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...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.展开更多
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 immobili...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.展开更多
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 ...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.展开更多
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 o...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.展开更多
[ 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]...[ 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.展开更多
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 pro...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.展开更多
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 l...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.展开更多
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 Mende...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.展开更多
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 physiopatho...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.展开更多
Obesity has been reported to increase postmenopausal breast cancer risk by 30% to 50%, and obese breast cancer patients have been shown to present more aggressive breast cancer pathological features As most breast can...Obesity has been reported to increase postmenopausal breast cancer risk by 30% to 50%, and obese breast cancer patients have been shown to present more aggressive breast cancer pathological features As most breast cancers are sex hormone-dependent, adipocytokines derived from adipose tissue, such as leptin, may account for the positive association between obesity and breast cancer. Leptin, a 16-kDa protein product of the obese gene, was initially regarded as a neuroendocrine factor in the hypothalamus to maintain homeostasis of body weight by regulating food intake and energy expenditure.展开更多
Objective: In postmenopausal women, an increased leptin concentration and reduced levels of ghrelin and adiponectin were observed. The aim of this study was to evaluate the concentrations of the active form of ghreli...Objective: In postmenopausal women, an increased leptin concentration and reduced levels of ghrelin and adiponectin were observed. The aim of this study was to evaluate the concentrations of the active form of ghrelin, total ghrelin, leptin receptor, lipoprotein(a) (Lp(a)), and plasminogen activator inhibitor type 1 (PAl-l) in postmenopausal women who received oral or transdermal menopausal hormonal therapy (MHT). Methods: The study involved 76 healthy women: 46 women aged from 44 to 58 years who received oral (26) or transdermal (20) MHT; the control group consisted of 30 women aged from 44 to 54 years who did not receive MHT. The plasma concentrations of total ghrelin, the active form of ghrelin, Lp(a), and PAI-I:Ag were measured by enzyme-linked immunosorbent assay (ELISA). The concentration of the leptin receptor was measured by enzyme immunometric assay (EIA). Results: We observed a significantly higher concentration o~ total ghrelin and the active form of ghrelin in women who received transdermal MHT in comparison with those who took oral MHT. We also found a significantly lower concentration of total ghrelin in women who received oral MHT compared with the control group. A higher concentration of PAl-1 :Ag was found in the group of women who took transdermal MHT in comparison with those who took oral MHT and with the control group. The differences were statistically significant. Additionally, we found a significant negative correlation between the concentrations of total ghrelin and PAl-1 :Ag and a positive correlation between the concentrations of total ghrelin and leptin receptor in women who received transdermal MHT. Conclusions: The study showed that women who used transdermal MHT had higher levels of total ghrelin than women who took oral MHT. This indicates a beneficial effect of the transdermal route of MHT. However, transdermal therapy was associated with adverse effects with regard to the observed higher levels of PAl-1 :Ag, which in turn, can lead to a reduction in fibrinolytic activity.展开更多
The product of the obesity gene, called leptin, is an important regulator of adiposity, which mainly functions via its regulation of feed intake and energy metabolism. Both obesity gene (ob gene) and leptin receptor g...The product of the obesity gene, called leptin, is an important regulator of adiposity, which mainly functions via its regulation of feed intake and energy metabolism. Both obesity gene (ob gene) and leptin receptor gene (OBR gene) are thought to play a major role in controlling of body fat mass as well as body weight. The result of RT-PCR shows that levels of pig OBR mRNA are higher in hypothalamus, lung and liver, and lower expression can be detected in other tissues. Total RNA purified from 11 different organs and tissues have been hybridized with pig OBR cDNA probes. The hybridization signals are shown in 7 organs and tissues. 4.1 and 3.8 kb bands were observed from hypothalamus, whereas 3.8 and 3.5 kb bands were observed in other tissues instead. The nearly complete sequence of the extracellular domain of pig OBR gene was obtained. The homology of sequence is 89.2% between pig and human, 80.3% between pig and mouse. Alignment of the predicted ammo acid sequence of OBR in pig, human and mouse shows展开更多
Leptin resistance is a main mechanism of acquired childhood obesity,and the suppression of long form of leptin receptor(OBRb)gene expression in diet-induced obese rats indicates that the down-regulation of OBRb gene e...Leptin resistance is a main mechanism of acquired childhood obesity,and the suppression of long form of leptin receptor(OBRb)gene expression in diet-induced obese rats indicates that the down-regulation of OBRb gene expression plays a pivotal role in the mechanism of leptin resistance.The aim of the present study was to construct the lentiviral RNA interference(RNAi)vector of rat OBRb gene and evaluate the effects of siRNA on silencing OBRb gene expression.The target sequence of siRNA-OBRb was designed,and the com-plementary DNA containing both sense and antisense oligonucleotides was synthesized.After phosphorylation and annealing,these double-stranded DNA was cloned to pRNA-lentivector-VGFP to construct pRNA-Lenti-OBRb-VGFP recombinants with U6-containing promoter,target sequence and Poly III terminator.Then,the products were confirmed by electrophoresis and sequencing analy-sis,and the effects of RNAi on reducing gene expression were further confirmed by real-time polymerase chain reaction in transfected rat glioma cells expressing OBRb.The target sequence of siRNA-OBRb was successfully cloned to pRNA-lentivector-VGFP,and the RNAi protocol specifically reduced the expression of OBRb mRNA by approximately 80%compared with controls in transfected rat glioma cells.The successful construction of rat lentivirus vectors expressing OBRb-specific shRNA may be useful for further investigation in vivo.展开更多
Objective:To investigate the adjusting malnutrition mechanism by the Reinforcing Kidney and Exhausting Toxic Mixture(REM)on the chronic renal failure (CRF) rat.Methods:60 wistar rats weved ivided into 3 groups randoml...Objective:To investigate the adjusting malnutrition mechanism by the Reinforcing Kidney and Exhausting Toxic Mixture(REM)on the chronic renal failure (CRF) rat.Methods:60 wistar rats weved ivided into 3 groups randomly :the normal controc group(group Ⅰ),CRF group(group Ⅱ),and CRF rat perfusingwithREM group(group Ⅲ). Taking theirfat,kidneytissuefor detecting the protein expression of the leptin,leptin receptor(Ob-R) by the means ofimmunohistochemistry.Result:Comparing with control group, the leptinprotein express intensely in CRF rat ; In kidney tissue,the ob-R express weakly. After perfusing the REM ,comparing with CRF groupthe renal ob-R express strongly than CRF group. Conclusion: Maybe the REM could do a little better with the malnutritionof CRFratsby adjusttingthe activity of ob-R in kidney.展开更多
文摘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.
基金supported by the National Natural Science Foundation of China,No.30672578,81072756and81202644China National Funds for Distinguished Young Scientists,No.30825046+2 种基金Program for Innovative Research Team in Beijing University of Chinese Medicine,No.2011CXTD-07Program for University Key Teacher of Hebei Medical UniversitySpecialized Research Fund for the Doctoral Program of Higher Education,No.20121323120016
文摘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.
文摘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.
文摘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.
文摘[ 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.
文摘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.
文摘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.
文摘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.
文摘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.
基金This work was supported by the grants from Capital Foundation for Development of Medical Science (No. 2005-2031) and National Natural Science Foundation of China (No. 30772121).
文摘Obesity has been reported to increase postmenopausal breast cancer risk by 30% to 50%, and obese breast cancer patients have been shown to present more aggressive breast cancer pathological features As most breast cancers are sex hormone-dependent, adipocytokines derived from adipose tissue, such as leptin, may account for the positive association between obesity and breast cancer. Leptin, a 16-kDa protein product of the obese gene, was initially regarded as a neuroendocrine factor in the hypothalamus to maintain homeostasis of body weight by regulating food intake and energy expenditure.
基金Project supported by the Collegium Medicum in Bydgoszcz,Nicolaus Copernicus University in Toruń (No.73/04),Poland
文摘Objective: In postmenopausal women, an increased leptin concentration and reduced levels of ghrelin and adiponectin were observed. The aim of this study was to evaluate the concentrations of the active form of ghrelin, total ghrelin, leptin receptor, lipoprotein(a) (Lp(a)), and plasminogen activator inhibitor type 1 (PAl-l) in postmenopausal women who received oral or transdermal menopausal hormonal therapy (MHT). Methods: The study involved 76 healthy women: 46 women aged from 44 to 58 years who received oral (26) or transdermal (20) MHT; the control group consisted of 30 women aged from 44 to 54 years who did not receive MHT. The plasma concentrations of total ghrelin, the active form of ghrelin, Lp(a), and PAI-I:Ag were measured by enzyme-linked immunosorbent assay (ELISA). The concentration of the leptin receptor was measured by enzyme immunometric assay (EIA). Results: We observed a significantly higher concentration o~ total ghrelin and the active form of ghrelin in women who received transdermal MHT in comparison with those who took oral MHT. We also found a significantly lower concentration of total ghrelin in women who received oral MHT compared with the control group. A higher concentration of PAl-1 :Ag was found in the group of women who took transdermal MHT in comparison with those who took oral MHT and with the control group. The differences were statistically significant. Additionally, we found a significant negative correlation between the concentrations of total ghrelin and PAl-1 :Ag and a positive correlation between the concentrations of total ghrelin and leptin receptor in women who received transdermal MHT. Conclusions: The study showed that women who used transdermal MHT had higher levels of total ghrelin than women who took oral MHT. This indicates a beneficial effect of the transdermal route of MHT. However, transdermal therapy was associated with adverse effects with regard to the observed higher levels of PAl-1 :Ag, which in turn, can lead to a reduction in fibrinolytic activity.
基金the National Natural Science Foundation of China (Grant No. 39725022 ) the State Key Basic Research Development Program (Grant No. 2000016100).
文摘The product of the obesity gene, called leptin, is an important regulator of adiposity, which mainly functions via its regulation of feed intake and energy metabolism. Both obesity gene (ob gene) and leptin receptor gene (OBR gene) are thought to play a major role in controlling of body fat mass as well as body weight. The result of RT-PCR shows that levels of pig OBR mRNA are higher in hypothalamus, lung and liver, and lower expression can be detected in other tissues. Total RNA purified from 11 different organs and tissues have been hybridized with pig OBR cDNA probes. The hybridization signals are shown in 7 organs and tissues. 4.1 and 3.8 kb bands were observed from hypothalamus, whereas 3.8 and 3.5 kb bands were observed in other tissues instead. The nearly complete sequence of the extracellular domain of pig OBR gene was obtained. The homology of sequence is 89.2% between pig and human, 80.3% between pig and mouse. Alignment of the predicted ammo acid sequence of OBR in pig, human and mouse shows
基金supported by the National Natural Science Foundation of China(Grant Nos.30571577 and 30771798).
文摘Leptin resistance is a main mechanism of acquired childhood obesity,and the suppression of long form of leptin receptor(OBRb)gene expression in diet-induced obese rats indicates that the down-regulation of OBRb gene expression plays a pivotal role in the mechanism of leptin resistance.The aim of the present study was to construct the lentiviral RNA interference(RNAi)vector of rat OBRb gene and evaluate the effects of siRNA on silencing OBRb gene expression.The target sequence of siRNA-OBRb was designed,and the com-plementary DNA containing both sense and antisense oligonucleotides was synthesized.After phosphorylation and annealing,these double-stranded DNA was cloned to pRNA-lentivector-VGFP to construct pRNA-Lenti-OBRb-VGFP recombinants with U6-containing promoter,target sequence and Poly III terminator.Then,the products were confirmed by electrophoresis and sequencing analy-sis,and the effects of RNAi on reducing gene expression were further confirmed by real-time polymerase chain reaction in transfected rat glioma cells expressing OBRb.The target sequence of siRNA-OBRb was successfully cloned to pRNA-lentivector-VGFP,and the RNAi protocol specifically reduced the expression of OBRb mRNA by approximately 80%compared with controls in transfected rat glioma cells.The successful construction of rat lentivirus vectors expressing OBRb-specific shRNA may be useful for further investigation in vivo.
文摘Objective:To investigate the adjusting malnutrition mechanism by the Reinforcing Kidney and Exhausting Toxic Mixture(REM)on the chronic renal failure (CRF) rat.Methods:60 wistar rats weved ivided into 3 groups randomly :the normal controc group(group Ⅰ),CRF group(group Ⅱ),and CRF rat perfusingwithREM group(group Ⅲ). Taking theirfat,kidneytissuefor detecting the protein expression of the leptin,leptin receptor(Ob-R) by the means ofimmunohistochemistry.Result:Comparing with control group, the leptinprotein express intensely in CRF rat ; In kidney tissue,the ob-R express weakly. After perfusing the REM ,comparing with CRF groupthe renal ob-R express strongly than CRF group. Conclusion: Maybe the REM could do a little better with the malnutritionof CRFratsby adjusttingthe activity of ob-R in kidney.