基于动脉管壁的脂联素球状域保护机理

脂肪细胞分泌产物脂联素(adiponectin,APN)的发现是脂肪内分泌学研究领域的重大进展。它主要通过与相应受体结合,发挥相应的生物学效应,且其心血管保护作用目前已成为研究热点。动脉管壁上也存在其受体,在此基础上,将APN活性区域的脂联素球状域(globular domain of adiponectin,gAd)设计为新靶点,研究其对动脉管壁的保护作用及其相关机理,将为动脉粥样硬化疾病的防治提供新方案。     

尿毒症血透患者血清脂联素和血脂的相关性研究

目的:探讨血液透析患者血清脂联素水平与其血脂之间的相关性。方法:维持性血液透析病人72例(实验组)及健康体检合格者20人(对照组),用酶联免疫吸附法测定实验组血液透析前、后及对照组血清脂联素(APN)浓度,血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL)及低密度脂蛋白(LDL)的含量。结果:实验组血清APN水平显著高于对照组[(28.526±18.780) mg/L vs(9.278±3.712)mg/L,p<0.01],并且在血液透析后血清APN水平反而增高;多元回归分析表明实验组血清APN与甘油三酯(TG)等呈负相关,与高密度脂蛋白(HDL)呈正相关。结论:血液透析患者血清APN水平明显高于正常人,血清APN水平与甘油三酯等呈负相关,与高密度脂蛋白呈正相关。     

老年男性血清脂联素与骨密度的关系

目的：研究老年男性血清脂联素与骨密度和骨转化指标之间的关系。方法：对165例男性老年患者采用双能量X线吸收测量仪测定骨密度、肌肉及脂肪量,同时测定患者血清脂联素、骨碱性磷酸酶、甲状旁腺素、25羟维生素D和I型胶原β羧基端肽水平。结果：165例年龄超过58岁男性患者（平均年龄69.4±6.4岁,体重指数24.9±3.1 kg/m2）,脂联素与股骨颈骨密度相关系数为-0.31（P〈0.05）、与全髋骨密度相关系数为-0.23（P〈0.05）,年龄、BMI和脂肪量校正后,脂联素仅与股骨颈骨密度有显著相关（r=-0.25,P〈0.05）;脂联素与骨碱性磷酸酶正相关（r=0.28,P〈0.01）,混杂因素校正后,相关仍具有显著性（r=0.19,P〈0.05）;脂联素与I型胶原β羧基端肽呈正相关（r=0.15,P〈0.05）。结论：老年男性血清脂联素与股骨颈骨密度和骨ALP密切相关。     

脂联素在应激状态下对小鼠卵泡发育的影响

目的:利用饥饿刺激探讨应激状态下脂联素缺失对小鼠卵泡发育的影响。方法:C57BL/6、脂联素半缺失(APN+/-)、脂联素全缺失(APN-/-)三种基因型小鼠以正常进食量的一半给予饥饿刺激,建立应激模型,30天后处死小鼠取卵巢,计数三种基因型小鼠各级卵泡数目。结果:1经过30天饥饿后饥饿组小鼠体重下降与初始体重比较有统计学意义(P0.001),应激模型建立。2应激状态下三种基因型小鼠卵巢重量未见统计学差异(P0.05)。3正常饮食组三种基因型小鼠各级卵泡比例未有统计学差异(P0.05)。饥饿后C57BL/6小鼠原始卵泡比例为(47±2.966)%,APN+/-原始卵泡比例为(36.5±1.555)%(P0.05),APN-/-原始卵泡比例为(36.8±2.200)%(P0.05);C57BL/6闭锁卵泡比例为(12±1.225)%,APN+/-闭锁卵泡比例为(19.75±1.887)%(P0.01),APN-/-闭锁卵泡比例为(20±0.8367)%(P0.001),与野生型闭锁卵泡比例比较差异有统计学意义。结论:饥饿刺激下脂联素缺失小鼠原始卵泡消耗增加,而闭锁卵泡的发生增加,处于生长状态的卵泡减少,提示在应激状态下脂联素水平的下降可导致卵泡成熟的过程受阻。     

糖尿病患者的MPV、脂联素水平与冠心病的关系

目的:研究糖尿病(Diabetes Mellitus,DM)患者血小板体积(mean platelet volume,MPV)和血清脂联素水平与冠心病的关系。方法:选取研究对象共150例分为三组,其中101名糖尿病患者根据冠脉造影结果分为:A组(糖尿病合并冠心病组)共72人,B组(糖尿病非冠心病组)共29人。对照组为排除糖尿病且冠脉造影正常者共49人。入院次日检测空腹血常规(含MPV),应用ELISA法检测各组血清脂联素水平。应用Gensini评分系统评估冠状动脉的狭窄程度。结果:A组和B组的脂联素水平均低于对照组(P0.05),且A组脂联素水平低于B组(P0.05)。A组与B组MPV水平均高于对照组(P0.05),且A组MPV水平高于B组(P0.05)。相关性分析显示Gensini评分与脂联素水平负相关(r=-0.59,P0.001),Gensini评分与MPV正相关(r=0.56,P0.001)。结论:脂联素、MPV与糖尿病合并冠心病的发生显著相关,而脂联素可能通过拮抗糖尿病患者血小板活性程度,延缓心血管并发症的发生。     

糖基化终末产物对3T3-L1脂肪细胞脂联素分泌的影响

目的糖基化终末产物(Advanced glycation end products,AGE)对3T3-L1脂肪细胞脂联素(adiponectin,APN)分泌的影响。方法3T3-L1小鼠前脂肪细胞体外培养并诱导分化为成熟的脂肪细胞,以PBS和BSA作为阴性对照,用含不同浓度梯度(50μg/ml、100μg/ml、150μg/ml)AGE的培养液对成熟的脂肪细胞体外培养48h,收集细胞和上清液,用RT-PCR方法检测脂联素mRNA的表达,ELISA方法检测培养液中脂联素蛋白的分泌情况。结果AGE干预组脂联素的表达在mRNA和蛋白水平较对照组均明显下降(P<0.05),并且随着AGE浓度的升高脂联素的合成和分泌逐渐减少,其中100μg/ml、150μg/ml AGE干预组脂联素的减少较对照组有显著差异(P<0.001)。结论糖基化终末产物能够通过抑制3T3-L1细胞脂联素mRNA的合成,近而抑制脂联素的分泌,且这种抑制呈浓度依赖性。     

中国汉族人群PNPLA3 I148M 多态性影响脂联素水平及非酒精性脂肪性 肝病遗传易感性的相关性研究*

目的:探讨在中国人群中PNPLA3 I148M基因型、脂联素与非酒精性脂肪性肝病的遗传易感性的相关性,及PNPLA3基因型与空腹血清脂联素水平的关系。方法:对96例NAFLD患者和76名正常对照,采用多聚酶链反应(PCR)及直接测序法检测PNPLA3基因型。计量资料结果均用均数±标准差(X±S)表示,经方差齐性检验后,行t检验;性别、基因型及等位基因频率的比较行X2检验。结果:中国汉族人群中,存在PNPLA3基因I148M多态性,I148M G等位基因频率分布在NAFLD(64.89%)与正常对照组(34.87%)、NASH组(71.70%)与SS组(56.09%)中比较差异均有统计学意义(P<0.05)。病例对照分析显示:148GG基因携带者与148CC基因携带者相比较,前者发生NAFLD的比值比(OR)为3.45(95%CI:2.21~5.41,P<0.05),发生NASH的OR为1.98(95%CI=1.08~3.64,P<0.05)。PNPLA3基因rs738409多态性与血清ALT水平有关(P<0.05),对NASH组分层分析,148GG基因型BMI、ALT、FINS均高于148CC基因型(P<0.05),血清HDL水平低于148CC基因型和148GC基因型(P<0.05),这些结果提示等位基因G与肝脏炎症和肝脏脂肪增加有相关性.Ordinal Logistic回归分析显示PNPLA3 I148M多态性与低浓度血清脂联素水平相关(<6μg/ml)(OR=2.78,95%CI=1.765~4.384,P<0.05)。结论:中国汉族人群中,PNPLA3基因I148M多态性与NAFLD的遗传易感性及脂联素的分泌调节相关,是决定NAFLD个体遗传易感性的重要因素。     

血清脂联素与载脂蛋白A5 及2 型糖尿病的关系

目的:检测血清脂联素(APN)水平,分析血清APN浓度与血脂、血清载脂蛋白A5(apoA5)及2型糖尿病的关系。方法:收集2型糖尿病(T2DM)210例,健康体检者112例,采用ELISA法检测血浆脂联素水平,双抗体夹心ELISA法检测血清载脂蛋白A5(apoA5)水平,7600-020E全自动生化分析仪检测总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)等,放射免疫分析仪检测血胰岛素水平。结果:T2DM患者血清APN浓度明显低于健康对照组,LDL-C、TG及TC均高于对照组(P<0.05)。T2DM患者血清apoA5浓度(200.3±51.2)ng/ml,显著低于健康对照组(229.8±56.5)ng/ml,P<0.05。Pearson相关分析显示经年龄、性别校正后APN水平与LDL-C、TG呈负相关,与HDL-C呈正相关;T2DM组APN与apoA5呈正相关(P<0.05)。结论:T2DM患者血清APN水平显著降低,本研究证实低水平血清APN和apoA5不仅与血脂代谢密切相关,还可作为T2DM患者早期监测的指标,对其预后评价具有积极的意义。     

褪黑素受体激动剂改善高糖高脂喂养大鼠脂联素敏感性

目的观察褪黑素受体激动剂（NEU-P11）对高糖高脂饲养大鼠脂联素敏感性的影响。方法将30只SD大鼠随机分为对照组（CD组）,高糖高脂组（HFSD组）,褪黑素组（Mel组）,褪黑素受体激动剂组（NEU-P11组）。CD组饲以正常饲料;其余3组饲以高糖高脂饲料。6个月后,给药治疗2个月。治疗期间,Mel组每天注射Mel（4mg／kg）;NEU—P11组每天注射NEU-P11（10mg／kg）;CD组以及HFSD组注射生理盐水（5ml／kg）。测定糖脂代谢指标并做口服葡萄糖耐量实验（oral glucose tolerant test,OG-TY）,Western印迹检测脂联素（adiponectin,APN）在脂肪组织及脂联素受体（AdipoR）在骨骼肌组织中的表达变化。结果高糖高脂饮食可诱导SD大鼠产生胰岛素抵抗,脂联素表达增加。Neu-P11治疗后,胰岛素敏感性增强．脂联素表达降低至正常水平。结论Neu-P11能提高胰岛素敏感性,改善脂联素抵抗。     

双歧杆菌三联活菌胶囊联合多烯磷脂酰胆碱对NAFLD患者肝功能、脂糖代谢及炎症因子的影响

目的:探讨双歧杆菌三联活菌胶囊联合多烯磷脂酰胆碱对非酒精性脂肪性肝病(NAFLD)患者肝功能、脂糖代谢及炎症因子的影响。方法:选取我院收治的123例NAFLD患者,根据乱数表法将患者分为对照组(n=61)和研究组(n=62),其中对照组给予多烯磷脂酰胆碱治疗,研究组在对照组的基础上联合双歧杆菌三联活菌胶囊治疗,比较两组临床疗效、肝功能、脂糖代谢及炎症因子,记录两组治疗期间不良反应情况。结果:研究组治疗12周后的临床总有效率为82.26%(51/62),高于对照组的63.93%(39/61)(P0.05)。两组治疗12周后谷氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBIL)、白介素-6(IL-6)、C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)均下降,且研究组低于对照组(P0.05)。研究组治疗12周后空腹血糖(FPG)、总胆固醇(TC)、低密度脂蛋白(LDL-C)、甘油三酯(TG)均降低,且研究组低于对照组(P0.05)。高密度脂蛋白(HDL-C)升高,且研究组高于对照组(P0.05)。两组不良反应发生率对比未见显著性差异(P0.05)。结论:双歧杆菌三联活菌胶囊联合多烯磷脂酰胆碱治疗NAFLD,用药安全性较好,疗效确切,可有效改善患者肝功能、炎症因子水平及脂糖代谢。     

High-molecular weight adiponectin isoforms increase after biliopancreatic diversion in obese subjects

Objective: Our objective was to test the effect of biliopancreatic diversion (BDP) in adiponectin multimerization. Adiponectin, the major protein secreted by adipose tissue, circulates in plasma in different isoforms. The most clinically relevant oligomers are high‐molecular weight (HMW) multimers and low‐molecular weight (LMW) trimers. Contrasting data on the effect of weight loss on adiponectin isoforms have been reported. Research Methods and Procedures: We measured total plasma adiponectin and HMW and LMW adiponectin oligomers (by Western blot analysis) before and 1 month after BPD, in 18 severely obese subjects. Results: One month after BPD, body weight decreased ～11%. Total adiponectin showed significant increase after BPD. In addition, we found a significant increase in HMW (percentage) adiponectin oligomers. We found a significant inverse correlation between HMW (percentage) and BMI before and after BPD. Homeostasis model of assessment‐insulin resistance decreased significantly after the BPD, without any significant correlation with total serum adiponectin and adiponectin oligomers. Discussion: A moderate weight loss after BPD increases total and HMW adiponectin oligomers. The significant correlation between BMI and HMW (percentage) adiponectin oligomers but not between BMI and total adiponectin might indicate a role of body fat mass in regulation of adiponectin multimerization. These data suggest that HMW oligomers represent a very sensitive parameter to short‐term BMI changes after BPD.     

Molecular expression of adiponectin in human saliva

Adiponectin (APN) is an adipocyte-specific secretory protein that is highly and specifically expressed in adipose tissue. Serum APN consists of trimers, hexamers, and larger high-molecular-weight (HMW) multimers, and these HMW multimers appear to be of more bioactive forms. Evidence indicates that APN is produced by salivary gland epithelial cells, might be implicated in the regulation of local immune responses.     

Independent associations of total and high molecular weight adiponectin with cardiometabolic risk and surrogate markers of enhanced early atherogenesis in black and white patients with rheumatoid arthritis: a cross-sectional study

IntroductionWhether adiponectin levels associate with atherogenesis in RA is uncertain. We examined the independent relationships of total and high molecular weight (HMW) adiponectin concentrations with cardiometabolic risk and surrogate markers of enhanced early atherogenesis in black and white patients with RA.MethodsWe determined total and HMW adiponectin concentrations and those of endothelial activation molecules including soluble E-selectin, vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1), in 210 (119 black and 91 white) RA patients. Associations were determined in potential confounder and mediator adjusted mixed regression models.ResultsTotal and HMW adiponectin concentrations related similarly to metabolic risk factors and endothelial activation. In all patients, total and HMW adiponectin concentrations associated paradoxically with high systolic, diastolic and mean blood pressure (partial R = 0.155 to 0.241, P ≤0.03). Ethnic origin did not impact on these relationships (interaction P ≥0.09). Total and HMW adiponectin concentrations associated with those of glucose in white and black patients respectively (partial R = -0.304, P = 0.006 and -0.246, P = 0.01). In black but not white participants, total and HMW adiponectin concentrations also related favorably to lipid profiles (partial R = 0.292 to 0.360, P ≤0.003 for HDL cholesterol concentrations, -0.269 to -0.299, P ≤0.006 for triglyceride concentrations and -0.302 to -0.390, P ≤0.002 for total-HDL cholesterol ratio) and the number of metabolic risk factors (partial R = -0.210 to -0.238, P ≤0.03). In white but not black patients, total and HMW adiponectin concentrations associated paradoxically with overall endothelial activation as estimated by a standard z-score of endothelial activation molecule concentrations (partial R = 0.262, P = 0.01 and 0.252, P = 0.02); in the respective models, the extent of effect of total and HMW adiponectin concentrations on endothelial activation was larger in white compared to black participants (standardized β (SE) = 0.260 (0.107) versus -0.106 (0.107), P = 0.01 and 0.260 (0.120) versus -0.100 (0.111), P = 0.02). The HMW-total adiponectin ratio related inconsistently to metabolic risk factors and not to endothelial activation.ConclusionIn this study, total and HMW adiponectin concentrations associated with increased blood pressure parameters, and in white patients additionally with endothelial activation. The potential mechanism(s) underlying these paradoxical relationships between adiponectin concentrations and cardiovascular risk in RA merit further investigation.     

Effects of pronounced weight loss on adiponectin oligomer composition and metabolic parameters

Objective: Adiponectin is an adipocytokine secreted into circulation in three isoforms. The aim of the study was to investigate changes of adiponectin isoforms during profound weight loss and its relation to anthropomorphometric and metabolic parameters. Research Methods and Procedures: Thirteen severely obese female subjects were examined before and 1 year after surgical treatment. Total adiponectin was determined by radioimmunosorbent assay, and oligomer composition was detected by nondenaturing Western blot. Results: BMI decreased substantially (p < 0.001), which was associated with an increase of total adiponectin from 12.9 ± 5.9 to 14.3 ± 6.1 μg/mL (p = 0.055). Medium molecular weight (MMW) adiponectin increased from 7.5 ± 3.6 to 9.1 ± 4.1 μg/mL (p = 0.009), whereas high (HMW) and low molecular weight adiponectin remained unchanged. Δ values of total adiponectin correlated significantly with Δ values of anthropometric parameters. Similar correlations were found for Δ values of MMW (Δ weight: r² = 0.4132, p = 0.0178; Δ BMI: r² = 0.3319, p = 0.0393; Δ fat mass: r² = 0.5202, p = 0.0054). Discussion: Thus, profound weight loss was associated with an increase in total adiponectin, which was mainly and consistently caused by increases in MMW adiponectin (p = 0.009). These changes result in a shift from low molecular weight to MMW and HMW adiponectin isoforms, which may be related to improvements in both anthropometric and metabolic parameters.     

Preatherosclerosis and adiponectin subfractions in obese adolescents

We evaluated total adiponectin, high-molecular weight (HMW), medium-molecular weight (MMW), low-molecular weight (LMW) adiponectin subfractions, clinical parameters, routine lab parameters, lipids, metabolic, inflammatory biomarkers, and intima-media thickness (IMT) of common carotid arteries in 70 obese juveniles and adolescents with preatherosclerosis and 55 normal weight controls of similar age and gender distribution. Compared with the controls, the obese probands had a significantly increased IMT (P < 0.001) and elevated ultra-sensitive C-reactive protein (P < 0.001) indicating early vascular burden. Total and HMW adiponectin were significantly decreased in the obese cohort. The ratio between HMW and total adiponectin was significantly decreased in obese probands whereas the LMW/total adiponectin ratio was increased. Overall, total-, HMW, and MMW adiponectin were significantly negatively correlated with carotid IMT. The HMW/total adiponectin ratio correlated significantly negatively, and the LMW/total adiponectin ratio significantly positively with the IMT. Furthermore, HMW adiponectin was significantly positively correlated with high-density lipoprotein (HDL)-cholesterol and serum apolipoprotein A1, and negatively with BMI, triglycerides, homeostatic model assessment (HOMA)-index, leptin, liver transaminases, and uric acid. This remained stable after controlling for gender. Multiple regression analysis of body measures and all other lab parameters showed the strongest correlation between HMW adiponectin and carotid IMT (beta = -0.35, P < 0.001). Taken together, our study provides the first evidence that preatherosclerosis in obese juveniles and adolescents is associated with altered subfractions of adiponectin, whereas after multiple testing the HMW subfraction showed a better correlation to IMT compared with total adiponectin.     

Enhanced adiponectin multimer ratio and skeletal muscle adiponectin receptor expression following exercise training and diet in older insulin-resistant adults

Circulating adiponectin is reduced in disorders associated with insulin resistance. This study was conducted to determine whether an exercise/diet intervention would alter adiponectin multimer distribution and adiponectin receptor expression in skeletal muscle. Impaired glucose-tolerant older (>60 yr) obese (BMI 30-40 kg/m(2)) men (n = 7) and women (n = 14) were randomly assigned to 12 wk of supervised aerobic exercise combined with either a hypocaloric (ExHypo, approximately 500 kcal reduction, n = 11) or eucaloric diet (ExEu, n = 10). Insulin sensitivity was determined by the euglycemic (5.0 mM) hyperinsulinemic (40 mU x m(-2) x min(-1)) clamp. Adiponectin multimers [high (HMW), middle (MMW), and low molecular weight (LMW)] were measured by nondenaturing Western blot analysis. Relative quantification of adiponectin receptor expression through RT-PCR was determined from skeletal muscle biopsy samples. Greater weight loss occurred in ExHypo compared with ExEu subjects (8.0 +/- 0.6 vs. 3.2 +/- 0.6%, P < 0.0001). Insulin sensitivity improved postintervention in both groups (ExHypo: 2.5 +/- 0.3 vs. 4.4 +/- 0.5 mg x kg FFM(-1) x min(-1), and ExEu: 2.9 +/- 0.4 vs. 4.1 +/- 0.4 mg x kg FFM(-1) x min(-1), P < 0.0001). Comparison of multimer isoforms revealed a decreased percentage in MMW relative to HMW and LMW (P < 0.03). The adiponectin SA ratio (HMW/total) was increased following both interventions (P < 0.05) and correlated with the percent change in insulin sensitivity (P < 0.03). Postintervention adiponectin receptor mRNA expression was also significantly increased (AdipoR1 P < 0.03, AdipoR2 P < 0.02). These data suggest that part of the improvement in insulin sensitivity following exercise and diet may be due to changes in the adiponectin oligomeric distribution and enhanced membrane receptor expression.     

Effects of TNF-alpha neutralization on adipocytokines and skeletal muscle adiposity in the metabolic syndrome

In a prior study, we have shown that tumor necrosis factor (TNF)-alpha neutralization improves inflammatory markers and total adiponectin in patients with the metabolic syndrome, without improving insulin sensitivity. In this study, we sought to extend our understanding of the effects of TNF-alpha neutralization in this human model of obesity by investigating the responses of high-molecular-weight (HMW) adiponectin, resistin, leptin, and muscle adiposity to etanercept in patients with the metabolic syndrome. Fifty-six men and women with the metabolic syndrome enrolled in a double-blind randomized placebo-controlled trial. Circulating concentrations of total and HMW adiponectin, resistin, and leptin were determined at baseline and after 4 wk of treatment with etanercept. Muscle adiposity was measured by computed tomography (CT). Although etanercept increased total adiponectin concentration, the HMW form, which is thought to mediate insulin sensitivity, was unchanged. Thus the ratio of HMW to total adiponectin decreased following etanercept treatment compared with placebo (-0.03 +/- 0.03 vs. 0.06 +/- 0.03, P = 0.02). Resistin tended to decrease in the etanercept-treated group compared with placebo (-0.6 +/- 0.7 vs. 1.2 +/- 0.7 ng/ml, P = 0.06), whereas leptin was not altered. Etanercept decreased muscle attenuation on CT [-0.61 +/- 0.64 Hounsfield units (HU) vs. 1.54 +/- 0.77 HU in placebo, P = 0.04], suggesting an increase in muscle adiposity. Together, these results demonstrate that neutralization of TNF-alpha in obese humans results in differential effects on critical adipokines and body composition indexes. These findings may help to explain the lack of effect on insulin sensitivity and extend our knowledge of the biological effects of TNF-alpha neutralization in obesity.     

Association of Adiponectin Gene Polymorphism with Nonalcoholic Fatty Liver Disease in Taiwanese Patients with Type 2 Diabetes

Objective

Patients with type 2 diabetes and nonalcoholic fatty liver disease (NAFLD) have a higher prevalence of cardiovascular diseases. In this study we investigated the frequency of single nucleotide polymorphisms (SNPs) of several candidate genes associated with NAFLD in Taiwanese patients with type 2 diabetes mellitus (DM) and NAFLD and in those with DM but without fatty liver disease.

Methods

We enrolled 350 patients with type 2 DM and NAFLD and 209 patients with DM but without NAFLD. Body mass index (BMI), % body fat (% BF), glycated hemoglobin (HbA1c), high molecular weight (HMW) isoform of adiponectin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride (TG) levels were measured. Thirteen SNPs in 5 genes (adiponectin, leptin, peroxisome proliferator-activated receptor alpha, adiponutrin/patatin-like phospholipase domain-containing protein 3 and peroxisome proliferator-activated receptor γ co-activator 1α ) were measured.

Results

Only adiponectin rs266729 polymorphism was associated with susceptibility to NAFLD (p = 0.001). Subgroup analysis revealed that the proportion of subjects with homozygous genotype GG was higher in patients with NAFLD (31%) than in controls (11%) and that the proportions of heterozygous CG and homozygous CC were higher in controls (37% and 52%, respectively) than in patients with NAFLD (33% and 36%, respectively). Patients with NAFLD carrying the GG genotype of rs266729 showed significantly lower serum HMW adiponectin levels than patients carrying the GC or CC genotype (3.75±0.37 vs. 3.99±0.66 vs. 4.79±0.58 μg/ml, p< 0.001). Body fat and serum HMW adiponectin levels were the strongest predictors of developing NAFLD (p < 0.001 and 0.004, respectively).

Conclusions

In patients with type 2 diabetes gene polymorphism of adiponectin rs266729 is associated with risk of NAFLD. G allele of rs266729 is associated with hypoadiponectinemia. Low serum adiponectin level may precipitate liver steatosis in patients with type 2 diabetes.     

Hyperglycemia prevents the suppressive effect of hyperinsulinemia on plasma adiponectin levels in healthy humans

Adiponectin is a fat-derived hormone with insulin-sensitizing properties. In patients with type 2 diabetes plasma adiponectin levels are decreased. Since these patients are characterized by high plasma insulin and glucose concentrations, hyperinsulinemia and hyperglycemia could be responsible for the downregulation of adiponectin. Insulin decreases adiponectin levels in humans. The effect of hyperglycemia is unknown. To determine the selective effects of insulin, glucose, or their combination on plasma adiponectin, clamps were performed in six healthy males on four occasions in a crossover design: 1) lower insulinemic-euglycemic clamp (100 pmol/l insulin, 5 mmol/l glucose) (reference clamp); 2) hyperinsulinemic-euglycemic clamp (400 pmol/l insulin, 5 mmol/l glucose); 3) lower insulinemic-hyperglycemic clamp (100 pmol/l insulin, 12 mmol/l glucose); and 4) hyperinsulinemic-hyperglycemic clamp (400 pmol/l insulin, 12 mmol/l glucose). Adiponectin concentrations and high-molecular-weight (HMW)-to-total adiponectin ratio were measured at the start and end of the 6-h clamps. After the 6-h study period, total plasma adiponectin levels were significantly (P = 0.045) decreased by 0.63 microg/ml in the lower insulinemic-euglycemic clamp (clamp 1). In both euglycemic groups (clamps 1 and 2) adiponectin concentrations significantly declined (P = 0.016) over time by 0.56 microg/ml, whereas there was no change in both hyperglycemic groups (clamps 3 and 4) (P = 0.420). In none of the clamps did the ratio of HMW to total adiponectin change. We conclude that insulin suppresses plasma adiponectin levels already at a plasma insulin concentration of 100 pmol/l. Hyperglycemia prevents the suppressive effect of insulin. This suggests that, in contrast to glucose, insulin could be involved in the downregulation of plasma adiponectin in insulin-resistant patients.     

脂联素改善阿尔茨海默病模型小鼠焦虑情绪及工作记忆

目的：探讨脂联素（APN）预处理对9月龄三转基因阿尔茨海默病（3xTg-AD）模型小鼠学习记忆能力和焦虑情绪的影响。方法：选取9月龄3xTg-AD小鼠及C57BL/6J小鼠,分为4组：WT+Saline组、3xTg-AD+Saline组、WT+APN组和3xTg-AD+APN组,每组8只。将全部小鼠进行侧脑室埋管术后,恢复7 d,在自由清醒状态下分别经侧脑室给予生理盐水或APN,采用旷场、新物体识别及Y-迷宫3种行为学手段检测小鼠的情绪及学习记忆能力。结果：①在旷场实验中,与WT+Saline组小鼠相比,3xTg-AD+Saline组小鼠在中央区域的活动时间明显缩短,在外周区域的活动时间明显延长,给予APN后可有效逆转3xTg-AD小鼠的该现象,表明脂联素可有效缓解3xTg-AD小鼠的焦虑情绪。②新物体识别实验中,3xTg-AD+Saline组小鼠的辨别指数为（-16.7±10.1）%,明显低于WT+Saline组的（18.0±8.2）%（P<0.01）和3xTg-AD+APN组的（15.7±8.8）%（P<0.01）,表明脂联素可明显改善3xTg-AD小鼠的识别记忆能力损伤。③Y-迷宫实验中,3xTg-AD+Saline组小鼠的自发交替正确率为（40.0±1.7）%,明显低于WT+Saline组的（56.6±4.6）%（P<0.01）和3xTg-AD+APN组的（53.9±5.6）%（P<0.01）,表明脂联素能够逆转3xTg-AD小鼠工作记忆能力的损伤。结论：脂联素可以改善9月龄3xTg-AD小鼠的焦虑情绪及识别记忆和工作记忆能力损伤,可能在AD的预防和治疗中发挥有效作用。