Tumor necrosis factor alpha system and plasma adiponectin concentration in women with gestational diabetes.

Plasma concentrations of adiponectin, tumor necrosis factor-alpha (TNF-alpha) and its soluble receptors sTNFR-1 and sTNFR-2 were measured in 80 patients with gestational diabetes (GDM) (mean age 29.0 +/- 4.9 years) and 30 pregnant women with normal glucose tolerance (NGT) (mean age 28.2 +/- 6.0 years). We found that GDM patients had significantly lower concentrations of adiponectin (11.28 +/- 5.91 vs. 16.31 +/- 6.04 microg/ml, p = 0.00009) and elevated levels of TNF-alpha (1.71 +/- 0.92 vs. 1.27 +/- 0.42 pg/ml, p = 0.0175) in comparison to NGT women. The differences remained statistically significant after adjusting for BMI. Plasma levels of sTNFR-1 and sTNFR-2 also tended to be higher in GDM patients. In the GDM group TNF-alpha concentrations correlated significantly with sTNFR-1 (r = 0.444, p = 0.00008), sTNFR-2 (r = 0.364, p = 0.0016) and with C-peptide concentrations (r = 0.318, p = 0.016), whereas in women with NGT TNF-alpha correlated only with TG levels (r = 0.50, p = 0.024). Multivariate linear regression analysis revealed that prepregnant BMI was the most predictive indicator of TNF-alpha concentrations in GDM women. TG concentrations as well as BMI before pregnancy and at the time of sampling in pregnant NGT women were significant predictors, explaining 62% of the variance in TNF-alpha concentration. There were also negative correlations between adiponectin concentrations and a pregestational BMI (r = - 0.298, p = 0.009), BMI at the time of sampling (r = - 0.239, p = 0.034) and TG concentrations (r = - 0.379, p = 0.039) in GDM patients, whereas women with NGT showed only a negative correlation between adiponectin and TG concentrations (r = - 0.488, p = 0.025). In a multivariate regression analysis, prepregnancy BMI and TG levels remained significant predictors, explaining 39% of the variation in plasma adiponectin concentration in GDM women. In conclusion, our results suggest that decreased adiponectin concentration in GDM may not simply reflect maternal adiposity and insulin resistant state, but may contribute to the impaired glucose metabolism during pregnancy, with potential implications for screening and prevention of the disease.     

Systemic blockade of TNF-α does not improve insulin resistance in humans

The purpose of this study was to determine whether long-term modulation of inflammatory activity by tumor necrosis factor (TNF)-α inhibitors has some influence on insulin resistance (IR). 16 active rheumatoid arthritis (RA) patients without CV risk factors treated with anti-TNF-α agents were included in this study. RA activity by disease activity score 28, IR by HOMA2-IR, body composition by impedance analysis, physical activity by accelerometry, abdominal fat distribution by magnetic resonance imaging, and serum level of key adipokines by ELISA were measured at baseline and during a 1-year follow-up period. Patient body mass index increased significantly (26.94 ± 3.88 vs. 28.06 ± 4.57 kg/m2, p=0.02) after 1 year of treatment. Body composition, in terms of fat and fat-free mass, remained unchanged except for a significant elevation in body cell mass (25.50 ± 4.60 vs. 26.60 ± 3.17 kg, p=0.02). Basal levels of IR in the RA patients included in this study were significantly higher than healthy controls (1.6 ± 0.8 vs. 1.11 ± 0.56, p=0.011) but did not change during the follow-up. Nor did basal concentrations of adiponectin, visfatin, leptin, ghrelin, resistin, and apelin in response to anti-TNF-α treatment; only retinol-binding protein 4, showed a significant increase (51.7 ± 32.7 vs. 64.9 ± 28.4 μg/ml, p=0.03) at the end of the study. IR, adiposity distribution, and serum levels of most adipokines are not significantly affected by long-term inhibition of TNF-α in RA patients. Our data suggest that although systemic blockade of TNF-α exerts an anticachectic effect in RA patients, it does not seem to play a major role in IR.     

Relationship of Adipokines and Proinflammatory Cytokines Among Asian Indians With Obesity and Youth Onset Type 2 Diabetes

Objective: It is well known that inflammation is associated with diabetes, but it is unclear whether obesity mediates this association in individuals with youth-onset type 2 diabetes mellitus (T2DM-Y).Methods: We recruited individuals with T2DM-Y (age at onset <25 years) and age-matched normal glucose tolerance (NGT) subjects. Participants were further classified using Asia-Pacific body mass index cut-points for obesity and categorized as: nonobese NGT (n = 100), Obese NGT (n = 50), nonobese T2DM-Y (n = 50), and obese T2DM-Y (n = 50). We compared adipokines (adiponectin and leptin) and proinflammatory cytokines (tumor necrosis factor alpha &lsqb;TNF-α] and monocyte chemotactic protein-1 &lsqb;MCP-1]) across groups.Results: Compared to nonobese NGT, the other 3 groups (obese NGT, nonobese T2DM-Y, and obese T2DM-Y) were found to have lower adiponectin (7.7 vs. 5.7, 4.2, 3.8 μg/mL, P<.01), and higher leptin (3.6 vs. 5.4, 5.7, 7.9 μg/mL, P<.001) and MCP 1 (186 vs. 272, 340, 473 pg/mL, P<.001) respectively. However, TNF-α levels were higher only among nonobese T2DM-Y (112 pg/mL) and obese T2DM-Y (141 pg/mL, P<.01 for each). After adjusting for age, sex, waist, hypertension, homeostatic model assessment of insulin resistance (HOMA-IR), serum cholesterol, triglycerides, and family history of diabetes, adiponectin was associated with 33% and 41% lower odds of being nonobese T2DM and obese T2DM, respectively. However, adjusted for same factors, leptin, TNF-α, and MCP-1 were associated with markedly higher odds (5- to 14-fold) of nonobese and obese T2DM.Conclusion: In young Asian Indians, leptin and proinflammatory cytokines are positively, and adiponectin negatively, associated with both nonobese and obese T2DM-Y compared to nonobese NGT individuals.Abbreviations: BMI = body mass index CI = confidence interval FPG = fasting plasma glucose HOMA-IR = homeostatic model assessment of insulin resistance IGT = impaired glucose tolerance MCP-1 = monocyte chemotactic protein-1 NGT = normal glucose tolerance OGTT = oral glucose tolerance test OR = odds ratio T2DM-Y = youth-onset type 2 diabetes TNF-α = tumor necrosis factor-α     

miR-27a-3p通过靶向Sema7A调控病毒性心肌炎心肌细胞损伤的机制研究

目的探讨微小RNA-27a-3p(miR-27a-3p)过表达对病毒性心肌炎(VMC)细胞损伤的影响及其可能的作用机制。方法原代培养大鼠心肌细胞,柯萨奇B3病毒(CVB3)感染心肌细胞建立VMC模型(CVB3组)。正常心肌细胞作为对照组,分别将miR-NC、miR-27a-3p mimics、si-NC,si-Sema7A分别转染至CVB3感染的心肌细胞,记为CVB3+miR-NC组、CVB3+miR-27a-3p组、CVB3+si-NC组、CVB3+si-Sema7A组。分别将miR-27a-3p mimics与pcDNA,miR-27a-3p mimics与pcDNA-Sema7A共转染至CVB3感染的心肌细胞,记为CVB3+miR-27a-3p+pcDNA组、CVB3+miR-27a-3p+pcDNA-Sema7A组。采用实时荧光定量聚合酶链反应(qRT-PCR)与Western blot法分别检测细胞中miR-27a-3p、信号蛋白7A(Sema7A)的表达水平;流式细胞术检测miR-27a-3p过表达或干扰Sema7A表达后心肌细胞的凋亡率;酶联免疫吸附(ELISA)法检测细胞中肿瘤坏死因子-α(TNF-α)、白细胞介素-1(IL-1)的含量;双荧光素酶报告基因验证miR-27a-3p与Sema7A的靶向关系;Western blot检测B淋巴细胞瘤-2相关蛋白(Bax)、活化的含半胱氨酸的天冬氨酸蛋白水解酶3(cleaved caspase-3)、B淋巴细胞瘤-2(Bcl-2)蛋白表达。两组间比较采用独立样本t检验。结果与对照组比较,CVB3组miR-27a-3p的表达水平(1.01±0.09比0.42±0.04)降低,Sema7A的mRNA和蛋白表达水平(1.02±0.09比2.15±0.21、0.43±0.04比0.94±0.09)升高,TNF-α、IL-1水平[(403.56±38.16)pg/mL比(1156.48±63.59)pg/mL>(29.45±3.54)pg/mL比(136.57±12.47)pg/mL]升高,细胞凋亡率[(5.36±0.54)%比(24.58±2.14)%]升高,Bax、cleaved caspase-3的表达水平升高,Bcl-2的表达水平降低(P均<0.05);与CVB3+miR-NC组比较,CVB3+miR-27a-3p组TNF-α,IL-1水平[(1187.69±71.42)pg/mL比(516.28±48.31)pg/mL、(147.25±14.05)pg/mL比(43.68±5.02)pg/mL]和细胞凋亡率[(26.38±2.55)%比(10.24±1.15)%]降低,Bax、cleaved caspase-3表达水平降低,Bcl-2表达水平升高(P均<0.05);双荧光素酶报告实验证实miR-27a-3p可靶向调控Sema7A的表达;Sema7A过表达可逆转miR-27a-3p过表达对CVB3诱导的VMC细胞损伤的作用。结论miR-27a-3p过表达可降低VMC细胞中炎症因子的表达及抑制细胞凋亡从而减轻心肌损伤,其作用机制可能与靶向调控Sema7A的表达有关。     

Adipokine serum concentrations, anthropometric measurements and socio-economic status in two ethnic groups with different prevalence levels for cardiovascular diseases and type 2 diabetes

Obesity is more common in African than Asian-Indian populations and yet type 2 diabetes and cardiovascular diseases are more common in the latter populations. The main purpose of the current study was therefore to determine whether ethnic differences in body fat distribution, adipokine levels, and socio-economic status may explain population differences in the prevalence of these metabolic disorders. Leptin, IL-6, CRP, visceral fat, education level, and socio-economic status were measured in 50 African and the same number of Indian women residing in Johannesburg, South Africa. Serum leptin levels were significantly higher in Indian than African subjects (41.3±2.0 and 34.2±2.9?ng/ml, respectively; p<0.05). TNF-α levels were significantly higher in the African group, (5.22±0.86 vs. 2.54±0.52?pg/ml; p<0.05), whilst visceral fat levels were significantly lower (56.1±5.5 vs. 77.9±6.5?cm(2); p<0.05). The CRP and IL-6 levels were not different between groups. Education levels (p<0.005) and socio-economic status (p<0.0001) were both lower in the African subjects, however, adjusting for these variables in ANCOVA did not attenuate differences in adipokine or visceral fat levels. We hypothesise that one of the reasons for the higher prevalence of obesity in the African than Indian population may be related to lower leptin levels, whilst ethnic differences in the prevalence of metabolic disorders cannot be explained by differences in adipokine levels, but maybe related to higher visceral adiposity in the Indian group.     

CRP is related to higher leptin levels in minority peripubertal females regardless of adiposity levels

Overweight is related to higher levels of C-reactive protein (CRP) and leptin, which have been independently associated with increased risk for diabetes, cardiovascular disease, and the metabolic syndrome. Elevated CRP may trigger leptin resistance by inhibiting the binding of leptin to its receptors. We cross-sectionally examined the relationship between CRP, leptin, BMI z-score, percent body fat (%BF) assessed by air plethysmography (BodPod), and insulin sensitivity (SI) and acute insulin response (AIRg) measured by intravenous glucose tolerance test in 51 Latina and African-American females (77% Latina), mean age 9.2 (±0.9) years, at either Tanner Pubertal Stage (TPS) 1 (n = 25) or TPS 2 (n = 26). Females at TPS 2 had higher BMI z-scores, %BF (23% ± 10.1 vs. 30% ± 10.0, P = 0.02), AIRg (976.7 ± 735.2 vs. 1555.3 ± 1,223 μIU/ml, P = 0.05), fasting insulin (11.0 ± 10.8 vs. 17.2 ± 13.6 μlU/ml, P = 0.00) and leptin levels (11.0 ± 7.1 vs. 19.6 ± 10.9 ng/ml, P < 0.001) than those at TPS 1. There were no ethnic differences in any of the measured variables. CRP was positively correlated with BMI z-score (P = 0.001), %BF (P = 0.006), fasting insulin and AIRg (P = 0.02), and fasting leptin (P = 0.00), and negatively correlated with SI (P = 0.05). A linear regression model showed that CRP independently explained 10% (P = 0.00) of the variance in leptin after adjusting %BF, TPS, ethnicity, habitual physical activity and SI. Hence, low-grade inflammation may contribute to prolonged leptin exposure and leptin resistance, even in healthy children.     

Serum Adiponectin Confers Little Protection Against Diabetes and Hypertension in Turkish Men

We determined serum adiponectin's role as a biomarker of metabolic syndrome (MetS), type 2 diabetes (DM) and hypertension among Turkish adults who have a high prevalence of MetS. Individuals with measured serum adiponectin concentrations, constituting a random sample of Turkish adults, were studied cross‐sectionally. MetS was identified by criteria of the Adult Treatment Panel‐III modified for male abdominal obesity. Median age of 547 men and 652 women was 54 years. MetS was identified in 46%. Linear regression analysis among nine variables revealed homeostatic model assessment (HOMA) index in both sexes and C‐reactive protein (CRP) only in men as inversely associated covariates of adiponectin, and sex hormone‐binding globulin (SHBG) as positive covariate in women. Age‐adjusted sex‐specifically dichotomized high vs. low adiponectin levels were significantly associated with DM (odds ratio (OR) 0.55, P = 0.01) and hypertension (OR 0.64, P = 0.012) in women, but not in men. Further adjustment for smoking status and presence of high/low BMI did not alter this sex‐based relationship. As regards association with MetS, low adiponectin and high BMI interacted significantly in each sex. Yet adiponectin was associated only in men additively to the simultaneously adjusted five MetS components. We conclude that adiponectin concentrations, clearly linked to metabolic disorders, may diverge among sexes regarding protection against cardiometabolic risk through anti‐inflammatory or antioxidative function, Turkish men alone revealing significant dysfunction independent of obesity. This dysfunction may underlie also the association of adiponectin levels with MetS in men to be independent of the MetS components.     

Inflammations mediators and circulating levels of matrix metalloproteinases: Biomarkers of diabetes in Tunisians metabolic syndrome patients

AimsThis study investigates the relationships between matrix metalloproteinases, inflammations mediators and type 2 diabetes mellitus in Tunisians metabolic syndrome (Mets) patients.MethodsThe study has included 239 MetS patients and 247 controls. Mets was defined according to the NCEP–ATPIII report. Mets patients were also divided into two categories: 29 MetS non-diabetics and 210 MetS diabetics. Dysglycemia markers, matrix metalloproteinase-9 (MMP-9), Tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2), tumor necrosis factor α (TNF-α), C-reactive protein (CRP) levels and White Blood Cells (WBC) counts were determined in patients and controls.ResultsIn our study, the level of inflammatory markers WBC, TNF-α and matrix metalloproteinases (MMP-8 and MMP-9) were significantly higher in diabetic patients with MetS, as compared with non-diabetic MetS patients. Inflammation mediators and MMP-9 were significantly associated with many clinical characteristics of MetS. The use of ROC “Receiver Operating Characteristic” analysis revealed the impact of TNF alpha on diabetes patients with MetS. In fact TNF alpha was found as a sensitive parameter in these patients with a sensitivity of 85%.ConclusionInflammation, matrix metalloproteinases and dysglycemia markers are not expressed in isolation but rather concurrently and are continuously interacting with each other, in MetS and diabetics patients. These markers fit with an early stage of cardiovascular disease (CVD); and measuring them could improve the risk evaluation, an early diagnosis, and the prognosis of CVD.     

Chemerin and adiponectin contribute reciprocally to metabolic syndrome

Obesity and metabolic syndrome (MetS) are considered chronic inflammatory states. Chemerin, a novel adipokine, may play an important role in linking MetS and inflammation. We investigated the association of chemerin with inflammatory markers and with characteristics of MetS in apparently healthy overweight and obese adults. We studied 92 adults; 59 men and 33 women whose average body mass index (BMI) was 28.15 ± 5.08 kg/m(2). Anthropometric parameters, insulin resistance indices, lipid profiles, and inflammatory markers including high sensitivity C-reactive protein (hsCRP), pentraxin 3 (PTX3), adiponectin, and chemerin were measured. Controlling for age, gender, and BMI, serum chemerin level was positively correlated with body fat and serum triglyceride, and negatively correlated with adiponectin and high density lipoprotein cholesterol (HDL- C), and was not correlated with altered hsCRP or PTX3 levels. Among the low, moderate and high chemerin groups, high chemerin individuals are more likely to have lower HDL-C. Conversely, individuals in the low adiponectin group are more likely to have lower HDL-C and show more MetS phenotypic traits than moderate and high adiponectin subjects. To determine the relationships of chemerin and adiponectin to MetS and its components, participants were stratified into four groups based on their chemerin and adiponectin levels (high chemerin/high adiponectin, high chemerin/low adiponectin, low chemerin/high adiponectin, or low chemerin/low adiponectin). Participants who were in the high chemerin/low adiponectin group more likely to have dyslipidemia and MetS (OR: 5.79, 95% CI:1.00-33.70) compared to the other three group. Our findings suggest that chemerin and adiponectin may reciprocally participate in the development of MetS.     

The newly identified anorexigenic adipokine nesfatin-1 in hemodialysis patients: Are there associations with food intake, body composition and inflammation?

Nesfatin-1 is a recently identified anorexigenic peptide that has been implicated in appetite regulation, weight loss and/or malnutrition. Anorexia and malnutrition are common features of chronic kidney disease (CKD) that predispose patients to worse outcomes. However, the reasons for the occurrence of anorexia in CKD patients are not fully elucidated. The aim of this study was to investigate the association between nesfatin-1 and protein intake and body composition in patients undergoing hemodialysis (HD). Twenty five HD patients from a private Clinic in Rio de Janeiro, Brazil were studied and compared with 15 healthy subjects that were matched for body mass index (BMI), % body fat mass (by anthropometrics) and age. Appetite was measured using a specific questionnaire, and food intake was evaluated based on 3-day food records. Nesfatin-1 levels were measured by ELISA and leptin, TNF-α and IL-6 levels were determined by a multiplex assay kit. Serum nesfatin-1 levels did not differ between HD patients (0.16±0.07ng/mL) and healthy subjects (0.17±0.10ng/mL). Nesfatin-1 levels showed significant negative correlations with protein intake (r=-0.42; p=0.03), but did not associate with inflammatory markers or appetite scores. Combining patients and controls, we observed positive correlations with BMI (r=0.33; p=0.03), % body fat (r=0.35; p=0.03), leptin (r=0.45; p=0.006) and the triceps skinfold thickness (r=0.36; p=0.02). In multivariate analysis % body fat was the main determinant of nesfatin-1 variance. In conclusion, nesfatin-1 levels did not differ between HD patients and healthy subjects and negatively correlated with protein intake. This pathway is likely not dysregulated in uremia.     

Influence of variants in the NPY gene on obesity and metabolic syndrome features in Spanish children

Variants in the neuropeptide Y (NPY) gene have been associated with obesity and its traits. The objective of the present study was to evaluate the association of single nucleotide polymorphisms (SNPs) in the NPY gene with obesity, metabolic syndrome features, and inflammatory and cardiovascular disease (CVD) risk biomarkers in Spanish children. We recruited 292 obese children and 242 normal-body mass index (BMI) children. Height, weight, BMI, waist circumference, clinical and metabolic markers, adipokines, and inflammatory (PCR, IL-6, IL-8 and TNF-α) and CVD risk biomarkers (MPO, MMP-9, sE-selectin, sVCAM, sICAM, and PAI-1) were analyzed. Seven SNPs in the NPY gene were genotyped. The results of our study indicate that anthropometric measurements, clinical and metabolic markers, adipokines (leptin and resistin), and inflammatory and CVD risk biomarkers were generally elevated in the obese group. The exceptions to this finding included cholesterol, HDL-c, and adiponectin, which were lower in the obese group, and glucose, LDL-c, and MMP-9, which did not differ between the groups. Both rs16147 and rs16131 were associated with the risk of obesity, and the latter was also associated with insulin resistance, triacylglycerols, leptin, and HDL-c. Thus, we confirm the association of rs16147 with obesity, and we demonstrate for the first time the association of rs16131 with obesity and its possible impact on the early onset of metabolic syndrome features, mainly triacylglycerols, in children.     

Wild blueberry (Vaccinium angustifolium) consumption improves inflammatory status in the obese Zucker rat model of the metabolic syndrome

The metabolic syndrome (MetS) is a major public health problem in the United States. Chronic inflammation is a critical component of the MetS, leading to dramatically increased risk of type II diabetes and cardiovascular disease.This study investigates the ability of a wild-blueberry-enriched diet to improve the proinflammatory status associated with MetS in the obese Zucker rat (OZR). Circulating levels of key inflammatory markers and their expression in the liver and abdominal adipose tissue were examined in OZR and its genetic control, the lean Zucker rat (LZR), after feeding a control or an 8% wild blueberry diet (WB) for 8 weeks from age 8 to 16 weeks.In the OZR, WB consumption resulted in decreased plasma concentrations of tumor necrosis factor (TNF)-α (?25.6%, P<.05), interleukin (IL)-6 (?14.9%, P<.05) and C-reactive protein (CRP) (?13.1%, P<.05) and increased adiponectin concentration (+21.8%, P<.05). Furthermore, expression of IL-6, TNF-α and nuclear factor (NF)-kB was down-regulated in both the liver (?65%, ?59% and ?25%, respectively) and the abdominal adipose tissue (?64%, ?52% and ?65%), while CRP expression was down-regulated only in the liver (?25%). In the abdominal adipose tissue, similar trends were also observed in LZR following WB treatment, with decreased liver expression of NF-kB, CRP, IL-6 and TNF-α (?24%, ?16%, ?21% and ?50%) and increased adiponectin expression (+25%).Results of this study suggest that wild blueberry consumption exerts an overall anti-inflammatory effect in the OZR, a model of the metabolic syndrome.     

Serum leptin and adiponectin concentrations in patients infected with human immunodeficiency virus type 1 (HIV-1) on antiretroviral therapy

The lipodystrophy syndrome with dyslipidaemia and insulin resistance is side-effect of combined antiretroviral therapy (CART). Aim of the study: to describe the influence of CART on leptin and adiponectin concentration in connection with lipids levels in HIV-infected patients on antiretroviral therapy. BMI, serum leptin, adiponectin, triglycerides, total cholesterol, HDL- and LDL-cholesterol concentrations were measured in 56 HIV(+) patients before and on CART; average of treatment duration 38.4 +/-13.2 months. Significant increase of BMI (p=0.0268) of (22.6 +/- 3.3 before and 23.5 +/- 3.4 kg/m2 on therapy, respectively) and all analyzed lipids were found. Mean adiponectin concentration in treated patients was significantly (7.256 +/- 3.551 microg/ml) lower than mean value before treatment (8.395 +/- 3.568 microg/ml; p=0.0011). Mean values of leptin concentrations did not differ significantly (before therapy 3.721 +/- 0.347 log10; on therapy 3.1737 +/- 0.353 log10). Significant positive correlation between BMI and leptin concentrations was found before, as well as during CART (r=0.5333; p<0.0001), but negative correlation between adiponectin and leptin concentrations (r=-0.2677; p=0.042). Leptin and adiponectin concentrations did not revealed significant correlation with lipids levels before therapy. The decrease of adiponectin concentration on CART correlated negatively with total (r=-0.2912; p=0.0310) and LDL-cholesterol (r=-0.310; p=0.0225). CART lasting longer than 2 years resulted in the decrease of adiponectin concentration, with lack of influence on leptin concentration in analyzed group. The increase of total cholesterol and LDL-cholesterol in correlation with the decrease of adiponectin concentration confirms that CART induces metabolic disturbances related to higher risk of atherosclerosis and its sequel.     

Serum alanine aminotransferase is associated with serum adiponectin, C-reactive protein and apolipoprotein B in young healthy men.

Several studies have reported an association between markers of liver injury, including elevated concentrations of alanine aminotransferase (ALT) aspartate aminotransferase (AST), and prospective risk of type 2 diabetes. We therefore examined the relationship between ALT and AST on the one hand, and serum adiponectin and highly sensitive CRP on the other, both of which have been reported to be associated with prospective risk of type 2 diabetes; we also tested for variable components of metabolic syndrome in 198 male college students aged 18-20 years. ALT showed a positive relationship with percentage body fat (r = 0.19, p = 0.02), serum leptin (r = 0.21, p = 0.01), LDL cholesterol (r = 0.29, p = 0.0003), triglyceride (r = 0.28, p = 0.0004) and apolipoprotein B (r = 0.35, p < 0.0001) even after adjustment for body mass index (BMI). Although there was a significant relationship with serum insulin, adiponectin (inversely), homeostasis model assessment of insulin resistance, systolic and diastolic blood pressure, HDL cholesterol (inversely) and LDL particle diameter in simple regression analysis, significance disappeared after adjustment for BMI. In contrast, CRP (r = 0.16, p = 0.04) was associated with ALT after adjustment for BMI, although simple regression analysis revealed no association between the two. Relationships were smaller for AST, and significance disappeared after adjustment for BMI. Multiple regression analysis excluding lipid variables revealed significant and independent associations of ALT with adiponectin and percentage body fat. In a model including lipid variables, apolipoprotein B emerged as an independent predictor of ALT in addition to adiponectin and percentage body fat. These variables explained 29 % of ALT variability. In conclusion, serum ALT levels were associated with leptin and CRP as well as many components of the insulin resistance syndrome in young healthy men. Adiponectin, apolipoprotein B and percentage body fat emerged as significant and independent predictors of ALT. Since adiponectin and chronic subclinical inflammation have been reported to predict the development of type 2 diabetes and since abnormalities in apolipoprotein B metabolism occur in the early course of insulin resistance, these findings may be compatible with the association between liver markers and risk of diabetes.     

Lifestyle variables, non-traditional cardiovascular risk factors, and the metabolic syndrome in an Aboriginal Canadian population

Objective : To examine lifestyle factors associated with metabolic syndrome (MetS) and to explore the relationships between MetS and non‐traditional cardiovascular disease risk factors [adiponectin, leptin, C‐reactive protein (CRP), interleukin‐6 (IL‐6), and serum amyloid A (SAA)] in an isolated Aboriginal Canadian community. Research Methods and Procedures : Data were obtained from 360 non‐diabetic adults participating in a population‐based study of Aboriginal Canadians. Fasting samples were drawn for glucose, insulin, lipids, adiponectin, leptin, CRP, IL‐6, and SAA. Percentage body fat was measured using bioelectrical impedance analysis. Past year physical activity and fitness level were assessed. MetS was diagnosed according to the criteria of the National Cholesterol Education Program, the World Health Organization, and the International Diabetes Federation. Results : The results showed that older age, higher percentage body fat, and lower fitness levels were associated with increased odds of MetS regardless of MetS definition and subject gender. Past year physical activity was independently related with the World Health Organization‐MetS in male subjects. Subjects with MetS had significantly higher leptin, CRP, IL‐6, and SAA levels and lower adiponectin levels; however, only adiponectin remained significantly low after adjustment for age and percentage body fat. Discussion : The study showed that higher percentage body fat and lower physical activity and fitness were associated with a higher prevalence of MetS in this Aboriginal community and that hypoadiponectinemia was independently associated with MetS.     

间充质干细胞外泌体对海马星形胶质细胞活化的抑制作用研究

目的探讨间充质干细胞外泌体 (MSC-Exo)对海马星形胶质细胞活化的抑制作用。方法实验通过超速离心法提取脐带MSC-Exo,并使用PKH-26染料标记;MSC-Exo预处理原代海马星形胶质细胞后使用脂多糖 (LPS)诱导细胞活化,并分为对照组、LPS组和LPS+MSC-Exo组,进而行免疫细胞化学检测胶质纤维酸性蛋白(GFAP)、C3的表达、免疫印迹实验检测C3、GFAP的蛋白表达,以及酶联免疫吸附测定炎症因子白介素(IL)-1β、IL-6和肿瘤坏死因子(TNF)-α的水平,分别检测各组细胞的抗原表达、表型变化和炎症反应。统计采用单因素方差分析 (ANOVA)及最小显著性差异法 (LSD)检验。结果实验提取的MSC-Exo符合外泌体的一般生物学特性,且能迁移到星形胶质细胞胞体和突起。海马星形胶质细胞经LPS诱导后,其标记性抗原GFAP (1.47±0.15比0.95±0.17,P < 0.01)、A1型标记物C3 (1.32±0.23比0.87±0.16,P < 0.05)、IL-1β[(282.90±5.13)pg/ mL比 (252.53±5.51)pg/mL,P < 0.05]、TNF-α[(128.26±1.89) pg/ mL比(111.86±2.84)pg/mL,P < 0.01]和IL-6[(180.95±3.16) pg/ mL比(163.95±3.71)pg/mL,P < 0.05]的表达较正常组明显升高;MSC-Exo预处理后,GFAP(0.97±0.16 比1.47±0.15,P < 0.01)、C3 (0.83±0.12比1.32±0.23,P < 0.01)、IL-1β[(262.20±2.64)pg/mL比(282.90±5.13) pg/mL,P < 0.05]和TNF-α[(120.79±0.42)pg/mL比(128.26±1.89)pg/mL,P < 0.05]的表达较LPS组明显降低,IL-6[(187.25±0.64)pg/mL比(180.95±3.16)pg/mL,P > 0.05]的表达未见明显变化。结论 MSC-Exo对海马星形胶质细胞活化具有明显的抑制作用。     

Changes in placental adipocytokine gene expression associated with gestational diabetes mellitus

Leptin and adiponectin, two adipocytokines, may work together in regulating energy homeostasis and insulin action. Leptin gene expression has been investigated in term placental tissue complicated by gestational diabetes mellitus (GDM), but never in conjunction with all isoforms of the leptin receptor (LEPR A-D), or with adiponectin receptors (ADIPOR1 and 2). In this study we examined the association between changes in expression of these genes in placental tissue and GDM risk. We assessed placental gene expression of leptin, LEPR A-D and ADIPOR1 and 2 by real time PCR using mRNA from maternal and fetal biopsies. Tissues were collected from uncomplicated pregnancies (n=28) and those complicated by GDM (n=19). Gene expression was normalized to three endogenous housekeeping genes. Relative gene expression values were reported as fold change between groups. Adiponectin gene expression was out of the sensitive range of our assay. There were increases in leptin mRNA expression in GDM cases compared with controls for maternal-side (p=0.06), and fetal-side (p=0.09) placental biopsies. No significant changes were seen in GDM cases compared with controls in LEPR A-D or ADIPOR1 and 2. mRNA derived from maternal-side tissue was positively correlated with tissue from the fetal side for all genes studied (all p<0.01). Finally, we noted that absence or presence of GDM was a major factor in leptin mRNA expression after adjusting for maternal age, mode of delivery, parity and smoking status. In conclusion, increases in leptin mRNA expression in term placenta, but not that of its receptors, are associated with the diagnosis of GDM. Changes seen in the ligand, but not the receptor, of the leptin pathway in GDM-complicated pregnancies may also apply to the adiponectin pathway, as the ADIPOR1 and 2 mRNAs do not change with GDM diagnosis.     

Snoring, inflammatory markers, adipokines and metabolic syndrome in apparently healthy Chinese

Objective

Chronic low-grade inflammation and adipokines dysregulation are linked to mechanisms underscoring the pathogenesis of obesity-related metabolic disorders. Little is known about roles of these cytokines on the association between snoring and metabolic syndrome (MetS). We aimed to investigate whether a cluster of cytokines are related to snoring frequency and its association with MetS in apparently healthy Chinese.

Methods

Current analyses used a population-based sample including 1059 Shanghai residents aged 35–54 years. Self-reported snoring frequency was classified as never, occasionally and regularly. Fasting plasma glucose, lipid profile, insulin, C-reactive protein, interleukin-6, interleukin-18, lipopolysaccharide binding protein, high-molecular-weight adiponectin and leptin were measured. MetS was defined by the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian-Americans.

Results

Overweight/obese subjects had significantly higher prevalence of regular snorers than their normal-weight counterparts (34.8% vs. 11.5%, P<0.001). Regular snoring was associated with unfavorable profile of inflammatory markers and adipokines. However, those associations were abolished after adjustment for body mass index (BMI) or waist circumference. The MetS risk (multivariate-adjusted odds ratio 5.41, 95% confidence interval 3.72–7.88) was substantially higher in regular snorers compared with non-snorers. Controlling for BMI remarkably attenuated the association (2.03, 1.26–3.26), while adjusting for inflammatory markers and adipokines showed little effects.

Conclusion

Frequent snoring was associated with an elevated MetS risk independent of lifestyle factors, adiposity, inflammatory markers and adipokines in apparently healthy Chinese. Whether snoring pattern is an economic and no-invasive indicator for screening high-risk persons needs to be addressed prospectively.     

The influence of metabolic syndrome and chronic kidney disease on hemorheology assessed by the microchannel method

Metabolic syndrome (MetS) and chronic kidney disease (CKD) are individual risk factors for cardiovascular disease (CVD). Abnormal hemorheology may be associated with CVD in both disorders. The present study investigated the impact of MetS and CKD on hemorheology. We studied 138 adults (women/men=63/75, mean age=52.2 years), who included 87 participants with MetS and 33 with CKD. The hemorheology was assessed by the index of 'whole blood passage time (WBPT)' using the Micro Channel array Flow ANalyzer (MC-FAN). The WBPT values of MetS participants were significantly higher than those of non-MetS participants (52.5±13.1 vs. 46.3±7.7 sec, p=0.03). The WBPT values of CKD participants were significantly higher than those of non- CKD (55.5±12.7 vs. 48.6±11.0 sec, p=0.003). The significant influence of MetS and CKD on WBPT was qualified by their effect modification to WBPT (p=0.04). There was a significantly greater influence of the combination of MetS and CKD on WBPT (59.9±13.4 sec) in comparison to the influence of non-MetS and CKD (46.6±3.5) or non-CKD and MetS (50.0±12.2). The influence of the combination of MetS and CKD was clearer in men, relative to women. Abnormal hemorheology as assessed using MC-FAN may be enhanced by the combination of MetS and CKD.     

胰岛素抵抗大鼠的肝脏中丝氨酸/酪氨酸磷酸化异常与血清TNF-α相关

目的探讨胰岛素抵抗大鼠胰岛素受体底物-1丝氨酸/酪氨酸磷酸化与肿瘤坏死因子α（TNF-α）的关系。方法雄性Wistar大鼠30只（体质量80-120 g）,随机分为普通饮食组（NC）及高脂饮食组（FH）2组,每组15只。喂养10周,以高胰岛素-正常血糖钳夹技术评估胰岛素抵抗大鼠模型。应用ELISA法检测大鼠血清TNF-α含量,Western Blot法检测肝脏组织中胰岛素受体底物-1丝氨酸磷酸化（IRS-1Ser636）及酪氨酸磷酸化（IRS-1Tyr465）表达。结果FH组葡萄糖输注率（GIR）60-120水平明显低于NC组[（1.56±0.43 vs.5.15±0.66）mg/（kg.min）,P〈0.01];FH组大鼠TNF-αI、RS-1Ser636均高于NC组[（15.43±2.16 vs.5.4±2.16）pg/mL,P〈0.01;（109.45±13.75 vs.94.23±15.05）,P〈0.05],IRS-1Tyr456水平低于NC组[（111.08±14.28 vs.125.77±14.51）,P〈0.05]。TNF-α水平与IRS-1Ser636呈正相关（r=0.503,P=0.024）,与IRS-1Tyr465呈负相关（r=-0.521,P=0.019）。结论胰岛素抵抗大鼠TNF-α水平与IRS-1Tyr465负相关,与IRS-1Ser636正相关,提示TNF-α引起胰岛素抵抗机制可能与IRS-1磷酸化异常有关。