Serum leptin levels and insulin resistance are associated with gallstone disease in overweight subjects

AIM: To establish an association between the serum leptin levels and the development of gallstone disease (GD).METHODS: We carried out a non-matched case-controlled study in a university hospital in Mexico City. Two hundred and eighty-seven subjects were included: 97 cases with gallstones and 190 controls. Body mass index (BMI), fasting plasma leptin, insulin, serum lipid, and lipoprotein levels were measured. Insulin resistance was calculated by homeostasis model assessment (HOMA-IR). Unconditional logistic regression analysis (univariate and multivariate)stratified by BMI was used to calculate the risk of GD.RESULTS: The multivariate conditional regression analysis revealed a model for those patients with BMI ＜30. The selected variables in the model were HOMA-IR index with OR = 1.31, P= 0.02 and leptin higher than median with OR = 2.11, P= 0.05. In the stratum of BMI ≥30, we did not find a useful model.CONCLUSION: We concluded that insulin resistance and the development of GD appears to be associated with serum leptin levels in subjects with overweight, but not in obese subjects with similar metabolic profiles.

Obesity and leptin resistance: The role of growth hormone

Decreased growth hormone (GH) function in obese patients might contribute to associated metabolic abnormalities. This study aimed to investigate the effect of leptin, GH and periods of leptin sensitivity or/and insensitivity on the expression of the SOCS-3 gene in the ovine pituitary and to examine the influence of centrally administered leptin on GH release in sheep. Our first experiment investigated the periods of leptin resistance and leptin sensitivity, which are known as the long day (LD) and the short day (SD) periods, respectively, using ewes that were surgically fitted with third ventricular cannulae. The ewes were assigned randomly to one of three treatments and were centrally infused at 0, 1 and 2 h, beginning at sunset. The treatments consisted of central infusions of either Ringer-Locke buffer or leptin (0.5 or 1.0 μg/kg body weight (BW), respectively). Our next experiment examined the pituitaries isolated from ewes decapitated in either May or November. The explants were treated with control or GH (100 or 300 ng/ml) or leptin (50 or 100 ng/ml)—containing media and incubated for one of four different time intervals. The in vivo experiments demonstrated variable effects of leptin on GH release depending on the period of leptin sensitivity/ insensitivity. The in vitro experiments demonstrated that leptin significantly influenced the expression of the SOCS-3 gene during that SD compared to that?during the LD. During the SD, we observed that significantly low or high doses of GH affected the expression of SOCS-3. These results indicated a strong correlation between leptin or GH and SOCS-3, which might explain leptin resistance and the associated perturbations in GH signaling.

TaRAR1 is Required for Lr24-Mediated Wheat Leaf Rust Resistance

Virus-induced gene silencing （VIGS） offers a rapid and high throughout technology platform for the analysis of gene function in plants. The barley stripe mosaic virus （BSMV） VIGS system was optimized in studies silencing phytoene desaturase expression in wheat, and demonstrated that infection with BSMV construct carrying a 412 bp fragment of TaRAR1 caused conversion of incompatible to compatible interactions to Lr24-mediated resistance in wheat TcLr24 and cultivar 5R615 harboring Lr24 whereas infection with a control construct had no effect on resistance or susceptibility. RT- PCR analysis showed that BSMV-induced gene silencing could be detected at mRNA levels. These studies indicated that TaRAR1 was a required component for Lr24-mediated race-specific resistance and the BSMV-VIGS was a powerful tool for dissecting the genetic pathways of disease resistance in hexaploid wheat.

Effects of pioglitazone on serum leptin and adiponectin in polycystic ovary syndrome patients with insulin resistance

Objective To investigate the effects of pioglitazone on serum leptin and adiponectin in polycystic ovary syndrome(PCOS)patients with insulin resistance(IR).Methods Thirty-five PCOS patients with IR were treated with pioglitazone 15mg/d for 12 weeks.The results of ovulation induction were observed.The changes of fasting plasma glucose(FPG),fasting serum insulin(FINS),serum levels of leptin,adiponectin,follicle-stimulating hormone(FSH),luteinizing hormone(LH),testosterone(T)and blood fat were examined at the baseline and after the therapy by enzyme-linked immunosorbent assay(ELISA)and radioimmunoassay(RIA).Results After the treatment,the rate of ovulation per cycle was improved in 31(88.5%)out of the 35 patients.After treatment,the level of serum leptin was decreased(P<0.05)while the level of serum adiponectin was increased(P<0.05).After 12 weeks’ treatment,waist-to-hip ratio and F-G score were significantly decreased(P<0.05),BMI declined but without significant difference(P>0.05).The levels of LH,T,FINS,Homa-IR,total cholesterol,triglyceride and low density lipoprotein-cholesterol were significantly decreased(P<0.01,P<0.05),whereas the level of high density lipoprotein-cholesterol was significantly increased(P<0.01).No significant difference was seen in FSH and FPG following treatment(P>0.05).Conclusion Pioglitazone treatment can effectively improve PCOS with IR patients’ clinical syndromes,insulin sensitivity,glucose and lipid metabolism at least partly through improving the profiles of leptin and adiponectin.

Cellular and Molecular Basis of Leptin Resistance in Obese Patients

Obesity is a major risk factor for diabetes,cardiovascular disease,and certain cancers.It arises from a chronic positive energy balance.This is usually due to unrestricted access to food in the context of genetic and epigenetic vulnerabilities.And an increasingly sedentary lifestyle.Over the past few decades,our understanding of the fluid and nervous systems that mediate energy balance control has greatly improved.However,our ability to formulate effective strategies to slow the current obesity epidemic has been hampered,mainly because we have limited knowledge of the resistance mechanisms of metabolic hormones such as leptin.Resistance to leptin is a sign of obesity,leptin is a key hormone for neuroendocrine control of energy balance.In the past few years,we have made tremendous progress in our in-depth research on the cellular pathways that disrupt the action of leptin.In this review,we discuss the molecular mechanisms of leptin resistance and how to use them as targets for obesity drug therapy.

The Mechanism of Regulating Leptin Resistance in Obesity and the Influence of Adjusting Methylation of OB-R,POMC Gene Promoter of Wendan Decoction (温胆汤)

Objective:To explore the mechanism of Wendan Decoction(温胆汤)regulating leptin resistance in obesity by analyzing the level of leptin in peripheral blood,the expression of leptin receptor and signal pathway molecule POMC in hypothalamus.To analyze the methylation status of the gene promoters of leptin receptor and POMC in obese rats fed with high fat diet,and the influence of adjusting methylation of OB-R,POMC gene promoter about Wendan decoction.Methods:Model rats were randomly divided into model control group and drug observation group,additional normal rats with 8 rats in each group.The models were established by high fat diet.The observation group was treated with Wendan Decoction(温胆汤)and the other two groups were treated with sterilized drinking water once a day for 6 weeks.Body weight was recorded every week during the intervention.Peripheral blood and hypothalamus were collected at the end of the experiment.The serum leptin level was measured by ELISA method,and the expression of OB-R and POMC in hypothalamus was detected by RT-qPCR method.Methylation level of OB-R and POMC promoter detected by methylation specific PCR.Results:Our results revealed that Wendan Decoction(温胆汤)could effectively reduce body weight,the body weight in the drug observation group was significantly lower than that in the model control group,and the difference between the two groups was statistically significant.The level of leptin in peripheral blood and the expression of OB-R in hypothalamus were consistent with the trend of body weight.The heavier the weight,the higher the level of leptin and OB-R.Wendan Decoction(温胆汤)could reduce the level of leptin and OB-R in peripheral blood while reducing body weight.Compared with the model control group,the difference was statistically significant.The heavier the weight,the lower the level of POMC expression.Wendan Decoction(温胆汤)could increase the expression of POMC while reducing body weight,which had statistical significance compared with the model control group.The methylation status of OB-R and POMC promoter in hypothalamus was not significantly associated with obesity induced by high fat diet,and Wendan Decoction(温胆汤)had no effect on methylation status.Conclusions:Wendan Decoction(温胆汤)could inhibit obesity by affecting the expression of leptin receptor and POMC mRNA in hypothalamus to a large degree.There was no obvious change about the methylation status of the gene promoters of leptin receptor and POMC in obese rats fed with high fat diet.And it was not related to the change of methylation status of gene promoter about the mechanism of Wendan Decoction(温胆汤).

Obesity, insulin resistance, adipocytokines and breast cancer: New biomarkers and attractive therapeutic targets

Worldwide, breast cancer(BC) represents the most common type of non-skin human malignancy and the second leading cause of cancer-related deaths amid women in Western countries. Obesity and its metabolic complications have rapidly become major global health issues and are associated with increased risk for cancer, especially BC in postmenopausal women. Adipose tissue is considered as a genuine endocrine organ secreting a variety of bioactive adipokines, such as leptin, adiponectin, resistin and nicotinamide phosphoribosyltransferase/visfatin. Recent evidence has indicated that the constellation of obesity, insulin resistance and adipokines is associated with the risk and prognosis of postmenopausal BC. Direct evidence is growing rapidly supporting the stimulating and/or inhibiting role of adipokines in the process of development and progression of BC. Adipokines could exert their effects on the normal and neoplastic mammary tissue by endocrine, paracrine and autocrine mechanisms. Recent studies support a role of adipokines as novel risk factors and potential diagnostic and prognostic biomarkers in BC. This editorial aims at providing important insights into the potential pathophysiological mechanisms linking adipokines to the etiopathogenesis of BC in the context of a dysfunctionaladipose tissue and insulin resistance in obesity. A better understanding of these mechanisms may be important for the development of attractive preventive and therapeutic strategies against obesity-related breast malignancy.

脂联素、瘦素、Pref-1与胰岛素抵抗关系及联合检测预测糖尿病前期病情进展风险的效能

目的探讨脂联素、瘦素、前脂肪细胞因子-1(Pref-1)与胰岛素抵抗的关系及联合检测预测糖尿病前期病情进展风险的效能。方法选取2019年1月至2023年1月郑州大学第一附属医院收治的304例糖尿病前期患者进行前瞻性队列研究。根据1年内是否进展为糖尿病分为糖尿病组(62例)、糖尿病前期组(242例),另选同期正常糖耐量人群60例作为对照组。比较三组受检者的基线资料及血清脂联素、瘦素、Pref-1表达水平,采用Pearson法分析血清脂联素、瘦素、Pref-1水平与胰岛素抵抗(IR)的相关性,采用Logistic回归分析血清脂联素、瘦素、Pref-1水平对糖尿病前期病情进展的影响,采用受试者工作特征曲线(ROC)分析血清脂联素、瘦素、Pref-1单独及联合检测对糖尿病前期病情进展风险的预测效能。结果三组受检者的年龄、体质量指数(BMI)、甘油三酯、空腹血糖、胰岛素抵抗指数(HOMA-IR)比较,糖尿病组高于糖尿病前期组,且糖尿病前期组高于对照组,差异均有统计学意义(P<0.05);糖尿病组患者的脂联素、Pref-1分别为(2.82±0.93)mg/L、(0.30±0.10)μg/L,明显低于糖尿病前期组的(6.76±2.17)mg/L、(0.51±0.16)μg/L,且糖尿病前期组患者的脂联素、Pref-1明显低于对照组的(8.45±2.80)mg/L、(0.84±0.27)μg/L,而糖尿病组患者的瘦素为(12.00±2.98)μg/L,明显高于糖尿病前期组的(8.79±2.87)μg/L,且糖尿病前期组患者的瘦素明显高于对照组的(3.56±1.09)μg/L,差异均有统计学意义(P<0.05);脂联素(r=-0.694)、Pref-1(r=-0.853)与HOMA-IR呈负相关(P<0.05),瘦素(r=0.660)与HOMA-IR呈正相关(P<0.05);Logistic回归分析结果显示,年龄、BMI、甘油三酯、空腹血糖、脂联素、瘦素、Pref-1是糖尿病前期患者病情进展的独立影响因素,将年龄、BMI、甘油三酯、空腹血糖进行校正,以脂联素、瘦素、Pref-1作为自变量,脂联素、瘦素、Pref-1仍是糖尿病前期患者病情进展的独立影响因素(P<0.05);ROC曲线分析结果显示,脂联素预测糖尿病前期病情进展风险的曲线下面积(AUC)为0.730,截断值≤3.51 mg/L,敏感度为79.03%,特异度为59.09%,瘦素预测的AUC为0.760,截断值>10.78μg/L,敏感度为67.74%,特异度为73.55%,Pref-1预测的AUC为0.795,截断值≤0.37μg/L,敏感度为80.65%,特异度为65.70%,且联合检测预测糖尿病前期病情进展的AUC为0.904,敏感度为87.10%,特异度为82.23%(P<0.05)。结论血清脂肪因子脂联素、Pref-1与不同糖耐量受损人群IR呈负相关,瘦素与之呈正相关,且联合检测对糖尿病前期病情进展风险具有一定预测价值,可作为临床早期预测病情进展风险的辅助指标。

血清microRNA-155、microRNA-21、趋化素、瘦素与糖尿病肥胖患者胰岛素抵抗的相关性

目的 探讨糖尿病肥胖患者血清microRNA-155(miR-155)、microRNA-21(miR-21)、趋化素、瘦素水平与胰岛素抵抗(IR)的相关性。方法 选取2022年1月—2023年4月山东中医药大学第二附属医院收治的138例2型糖尿病(T2DM)患者为研究对象,其中肥胖患者73例(肥胖组),非肥胖患者65例(非肥胖组)。肥胖组中有IR 45例(IR组),无IR 28例(非IR组)。收集患者一般资料,包括性别、体质量指数(BMI)、年龄、颈围(NC)、腰围(WC)、空腹血糖(FPG)、甘油三酯(TG)、空腹胰岛素(FINS)、高密度脂蛋白胆固醇(HDL-C)、miR-155、miR-21、趋化素、瘦素、胰岛素抵抗指数(HOMA-IR)水平;通过多因素逐步Logistic回归模型分析T2DM肥胖患者发生IR的危险因素;绘制受试者工作特征(ROC)曲线,分析miR-155、miR-21、趋化素、瘦素诊断T2DM肥胖患者IR的效能;Pearson法分析miR-155、miR-21、趋化素、瘦素与HOMA-IR的相关性。结果 肥胖组miR-155相对表达量低于非肥胖组(P <0.05),miR-21、趋化素、瘦素、HOMA-IR高于非肥胖组(P <0.05)。IR组miR-155相对表达量低于非IR组(P <0.05),NC、WC、miR-21、趋化素、瘦素水平高于非IR组(P<0.05)。多因素逐步Logistic回归分析结果显示:NC [O^R=1.416(95%CI:1.038,1.932)]、WC [O^R=1.227(95%CI:1.049,1.435)]、miR-155 [O^R=1.763(95%CI:1.205,2.579)]、miR-21[O^R=1.932(95%CI:1.356,2.753)]、趋化素[O^R=2.074(95%CI:1.492,2.883)]、瘦素[O^R=1.628(95%CI:1.246,2.127)]是T2DM肥胖患者发生IR的危险因素(P <0.05)。ROC曲线分析结果显示,miR-155、miR-21、趋化素、瘦素诊断T2DM肥胖患者IR的曲线下面积分别为0.865、0.909、0.874和0.871;敏感性为77.8%(95%CI:0.614,0.825)、86.7%(95%CI:0.792,0.917)、95.6%(95%CI:0.713,0.965)和80.0%(95%CI:0.692,0.917);特异性为85.7%(95%CI:0.647,0.903)、82.1%(95%CI:0.732,0.914)、75.0%(95%CI:0.675,0.928)和89.3%(95%CI:0.656,0.944)。miR-155与HOMA-IR呈负相关(r=-0.573,P=0.000),miR-21、趋化素、瘦素与HOMA-IR均呈正相关(r=0.531、0.558和0.568,均P=0.000)。结论 T2DM肥胖患者中IR较多,且miR-155、miR-21、趋化素、瘦素是T2DM肥胖患者发生IR的危险因素。

重组leptin干预对营养性肥胖大鼠血清胰岛素、C-肽、内源性leptin含量及ob基因表达水平的影响

目的:探讨重组leptin侧脑室注射后,营养性肥胖大鼠模型腹膜后脂肪组织obese基因表达、内源性leptin含量以及血清胰岛素、C肽的变化,以期进一步探讨leptin中枢干预对肥胖大鼠leptin抵抗、胰岛素抵抗的改善作用。方法:(1)应用高营养饮食诱导的肥胖大鼠模型,用ELISA双抗体夹心法和放免法测定血清中leptin及胰岛素、C肽的含量;(2)应用RT鄄PCR技术检测各组大鼠脂肪组织中obese基因的表达水平。结果:(1)肥胖组大鼠经leptin干预后血清胰岛素和C肽明显降低,与正常各组之间无显著性差异;肥胖对照组、生理盐水组血清胰岛素、C肽较正常组明显升高。(2)肥胖大鼠经重组leptin干预后,脂肪组织obmRNA含量明显低于肥胖对照组、肥胖生理盐水组;其与正常对照组、正常leptin、生理盐水干预组之间无显著性差异。(3)肥胖对照组、肥胖生理盐水组大鼠血清leptin含量明显高于肥胖leptin干预组以及正常对照组、正常各干预组;肥胖leptin干预组与正常对照组、正常各干预组之间无显著性差异。(4)各组大鼠脂肪组织中obmRNA含量与其血清leptin含量、呈显著正相关关系。大鼠血清leptin含量与血清胰岛素、C肽浓度呈显著正相关。结论:侧脑室给予leptin可以显著减少肥胖大鼠脂肪组织中ob基因的表达以及血清leptin、胰岛素和C肽的含量。

2型糖尿病患者血清Leptin浓度的变化及其与胰岛素抵抗、β-细胞功能的关系

目的了解2型糖尿病(T2DM)患者血浆瘦素(Leptin)浓度的改变,并探讨与胰岛素抵抗、β-细胞功能的关系。方法测定64例2型糖尿病和30例正常对照组的血浆Leptin、空腹血糖(FPG)、糖化血红蛋白(Hba1c)、空腹血浆胰岛素(FINS)、血脂、体重指数(BMI),计算胰岛素抵抗指数(HOMA-IR)及β-细胞功能指标(HOMA-β)。比较Leptin浓度的改变,以及与其它因素的相关性。结果肥胖的糖尿病组与正常对照组比较Leptin明显升高,并且有统计学意义。而在肥胖的糖尿病组对非肥胖糖尿病组,以及非肥胖的糖尿病组对正常对照组的比较中,尽管Leptin数值有差异,但都没有统计学意义。在糖尿病患者中血浆Leptin与BMI、TG及TC呈正相关,与FBG、FINS、HbA1c、HDL-c、LDL-c及HOMA-IR、HOMA-β相关性不明显。结论:肥胖的2型糖尿病患者存在Leptin抵抗,Leptin抵抗与胰岛素抵抗、β-细胞功能减退以及2型糖尿病的发生有一定的关系。

肥胖大鼠胰岛素抵抗和leptin抵抗的关系研究

目的 探讨在肥胖形成的过程中Leptin抵抗和胰岛素抵抗何时出现及其因果关系。方法 选取雄性Wistar大鼠2 0只按体重随机分为基础对照和肥胖 2组 ,喂养 5周。每周末称重 ,采尾血测定血糖、胰岛素和Leptin。 结果 肥胖组体重、血糖、胰岛素和Leptin均高于基础对照组。在肥胖形成的过程中Leptin抵抗的发生先于胰岛素抵抗。肥胖组Leptin抵抗首先出现在第 2周末而胰岛素抵抗出现在第 3周末 ,推测Leptin抵抗是胰岛素抵抗的诱因。结论 肥胖是糖尿病重要的危险因素。

肥胖症患者Leptin与胰岛素抵抗的关系

目的 研究肥胖症患者血清leptin水平与胰岛素抵抗的相关关系。方法 以稳态模型 (Homamodel)公式计算IR值作为评估胰岛素抵抗程度的指标 ,采用放射免疫分析法测定血清真胰岛素、1eptin水平。对两组BMI、WHR、胰岛素、1eptin水平及IR值进行比较分析。并通过相关分析确定 1eptin与各参数间相关性。 结果 leptin血清浓度有明显的性别差异 ,男 :女均约为 1∶4。肥胖组空腹胰岛素、IR值及leptin均明显高于正常对照组 (P <0 .0 1)。直线回归相关分析表明leptin值与BMI(r =0 .4 19,P <0 .0 1)相关。在校正性别及体重指数的影响后与空腹真胰岛素 (r =0 .4 2 7,P <0 .0 1)相关 ,与IR值 (r =0 .0 77,P >0 .0 5 )无相关。结论 肥胖症发病与胰岛素抵抗和高胰岛素血症有关 ,且leptin可能参与胰岛素抵抗和高胰岛素血症的发生进而导致肥胖的发生。

胰岛素抵抗大鼠Orexin/leptin系统变化及其影响因素的研究(英文)

目的研究IR大鼠下丘脑及脂肪组织中orexin和leptin系统的变化,分析其可能的调控因素。方法IR大鼠模型采用高脂肪膳食诱导并经钳夹技术证实;RT-PCR技术检测orexin/leptin及其受体(OX1R、OX2R、LR)mRNA的表达;生化比色法测定血清FFA、放免法测定血清TNF-α。结果该模型大鼠下丘脑中Prepro-orexin 表达减少约80%,OX1R、OX2R分别增加3.4及3.2倍,leptin mRNA 增加约8倍;LR减少78%;血清FFA和TNF-α均升高;钳夹技术中葡萄糖输注率(GIR60-120)明显低于对照组。结论高脂肪膳食可诱导大鼠体内IR;并导致orexin/leptin系统平衡状态的破坏;orexin与leptin相互作用共同维持机体能量代谢的稳定;FFA和TNF-α可能参与该系统的调控。

糖肾胶囊对FFR胰岛素抵抗性与leptin浓度的影响

观察糖肾胶囊对高果糖餐大鼠模型的胰岛素抵抗性与leptin 水平的影响。结果糖肾胶囊对大鼠的收缩期血压无显著改善作用;胰岛素敏感性( 即胰岛素抵抗性改善) 指标M 值及leptin 浓度,TSJN 组较FFR组有非常显著的差异,与空白组比较无显著差异;M 值与血浆leptin 浓度呈非常显著的负相关关系。

男性肥胖患者皮下脂肪组织PPARγ_2、leptin、TNF-α mRNA的表达与胰岛素抵抗

目的:研究肥胖患者腹部皮下脂肪组织过氧化物酶体增殖物激活受体γ-2(PPARγ2)、瘦素(leptin)、肿瘤坏死因子-α(TNF-α) mRNA与胰岛素抵抗(IR)的关系。方法:应用RT-PCR凝胶成像半定量技术测定男性肥胖患者皮下脂肪组织PPARγ2 mRNA、leptin mRNA及TNF-α mRNA,以及空腹血清leptin、胰岛素(FINS)、空腹血糖(FBS),计算胰岛素抵抗指数(IRI),分析观察指标与肥胖之间的相关关系。结果:①肥胖组FINS、leptin、IRI、脂肪组织mRNA、leptin mRNA及TNF-α mRNA高于非肥胖组(P<0.05);②IRI与leptin mRNA、TNF-α mRNA、PPARγ2 mRNA、leptin、BMI、FINS成正相关(P<0.05);③以IRI为应变量,TNF-α mRNA、PPARγ2 mRNA、leptinmRNA、血清leptin、BMI为自变量做多元逐步回归分析,回归方程:Y=0.358+0.813PPARγ2mRNA。结论:①男性肥胖患者leptin及腹部皮下脂肪组织PPARγ2 mRNA、leptin mRNA、TNF-α mRNA较非肥胖者升高;②男性患者PPARγ2 mRNA与IR密切相关,可以反映IR的程度。

肥胖患者大网膜脂肪组织中Leptin基因的表达及意义

目的 研究大网膜脂肪组织中 L eptin基因的表达及在肥胖和胰岛素抵抗发病机制中的作用。 方法 选择肥胖患者 (BMI(30 kg/m2 )和正常人 (BMI<2 5 kg/m2 )各 10例 ,抽提大网膜脂肪组织 RNA;用半定量 RT-PCR方法研究肥胖合并胰岛素抵抗患者和正常人大网膜脂肪组织中 L eptin基因的表达。 结果 实验组 L eptinm RNA水平显著高于对照组 (P<0 .0 1)。 结论 肥胖患者体内可能存在 L eptin抵抗。

金匮肾气丸对实验性2型糖尿病胰岛素抵抗大鼠血清TNF-α、Leptin的影响

目的探讨金匮肾气丸改善胰岛素抵抗的作用。方法采用高糖、高脂饲料喂养动物,诱发大鼠胰岛素抵抗,待模型成功后,再用金匮肾气丸治疗。40只大鼠随机分为空白对照组、模型对照组、罗格列酮治疗组、金匮肾气丸低剂量组、高剂量组。除空白对照组外,其他组造模,均用胰岛素敏感性指数(ISI)判定胰岛素抵抗(IR)改善情况,第14周处死大鼠,取血检测血清中(肿瘤坏死因子)TNF-α、(瘦素)Leptin的含量。结果金匮肾气丸高、低剂量组、罗格列酮治疗组ISI,较模型对照组升高(P<0.05或P<0.01),2型糖尿病模型大鼠经金匮肾气丸治疗后ISI升高,与罗格列酮治疗组有相似的治疗作用(P>0.05)。罗格列酮治疗组、金匮肾气丸高、低剂量组血清TNF-α、Leptin值均降低,与模型对照组相比具有统计学意义(P<0.05或P<0.01)。结论金匮肾气丸可提高大鼠ISI,增强胰岛素的敏感性,降低2型糖尿病模型大鼠TNF-α、Leptin含量。

The Leptin Paradox-A Treacherous Art in cardiac sequelae of obesity

Leptin is the first identified obese gene product which participates in the regulation of food intake, energy expenditure, glucose and lipid metabolism. Leptin initiates both hypertrophic and antihypertrophic effects on hearts in addition to its cardiac depressant effect. Circulating leptin levels correlate with the body mass index (BMI) and total amount of body fat, which may be associated with changes of cardiac morphology and function. It has been shown that cardiac function is present in both hyperleptinemic (db/db) and hypoleptinemic (ob/ob) mouse models. Leptin replenishment reconciles the compromised myocardial function in ob/ob mice, indicating the premises of leptin on heart function. Interestingly, elevated plasma leptin levels may trigger leptin resistance and serve as an independent risk factor for cardiovascular diseases. Therefore, physiological range of leptin is essential for normal cardiac geometry and function whereas disrupted leptin signaling (hyperand hypoleptinemia) results in functional and morphological aberrations leading to heart problem. Given that human obesity is a syndrome of leptin resistance, which is unlikely amenable to leptin treatment, the identification of novel parallel signal transduction pathways is of particular therapeutic value for obesityassociated cardiac dysfunction.

营养性肥胖大鼠TNF-α、leptin水平和胰岛素敏感指标的研究

目的:探讨饮食诱导肥胖(DIO)大鼠血清肿瘤坏死因子-α(TNF-α)、瘦素(leptin)和胰岛素敏感指标的变化及意义。方法:采用放免法检测大鼠血清TNF-α和leptin水平。结果:实验3周末,DIO大鼠leptin水平高于对照组(P<0.05);实验12周末,DIO大鼠TNF-α和leptin水平均显著高于对照组和DIO-R大鼠(P<0.01);DIO大鼠血清TNF-α,leptin水平均和胰岛素敏感指数(ISI)呈负相关(P<0.05)。结论:TNF-α,leptin可能在肥胖相关的胰岛素抵抗(IR)发生中起协同作用。