脂联素和抵抗素与高血压关系的研究进展

长期以来,脂肪组织一直被认为是仅供能量储备的终末分化器官,然而自1994年瘦素(1eptin,LEP)的发现以及对脂肪细胞因子研究的深入,众多脂肪因子如瘦素、脂肪源性肿瘤坏死因子、脂联素(adiponectin)、抵抗素(resistin)和内脏脂肪素等的发现,脂肪组织旺盛的内分泌功能亦逐渐为人们所认识.高血压患者体内血清脂联素水平低于正常、抵抗素水平高于正常,脂联素、抵抗素可能通过多方面因素影响血压的变化.现将脂联素、抵抗素与高血压关系的研究进展综述如下.     

腹部内脏脂肪沉积的老年非代谢综合征患者脂联素瘦素比值的变化

目的 观察体质指数正常、腹部内脏脂肪沉积的非代谢综合征老年男性患者血清脂联素、瘦素水平及脂联素瘦素比值的变化.方法 将入选的老年非代谢综合征男性患者109例分为2组,内脏无脂肪沉积组67例,内脏脂肪沉积组42例.采用CT方法测定内脏脂肪面积,当腹部内脏脂肪面积≥100cm2,为内脏脂肪沉积;采用LINCO公司提供的放射免疫试剂盒测定空腹血脂联素、瘦素水平;代谢综合征的诊断采用2004年中国糖尿病学会制定的标准.结果 (1)脂肪沉积组与无脂肪沉积组比较,体质指数、内脏脂肪面积均显著升高,体质指数分别为(22.94±1.35)kg/m2对(21.38±2.55)kg/m2(P＜O.001),内脏脂肪面积(135.6±31.7)cm2对(68.6±22.6)cm2(P＜O.001);脂联素瘦素比值降低.分别为2.17±1.77对4.54±7.00(P=0.031);而脂联素、瘦素水平在两者间差异无统计学意义;(2)脂联素瘦素比值与体质指数(r=-0.552,P＜0.001)、腰围(r=-0.390,P＜0.001)、腹部内脏脂肪面积(r=-0.311,P＜0.001)呈负相关.结论 体质指数正常有内脏脂肪沉积与无内脏脂肪沉积的老年男性比较.脂联素瘦素比值明显下降.并与腹部脂肪面积显著负相关.提示血清脂联素瘦素比值可能可用于筛选体质指数正常有腹部内脏脂肪肪沉积的患者.     

急性冠状动脉综合征患者血清脂肪细胞因子的变化与冠状动脉病变程度的关系

目的观察急性冠状动脉综合征(acute coronary syndrome,ACS)患者血清脂肪细胞因子:脂联素、瘦素、抵抗素水平变化及其对冠状动脉病变程度的影响。方法选择2009年1月~2011年10月在我院经冠状动脉造影确诊为ACS的患者95例作为ACS组,另选择冠状动脉造影正常的95例作为对照组。ACS组根据病变支数分为单支组(43例)、双支组(33例)、三支组(19例)。所有患者检查脂联素、瘦素、抵抗素水平及生化检查。结果 ACS组抵抗素[(4.63±1.44)μg/L vs(2.42±0.93)μg/L,P=0.017]、瘦素[(9.60±1.39)μg/L vs(6.70±1.38)μg/L,P=0.009]水平明显高于对照组,脂联素[(8.99±1.66)μg/L vs(12.11±1.97)μg/L,P=0.006]水平明显低于对照组。随着病变支数增多,脂联素水平明显降低,瘦素、抵抗素水平明显升高,差异有统计学意义(P<0.05)。logistic回归分析,ACS患者的脂联素OR=0.078,95%CI:0.017~0.364,P=0.001;抵抗素OR=16.56,95%CI:2.298~119.280,P=0.005;瘦素OR=7.17,95%CI:1.594~32.261,P=0.010。结论脂联素、瘦素、抵抗素在诊疗ACS方面具有重要价值。     

抵抗素、脂联素浓度与高血压病血瘀证关系的研究

目的比较高血压病血瘀证与非血瘀证患者抵抗素、脂联素等差异,探讨高血压病患者脂肪因子与血瘀证的关系。方法空腹取静脉血制备血浆、血清,酶免检测血清脂联素、抵抗素,放免检测血清瘦素、胰岛素和血浆内皮素、肿瘤坏死因子,酶法检测空腹血清血糖、总胆固醇、三酰甘油、高密度脂蛋白胆固醇及低密度脂蛋白胆固醇浓度。结果血瘀证检出率为25%。与非血瘀证组相比,血瘀证组瘦素、内皮素浓度升高(P0.05),脂联素水平降低(P0.05);抵抗素、胰岛素、肿瘤坏死因子水平差异无统计学意义(P0.05);抵抗素、脂联素二者与瘦素、胰岛素、内皮素均未见明显相关关系(P0.05)。胰岛素与瘦素呈正相关(r=0.714 2,P0.01)。结论肥胖与血瘀证相关;瘦素与血瘀证的联系可能是通过调节血管活性因子水平实现的,脂联素具有防止血瘀证形成的作用;高血压病肥胖者血瘀证的形成可能与抵抗素无关。     

戒烟对大鼠血清瘦素、脂联素等炎症因子的影响

目的 通过研究戒烟对大鼠血清瘦素、脂联素、白介素6(IL-6)及C反应蛋白(CRP)水平的影响,探讨瘦素和脂联素等炎症因子在吸烟所致慢性阻塞性肺疾病炎症反应中的作用.方法 雄性Wistar大鼠30只,随机分为吸烟组、戒烟组及对照组,每组各10只.吸烟组每次吸烟10支,每天吸烟2次,每周吸烟6 d,共吸烟20周;戒烟组为吸烟20周后戒烟10周.采用酶联免疫吸附法检测各组大鼠血清瘦素、脂联素及CRP水平,采用双抗体夹心酶联免疫吸附法检测各组大鼠血清IL-6水平.结果 ①与对照组[(128.00±13.25) ng/L]比较,吸烟组[(56.23±8.64)ng/L]及戒烟组[(60.36±7.42)ng/L]血清瘦素水平均降低(P值均<0.05);戒烟组与吸烟组比较差异无统计学意义.②与对照组L(0.369±0.032)μg/L]比较,吸烟组[0.322±0.045)μg/L]血清脂联素水平降低(P<0.05),而戒烟组L(0.333±0.059)μg/L]与对照组、吸烟组比较差异无统计学意义.③与对照组[(23.94±4.44)ng/L]比较,吸烟组[(39.67±3.13)ng/L]及戒烟组[(34.27±7.01)ng/L]血清IL-6水平均升高(P值均<0.05);戒烟组较吸烟组水平降低(P<0.05).④与对照组[(494.49±124.44)μg/L]比较,吸烟组[(809.50±141.66)μg/L]及戒烟组[(632.60±182.85)μg/L]血清CRP水平均升高(P值均<0.05);戒烟组较吸烟组水平降低(P<0.05).⑤脂联素水平分别与IL-6和CRP呈负相关(γ值分别为-0.198、-0.489,P值均<0.05);IL-6水平与CRP呈止相关(γ=0.598,P<0.05).结论吸烟可使大鼠血清瘦素与脂联素水平下降,IL-6与CRP水平升高;戒烟后,瘦素、脂联素水平呈上升趋势,IL-6和CRP水平则相应下降.此外,脂联素水平分别与IL-6和CRP呈负相关.提示瘦素、脂联素等炎症因子可能参与吸烟所致慢性阻塞性肺疾病的炎症反应.     

高血压患者血清抵抗素和脂联素水平的研究

目的:探讨高血压患者血清抵抗素、脂联素等水平与血压之间的关系及其在原发性高血压和肥胖症发病中的作用。方法:随机选取符合研究条件的门诊高血压病人40例,按照体重指数分为肥胖和非肥胖的两个亚组,进行病史采集、体格检查,并测定其血抵抗素、脂联素瘦素和空腹胰岛素等水平,并选取健康查体者45例为正常对照组。结果:与正常对照组相比,高血压非肥胖和肥胖两个亚组,抵抗素水平升高[分别为(23.55±2.05)μg/L比(25.95±1.77)μg/L,P<0.001;比(27.67±1.72)μg/L,P<0.001];脂联素水平降低[分别为(16.45±3.59)μg/ml比(13.45±3.26)μg/ml,P=0.001;比(11.48±2.50)μg/ml,P<0.001];两个亚组比较,抵抗素(P=0.0140)和瘦素(P=0.041)均有统计学差别;两亚组抵抗素均与收缩压(r=0.445,P=0.049;r=0.516,P=0.020)、胰岛素(r=0.506,P=0.023;r=0.871,P<0.001)、瘦素(r=0.494,P=0.027;r=0.449,P=0.047)呈正相关,与脂联素(r=-0.711,P<0.001;r=-0.868,P<0.001)呈负相关;对照组抵抗素与收缩压(r=0.352,P=0.026)、平均动脉压(r=0.486,P=0.001)、胰岛素(r=0.392,P=0.012)、瘦素(r=0.640,P<0.001)呈正相关,与脂联素(r=-0.337,P=0.034)呈负相关。逐步线性回归显示两个亚组中脂联素是影响抵抗素的独立因素。结论:高血压患者的血清抵抗素、瘦素、胰岛素水平升高而脂联素水平下降,与血压之间有一定的相关性,说明脂肪分泌的相关激素可能参与高血压的发生和代偿。     

非酒精性脂肪性肝病患者血清瘦素、脂联素的变化

目的:探讨非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)患者血清瘦素、脂联素的变化.方法:选取NAFLD患者60例,与健康组60例相对照.ELISA法测定血清瘦素、脂联素水平,并与体质量指数(BMI)、腰臀比(WHR)、甘油三脂(TG)、总胆固醇(Tchol)、高密度脂蛋白胆固醇(HDL-C)、血糖(FBG)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、谷氨酰转肽酶(GGT)、稳态模型评估的胰岛素抵抗指数(HOMA-IR)相结合,从而判定瘦素、脂联素在NAFLD中的作用.结果:NAFLD组与正常对照组相比,血清瘦素水平升高(12.37±1.99μg/L vs 5.20±41.03 μg/L,P<0.01),脂联素水平降低(12.69±2.83 mg/Lvs 22.83±4.61 mg/L,P<0.01).Logistic多因素回归分析显示瘦素与WHR、HOMA-IR、FBG呈独立正相关(β=8.175,0.974,0.564,P<0.01).脂联素与HOMA-IR、BMI呈独立负相关(β=-0.495,-0.3 14,P<0.01).结论:NAFLD患者血清瘦素水平升高,脂联素水平降低,这两种细胞因子均与胰岛素抵抗相关.     

超重、肥胖患者血清抵抗素、脂联素的水平变化

目的 探讨在超重和肥胖患者血清抵抗素和脂联素的水平及其影响因素.方法 37例正常体重者、21例超重和24肥胖患者常规测量血压、体重、身高,计算体重指数,抽取空腹静脉血检测其血糖、血脂、胰岛素、IL-6、C-反应蛋白、肿瘤坏死因子(TNF)-α、瘦素、脂联素、抵抗素以及服糖后2小时血糖.结果 与正常体重人群相比,超重人群中血清抵抗素和脂联素水平正常;在肥胖患者中血清抵抗素水平升高[(16.03±8.59)vs( 10.62±6.97)ng/ml,P =0.037],脂联素水平正常.超重人群中,血清抵抗素与脂联素(r=0.473,P=0.030)、年龄(r=0.437,P-0.047)正相关,脂联素与瘦素(r =0.481,P=0.027)正相关;在肥胖人群中,血清抵抗素与年龄(r=0.476,P=0.019)正相关,脂联素与收缩压(r=0.409,P=0.047)、HDL-C(r=0.463,P=0.023)正相关.结论 在肥胖患者中,血清抵抗素增高,与年龄有关,脂联素水平正常,与收缩压、HDL-C相关.     

溃疡性结肠炎患者血清瘦素和脂联素的变化研究

目的观察溃疡性结肠炎(UC)患者血清瘦素和脂联素的变化。方法实验分为UC组和健康对照组,测定两组患者的血清瘦素和脂联素并进行比较。结果 UC组患者血清瘦素(10.95±1.10)ng/ml明显高于对照组(10.41±1.05)ng/ml,而血清脂联素(7.21±0.80)μg/ml明显低于对照组(7.80±1.24)μg/ml,差异有统计学意义。结论 UC患者血清瘦素水平增高、脂联素水平降低,二者在炎症反应过程中具有一定意义。     

球状脂联素抑制波动性高血糖诱导人脐静脉内皮细胞凋亡与脂联素受体1有关

目的 探讨球状脂联素在抑制波动性高血糖诱导人脐静脉内皮细胞凋亡中的机制.方法 不同条件下体外培养人脐静脉内皮细胞5天.实验分为对照组(葡萄糖5.5 mmol/L)、高糖组(葡萄糖25 mmol/L)、葡萄糖交替组(葡萄糖5.5/25 mmol/L,每8 h更换培养液一次)、高渗组(甘露醇25 mmol/L)和高渗交替组(甘露醇5.5/25 mmol/L,每8 h更换培养液一次).葡萄糖交替组中部分细胞用不同浓度(0、0.5、1.0和3 mg/L)球状脂联素干预,用脂联素受体1特异性小干扰RNA作用内皮细胞.采用流式细胞仪检测细胞凋亡及RT-PCR检测脂联素受体1和受体2 的mRNA表达.结果 与对照组比较,高糖组和葡萄糖交替组细胞凋亡明显增加,脂联素受体1 mRNA的表达显著降低(P<0.01).与高糖组比较,葡萄糖交替组细胞凋亡显著增加,脂联素受体1 mRNA的表达显著降低(P<0.01).不同浓度(0、0.5、1.0和3 mg/L)球状脂联素作用内皮细胞,发现3 mg/L球状脂联素能显著抑制内皮细胞凋亡(P<0.01),并能显著拮抗波动性高血糖诱导的脂联素受体1 mRNA表达的下降(P<0.01).不同组间内皮细胞脂联素受体2 mRNA表达差异无显著性.siRNA作用内皮细胞后球状脂联素这种抑制凋亡作用显著减弱(P<0.01).结论 与持续性高血糖条件比较,波动性高血糖显著降低人脐静脉内皮细胞脂联素受体1 mRNA的表达,而对脂联素受体2 mRNA的表达无影响.球状脂联素可能通过脂联素受体1拮抗波动性高血糖诱导的人脐静脉内皮细胞凋亡.     

Changes in plasma levels of fat-derived hormones adiponectin, leptin, resistin and visfatin in patients with rheumatoid arthritis

BACKGROUND: Rheumatoid arthritis is a chronic autoimmune inflammatory condition characterised by polyarthritis and severe change in body mass and neuroendocrine environment. OBJECTIVES: To investigate plasma levels of adipocytokines (leptin, adiponectin, visfatin and resistin) in patients with rheumatoid arthritis and to compare them with levels in healthy controls. METHODS: Adiponectin, resistin, visfatin and leptin concentrations were measured in 31 patients with rheumatoid arthritis and 18 healthy controls by using specific enzyme-linked immunosorbent assays. RESULTS: Patients with rheumatoid arthritis showed considerably higher plasma levels of leptin, adiponectin and visfatin than healthy controls. No marked difference was observed in resistin levels between patients and controls. CONCLUSION: A marked increase in plasma levels of leptin, adiponectin and visfatin was noted in patients with rheumatoid arthritis, whereas resistin levels were similar to those observed in healthy controls. Coordinated roles for adiponectin, leptin and visfatin are suggested in the modulation of the inflammatory environment in patients with rheumatoid arthritis, whereas the lack of modulation in resistin levels is predictive of an irrelevant role for this peptide, suggesting that resistin level is probably not one of the main signals associated with the pathogenesis of this disease.     

Adipokines influencing metabolic and cardiovascular disease are differentially regulated in maintenance hemodialysis

Adipokines including leptin, adiponectin, visfatin, resistin, and interleukin (IL)-6 significantly influence energy metabolism, insulin sensitivity, and cardiovascular health. In the current study, we investigated serum levels of these adipokines in diabetic and nondiabetic patients on maintenance hemodialysis (MD) as compared with controls with a glomerular filtration rate greater than 50 mL/min. Serum leptin, adiponectin, high-molecular-weight (HMW) adiponectin, visfatin, resistin, and IL-6 were determined by enzyme-linked immunosorbent assay in control (n = 60) and MD (n = 60) patients and correlated to clinical and biochemical measures of renal function, glucose, and lipid metabolism, as well as inflammation. Adiponectin, visfatin, resistin, and IL-6 were significantly elevated in MD patients as compared with controls. In multivariate analyses, sex and body mass index were independently correlated with serum leptin levels in both controls and MD patients. Furthermore, insulin resistance was independently and negatively associated with adiponectin and HMW adiponectin in both groups. Moreover, circulating resistin levels were independently correlated with serum visfatin concentrations in control and MD patients. However, various independent associations were only found in either controls or patients on MD. Thus, serum IL-6 levels were strongly and independently associated with C reactive protein and resistin in MD patients but not control subjects. We show that levels of various adipokines are significantly increased in MD patients. Furthermore, regulation of adipokines in vivo strongly depends on renal function. Regulation of HMW adiponectin is similar as compared with total adiponectin in the patients studied.     

Leptin, adiponectin and other adipokines in gestational diabetes mellitus and pre-eclampsia

Proteins secreted from adipocytes - so-called adipokines - influence metabolic and vascular function. Recent data suggest that various adipokines are dysregulated in gestational diabetes mellitus (GDM) and pre-eclampsia (PE) and might be of pathophysiological and prognostic significance in these complications of pregnancy. This review gives an overview on the regulation and pathophysiology of leptin and adiponectin in GDM and PE. Furthermore, data on novel adipokines including resistin, visfatin, retinol-binding protein 4 and vaspin are summarized.     

Adipose Tissue as Regulator of Vascular Tone

Adipokines secreted by visceral, subcutaneous, and perivascular adipocytes are involved in the regulation of vascular tone by acting as circulatory hormones (leptin, adiponectin, omentin, visfatin, angiotensin II, resistin, tumor necrosis factor-α, interleukin-6, apelin) and/or via local paracrine factors (perivascular adipocyte-derived relaxing and contractile factors). Vascular tone regulation by adipokines is compromised in obesitas and obesity-related disorders. Hypoxia created in growing adipose tissue dysregulates synthesis of vasoactive adipokines in favor of harmful proinflammatory adipokines, while the levels of the cardioprotective adipokines adiponectin and omentin decrease. Considering the potential of the role of adipokines in obesity-related vascular diseases, strategies to counter these diseases by targeting the adipokines are discussed.     

Serum adipokine profiles in Kawasaki disease

Adipokines are cytokines derived from adipose tissue. Recently it has been established that adipokines are closely linked to the pathophysiology of not only metabolic diseases, such as diabetes mellitus, obesity, and atherosclerosis, but also to inflammation and immune diseases. In this study we measured serum levels of adipokines in patients with acute Kawasaki disease to investigate the role of adipokines in the pathophysiology of Kawasaki disease. Serum resistin, high-molecular-weight (HMW) adiponectin, leptin, and visfatin levels were measured by enzyme-linked immunosorbent assay in a total of 117 subjects: 56 patients with acute Kawasaki disease, 30 healthy children, and 31 patients with acute infectious diseases. Serum resistin levels in patients with Kawasaki disease were significantly higher than those of healthy children and patients with acute infectious diseases. In contrast, mean serum HMW adiponectin, leptin, and visfatin levels in patients with Kawasaki disease exhibited no statistically significant differences compared with those in healthy children and patients with infectious diseases. Serum resistin levels decreased significantly after administration of intravenous immune globulin. Serum resistin levels on admission were significantly higher in nonresponders compared with responders to intravenous immune globulin therapy. A multivariate model revealed that C-reactive protein was a factor that was significantly related to elevated serum resistin level in patients with Kawasaki disease. In patients with Kawasaki disease, serum resistin levels were elevated, but decreased to nearly normal after intravenous administration of immune globulin. In contrast, serum HMW adiponectin, leptin, and visfatin levels showed no statistically significant changes. These findings suggest that resistin plays an important role, while other adipokines do not play a major role, in the pathogenesis of Kawasaki disease.     

The relationship between serum resistin, leptin, adiponectin, ghrelin levels and bone mineral density in middle-aged men

OBJECTIVE: Body weight is a significant predictor of bone mass. Hormonal factors such as sex hormones, insulin, leptin and adiponectin are thought to play a role in the mechanisms controlling the association of body weight and fat mass with bone mass. However, contradictory results have been reported for the association between serum adipocytokines and bone mineral density (BMD). We therefore examined whether the serum adipocytokine and ghrelin levels, markers of fat metabolism, are associated with BMD in male adults. PATIENTS AND MEASUREMENTS: For 80 male adults (average age 54.5 +/- 6.4 years; average body mass index (BMI) 24.4 +/- 2.5 kg/m2), the correlations between serum resistin, leptin, adiponectin and ghrelin levels with BMD were investigated. RESULTS: Among the adipocytokines, serum resistin levels were negatively correlated with lumbar spine BMD (r = -0.237, P = 0.05). After adjustment was made for age and BMI, log-transformed serum leptin showed a significant negative correlation with lumbar spine BMD, which was not seen on bivariate analysis (r = -0.237, P = 0.039). Femoral neck BMD was marginally associated only with serum adiponectin levels (r = -0.226, P = 0.062). In multiple regression analyses, among the adipokines, only resistin was a significant determinant of lumbar spine BMD, although the variance was small (R2 = 0.256). Serum ghrelin levels were not correlated with the BMD of either body site. CONCLUSIONS: Serum resistin level showed a significant negative correlation with lumbar spine BMD, although the variance was small. Further studies are needed to elucidate the role of adipocytokines in bone metabolism.     

Insulin resistance, adipokines, and oxidative stress in nondiabetic, hypercholesterolemic patients: leptin as an 8-epi-prostaglandin F2alpha determinant

Limited data are available on the association of insulin resistance, adipokines, and in vivo lipid peroxidation. We investigated the relationships between insulin resistance, adipokines (leptin, adiponectin, and resistin), and oxidative stress in nondiabetic, hypercholesterolemic patients. Seventy-six nondiabetic patients with hypercholesterolemia participated in this cross-sectional study. Fasting glucose and insulin concentrations were analyzed. Serum leptin, adiponectin, and resistin concentrations and urinary excretion of 8-epi-prostaglandin F(2alpha) (8-epi-PGF(2alpha)) were determined using enzyme-linked immunosorbent assay. We divided all subjects into 3 groups, classified by the tertiles of homeostasis model assessment of insulin resistance (HOMA-IR) values, and clinical parameter comparisons were made among the 3 groups. The results showed that serum leptin (P < .001) and adiponectin levels (P < .05) were significantly different among the groups, although serum resistin was not different. Furthermore, the group with the highest HOMA-IR had a significantly higher urinary 8-epi-PGF(2alpha) excretion than the group with the lowest HOMA-IR (P = .017). Circulating leptin was positively correlated with urinary 8-epi-PGF(2alpha) (r = 0.323, P < .01) and HOMA-IR (r = 0.524, P < .001). Circulating adiponectin was negatively correlated with body mass index (r = -0.252, P < .05) and HOMA-IR (r = -0.228, P < .05). We could not find a relationship between circulating adiponectin or resistin and urinary 8-epi-PGF(2alpha) excretion. Stepwise multiple linear regression analysis showed that leptin was associated with the urinary 8-epi-PGF(2alpha) excretion after adjusting for age, sex, body mass index, blood lipids, and HOMA-IR (P = .002). In conclusion, our results show that more insulin-resistant state of nondiabetic, hypercholesterolemic patients is associated with decreased adiponectin and increased leptin and urinary 8-epi-PGF(2alpha) levels, although no relationship with resistin was observed. Furthermore, serum leptin independently contributed to urinary 8-epi-PGF(2alpha) excretion.     

Splanchnic concentrations and postprandial release of visceral adipokines

No detailed data are available on hepatic clearance, postprandial release, and distribution profile of metabolically active adipokines in splanchnic blood compartments such as portal and hepatic veins. This would be a prerequisite for understanding the role of visceral adipose tissue-derived adipokines in metabolism. Adiponectin, resistin, leptin, and visfatin concentrations were measured by enzyme-linked immunosorbent assay in peripheral veins, arterial blood, hepatic veins, and portal veins in 50 patients with liver cirrhosis undergoing transjugular intrahepatic portosystemic shunt implantation, in 6 patients with normal liver function, and in fasted and fed rats. Adiponectin, leptin, resistin, and visfatin did not differ among blood compartments in normal-weight probands in the fasted state. Adiponectin and leptin levels were similar in patients with and without liver cirrhosis. Systemic visfatin levels were decreased and resistin levels were increased in liver cirrhosis. Visfatin secretion was higher from visceral than from peripheral subcutaneous adipose tissue in liver cirrhosis. There was no hepatic clearance of visfatin. Leptin secretion was higher from peripheral than from visceral adipose tissue. Leptin did not undergo hepatic clearance. Resistin and adiponectin did not differ between blood compartments in liver cirrhosis. Resistin concentrations increased upon feeding in rats, and there was an increase in the postprandial clearance of adiponectin by the liver. A postprandial increase of leptin concentrations was restricted to peripheral adipose tissue in rats. The results give insight into the dynamics of splanchnic adipokine concentrations and help critically interpret data derived from messenger RNA expression studies.     

波动性高血糖与恒定性高血糖对脂肪细胞脂联素和抵抗素表达的影响

目的 比较波动性高血糖与恒定性高血糖对脂肪细胞脂联素和抵抗素表达的影响.方法 体外培养3T3-L1脂肪细胞,制作血糖波动和氧化应激模型.细胞分为2组,A组观测波动性高血糖、锰苯甲酸卟啉、噻吩甲酰三氟丙酮对脂联素和抵抗素mRNA、细胞上清含量、硝基酪氨酸和8-羟基脱氧鸟苷的影响,B组观察氧化应激波动对脂联素和抵抗素表达的影响.采用逆转录-聚合酶链反应(RT-PCR)及ELISA法分别检测脂联素、抵抗素mRNA和蛋白表达水平.硝基酪氨酸和8-羟基脱氧鸟苷分别采用间接竞争ELISA法及双抗夹心ELISA法测定.采用t检验及方差分析进行统计学分析.结果 与恒定性高血糖组比较,波动性高糖组脂联素mRNA和细胞上清含量明显降低(t值分别为7.29、7.13,均P<0.01),抵抗素mRNA和细胞上清含量明显升高(t值分别为6.85、6.94,均P<0.01),硝基酪氨酸和8-羟基脱氧鸟苷含量显著增多(t值分别为4.74、6.93,均P<0.01);用锰苯甲酸卟啉或噻吩甲酰三氟丙酮处理后,脂联素细胞上清含量水平均显著升高(t=7.47,P<0.01),抵抗素细胞上清含量水平均显著降低(t=6.91,P<0.01),硝基酪氨酸和8-羟基脱氧鸟苷的含量显著降低(t值分别为4.87、6.90,均P<0.01).氧化应激作用波动组脂联素mRNA表达水平明显降低(t=7.21,P<0.01),抵抗素mRNA表达水平明显升高(t=6.79,P<0.01).结论 波动性高血糖明显引起脂肪细胞内脂联素和抵抗素表达异常,其机制町能与线粒体电子传递链上活性氧族生产过剩有关.     

GW4064, a farnesoid X receptor agonist,upregulates adipokine expression in preadipocytes and HepG2 cells

AIM: To investigate the effect of GW4064 on the expression of adipokines and their receptors during differentiation of 3T3-L1 preadipocytes and in HepG2 cells.METHODS: The mRNA expression of farnesoid X receptor (FXR), peroxisome proliferator-activated receptor-gamma 2 (PPAR-γ2), adiponectin, leptin, resistin, adiponectin receptor 1 (AdipoR1), adiponectin receptor 2 (AdipoR2), and the long isoform of leptin receptor (OB-Rb) and protein levels of adiponectin, leptin, and resistin were determined using fluorescent real-time PCR and enzyme linked immunosorbent assay, respectively, on days 0, 2, 4, 6, and 8 during the differentiation of 3T3-L1 preadipocytes exposed to GW4064. Moreover, mRNA expression of AdipoR2 and OB-Rb was also examined using fluorescent real-time PCR at 0, 12, 24, and 48 h in HepG2 cells treated with GW4064.RESULTS: The mRNA expression of FXR, PPAR-γ2, adiponectin, leptin, resistin, AdipoR1, AdipoR2, and OB-Rb and protein levels of adiponectin, leptin, and resistin increased along with differentiation of 3T3-L1 preadipocytes (P < 0.05 for all). The mRNA expression of FXR, PPAR-γ2, adiponectin, leptin, and AdipoR2 in 3T3-L1 preadipocytes, and AdipoR2 and OB-Rb in HepG2 cells was significantly increased after treatment with GW4064, when compared with the control group (P < 0.05 for all). A similar trend was observed for protein levels of adipokines (including adiponectin, leptin and resistin). However, the expression of resistin, AdipoR1, and OB-Rb in 3T3-L1 cells did not change after treatment with GW4064.CONCLUSION: The FXR agonist through regulating, at least partially, the expression of adipokines and their receptors could offer an innovative way for counteracting the progress of metabolic diseases such as nonalcoholic fatty liver disease.