瘦素及其受体在胃癌中的表达

目的研究瘦素(Leptin)和瘦素受体(ob-R)在胃癌组织中的表达并探讨其在胃癌发生、发展过程中的作用。方法采用免疫组织化学染色方法检测54例胃癌组织中瘦素和瘦素蛋白的表达。并就其表达与临床病理组织学参数之间的关系进行了相关性分析。结果54例胃癌组织中瘦素和瘦素受体的的表达率为72．22％(39／54)和74．07％(40／54)，肠型胃癌瘦素表达率明显高于弥漫性胃癌。瘦素的表达率与肿瘤组织分化、癌肿大小、转移、TNM分期有关。结论瘦素和瘦素受体以双重表达方式存在于胃癌组织中，参与胃癌的早期发生过程并在其发展中起一定作用。     

Mutations in the human leptin and leptin receptor genes as models of serum leptin receptor regulation

A part of serum Ob leptin, an adipocyte-secreted peptide, is bound to a soluble Ob receptor (sObR). Immunoreactive sObR was measured in 125 lean or obese control subjects (group 1), 18 individuals with a mutation in the leptin gene impairing leptin secretion (group 2), and 10 individuals with a mutation in the ObR gene, leading to production of a truncated ObR not anchored to cell membranes (group 3). In group 1, sObR levels were negatively correlated with age and BMI in children and with BMI in adults. sObR levels were also negatively correlated with leptin levels. Leptin binding activity and sObR levels coeluted in gel-filtration chromatography. In group 2, sObR levels did not differ from those in lean control subjects and were not correlated with BMI. A single peak was detected in chromatographic fractions. In group 3, sObR levels were high and positively correlated with BMI. Immunoreactive sObR coeluted with leptin binding activity. These data demonstrate that leptin is not needed for ObR gene expression, and they suggest that leptin plays a role in receptor downregulation because sObR levels are negatively correlated with leptin levels and BMI in control subjects, whereas sObR levels are not depressed in obese leptin-deficient or leptin receptor-deficient individuals.     

高浓度瘦素自分泌诱导脂肪细胞瘦素抵抗的研究

目的:观察高浓度瘦素对人脂肪细胞分解代谢及脂肪蓄积的直接影响,探讨瘦素自分泌调节在肥胖发生中的作用。方法:取正常成人皮下脂肪组织,常规提取和培养前脂肪细胞,待细胞融合后诱导分化为脂肪细胞后分为二组:低浓度组、高浓度组;分别培养于瘦素终浓度为100ng/ml、1000ng/ml的培养液a中。于培养48h、72h收集培养液检测游离脂肪酸和甘油的浓度,取脂肪细胞行油红O染色并图像分析计算脂肪细胞中脂肪颗粒的积分光密度。结果:与低浓度组相比,瘦素作用48h、72h后,高浓度组培养液中游离脂肪酸浓度均下降[(0.16711±0.011900)mmol/L VS(0.20589±0.008738)mmol/L,(0.17544±0.013920)mmol/L VS(0.23567±0.026220)mmol/L,甘油含量均减少(28.1733±0.91377)μmol/L VS(30.2456±0.30084)μmol/L,(28.9367±0.79530)μmol/L VS(31.8567±0.79024)μmol/L],而脂肪颗粒积分光密度则升高(461136.89±12049.947 VS418570.33±5668.129,441566.56±5921.602 VS 390133.67±7001.304)。结论:高浓度瘦素长时程作用脂肪细胞,可延缓脂肪分解代谢,增加脂肪蓄积。高浓度瘦素经自分泌诱导脂肪细胞产生瘦素抵抗,可能对肥胖发生有重要影响。     

瘦素及瘦素受体在乳腺癌中的表达及临床意义

目的 探讨瘦素及其受体mRNA及蛋白的表达在乳腺癌发生、发展中的意义。方法 采用巢式逆转录-聚合酶链反应〈RT-PCR）和免疫组织化学方法检测39例乳腺癌及其周围正常乳腺组织瘦素及其受体的mRNA及蛋白表达，分析乳腺癌组织瘦素与瘦素受体表达的相关性及其与临床病理之间的关系。结果 瘦素mRNA及蛋白在正常乳腺及乳腺癌组织阳性表达率均为100．00％；瘦素受体mRNA和蛋白在乳腺癌组织阳性表达率为74．40％。正常乳腺组织mRNA阳性表达率7．69％；瘦素及其受体在乳腺癌组织的表达量高于正常组织。差异具有统计学意义（P〈0．01）；瘦素受体的表达与瘦素表达明显相关（P〈0．01）。瘦素及瘦素受体高表达与乳腺癌的转移及浸润明显相关（P〈0．01）。结论 瘦素在乳腺癌的发生发展中可能起着促进作用，瘦素及其受体表达情况可以作为乳腺癌诊断或预后的指标。     

瘦素和瘦素受体在食管癌中的表达及其意义

Objective To investigate the role of leptin and leptin receptor in carcinogensis and development of esophageal carcinoma. Methods The expression of leptin and leptin receptor was detected in 52 cases of esophageal carcinoma tissues and 49 cases of normal esophageal tissues by immunohistochemistry. The correlation between their expression and clinicopathological parameters was also analysized. Results The expression rate of leptin and leptin receptor in esophageal carcinoma was 78. 8% (41/52) and 82.7% (43/52) respectively, and the rate in normal esophagus was 58.3% (28/49) and 59.2% (29/49) respectively. The expression rate of leptin and leptin receptor both had statistically significantly differences between esophageal carcinoma and normal esophagus tissues (P ＜ 0. 05). The expression rate of leptin was associated with position, tumor size, differentiation, lymphatic metastasis and TNM stage (P ＜ 0. 05 ). Conclusion Leptin and leptin receptor were dually expressed in esophageal carcinoma.They played important roles in the process of carcinogensis and development of esophageal carcinoma.     

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.     

瘦素和瘦素受体在食管癌中的表达及其意义

Objective To investigate the role of leptin and leptin receptor in carcinogensis and development of esophageal carcinoma. Methods The expression of leptin and leptin receptor was detected in 52 cases of esophageal carcinoma tissues and 49 cases of normal esophageal tissues by immunohistochemistry. The correlation between their expression and clinicopathological parameters was also analysized. Results The expression rate of leptin and leptin receptor in esophageal carcinoma was 78. 8% (41/52) and 82.7% (43/52) respectively, and the rate in normal esophagus was 58.3% (28/49) and 59.2% (29/49) respectively. The expression rate of leptin and leptin receptor both had statistically significantly differences between esophageal carcinoma and normal esophagus tissues (P ＜ 0. 05). The expression rate of leptin was associated with position, tumor size, differentiation, lymphatic metastasis and TNM stage (P ＜ 0. 05 ). Conclusion Leptin and leptin receptor were dually expressed in esophageal carcinoma.They played important roles in the process of carcinogensis and development of esophageal carcinoma.     

瘦素和瘦素受体在食管癌中的表达及其意义

目的 探讨瘦素及其受体与食管癌发生发展的关系.方法 采用免疫组织化学染色方法检测52例食管癌和49例正常食管组织中瘦素及受体的表达,并分析其与临床病理组织学各参数之间的关系.结果 52例食管癌组织中瘦素与受体的表达率分别为78.8%(41/52)、82.7%(43/52).49例正常的食管组织两者的表达率分别为58.3%(28/49)、59.2%(29/49).瘦素及其受体在食管癌与正常食管组织中的表达差异均有统计学意义(P＜0.05),瘦素及其受体的表达与部位、肿瘤大小、组织学、淋巴结的转移及TNM分期明显相关(P均＜0.05).结论 瘦素及其受体的双重表达在食管癌的发生发展过程中起一定的促进作用.

Abstract：

Objective To investigate the role of leptin and leptin receptor in carcinogensis and development of esophageal carcinoma. Methods The expression of leptin and leptin receptor was detected in 52 cases of esophageal carcinoma tissues and 49 cases of normal esophageal tissues by immunohistochemistry. The correlation between their expression and clinicopathological parameters was also analysized. Results The expression rate of leptin and leptin receptor in esophageal carcinoma was 78. 8% (41/52) and 82.7% (43/52) respectively, and the rate in normal esophagus was 58.3% (28/49) and 59.2% (29/49) respectively. The expression rate of leptin and leptin receptor both had statistically significantly differences between esophageal carcinoma and normal esophagus tissues (P ＜ 0. 05). The expression rate of leptin was associated with position, tumor size, differentiation, lymphatic metastasis and TNM stage (P ＜ 0. 05 ). Conclusion Leptin and leptin receptor were dually expressed in esophageal carcinoma.They played important roles in the process of carcinogensis and development of esophageal carcinoma.     

Expression of leptin and leptin receptor in the testis of fertile and infertile patients

The aim of our study was to investigate the relationships between the expression of leptin, leptin receptor in the testis and spermatogenesis, and testosterone (T) concentration in infertile men. Testicular tissue samples were collected from the testes of five fertile volunteers, eight patients with obstructive azoospermia (OA), six patients with Sertoli cell-only syndrome (SCO) and 32 oligospermic patients with varicocele testis. In testicular tissue, leptin and leptin receptor were identified by staining with polyclonal antibodies. Serum follicle stimulating hormone, lutenising hormone (LH), and T were determined by chemiluminescence assays. Leptin was expressed on germ cells, mainly on spermatocytes. The ratio of immunostained germ cells to total germ cells was inversely correlated with the concentration of T (r = -0.32, P = 0.01), sperm concentration (r = -0.51, P = 0.002) and Johnsen's score (r = -0.44,P = 0.005). In contrast, leptin receptor immunostained cells were found in the interstitium, primarily in Leydig cells. Leptin receptor expression on Leydig cells was inversely correlated with serum T concentration (r = -0.50, P < 0.001). The dysfunction of spermatogenesis is associated with an increase in leptin and leptin receptor expression in the testis.     

高脂血症性胰腺炎大鼠瘦素、瘦素受体表达的动态变化

目的:探讨瘦素及瘦素受体在大鼠高脂血症性胰腺炎(HLAP)中的动态变化.方法:将60只SD雄性大鼠随机分为3组:正常对照组(NC组),高脂血症组(HL组),高脂血症性胰腺炎组(HLAP组).采用高脂饲料喂养3周后经腹腔注射L-精氨酸500 mg/100 9体重制作大鼠高脂血症性胰腺炎模型.各组分别于造模后24 h、36...     

不同能量平衡状态下瘦素及瘦素受体在小鼠肝细胞损伤中的作用机制

目的 探讨在不同能量平衡状态下瘦素(leptin)及瘦素受体(leptin receptor,LEPR)参与肝细胞损伤的作用机制研究.方法 选取4周龄FVB/N雌性小鼠18只,分为3组:Mex3c+/-突变组(文中简称Mex3c+/-组,n=6),HFD组(给予高脂饮食,n=6)和Control组(给予普通饲料,n=6...     

Peripheral leptin regulates bone formation

Substantial evidence does not support the prevailing view that leptin, acting through a hypothalamic relay, decreases bone accrual by inhibiting bone formation. To clarify the mechanisms underlying regulation of bone architecture by leptin, we evaluated bone growth and turnover in wild‐type (WT) mice, leptin receptor‐deficient db/db mice, leptin‐deficient ob/ob mice, and ob/ob mice treated with leptin. We also performed hypothalamic leptin gene therapy to determine the effect of elevated hypothalamic leptin levels on osteoblasts. Finally, to determine the effects of loss of peripheral leptin signaling on bone formation and energy metabolism, we used bone marrow (BM) from WT or db/db donor mice to reconstitute the hematopoietic and mesenchymal stem cell compartments in lethally irradiated WT recipient mice. Decreases in bone growth, osteoblast‐lined bone perimeter and bone formation rate were observed in ob/ob mice and greatly increased in ob/ob mice following subcutaneous administration of leptin. Similarly, hypothalamic leptin gene therapy increased osteoblast‐lined bone perimeter in ob/ob mice. In spite of normal osteoclast‐lined bone perimeter, db/db mice exhibited a mild but generalized osteopetrotic‐like (calcified cartilage encased by bone) skeletal phenotype and greatly reduced serum markers of bone turnover. Tracking studies and histology revealed quantitative replacement of BM cells following BM transplantation. WT mice engrafted with db/db BM did not differ in energy homeostasis from untreated WT mice or WT mice engrafted with WT BM. Bone formation in WT mice engrafted with WT BM did not differ from WT mice, whereas bone formation in WT mice engrafted with db/db cells did not differ from the low rates observed in untreated db/db mice. In summary, our results indicate that leptin, acting primarily through peripheral pathways, increases osteoblast number and activity. © 2013 American Society for Bone and Mineral Research     

正常月经周期子宫内膜瘦素和瘦素受体的表达

目的　探讨瘦素和瘦素受体系统在正常月经周期子宫内膜表达特点及其意义。　方法　应用免疫组织化学方法检测 60例正常月经周期子宫内膜瘦素和瘦素长受体蛋白的表达。原位杂交技术测定 2 5例子宫内膜瘦素和瘦素长受体mRNA。　结果　瘦素蛋白在子宫内膜腺体和间质呈阳性或强阳性表达 ,月经周期各期间无显著差异 ;瘦素长受体蛋白在子宫内膜间质中呈弱阳性或阴性表达 ,月经周期各期间无显著差异 ;瘦素长受体蛋白在子宫内膜腺体的表达分泌期显著高于增殖期 (P <0 .0 0 1 )。瘦素和瘦素长受体mRNA在增殖期和分泌期子宫内膜的腺体和间质中均呈阳性表达。　结论　瘦素长受体蛋白在分泌期子宫内膜腺体表达增强 ,有可能在孕卵着床过程中发挥作用     

糖尿病大鼠血清瘦素与肾脏瘦素受体表达观察

目的研究2型糖尿病大鼠血清瘦素（leptin）及肾脏瘦素受体（Ob-R）表达变化。方法高糖高脂饮食结合小剂量链脲佐菌素建立2型糖尿病大鼠动物模型。在8周末测量大鼠体质量、血压、空腹血糖、三酰甘油、胆固醇和24h尿蛋白排泄量等指标，用酶联免疫吸附法测定大鼠的血清瘦素、胰岛素，计算胰岛素抵抗指数。免疫组化检测Ob-R在肾脏的表达情况。结果糖尿病大鼠体质量、血糖、总胆固醇、三酰甘油、血清胰岛素较对照组均明显升高，24h尿蛋白排泄量轻度升高。与对照组比较，大鼠血清瘦素明显升高，同时糖尿病组肾脏Ob—R的表达水平下降，二者呈负相关。结论2型糖尿病大鼠高血清瘦素可能对肾脏0b-R表达有抑制作用。     

Baseline leptin levels predict change in leptin levels during weight loss in obese breast cancer survivors

Leptin is an adipocyte-derived hormone involved in regulation of satiety, and it also appears to have a role in breast cancer risk. Leptin therefore might be a useful indicator of the potential preventive effects of weight loss in breast cancer survivors. In this study we examined whether the change in leptin levels could be predicted by weight loss in obese breast cancer survivors. The subjects in this study were participating in a randomized trial of an individualized approach towards weight loss in Detroit, MI. Breast cancer survivors (body mass index of 30-44 kg/m(2)) were enrolled and fasting blood samples were obtained for leptin analysis over 1 year of study. Leptin levels were available from at least two time points for 36 women, and weight change ranged from a gain of 11% to a loss of 25% of baseline weight. Using a repeated-measures regression model, both baseline leptin level and concurrent percent body fat were found to synergistically predict leptin levels. Thus, for women with the same body fat, those with higher baseline leptin levels are predicted to exhibit smaller decreases in leptin with weight loss. Similar results were obtained for body weight and body weight change, but the associations with body fat were stronger. Breast cancer survivors with initially higher leptin levels may differ with regard to regulation of change in leptin during weight loss resulting in relatively smaller changes in leptin with equivalent amounts of weight loss.     

瘦素自分泌调节及瘦素抵抗

肥胖是整形美容外科的常见病，也是体形塑造的重要内容，严重危害身心健康。肥胖机理不明确，极大地制约了临床防治。瘦素的发现为肥胖发病机制及防治的研究开辟了崭新领域，瘦素的自分泌调节及瘦素抵抗在肥胖发病中可能起重要作用，本文就此作一综述。     

瘦素在胆囊胆固醇结石形成中的作用

目的 通过临床病例研究,探讨血清及胆汁中的瘦素在胆囊胆固醇结石形成中的作用与影响.方法 选取2016年3月1日-11月30日在内蒙古自治区人民医院肝胆胰脾外科住院行腹腔镜下或开腹胆囊切除术患者共91例,分为胆囊胆固醇结石组(A组)58例和非胆囊胆固醇结石组(B组)33例,以体重指数=24 kg/m2为标准,又将A组分成A1组30例(体重指数≥24 kg/m2)和A2组28例(体重指数＜24 kg/m2);B组分成B1组18例(体重指数≥24 kg/m2)和B2组15例(体重指数＜24 kg/m2).对A、B两组病例一般情况、体重指数、血清瘦素含量、胆汁瘦素含量、高密度脂蛋白、低密度脂蛋白、脂蛋白(a)、载脂蛋白AI、载脂蛋白B、载脂蛋白AI/载脂蛋白B比值、血清总胆固醇、血清总胆汁酸、三酰甘油等指标进行检测.计量资料用均数±标准差(-x±s)表示,组间比较使用t检验或t’检验.计数资料用频数和百分数表示,组间比较使用x2检验.体重指数和血清瘦素的相关性采用Pearson相关系数描写.结果 胆囊胆固醇结石组患者血清瘦素含量与非胆囊胆固醇结石组血清瘦素含量分别为(7.92 +7.34) ng/ml和(4.81±1.79) ng/ml,差异有统计学意义(P＜0.05),同时该组血清瘦素水平与体重指数呈正相关(r=0.65,P=0.01),当体重指数≥24 kg/m2时相关性明显(r =0.73,P ＜0.01).胆囊胆固醇结石组血清总胆固醇、低密度脂蛋白、载脂蛋白B、三酰甘油水平分别为(4.85±0.74) mmol/L、(2.53±0.69) mmol/L、(0.97±0.3) g/L、(1.92±0.61) mmol/L,非胆囊胆固醇结石组分别为(4.47±0.8) mmol/L、(2.22±0.50) mmol/L、(0.8 ±0.2) g/L、(1.49 ±0.69) mmol/L,与后者相比前者含量显著性增高(P＜0.05).胆囊胆固醇结石组高密度脂蛋白和载脂蛋白AI含量分别为(0.93±0.28) mmol/L、(1.38±0.27) g/L,与非胆囊胆固醇结石组(1.24 ±0.26) mmol/L、(1.53±0.21) g/L相比显著性降低(P＜0.05);两组胆汁瘦素含量、总胆汁酸、脂蛋白(a)差异无统计学意义(P＞0.05).结论 血清瘦素含量的改变,可能通过影响血液脂质、脂蛋白水平,以及胆汁中瘦素的含量,最终影响胆固醇结石的形成过程.     

Impaired leptin responsiveness in aged rats

We previously reported that adiposity and serum leptin levels increase with age in male F-344xBN rats and that when physiological levels of serum leptin are manipulated by fasting, there is a corresponding reciprocal change in hypothalamic neuropeptide Y (NPY) mRNA in young rats, but there are no changes in older rats. These findings suggest that the regulation of hypothalamic NPY mRNA by leptin may be impaired with age. To test this hypothesis, we infused saline or leptin for 7 days into ad libitum-fed rats and compared these with saline-infused rats that were pair-fed the amount of food consumed by the leptin-treated rats. We examined daily food consumption, body weight, whole-body oxygen consumption, serum leptin, and NPY mRNA in the hypothalamus. Food consumption decreased by 50% in the leptin-infused compared with the saline-infused young rats but only decreased by 20% in the aged rats. In the leptin-treated young rats, there was a 24% increase in oxygen consumption compared with the pair-fed rats, but there were no changes in oxygen consumption in the aged rats. Leptin infusion diminished hypothalamic NPY levels by nearly 50% compared with pair-fed young rats, whereas there were no changes in the hypothalamic NPY mRNA levels in senescent rats. In summary, aged rats demonstrate a reduced responsiveness to leptin, including a diminished decrease in food intake and no increase in energy expenditure. These diminished responses to leptin were associated with and may be the result of an impaired suppression of hypothalamic NPY mRNA levels. This leptin resistance may be due to either the elevated obesity and serum leptin with age or due to age itself, or both.