Disease relevance of Lepr

• METHODS: Leptin-receptor mutated Zucker diabetic fatty (ZDF) and lean control rats were treated with the ghrelin-receptor ligand, tabimorelin (50 mg/kg p.o.) for 18 days, and the effects on body weight, food intake and body composition were investigated [1].
• Arcuate nucleus-specific leptin receptor gene therapy attenuates the obesity phenotype of Koletsky (fa(k)/fa(k)) rats [2].
• Our results indicate that high birth weight is related to shortened latency to develop mammary tumors--perhaps reflecting an increase in activated MAPK levels and increased tumor growth--perhaps caused by a lower apoptotic response due to higher leptin receptor and activated Akt levels in the tumors [3].
• The effect of treatment with a 0.03% fatty acid (FA) cocktail on leptin-receptor-mediated STAT (signal transducers and activators of transcription) activation in the rat insulinoma cell line BRIN-BD11 was investigated [4].
• The Koletsky ("corpulent) obese rat is homozygous for an autosomal recessive mutation of the leptin receptor (Lepr) that results in hyperphagia, obesity, and hyperlipidemia [5].

Psychiatry related information on Lepr

• Food deprivation enhanced NPY and suppressed leptin receptor expression in the ARN and PVN of the hypothalamus [6].
• Products of the proopiomelanocortin (POMC) gene are known to affect feeding behavior, and POMC neurons share a similar distribution with leptin receptor mRNA in the arcuate nucleus [7].

High impact information on Lepr

• Leptin receptor missense mutation in the fatty Zucker rat [8].
• Leptin is thought to exert its actions on energy homeostasis through the long form of the leptin receptor (OB-Rb), which is present in the hypothalamus and in certain peripheral organs, including adipose tissue [9].
• PPARalpha is a OB-R-dependent factor required for normal fat homeostasis in islet cells [10].
• Overexpression of normal OB-R in islets of fa/fa rats corrects all of the foregoing abnormalities and reverses the diabetic phenotype [10].
• Expression of peroxisome proliferator-activated receptor alpha (PPARalpha) and enzymes of fatty acid (FA) oxidation is markedly reduced in the fat-laden, dysfunctional islets of obese, prediabetic Zucker diabetic fatty (fa/fa) rats with mutated leptin receptors (OB-R) [10].

Chemical compound and disease context of Lepr

• Zucker fa/fa and Fa/? rats were infused with Escherichia coli lipopolysaccharide (LPS; 10 microg/kg) through a jugular catheter (infectious fever) or with saline through the catheter (control) or received a painful intramuscular injection of saline (stress fever) [11].
• We investigated the effect of inhibition of 11beta-HSD with glycyrrhetinic acid (GE), an effective 11beta-HSD inhibitor, on body weight regulation in obese Zucker rats, which have a defect in the leptin receptor gene [12].
• The obese Zucker rat, an animal model of genetic obesity, exhibits differences in serotonin signaling as well as a mutated leptin receptor [13].

Biological context of Lepr

• The anti-OB-R had no effect on either leukemic cell growth or angiogenesis in leukemic fa/fa rats with a mutated leptin receptor [14].
• The weight-reducing action of leptin is thought to be mediated primarily by signal transduction through the leptin receptor (LR) in the hypothalamus [15].
• In an attempt to further investigate leptin's role in bone formation, we examined the skeleton of obese leptin receptor-deficient Zucker rats [16].
• Total leptin receptor (Ob-R) and the long form of the leptin receptor (Ob-Rb) gene expression were lower in the arcuate (ARC) and ventromedial nuclei (VMN) in Lou/C rat [17].
• In GK rats, leptin-induced phosphorylation of signal transducer and activator of transcription 3 was significantly reduced in the cells of the hypothalamic arcuate nucleus (ARC), but not of the ventromedial hypothalamus, whereas the mRNA level of functional leptin receptor was unaltered [18].

Anatomical context of Lepr

• Treatment with anti-OB-R for 3 weeks more than halved the content of bone marrow leukemic cells with a concomitant, substantial decrease in angiogenesis [14].
• Leptin receptor immunoreactivity in chemically defined target neurons of the hypothalamus [15].
• In +/+ but not in fa/fa rats, plasma catecholamine levels rose, and both P-STAT3 and P-CREB increased in adipose tissue, suggesting that both direct and indirect (hypothalamic) leptin receptor-mediated actions of hyperleptinemia are involved in depletion of adipocyte fat [19].
• Double in situ hybridization histochemistry revealed that, in contrast to the situation in the arcuate nucleus, NPY and leptin receptor mRNA-expressing neurons were not colocalized in the DMH [20].
• Leptin receptor mRNA levels in the uterus are also regulated with an increase about 2.7-fold during this same period, whereas there is no change in other tissues examined [21].

Associations of Lepr with chemical compounds

• The present study was designed to elucidate the effects of two different treatments with 17beta-estradiol on leptin receptor and serum leptin levels in ovariectomized rats, a model of postmenopausal condition [22].
• Leptin receptor-deficient obese Zucker rats reduce their food intake in response to a systemic supply of calories from glucose [23].
• On the other hand, we found that chronic nicotine administration increased the expression levels of OB-Rb mRNA by 12% and OB-R mRNA by 25% in the medial basal hypothalamus compared to control rats [24].
• Furthermore, leptin receptor protein, as determined by immunocytochemistry, was colocalized in virtually all vasopressin and oxytocin cells in the supraoptic nucleus [25].
• The fluctuations in leptin receptor mRNA content may be a response to the concentrations of circulating steroid hormones and leptin [26].

Physical interactions of Lepr

• Plasma leptin-binding activity and hypothalamic leptin receptor expression during pregnancy and lactation in the rat [27].

Enzymatic interactions of Lepr

• Phosphorylated leptin receptor and phosphorylated signal transducer and activator of transcription-3 (p-STAT3) remained elevated in association with a sustained elevation in DNA-binding activity of STAT3 in the hypothalamus throughout 16-d period of leptin infusion [28].

Regulatory relationships of Lepr

• In addition, hypocretin-containing neurons also express leptin receptor immunoreactivity [29].
• These neuropeptide Y neurons express the Ob-Rb leptin receptor and are overactive in the fatty (fa/fa) Zucker rat [30].
• Leptin plays an important role in the control of food intake and energy metabolism by interacting with its receptor (OB-R) in the brain [31].
• Leptin is a JAK2-activating cytokine via the long form leptin receptor (Ob-Rb) [32].
• We used double label in situ hybridization and computerized image analysis to test the hypothesis that POMC neurons coexpress the leptin receptor [7].

Other interactions of Lepr

• Leptin receptor mRNA identifies a subpopulation of neuropeptide Y neurons activated by fasting in rat hypothalamus [33].
• In conclusion, we suggest that ghrelin-receptor ligands exert their adipogenic and orexigenic effects via hypothalamic mechanisms that are dependent on intact leptin-receptor signalling [1].
• These data demonstrate that the rat pancreatic tumor cell line AR42J expresses a functional form of the leptin receptor that modulates the action of CCK in calcium mobilization and amylase release [34].
• TaqMan analysis of gene expression following chronic FA treatment showed neither a decrease in the amount of leptin receptor (Ob-R) mRNA, nor an increase in the negative regulators of STAT signalling, SOCS3 (suppressors of cytokine signalling) or cytokine inducible sequence (CIS) [4].
• The long-form membrane leptin receptor OB-Rb, the protease activator furin, and proprotein convertase 7 were found in Chief cell granules but not in those of endocrine cells [35].

Analytical, diagnostic and therapeutic context of Lepr

• We have used immunohistochemistry to localize LR-immunoreactive (LR-IR) cells in the rat brain using an antiserum against a portion of the intracellular domain of LR that is common to all LR isoforms [15].
• In addition, we studied the effects of both fatty acids on OB-R mRNA expression using semi-quantitative RT-PCR [36].
• Comparing with the control group, the CTA group had an increase on count of OB-R immunohistochemistry positive-stained cells in the BLA (127+/-12 vs 48+/-9 per 1 mm(2)) [37].
• Immunocytochemistry and Western blot analysis further showed the expression of OB-R protein in VSMCs [38].
• Leptin receptor (ObR) expression was measured using ObR enzyme-linked immunosorbent assay [39].

References