Disease relevance of LEPROT

• Interestingly, in the 96 leptin- or OB-R-positive tumors, hematogenous metastasis was detected preoperatively in 3 (3.1%) patients [1].
• CONCLUSION: Overexpression of leptin and expression of OB-R may play a positive role in the process of progression in gastric cancer [1].
• In contrast, none of the carcinomas that lacked expression of leptin and OB-R showed hematogenous metastasis [1].
• This study was designed to test the hypothesis that long-term hypoxia (LTH) increases fetal plasma leptin and fetal adipose or placental leptin expression and alters hypothalamic and adrenocortical leptin receptor (OB-R) expression [2].
• CONCLUSION: This case-control study showed no significant association between leptin receptor gene polymorphisms and the risk of young-onset prostate cancer, suggesting that genetic variations in OBR are unlikely to have a major role in the development of early-onset prostate cancer in the UK [3].

High impact information on LEPROT

• We here report that primary acute promyelocytic leukemia (APL) cells express high levels of the leptin-receptor (OB-R) long isoform [4].
• For patients without distant metastasis at the time of recurrence, the 5-year actuarial rate of development of distant metastasis was 60% for SR patients compared with 39% for invasive OBR patients (P = .07), and the corresponding 5-year actuarial survival rates beyond the time of local failure were 51% and 79%, respectively (P = .06) [5].
• In three human bladder carcinoma cell lines (OBR, T24, and 647V), we show that two EGF receptor ligands, namely EGF and transforming growth factor alpha, enhanced the apoptosis due to serum starvation on cells cultured as monolayers [6].
• VPS55 belongs to a family of genes of unknown function, including the human gene encoding the obesity receptor gene-related protein (OB-RGRP) [7].
• The leptin receptor (OB-R) mediates the weight regulatory effects of the adipocyte secreted hormone leptin (OB) [8].

Biological context of LEPROT

• Functional upregulation of leptin/OB-R may have a positive role in the development and initial phase of progression in gastric cancer [1].
• In the second stage of analysis, an important chromosome 1 positional candidate gene, the leptin receptor (LEPR), was studied [9].
• RESULTS: Multipoint analysis of the genome scan data identified linkage (log of odds, LOD, 3.4) of leptin levels to a chromosomal region defined by D1S3728 and D1S1665, flanking the leptin receptor (LEPR) gene by approximately 9 and 3 cM, respectively [9].
• The mRNA and protein of the long form leptin receptor (OB-R(L)) but not of leptin are expressed in the human endometrium and the abundance of OB-R mRNA expression varies during the menstrual cycle with a peak in the early secretory phase [10].
• We investigated associations between bone mineral density (BMD) and polymorphisms of the leptin receptor (LEPR) and estrogen receptor alpha (ERalpha) genes in young men [11].

Anatomical context of LEPROT

• AIM: To examine the expression of leptin and its receptor, OB-R, in normal gastric mucosa and neoplasia [1].
• In cases with OB-R staining, carcinoma cells showed OB-R-positive expression, but the intensity was weaker than that in normal mucosa [1].
• Lymph node metastasis was detected in 49.5% (47/95) of leptin-strong cases and in 50.5% (48/95) of OB-R-positive cases, and the rate was 33% (37/112) in leptin-weak cases and 17% (19/112) in OB-R-negative cases [1].
• Immunohistochemical detection of leptin receptor immunoreactivity (all forms) revealed the presence of OBR-like protein in pituitary and hypothalamus as early as PD 4 [12].
• Leptin plays an important role in the regulation of body fat homeostasis, and potential associations of leptin receptor gene (LEPR) polymorphisms with obesity have been suggested [13].

Associations of LEPROT with chemical compounds

• OBJECTIVE: Genetic variation in leptin receptor (LEPR) gene has been reported to associate with insulin and glucose metabolism and adiposity in different study settings and various populations [14].

Analytical, diagnostic and therapeutic context of LEPROT

• Overlapping and distinct signals through leptin receptor (OB-R) and a closely related cytokine signal transducer, gp130 [15].
• A meta-analytic investigation of linkage and association of common leptin receptor (LEPR) polymorphisms with body mass index and waist circumference [16].
• RT-PCR was used to detect the presence of OB-R and, more specifically, the long, biologically active isoform (OB-Rb), in CL, collected on days 2-18 of the oestrous cycle (n = 18) [17].
• We assessed placental gene expression of leptin, LEPR A-D and ADIPOR1 and 2 by real time PCR using mRNA from maternal and fetal biopsies [18].
• In animal models, the leptin (LEP) and the leptin receptor (LEPR) genes have been shown to be very important in obesity because leptin functions as a negative feedback signal in regulating body-weight through reducing food intake and stimulating energy expenditure [19].

References