Serum leptin and soluble leptin receptor in non-alcoholic fatty liver disease

AIM: To determine the role of leptin system in non-al- coholic fatty liver disease (NAFLD) development by deli- neating the changes in serum levels of leptin and soluble leptin receptor (sOB-R). METHODS: Blood samples were collected from 30 consecutive patients with liver-biopsy-proven NAFLD and 30 patients with cholecystolithiasis (stationary phase) as controls. Serum leptin levels were determined by radio- immunoassay and concentration of sOB-R was measured by ELISA. Body mass index (BMI) was calculated for all subjects, and serum insulin, C-peptide, and lipoprotein levels were also detected. RESULTS: Mean serum leptin level and BMI in the NAFLD group were significantly higher than in the con- trols (both P < 0.001), but mean sOB-R level was lower in the NAFLD group when compared to the controls. Both men and women in the NAFLD group had higher mean serum leptin levels and lower sOB-R levels than did the men and women in the control group (all P < 0.001). The- re was a significant negative correlation between serum leptin and sOB-R levels (r = -0.725, P < 0.001). Multiva- riate analysis showed that the percentage of hepatocyte steatosis, sex, BMI, and homeostasis model assessment of insulin resistance (HOMA IR) were independently rela- ted to serum leptin levels. CONCLUSION: Elevated serum leptin seems to be afeature of steatosis, and serum leptin seems to increase as hepatocyte steatosis develops. An enhanced release of leptin is accompanied by an decrease in sOB-R con- centration, which suggests higher resistance of periphe- ral tissues towards the action of leptin.

Effects of Metformin Treatment on Soluble Leptin Receptor Levels in Women with Polycystic Ovary Syndrome

The effects of metformin treatment on soluble leptin receptor (sOB-R) levels in women with polycystic ovary syndrome (PCOS) were investigated.This prospective and open-label study was conducted by the Department of Obstetrics & Gynecology at Union Hospital,Tongji Medical College of Huazhong University of Science and Technology,China.Fifty-five women with PCOS and insulin resistance (IR) were treated with metformin for 6 months.According to body mass index (BMI),the patients were divided into two groups:lean PCOS group (BMI <23 kg/m^2,n=34) and overweight or obese PCOS group (BMI >23 kg/m^2,n=21).Before and after treatment,serum luteinizing hormone (LH),follicle stimulating hormone (FSH),testosterone (T),androstenedione (A),dehydroepiandrosterone sulfate (DHEAS),insulin and sOB-R levels were determined.Thirty-one BMI-matched ovulatory women served as controls.The results showed:(1) The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR),androgen levels and hirsutism scores were higher,and sOB-R levels were lower in PCOS groups than in control group.A subgroup analysis of lean and overweight or obese PCOS patients revealed there was significant difference in sOB-R level between lean PCOS group and overweight or obese PCOS group.There were no significant differences in anthropometric parameters between lean PCOS patients and BMI-matched controls.However,sOB-R level was significantly lower in lean PCOS women than in controls.(2) There was no correlation between sOB-R level and BMI,waist and hip circumference,total testosterone,androstendione,DHEAS,LH or hirsutism scores in PCOS patients,but there was a significant negative correlation between sOB-R and HOMA-IR.(3) After treatment with metformin for 6 months,serum insulin levels decreased,and sOB-R levels increased significantly (P<0.01).It was suggested that considering low sOB-R levels supposedly compensate diminished leptin action,PCOS per se might cause leptin resistance.It is likely that reduction of hyperinsulinemia produced by metformin effectively improves the sOB-R levels in PCOS.

血清FGFR2、Leptin对特发性矮小症患儿的诊断价值及其水平与骨代谢指标的相关性

目的探讨血清成纤维生长因子受体2(FGFR2)、瘦素(Leptin)水平与特发性矮小症患儿骨代谢指标的相关性及其对疾病的诊断价值。方法选取2021年9月至2023年9月于该院就诊的138例特发性矮小症患儿为观察组,另选取同期于该院进行健康体检的141例健康儿童为对照组。采用酶联免疫吸附试验检测血清FGFR2、Leptin水平;采用全自动生化分析仪检测25-羟基维生素D[25-(OH)D]、Ⅰ型前胶原氨基酸前肽(PⅠNP)、骨钙素(OC)、骨特异性碱性磷酸酶(BAP)等骨代谢指标水平;采用Pearson相关分析特发性矮小症患儿血清FGFR2、Leptin水平与骨代谢指标水平的相关性;采用多因素Logistic回归分析影响特发性矮小症发病的因素;绘制受试者工作特征(ROC)曲线分析血清FGFR2、Leptin单独及联合检测对特发性矮小症的诊断价值。结果观察组体质量、身高及25-(OH)D、PⅠNP、OC、BAP、FGFR2、Leptin水平显著低于对照组,性发育状态Ⅱ~Ⅴ期患儿比例显著高于对照组,差异均有统计学意义(P<0.05)。Pearson相关性分析结果显示,特发性矮小症患儿血清FGFR2、Leptin水平与25-(OH)D、PⅠNP、OC、BAP水平均呈正相关(P<0.05)。多因素Logistic回归分析结果显示,FGFR2、Leptin水平升高是特发性矮小症发病的保护因素(P<0.05)。ROC曲线结果显示,血清FGFR2、Leptin单独及联合诊断特发性矮小症的曲线下面积分别为0.834、0.851、0.914。结论特发性矮小症患儿血清FGFR2、Leptin水平均较低,且二者均与骨代谢指标显著相关,推测其在诊断特发性矮小症中具有一定价值。

Expression of Leptin Long-form Receptor mRNA in Luteinized Granulosa Cells of Obese Women with Polycystic Ovary Syndrome

To investigate the expression of mRNA of leptin long-form receptor （OB-Rb） in luteinized granulosa ceils of obese women with polycystic ovary syndrome （PCOS）, and to determine the role of leptin in the physiopathology of PCOS, luteinized granulosa cells were collected from the follicle fluid of 10 obese women who met the diagnostic criteria for PCOS and their BMI was equal to or greater than 25 kg/m^2, and at the same time, granulosa cells were collected from 10 normal women undergoing IVF-ET who served as the control group. Some luteinized granulosa cells were taken from normal women for in-vitro culture, into which human leptin of different concentrations was added （0, 10, 100 and 1000 ng/mL）. After stimulation with leptin for 48 h, RT-PCR was employed for the detection of the expression of OB-RLInRNA in the luteinized granulosa cells. Our results showed that the level of OB-RLmRNA in luteinized granulosa cells of obese PCOS women was higher than those in the control （P〈0.05）. In luteinized granulosa cells cultured in vitro and stimulated by human leptin for 48 h, the level of OB-RLmRNA was higher than those without leptin stimulation （P〈0.01）, and when leptin concentration was at 100 ng/mL, and the level of OB-RLmRNA reached a peak, It is concluded that in obese PCOS women, the level of serum leptin is increased, which promotes the expression of OB-RL in luteinized granulosa cells and increases the sensitivity of the granulosa cells to leptin. Leptin may contribute to anovulation in obese women with PCOS.

Clinical significance of the leptin and leptin receptor expressions in prostate tissues

Aim： To evaluate the expression of leptin and leptin receptor in benign prostatic hyperplasia （BPH） and prostate cancer （PCa）, and to investigate whether they are associated with the development and progression of PCa. Methods： hnmunohistochemical staining was performed to examine the expression of leptin and leptin receptor in BPH and PCa. PCa was divided into three groups： localized PCa, locally advanced PCa and metastatic PCa. The positive staining was identified and the percentage of the positive staining was graded. We also assessed the relationship between both the Gleason score and body mass index （BMI） and PCa. Results： The percentage of the leptin expression in PCa was significantly higher than that in BPH （P 〈 0.01）. For the PCa group, the expressed levels of leptin showed a considerable correlation with localized PCa and metastatic PCa （P 〈 0.05）. Leptin receptor, however, did not reveal a definite difference between BPH and PCa. The expression of leptin indicated a significant difference between well-differentiated PCa （Gleason score ≤6） and poorly differentiated PCa （Gleason score 8-10） （P 〈 0.05）. The relation between the leptin expression level in PCa and the BMI was not remarkable （P = 0.447）. Conclusion： Our results suggest that leptin might have a promoting effect on the carcinogenesis and progression of PCa.

Possible involvement of leptin and leptin receptor in developing gastric adenocarcinoma

AIM： To investigate the expression of leptin and leptin receptor （ob-R） in intestinal-type gastric cancer and precancerous lesions, and to explore the possible mechanism and role of the leptin system in developing intestinal-type gastric adenocarcinoma.METHODS： Immunohistochemistry was performed to examine the expression of leptin and leptin receptor in archival samples of gastric adenocarcinoma and preneoplastic lesions, including intestinal metaplasia and mild to severe gastric epithelial dysplasia. Positive staining was identified and percentage of positive staining was graded.RESULTS： Dual expression of leptin and leptin receptor were detected in 80% （16/20） intestinal metaplasia, 86.3% （25/30） mild gastric epithelial dysplasia, 86.7% （26/30） moderate gastric epithelial dysplasia, 93.3% （28/30） severe gastric epithelial dysplasia, 91.3% （55/60） intestinal-type gastric adenocarcinoma and 30.0% （9/30） diffuse-type gastric carcinoma. The percentage of dual expression of leptin and leptin receptor in intestinal-type gastric adenocarcinoma was significantly higher than that in diffuse-type gastric adenocarcinoma （χ^2 = 37.022, P〈0.01）.CONCLUSION： Our results indicate the presence of an autocrine loop of leptin system in the development of intestinal-type gastric adenocarcinoma.

Neuropeptide Y and leptin receptor expression in the hypothalamus of rats with chronic immobilization stress

In this study, Sprague-Dawley rats were immobilized to a frame for 3 hours a day for 21 days to establish a model of chronic immobilization stress. The body weight and food intake of rats subjected to chronic immobilization stress were significantly decreased compared with the control group. Dual-labeling immunofluorescence revealed that the expression of leptin receptor and the co-localization coeffient in these leptic receptor neurons in the arcuate nucleus of the hypothalamus were both upregulated, while the number of neuropeptide Y neurons was decreased. Chronic immobilization stress induced high expression of leptin receptor in the arcuate nucleus and suppressed the synthesis and secretion of neuropeptide Y, thereby disrupting the pathways in the arcuate nucleus that regulate feeding behavior, resulting in diminished food intake and reduced body weight.

Association analyses of single nucleotide polymorphisms in the <i>leptin</i>and <i>leptin receptor</i>genes on milk and morphological traits in Holstein cows

To date, only a few SNP in the leptin receptor gene have been detected and analyzed while the leptin gene has been extensively characterized and several polymorphisms were detected and associated to functional and productive traits in cattle. In this work, for the first time, the bovine leptin receptor gene was fully characterized by sequencing the whole coding region and part of the 5’ flanking region. A group of 95 Holstein cows was genotyped in order to search for SNP at both the LEPR and LEP genes, and to associate them with milk and morphological traits. Nine novel SNP in the leptin receptor gene and one novel SNP in the leptin gene were detected. Four SNP of the leptin receptor gene and one SNP of leptin gene showed a significant effect on one or more analyzed traits, and, in all cases, the greatest effect was observed on fat content. This study provided knowledge of the existence of further polymorphisms in the leptin receptor and leptin genes that have an influence on some important economic traits.

蓝塘猪和长白猪leptin和leptin受体基因表达的变化

用实时荧光定量PCR方法研究了蓝塘猪和长白猪1、27、90、150和180日龄阶段脂肪组织中leptin基因mRNA和下丘脑中leptin受体基因mRNA的变化,并对2个品种不同生长阶段血液中leptin含量的变化规律进行了探讨。结果表明:(1)蓝塘猪180日龄时皮下脂肪中leptin基因表达量显著高于其它各阶段,而与长白猪相比,蓝塘猪除1日龄低于长白猪外,其它各个阶段均高于长白猪,180日龄两者差异极显著;长白猪各阶段间差异不显著;(2)蓝塘猪180日龄时下丘脑中leptin受体基因的表达量显著高于其它各阶段,长白猪180日龄时最高,且显著高于1日龄和27日龄,蓝塘猪与长白猪1日龄时差异显著;(3)蓝塘猪血清中leptin浓度各阶段均高于长白猪,两品种均是150日龄时最高,蓝塘猪150日龄显著高于27日龄和180日龄,长白猪各阶段差异不显著。

长型Leptin(瘦素)受体mRNA在大鼠消化道中的表达

本试验以 5只 SD雌性大鼠为研究对象 ,采用原位杂交技术研究了大鼠消化道长型 Leptin (瘦素 )受体 m RNA的表达及其分布。结果表明 ,长型 Leptin受体 m RNA在大鼠胃和十二指肠的粘膜及粘膜下层组织中广泛表达 ,从而证明了在大鼠消化道存在长型

长型Leptin(瘦素)受体mRNA在大鼠卵巢中的表达和分布

以5只SD雌性大鼠为研究对象,采用原位杂交技术研究了大鼠长型Leptin受体mRNA在大鼠卵巢中的表达及其分布。结果表明,Leptin受体mRNA在大鼠卵巢中,主要分布于黄体细胞以及黄体、初级卵泡、生长卵泡和成熟卵泡周围基质颗粒细胞内。而且在黄体细胞上有黄褐色阳性颗粒密集分布;在基质等其他部位中未能检测到Leptin受体mRNA杂交信号。

Leptin及其受体在急性髓系白血病中的研究

Leptin是一种由肥胖基因编码的分泌型蛋白质,与其受体结合后具有广泛的生物学效应。leptin的基本功能是调节能量代谢和摄食,主要由脂肪细胞产生,而脂肪细胞大量存在于骨髓,是造血微环境的基质细胞成分。Leptin及其受体不仅促进正常造血干细胞的增殖和分化,而且能够促进白血病细胞的增殖和活性。Leptin受体(leptin receptor,LEPR,又称OB-R)在急性髓系白血病(acute myeloid leukemia,AML)、急性淋巴细胞白血病和慢性髓系白血病的细胞上均有表达。此外,leptin在体内能够通过促进微血管的形成而促进白血病细胞的增殖。所有这些研究发现提示leptin及其受体在白血病的发生发展中起了一定的作用,阻断leptin与leptin受体的作用可能成为某些白血病治疗的靶点。本文就leptin及其受体的生物学特性、leptin及其受体与正常造血、leptin及其受体与AML的研究进展做一综述。

实验性肝硬化中Leptin及其受体的检测与表达意义

目的观察Leptin在实验性肝硬化大鼠血清水平及其受体在肝脏免疫组化表达和定位情况,探讨Leptin及其受体在实验性肝硬化发生病理机制中的作用。方法采用硫代乙酰胺(thioacetamide,TAA)腹腔注射诱导肝硬化动物模型,同时设立正常对照组;测量大鼠体长、体重、Lee’指数,分别测定血清血脂水平;采用酶联免疫分析法(enzymelinkedimmunosorbantassay,ELISA)检测血清Leptin含量;免疫组化与计算机图像分析技术观察Leptin受体在肝硬化组、正常对照组的表达和定位特点;各组间进行统计学分析。结果肝硬化动物模型复制成功。肝硬化组血清Leptin增高,与对照组比较差异有非常显著性(t=4.338,P<0.01);肝硬化组Leptin受体表达增高,与正常组比较差异有非常显著性(t=8.104,P<0.01);肝硬化组血清Leptin水平与胆固醇(TC)正相关(r=0.918,P<0.05)。肝硬化组血清Leptin水平与Leptin受体灰度值呈负相关(r=0.-0.80,P<0.01)。结论Leptin受体在肝硬化的肝脏中表达异常升高,尤其见于再生的肝细胞及窦内皮细胞等,提示Leptin参与肝纤维化的发生。

Differential Expression of Leptin and Leptin Receptor mRNA in Obese and Non-Obese Women across the Menstrual Cycle Title

OBJECTIVE: The aim of this study was to investigate the messenger ribonucleic acid expression of leptin (L-mRNA) and the leptin receptor (OB-RmRNA) in subcutaneous fat tissue and to determine their relationship with leptin and testosterone and steroid serum levels over the course of the menstrual cycle (MC), in obese (OBW) and non-obese women (NOW). DESIGN: Observational study investigating mRNA transcript expression of leptin and the leptin receptor from human subcutaneous fat specimens, as well as leptin serum levels, both in relation to the testosterone and sex hormones during the MC in obese and non-obese women. METHODS: Nineteen women, thirteen with a body mass index (BMI) > 25 Kg/m2 and 6 with BMI 2 were included. RT-PCR was used to detect L-mRNA transcripts of leptin and its receptor in samples from 28 fat biopsies taken from seven volunteers (20 from OW and 8 from NOW). The serum concentrations of leptin and steroid hormones were measured throughout the MC using radioinmuno analysis. RESULTS: The percentages of women expressing leptin L-mRNA during the phases of the MC were: early follicular (EF), 14.3%;late follicular (LF), 28.6%;early luteal (EL), 14.3%;and late luteal (LL), 42.9%. The percentages of OB-RmRNA were: EF, 71.4%;LF, 14.3%;EL, 28.6%;and LL, 71.4%. Leptin serum levels were directly related to BMI (p < 0.001), and testosterone (p < 0.001) and indirectly to SHBG (p < 0.001). CONCLUSION: The L-mRNA expression and its receptor in subcutaneous human tissue are regulated throughout the MC in a periodic manner. The physiological role of testosterone in regulation of expression L-mRNA and OB-RmRNA during the secretory phase of the MC in obese women requires further investigation.

Expression of Long Form Leptin Receptor mRNA in Pituitary of Pigs around Puberty

[ Objective] To study the expression of long form leptin receptor （Ob.Rb） mRNA in pituitary of pigs around puberty and explore the rela- tionship between Ob-Rb mRNA and porcine development around pituitary. [Method] Three Sujiang pigs were randomly selected at the age of 120 d, puberty and 180 d, respectively. A pair of primers was designed according to the Ob-Rb sequence published in the GenBank. Total RNAs were extracted from pituitary. The expression of Ob-Rb mRNA was detected by the real-time quantitative RT-PCR. [ Result] The Ob-Rb mRNA was de- tected in pituitaries of pigs at the age of 120 d, puberty and 180 d, respectively. The expression level of Ob-Rb mRNA was lowest at puberty. It was significantly different from that in the 120-day-old pigs and not significantly different from that in the 180-day-old pigs. [ Conclusion] The low expres- sion level of Ob-Rb mRNA is conductive to the arrival of puberty.

Breeding of Leptin Receptor Gene Knockout Mice and Genotype Identification of the Offspring

The leptin（ LP） receptor gene heterozygous mice were mated in four ways. Genomic DNA was extracted from offspring tails and analyzed by PCR. The result showed that the ratios of the offspring genotypes fit the Mendel＇s laws. The male and female LP^（-/-）mice（ DB / DB mice） were infertile. LP^（-/-）mice could be effectively bred by mating of male and female LP^（＋/-）mice. PCR methods could identify LP^（-/-）mice precisely.

Leptin及其受体研究进展

近2a来的研究表明:Leptin及其受体是动物与人体脂肪组织数量调控系统中的重要分子。Leptin,是OB基因在脂肪细胞中特异表达的指示脂肪组织数量的负反馈蛋白质因子,是连接脂肪组织中与中枢的信号。Leptin受体是DB基因表达的产物,介导Leptin信号的传递。Leptin及其受体的结构、基因及基因表达调控、信息传递分子机理的研究为脂肪组织数量调控理论和应用开拓了广阔前景。

实验性脂肪肝、肝硬化中Leptin及其受体的检测与表达意义

目的观察Leptin在实验性脂肪肝与肝硬化大鼠血清水平及其受体在肝脏免疫组化表达和定位情况,探讨Leptin及其受体在实验性脂肪肝与肝硬化发生病理机制中的作用。方法采用脂肪乳剂灌胃复制大鼠脂肪肝模型,用硫代乙酰胺腹腔注射诱导肝硬化动物模型,同时设立正常对照组。分别测定血清血脂水平;采用酶联免疫分析法检测血清Leptin含量;免疫组化与计算机图像分析技术观察Leptin受体在脂肪肝组、肝硬化组、正常对照组的表达和定位特点;各组间进行统计学分析。结果脂肪肝组、肝硬化组血清Leptin升高。脂肪肝组的肝脏Leptin受体表达降低,与正常组比较差异有非常显著性(t=4.058,P<0.01);肝硬化组Leptin受体表达增高,与正常组比较差异有非常显著性(t=8.104,P<0.01);肝硬化组Leptin受体表达高于脂肪肝组,其比较差异有非常显著性(t=10.107,P<0.01)。结论Leptin在脂肪肝中高表达,提示其参与肝脂肪变性形成。其受体在脂肪肝的肝脏中表达降低或受抑制,提示高脂肪酸抑制其受体的表达,或者存在着Leptin抵抗。Leptin受体在肝硬化的肝脏中表达异常升高,尤其见于再生的肝细胞及窦内皮细胞等,提示Leptin参与肝纤维化的发生。

Leptin受体在人牙髓干细胞中表达的实验研究

目的:研究体外培养人牙髓干细胞表型特征及生物学性状,检测Leptin受体在牙髓干细胞表面的表达。方法:采用组织块法和酶消化法分离培养人牙髓干细胞;免疫组化法、免疫荧光法检测细胞表面分子的表达;体外诱导分化实验检测细胞多向分化能力。免疫组化法检测Leptin受体在人牙髓干细胞表面的表达。结果:分离获得的牙髓干细胞波形丝蛋白和CD146表达阳性,具有向脂肪细胞和成骨细胞分化的潜能;Leptin受体在牙髓干细胞表面阳性表达。结论:分离培养的牙髓干细胞具有干细胞的表型特征及生物学性状,Leptin受体可表达于牙髓干细胞。

leptin及其受体的研究进展

leptin是肥胖基因 (obesegene ,OB基因 )的蛋白产物 ,具有广泛的生物学功能。据现有研究发现 ,leptin具有参与调节摄食、能量代谢、激素分泌、生长、生殖和免疫等过程的功能。leptin通过其受体发挥调节作用。笔者综述了leptin的受体、生物学功能、调控动物体重的作用机理及leptin抵抗。