Effects of major adipokines and the −420 C > G resistin gene polymorphism on the long-term outcome of patients with acute ischemic stroke

Abstract

Aim: The association between adiponectin, leptin, and resistin and the long-term outcome of ischemic stroke are controversial. We aimed to evaluate this relationship.

Methods: We prospectively studied 83 patients consecutively hospitalized for acute ischemic stroke (38.6% males, age 79.7?±?6.3?years). Serum adiponectin, leptin, and resistin levels and the ?420C?>?G polymorphism of the resistin gene were determined at admission. Stroke severity at admission was evaluated with the National Institutes of Health Stroke Scale (NIHSS). One year after discharge, functional status, incidence of cardiovascular events and all-cause mortality were recorded. Functional status was evaluated with the modified Rankin scale (mRS).

Results: Patients with the G allele had lower mRS (p?<?.05) and patients with adverse outcome had higher serum resistin levels (p?<?.05). The only independent predictor of adverse outcome was mRS at discharge (risk ratio (RR) 2.78, 95% confidence interval (CI) 1.54–5.00; p?<?.001). Higher adiponectin levels were an independent predictor of cardiovascular morbidity (RR 1.07, 95% CI 1.01–1.14; p?<?.05). Patients who died had higher serum adiponectin levels than those who survived (p?<?.05). The only independent predictor of all-cause mortality was NIHSS at admission (RR 1.19, 95% CI 1.04–1.35; p?<?.01).

Conclusions: In patients with acute ischemic stroke, the G allele of the ?420C?>?G polymorphism of the resistin gene promoter is more frequent in those with a more favorable functional outcome at one year after discharge. Patients with higher serum resistin levels appear to have worse long-term functional outcome, while higher serum adiponectin levels are associated with higher incidence of cardiovascular events.     

The Associations of Body Image Perception with Serum Resistin Levels in Highly Trained Adolescent Estonian Rhythmic Gymnasts

Rhythmic gymnasts (RGs) are more likely to be dissatisfied with their body mass and shape compared to untrained controls (UCs). However, due to the lack of information, the aim of this study was to investigate the associations of body image perception (BIP) with body composition, daily energy consumption and different blood biochemical markers in adolescent RGs compared to UCs. Thirty-three highly trained RG girls and 20 UC girls aged 14–18 years participated in this cross-sectional study. Height, body mass, body composition, energy intake, resting energy expenditure, training volume and different blood biochemical markers were measured. The body attitude test (BAT) was used to evaluate the BIP of the participants. There were no differences in the total BAT scores between the groups. In RGs, the BAT score correlated positively with the serum resistin level (r = 0.35; p = 0.047). A stepwise multiple regression analysis showed that 40.8% of the variability in the BAT score was determined by resistin and BMI. The association of BIP with resistin values was observed only in RGs. In conclusion, our findings add to the increasing evidence that resistin may be a link between BIP and body composition, most likely through fat mass, in adolescent female RGs.     

有氧锻炼结合饮食控制减体重对肥胖者血抵抗素及心血管疾病危险因素的影响

目的:观察通过运动锻炼和饮食控制减体重,对肥胖者血抵抗素及心血管疾病危险因素的影响。方法:对44名肥胖者采取6周封闭管理形式集中减肥,严格控制饮食,进行运动训练。减重前后采用酶联免疫法测定空腹血抵抗素,同时测定血胰岛素、血脂、血糖等指标。在减体重过程中,受试者每2周测定一次体重、腰臀围比、体成分和血压等。结果:通过6周减体重,肥胖者血清抵抗素水平明显降低,多元线性回归分析显示,减重前后心率的差值成为影响减重前后抵抗素水平差值的重要因素。减重后,受试者腰围、臀围、腰臀围比、体脂含量及百分比、静息血压较减重前显著降低(P<0.001);血清总胆固醇、甘油三酯、低密度脂蛋白胆固醇、胰岛素及胰岛素抵抗指数等心血管疾病危险因素相关指标较减重前亦明显下降(P<0.001)。结论:采取运动锻炼结合饮食控制的方法减轻肥胖者体重,可有效降低其血抵抗素水平及心血管系统疾病的危险因素。     

慢性肾病患者血清抵抗素与其炎症反应的关系

目的研究慢性肾病(CKD)患者血清抵抗素与其炎症反应的关系。方法选取57例CKD患者,23例性别和年龄相匹配的健康者作为对照组。双抗体夹心酶联免疫吸附法(ELISA)测定血清抵抗素,同时测定C反应蛋白(CRP)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、血清肌酐(Cr)、血白细胞(WBC)等指标,并作相关性分析。结果CKD患者血浆抵抗素水平较对照组明显高(P<0.01),同时CRP、IL-6、TNF-α、WBC也较对照组明显升高;抵抗素与CRP、IL-6、TNF-α、WBC呈显著正相关。结论CKD患者抵抗素水平明显升高,可能与CKD患者的炎症反应有关。     

Circulating resistin concentrations in children depend on renal function.

BACKGROUND: Resistin is a newly discovered peptide hormone that inhibits adipogenesis. Furthermore, it may be involved in regulative processes taking place in insulin resistance and inflammation. In human beings as well as in rodents, the exact physiological role of resistin is unknown. The objective of this study was to examine whether resistin serum concentrations in childhood are regulated by renal function. METHODS: Fifteen patients with end stage renal disease treated by haemodialysis (HD) (6m, 9f; age (median (25-75% percentile)) 16.1 (14.2-16.9) years; body mass index (BMI) 17.8 (17.6-20.6) kg/m2; glomerular filtration rate (GFR)<10 ml/min/1.73 m2), 11 patients with chronic renal failure (CRF) (4m, 7f; age 11.3 (9.2-16.9) years; BMI 17.9 (15.4-22.1) kg/m2; GFR 21.2 (19.8-39.4) ml/min/1.73 m2) and 23 healthy children (13m, 10f; age 7.8 (4.7-14.5) years; BMI 16.5 (14.9-18.1) kg/m2; GFR 168.5 (154.0-197.2) ml/min/1.73 m2) were included. Resistin concentration in serum was measured by ELISA, leptin by RIA. RESULTS: Resistin concentrations were significantly elevated in HD (6.6 (5.7-8.7) ng/ml) and CRF (4.8 (4.1-6.2) ng/ml) compared to healthy controls [2.7 (2.0-3.6) ng/ml; P<0.0001 by multiple regression analysis]. Furthermore, resistin concentrations showed a tendency to be higher in children below the age of 5.5 years (youngest tertile) and above 12.5 years of age (oldest tertile), compared to children aged between 5.5 and 12.5 years (P=0.053 and P=0.043, respectively). Gender (P=0.686) and BMI (P =0.663) did not have a significant influence on resistin concentrations. Resistin and leptin serum concentrations correlated in HD patients only (r=0.62, P=0.013 by Spearman correlation). Haemodialysis did not eliminate resistin. CONCLUSIONS: With decreasing renal function, resistin concentration in serum increases in our small paediatric cohort. Age possibly influences circulating resistin concentration. The hypothesis that elevated serum resistin in children with chronic renal failure or end stage renal disease may add to malnutrition and reduced BMI needs further investigation and is not supported by our data.     

Graves''''眼病患者眼眶前脂肪细胞抵抗素诱导的表达

目的通过检测抵抗素在Graves’眼病患者眼眶前脂肪细胞培养分化过程中的表达,进一步研究前脂肪细胞的分化过程。方法在体外通过组织块培养法获取前脂肪细胞,前脂肪细胞在分化液的作用下转化为成熟脂肪细胞。利用RT-PCR法检测前脂肪细胞及成熟脂肪细胞中抵抗素mRNA的表达情况,对前脂肪细胞及成熟脂肪细胞进行免疫组化检测抵抗素蛋白的表达情况。结果前脂肪细胞中无抵抗素mRNA及蛋白的表达。成熟脂肪细胞中有抵抗素mRNA及蛋白的表达。免疫组化结果显示抵抗素蛋白位于成熟脂肪细胞胞浆中。结论Graves’眼病患者眼眶组织中存在功能活跃的前脂肪细胞,能够在体外分化为脂肪细胞。抵抗素是脂肪细胞分泌的一种脂肪细胞因子,仅存在于成熟脂肪细胞中,可作为脂肪细胞分化的标记物。     

抵抗素在肝脏胰岛素抵抗中的作用及其机制探讨

目的探讨抵抗素在肝脏胰岛素抵抗中的作用及其可能的机制。方法将载有抵抗素基因的重组腺病毒经尾静脉注射构建高抵抗素血症小鼠模型,同时设正常对照组及病毒对照组,取肝脏组织切片行PAS糖原染色半定量观察肝糖代谢变化;以Western blot检测肝腺苷酸活化蛋白激酶(AMPK)的磷酸化,以磷酸化AMPK/总AMPK的比值代表AMPK激活程度;以实时PCR检测肝组织糖异生关键酶葡萄糖6磷酸酶(G6Pase)和磷酸烯醇式丙酮酸羧激酶(PEP-CK)mRNA表达水平的变化。结果重组腺病毒注射d5获得血中抵抗素高表达构建了高抵抗素血症动物模型,糖原染色示高抵抗素血症小鼠肝糖原含量较正常对照及病毒对照组降低(P<0.05);高抵抗素血症组肝AMPK磷酸化水平较正常对照及病毒对照组下降,磷酸化AMPK/总AMPK比值分别为0.78±0.06vs0.93±0.13,0.89±0.05(P<0.05)。高抵抗素血症小鼠G6Pase和PEPCK的mRNA表达升高,G6Pase分别为2.136±0.857vs1.353±0.49,1.250±0.77;PEPCK分别为3.54±0.90vs2.75±0.78,2.63±0.67(P<0.05)。结论抵抗素可能通过抑制肝脏AMPK活性,增加肝糖异生关键酶的表达而影响机体肝糖代谢,降低肝糖储量,参与肝脏胰岛素抵抗的形成。     

腹部脂肪组织分泌抵抗素样分子α促进清道夫受体表达

目的探讨腹部脂肪组织抵抗素样分子α(RELMα)mRNA及蛋白表达情况,研究其对与动脉粥样硬化密切相关的巨噬细胞清道夫受体B(CD36)及平滑肌细胞清道夫受体A(SR-A)表达的影响。方法取C57BL/6J小鼠腹部脂肪组织,体外培养巨噬细胞及平滑肌细胞,用氧化型低密度脂蛋白(ox-LDL,ox-LDC组)以及终浓度为3×10~(-6)mmol/L(A组)、9×10~(-6)mmol/L(B组)、2.7×10~(-5)mmol/L(C组)的RELMα刺激培养细胞,对照组加等量生理盐水刺激细胞。采用RT-PCR及免疫组织化学检测脂肪细胞内RELMα表达,采用流式细胞仪检测CD36及SR-A表达。结果小鼠腹部脂肪组织可见RELMαmRNA蛋白阳性表达。与对照组比较,ox-LDL组CD36荧光强度明显增强,SR-A表达阳性率明显升高(P<0.01);与ox-LDL组比较,A、B、C组SR-A表达阳性率明显升高(P<0.05)。结论小鼠腹部脂肪组织能分泌RELMα,其不影响巨噬细胞CD36的表达,但能促进ox-LDL诱导的平滑肌细胞SR-A表达,提示腹部脂肪组织可能通过RELMα,影响SR-A表达从而促进动脉粥样硬化进展。