,疗程3个月。结果:两组各个时间点的血糖和HbA1c与治疗前相比,均有显著下降(P<0.01);显著降低空腹、糖负荷后0.5h、1h、2h、3h胰岛素水平(P<0.01),与对照组相比,试验组降低糖负荷后0.5h胰岛素水平更具优势(P<0.01);明显降低HOMA-IR,升高ISI。结论:代谢调衡饮对于改善代谢综合征患者的胰岛素抵抗具有一定疗效。     

Mecp2影响Rett综合征中代谢功能的研究进展

Rett综合征(RTT)是一种由X连锁的甲基CpG结合蛋白2(Mecp2)基因突变引起的神经系统疾病,突变致病的具体调节机制尚不清楚.对RTT的研究大多聚焦在中枢神经系统,越来越多的研究显示Mecp2在各种代谢系统中也发挥着重要作用.回顾了RTT发展历史、Mecp2的发现及主要作用,并综述了MeCP2在脂质代谢、线粒体...     

Effect of Fenofibrate on Adiponectin and Inflammatory Biomarkers in Metabolic Syndrome Patients

Adiponectin is an adipose‐secreted hormone with anti‐inflammatory properties mediated by inhibition of nuclear factor‐κB (NF‐κB) signaling. This study investigates whether fenofibrate alters adiponectin levels in patients with hypertriglyceridemia and the metabolic syndrome, and examines the association of adiponectin with circulating inflammatory markers and whole blood cytokine production. The effects of fenofibrate (160 mg/day) on adiponectin and other inflammatory markers were investigated in a 12‐week randomized, placebo‐controlled trial in 55 patients with hypertriglyceridemia (plasma triglycerides ≥1.7 mmol/l and <6.8 mmol/l), central obesity and other characteristics of the metabolic syndrome who were not receiving lipid‐altering therapies. In the fenofibrate group, adiponectin levels increased from 4.10 to 4.50 µg/ml (+7.7%); in the placebo group, adiponectin levels increased by 1.8%; (P = 0.0005). In multivariate models including age, gender, and waist circumference, there were inverse correlations between changes in adiponectin and vascular cell adhesion molecule‐1 (VCAM‐1) (r = −0.54, P < 0.0001) and intercellular adhesion molecule‐1 (ICAM‐1) (r = −0.57, P < 0.0001), and C‐reactive protein (CRP) (r = −0.40, P = 0.0041); lipopolysaccharide (LPS)‐stimulated production of tumor necrosis factor‐α (TNF‐α) (r = −0.30, P = 0.035), interleukin (IL)‐1β (r = −0.44, P = 0.0016), monocyte chemotactic protein‐1 (MCP‐1) (r = −0.46, P = 0.001), and macrophage inflammatory protein‐1α (MIP‐1α) (r = −0.45, P = 0.0012). Fenofibrate (160 mg/day) raised adiponectin levels in patients with hypertriglyceridemia and the metabolic syndrome. Changes in adiponectin were significantly and inversely associated with changes in multiple inflammatory markers. These data suggest that adiponectin may contribute to the anti‐inflammatory effects of fenofibrate.     

Thyroid Function and Metabolic Syndrome: A Cross-Sectional Study in Obese and Overweight Patients

Objective: Metabolic syndrome (MetS) is associated with increased risks of developing cardiovascular disease and type 2 diabetes. Thyroid dysfunction is also a known cardiovascular risk factor. In obese patients, serum thyroid-stimulating hormone (TSH) levels tend to be higher than in lean controls. The objective of this study was to assess potential associations between serum TSH levels and MetS as well as individual components of MetS.Methods: This was a cross-sectional observational study of obese and overweight patients seen for initial evaluation at the Boston Medical Center weight-management clinic between February 1, 2013 and February 1, 2014. Demographic, anthropometric, and laboratory data including serum TSH, insulin, glucose, hemoglobin A_1c, and lipid levels were obtained from electronic medical records. Associations between serum TSH levels and presence of MetS and its components were assessed.Results: A total of 3,447 patients, 75.6% female and 38% African American, without known thyroid dysfunction, were included. Mean ± SD age was 46.74 ± 15.11 years, and mean ± SD body mass index was 36.06 ± 9.89 kg/m². Among 1,005 patients without missing data, the prevalence of MetS was 71.84%. In patients with MetS, the median serum TSH was 1.41 μIU/mL, compared with 1.36 μIU/mL in patients without MetS (P = .45). In multivariate models, there was no significant association between serum TSH levels and the presence of MetS, adjusting for age, sex, race, education, socioeconomic status, and smoking. There were also no significant associations between serum TSH and individual components of the MetS.Conclusion: Serum TSH level does not appear to be a potentially modifiable risk factor for MetS in obese and overweight individuals.Abbreviations: BMI = body mass index FT₄ = free thyroxine HDL-C = high-density-lipoprotein cholesterol HbA_1c = hemoglobin A_1c MetS = metabolic syndrome SE = standard error TSH = thyroid-stimulating hormone     

Expression and Function of mARC: Roles in Lipogenesis and Metabolic Activation of Ximelagatran

Recently two novel enzymes were identified in the outer mitochondrial membrane, mARC1 and mARC2. These molybdenum containing enzymes can reduce a variety of N-hydroxylated compounds, such as N-hydroxy-guanidines and sulfohydroxamic acids, as well as convert nitrite into nitric oxide (NO). However, their endogenous functions remain unknown. Here we demonstrate a specific developmental pattern of expression of these enzymes. mARC1, but not mARC2, was found to be expressed in fetal human liver, whereas both, in particular mARC2, are abundant in adult liver and also expressed in omental and subcutaneous fat. Caloric diet restriction of obese patients caused a decreased expression of mARC2 in liver, similar to that seen in the livers of starved rats. Knock down of mARC2 expression by siRNA in murine adipocytes had statistically significant effect on the level of diglycerides and on the fatty acid composition of some triglycerides, concomitantly a clear trend toward the reduced formation of most of triglyceride and phospholipid species was observed. The involvement of mARC2 in the metabolism of the hepatotoxic drug ximelagatran was evaluated in hepatocytes and adipocytes. Ximelagatran was shown to cause oxidative stress and knock down of mARC2 in adipocytes prevented ximelagatran induced inhibition of mitochondrial respiration. In conclusion, our data indicate that mARC1 and mARC2 have different developmental expression profiles, and that mARC2 is involved in lipogenesis, is regulated by nutritional status and responsible for activation of ximelagatran into a mitotoxic metabolite(s).     

The Relationship of Ectopic Lipid Accumulation to Cardiac and Vascular Function in Obesity and Metabolic Syndrome

Storage of lipid in ectopic depots outside of abdominal visceral and subcutaneous stores, including within the pericardium and liver, has been associated with obesity, insulin resistance, and cardiovascular risk. We sought to determine whether anatomically distinct ectopic depots were physiologically correlated and site‐specific effects upon cardiovascular function could be identified. Obese subjects (n = 28) with metabolic syndrome but without known atherosclerotic disease and healthy controls (n = 18) underwent magnetic resonance imaging (MRI) and proton MR spectroscopy (MRS) to quantify pericardial and periaortic lipid volumes, cardiac function, aortic compliance, and intrahepatic lipid content. Fasting plasma lipoproteins, glucose, insulin, and free‐fatty acids were measured. Pericardial and intrahepatic (P < 0.01) and periaortic (P < 0.05) lipid volumes were increased in obese subjects vs. controls and were strongly and positively correlated (P ≤ 0.01) but independent of BMI (P = NS) among obese subjects. Intrahepatic lipid was associated with insulin resistance (P < 0.01) and triglycerides (P < 0.05), whereas pericardial and periaortic lipid were not (P = NS). Periaortic and pericardial lipid positively correlated to free‐fatty acids (P ≤ 0.01) and negatively correlated to high‐density lipoprotein (HDL) cholesterol (P < 0.05). Pericardial lipid negatively correlated to cardiac output (P = 0.03) and stroke volume (P = 0.01) but not to left ventricular ejection fraction (P = 0.46). None of the ectopic depots correlated to aortic compliance. In conclusion, ectopic storage of lipid in anatomically distinct depots appeared tightly correlated but independent of body size. Site‐specific functional abnormalities were observed for pericardial but not periaortic lipid. These findings underscore the utility of MRI to assess individual differences in ectopic lipid that are not predictable from BMI.     

p53 Regulation of Metabolic Pathways

During the course of tumorigenesis, cells acquire a number of alterations that contribute to the acquisition of the malignant phenotype, allowing them to survive and flourish in increasingly hostile environments. Cancer cells can be characterized by perturbations in the control of cell proliferation and growth, resistance to death, and alterations in their interactions with the microenvironment. Underpinning many of these changes are shifts in metabolism that allow cancer cells to use alternative pathways for energy production and building the macromolecules necessary for growth, as well as regulating the generation of signaling molecules such as reactive oxygen species (ROS). In the past few years, it became clear that p53, the most studied, if not most important, tumor suppressor protein, can also directly control metabolic traits of cells.Given the importance of metabolic reprogramming in tumor development, it is no surprise that many oncogenes and tumor suppressor genes have been shown to help control these pathways (DeBerardinis et al. 2008a; Tennant et al. 2009). In most cases, these effects are fairly clear—proteins that can promote cancer development drive the metabolic transformation associated with malignancies and tumor suppressor proteins oppose these effects. p53 plays a central and key role in preventing cancer development (Vousden and Prives 2009), but the regulation of metabolism by p53 is proving to be far from straightforward. Although the explanation for this complexity is not clear, there are several obvious and ultimately testable models. What is evident, however, is that the regulation of metabolic pathways is an important facet of p53 function that may provide us with some novel and effective new therapeutic targets, for cancer and maybe also other diseases.     

Altered Clock Gene Expression in Obese Visceral Adipose Tissue Is Associated with Metabolic Syndrome

Clock gene expression was associated with different components of metabolic syndrome (MS) in human adipose tissue. However, no study has been done to compare the expression of clock genes in visceral adipose tissue (VAT) from lean and obese subjects and its clinical implications. Therefore, we studied in lean and obese women the endogenous 24 h expression of clock genes in isolated adipocytes and its association with MS components. VAT was obtained from lean (BMI 21–25 kg/m²; n = 21) and morbidly obese women (BMI >40 kg/m²; n = 28). The 24 h pattern of clock genes was analyzed every 6 hours using RT-PCR. Correlation of clinical data was studied by Spearman analysis. The 24 h pattern of clock genes showed that obesity alters the expression of CLOCK, BMAL1, PER1, CRY2 and REV-ERB ALPHA in adipocytes with changes found in CRY2 and REV-ERB ALPHA throughout the 24 h period. The same results were confirmed in VAT and stromal cells (SC) showing an upregulation of CRY2 and REV-ERB ALPHA from obese women. A positive correlation was observed for REV-ERB ALPHA gene expression with BMI and waist circumference in the obese population. Expression of ROR ALPHA was correlated with HDL levels and CLOCK with LDL. Obese subjects with MS exhibited positive correlation in the PER2 gene with LDL cholesterol, whereas REV-ERB ALPHA was correlated with waist circumference. We identified CRY2 and REV-ERB ALPHA as the clock genes upregulated in obesity during the 24 h period and that REV-ERB ALPHA is an important gene associated with MS.     

The Novel Fusion Proteins,GnRH-p53 and GnRHIII-p53, Expression and Their Anti-Tumor Effect

p53, one of the most well studied tumor suppressor factor, is responsible to a variety of damage owing to the induction of apoptosis and cell cycle arrest in the tumor cells. More than 50% of human tumors contain mutation or deletion of p53. Gonadotrophin-releasing hormone (GnRH), as the ligand of Gonadotrophin-releasing hormone receptor (GnRH-R), was used to deliver p53 into tumor cells. The p53 fusion proteins GnRH-p53 and GnRH iii-p53 were expressed and their targeted anti-tumor effects were determined. GnRH mediates its fusion proteins transformation into cancer cells. The intracellular delivery of p53 fusion proteins exerted the inhibition of the growth of H1299 cells in vitro and the reduction of tumor volume in vivo. Their anti-tumor effect was functioned by the apoptosis and cell cycle arrest induced by p53. Hence, the fusion protein could be a novel protein drug for anti-tumor therapy.     

脂肪因子与代谢综合征关系的研究进展

代谢综合症是一系列代谢和心血管功能失调的临床特征,包括中心性肥胖、高血压、血脂异常、高血糖及胰岛素抵抗等,其发病机制及如何预防及控制代谢综合症正日益成为目前的学术热点。目前已经公认,脂肪不仅是能量存储器官,也是一个重要的内分泌器官。脂肪组织分泌的生物活性分子被称为脂肪因子。近年来的研究表明,脂肪因子广泛参与肥胖、2型糖尿病、高血压病及心血管疾病等一系列代谢相关性疾病的病理生理过程。脂肪因子能通过介导一系列的信号转导通路,并广泛参与机体复杂的代谢平衡网络的调节。脂肪因子的失衡能导致机体发生对胰岛素敏感性改变等一系列的生物学反应,从而在肥胖和代谢综合症的病理过程中发挥重要的作用。本文综述了脂肪因子与代谢综合征的关系的研究进展。     

Hair Tissue Mineral Analysis and Metabolic Syndrome

Deficiency of minerals causes functional abnormality of enzymes, frequently resulting in metabolic disturbance. We investigated possible relationship between minerals and metabolic syndrome by analysis of hair tissue minerals. We selected 848 subjects older than 20 years of age at Ajou University Hospital from May 2004 to February 2007. We excluded the subjects who had cancers, steroid and thyroid medication, and incomplete record from the study. Finally, 343 subjects were eligible. We performed cross-sectional analysis for the relationship between minerals and metabolic syndrome. The contents of calcium, magnesium, and copper in the metabolic syndrome group were significantly lower than those of the normal group, whereas the amounts of sodium, potassium, and mercury in the metabolic syndrome group were significantly higher than those of the normal group. By dividing the subjects into quartile with the level of calcium, magnesium, and mercury concentrations, we carried out logistic regression analysis to study the subjects and found that the subjects in the third quartile of calcium and magnesium concentrations had significantly lower odds ratio (OR) of the metabolic syndrome compared with that of the lowest quartile group [OR = 0.30, confidence interval (CI) = 0.10–0.89; OR = 0.189, CI = 0.063–0.566] and that the subjects in the highest mercury quartile had significantly higher OR of the metabolic syndrome compared with that of the lowest mercury quartile group (OR = 7.35, CI = 1.73–31.1). As part of the metabolic syndrome, the optimal calcium and magnesium concentrations in hair tissue may reflect decreased risk of metabolic syndrome, whereas high mercury concentration in hair tissue may indicate increased risk of metabolic syndrome.     

组织因子与代谢性综合征的研究进展

组织因子(Tissue factor,TF)又称凝血因子III,是凝血因子VII/VIIa细胞表面的受体和辅因子,为外源性凝血的启动因子,在生理性止血、病理性血栓形成等发挥重要作用。近年临床研究发现,TF在代谢性综合征(Metabolic syndrome,MS)患者体内活性水平明显升高,并且与胰岛素抵抗、2型糖尿病、中心性肥胖、高血压、血脂紊乱等MS多种临床症候群密切相关。本文就近年国外相关进展作一综述,以期为针对TF这一作用靶点的MS病情演变预测及药物开发提供参考依据。     

DEK真核表达载体的构建及其对p53启动子活性的影响

目的：构建DEK的pcDNA3-Flag表达载体,研究其对抑癌基因p53启动子活性的影响。方法：以乳腺文库为模板,PCR扩增DEK编码序列,克隆到pcDNA3-Flag载体,构建成pcDNA3-Flag-DEK,转染293T细胞,Western印迹鉴定peDNA3-Flag载体介导的DEK的表达,萤光素酶报告基因活性实验研究DEK对p53启动子活性的影响。结果：双酶切实验证实得到pcDNA3-Flag-DEK阳性克隆;Western印迹实验发现DEK在293T细胞内表达;转录活性实验表明在ZR75-1乳腺癌细胞中,DEK呈剂量依赖性抑制p53启动子的活性。结论：构建了DEK的真核表达载体,并发现此表达载体能在ZR75-1乳腺癌细胞中抑制p53启动子活性。     

Effect of Adiponectin on Kidney Crystal Formation in Metabolic Syndrome Model Mice via Inhibition of Inflammation and Apoptosis

The aims of the present study were to elucidate a possible mechanism of kidney crystal formation by using a metabolic syndrome (MetS) mouse model and to assess the effectiveness of adiponectin treatment for the prevention of kidney crystals. Further, we performed genome-wide expression analyses for investigating novel genetic environmental changes. Wild-type (+/+) mice showed no kidney crystal formation, whereas ob/ob mice showed crystal depositions in their renal tubules. However, this deposition was remarkably reduced by adiponectin. Expression analysis of genes associated with MetS-related kidney crystal formation identified 259 genes that were >2.0-fold up-regulated and 243 genes that were <0.5-fold down-regulated. Gene Ontology (GO) analyses revealed that the up-regulated genes belonged to the categories of immunoreaction, inflammation, and adhesion molecules and that the down-regulated genes belonged to the categories of oxidative stress and lipid metabolism. Expression analysis of adiponectin-induced genes related to crystal prevention revealed that the numbers of up- and down-regulated genes were 154 and 190, respectively. GO analyses indicated that the up-regulated genes belonged to the categories of cellular and mitochondrial repair, whereas the down-regulated genes belonged to the categories of immune and inflammatory reactions and apoptosis. The results of this study provide compelling evidence that the mechanism of kidney crystal formation in the MetS environment involves the progression of an inflammation and immunoresponse, including oxidative stress and adhesion reactions in renal tissues. This is the first report to prove the preventive effect of adiponectin treatment for kidney crystal formation by renoprotective activities and inhibition of inflammation and apoptosis.