Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of the ob gene product leptin in adipose tissues has been previously described to be regulated by insulin in vivo and vitro. Akt, a ser/thr kinase with a pleckstrin homology domain, has recently been identified to function in the insulin receptor signaling cascade. The aim of this study was to investigate the role of Akt in the production of leptin by adipocytes. Therefore, we examined leptin production by 3T3-L1 adipocytes stably expressing a myristoylated version of Akt which is constitutively active. Leptin levels in the supernatants of serum starved, nonstimulated 3T3-L1 adipocytes were determined by radioimmunoassay (RIA). Expression of the constitutively active Akt was found to induce a more than 20-fold increase in leptin levels whereas a control non-myristoylated Akt had no effect. Leptin mRNA levels as determined by either RNase protection assay or reverse transcriptase (RT)-polymerase chain reaction (PCR) were not elevated by the constitutively active Akt. These results indicate that Akt can induce leptin production in 3T3-L1 adipocytes via a non-transcriptional mechanism.
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PMID:A constitutively active version of the Ser/Thr kinase Akt induces production of the ob gene product, leptin, in 3T3-L1 adipocytes. 923 12

The expression of leptin and its receptors was examined by reverse transcriptase-polymerase chain reaction and immunofluorescence in granulosa and cumulus cells of pre-ovulatory follicles and in meiotically mature oocytes obtained from women undergoing in-vitro fertilization. Leptin concentrations were measured in newly aspirated follicular fluids and in maternal serum before and after the administration of an ovulatory dose of human chorionic gonadotrophin. The findings demonstrate leptin expression at the mRNA and protein levels by granulosa and cumulus cells, and the presence of leptin in mature human oocytes. While an association between follicular leptin concentration and embryo development was not observed, a post-ovulatory increase in serum leptin concentration was associated with implantation potential. The results are discussed with respect to possible roles of leptin in early human development.
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PMID:The expression of leptin and its receptors in pre-ovulatory human follicles. 923 34

Leptin is the protein product of the recently cloned obesity gene. Leptin receptor mRNA is found in a number of central and peripheral locations. The hypothalamus is a presumed site of action. However, little is known about the specific locations of the receptor in peripheral organs. Epinephrine has potent anorectic effects and can cause weight loss by a variety of mechanisms. Excretion of epinephrine is reduced in the ob/ob mouse, which lacks leptin, suggesting an effect by leptin on the adrenal medulla. In the current study, the presence of the leptin receptor was identified on epinephrine-secreting cells in the adrenal medulla. Immunohistochemical studies found dense leptin receptor-like immunoreactivity in the adrenal medulla with no labeling in the adrenal cortex. Double immunofluorescent labeling confirmed that the leptin receptor was present on cells that were phenylethanolamine N-methyltransferase-like immunoreactive and therefore were epinephrine-secreting cells. Leptin receptor mRNA in the adrenal medulla was detected by reverse transcriptase-polymerase chain reaction, with the majority of the mRNA coding for the short isoform (Ob-Ra) of the receptor. Finally, autoradiography was performed using 125I-labeled leptin; specific binding was found in the adrenal medulla, with no specific binding in the adrenal cortex. These results suggest that leptin may have a direct effect on epinephrine-secreting cells in the adrenal medulla. Epinephrine may play a role in mediating the effects of leptin to reduce body weight.
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PMID:Leptin receptors in the adrenal medulla of the rat. 927

The present study has examined the short- and long-term effects of growth hormone (GH) treatment on the leptin system and energy expenditure. Thirty male individuals with abdominal obesity were randomised to GH or placebo treatment in a 9-month, double-blind study. The dose of GH was 9.5 microg/kg, administered subcutaneously every evening. Serum leptin concentrations were measured by a human leptin RIA. Total RNA was isolated from adipose tissue biopsies and leptin mRNA levels were determined by a semi-quantitative reverse transcriptase-PCR assay. Body composition was determined by potassium-40 and the basal metabolic rate (BMR) was measured by a computerised, ventilated, open-hood system. As compared with placebo, an overall decrease in serum leptin concentrations as assessed by the area under the curve (AUC) (P < 0.05) and an increase in BMR (AUC, P < 0.05) were observed during GH treatment. The overall GH-induced changes were due to marked changes in serum leptin concentrations and BMR after 6 weeks of treatment. After 9 months of GH treatment there was a significant reduction in body fat (BF) while serum leptin concentrations and BMR did not differ from baseline values. Leptin mRNA levels did not change over the study period. We speculate that long-term GH treatment induces a new energy balance steady state with decreased BF stores. The effects of GH on the leptin system is suggested to be of importance for the maintenance of a lower BF mass.
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PMID:Effects of growth hormone treatment on the leptin system and on energy expenditure in abdominally obese men. 957 8

Leptin and its structural gene, Ob, are exclusively expressed in adipose tissue. Leptin is secreted into the blood and is responsible for fat mass regulation via leptin receptors in the hypothalamus. This has been considered the major role of leptin, but leptin receptor isoforms are expressed not only in the brain but also in most other tissues in humans and rodents: heart, placenta, lung, liver, muscle, kidney, pancreas, spleen, thymus, prostate, testes, ovary, small intestine, and colon. This implicates leptin regulation in other systems apart from fat mass regulation, and leptin action has been demonstrated in human fetal development and reproductive development, liver metabolism, hematopoiesis, and insulin secretion. Four splice variants of the leptin receptor have been identified in humans: the long isoform huOb-R and the shorter isoforms B219.1 to B219.3. It is known that the long isoform has full intracellular signaling capacity, and is responsible for anorectic action in the hypothalamus. The roles of the other isoforms are yet to be elucidated. Here, we report the identification by reverse transcriptase-polymerase chain reaction (RT-PCR) of three leptin receptor isoforms coexpressed in human visceral adipose tissue: the long isoform huOb-R and the short isoforms huB219.1 and huB219.3. The possible roles of these isoforms are discussed.
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PMID:Leptin receptor isoforms expressed in human adipose tissue. 966 33

The influence of thyroid hormones on human adipose tissue leptin production and leptin gene expression was investigated in vitro and in vivo. Twelve women received 60 microg triiodothyronine (T3) per day for 7 days, which increased total T3 by 195% (1.78 +/- 0.07 to 5.25 +/- 0.39 mU/L, P < .001), significantly decreased thyrotropin ([TSH] 1.57 +/- 0.40 to 0.03 +/- 0.01 mU/L, P < .01), and increased energy expenditure (1,602 +/- 32 to 1,754 +/- 34 kcal/24 h, P < .05). However, serum leptin did not change (9.36 +/- 1.6 v 8.90 +/- 1.3 microg/L, nonsignificant). Human subcutaneous adipose tissue biopsies from eight healthy women were incubated in vitro as small fragments with T3 in concentrations from 1 to 50 nmol/L. Leptin production was inhibited dose-dependently. After 24 hours of incubation, a T3 concentration of 50 nmol/L reduced basal leptin production by 42% (P < .05) and the stimulated leptin production (dexamethasone 10 nmol/L) by 52% (P < .05). Leptin mRNA expression was measured by a semiquantitative multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) method. Fifty nanomolars T3 decreased basal leptin mRNA expression by 47% compared with controls (P < .001), and the stimulated leptin mRNA expression was reduced to a similar degree (53%). In conclusion, in human adipose tissue, T3 (>20 nmol/L) inhibited leptin production and leptin gene expression in vitro, whereas an elevation of T3 corresponding to a moderate thyrotoxic state (T3 5.25 +/- 0.39 nmol/L) was without any impact on serum leptin levels in vivo.
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PMID:Regulation of leptin by thyroid hormone in humans: studies in vivo and in vitro. 1059 95

Leptin is mainly produced in white adipose tissue and acts both at distant sites and locally at the tissue from which it originates. The cellular and subcellular localization of leptin and its receptor (Ob-receptor [Ob-R]) and their relationship to various stages of fat cell maturation have not been characterized as yet. Therefore, we analyzed leptin and Ob-R by using reverse transcriptase-polymerase chain reaction, immunohistochemistry, and ultrastructural immunogold labeling in human white adipose tissue and in human adipocyte cell cultures at early and late stages of differentiation. Both leptin and its receptor were present in mature unilocular fat cells. The thin cytoplasmic rim of the adipocytes exhibited the strongest expression of both leptin and Ob-R. At early stages of differentiating human adipocytes, leptin was mainly expressed in multilocular preadipocytes, whereas the Ob-R was found predominantly on fibroblast-like cells. Other cellular components of human white adipose tissue were characterized by anti-CD31 for endothelial cells, anti-CD68 for macrophages, and antibodies specifically labeling B-cells and T-cells. In addition to fat cells, endothelial cells were immunopositive for the full-length leptin receptor. On the ultrastructural level, leptin was mainly found attached to cellular membranes and in small alveolate vesicle-like structures in the cytoplasm of adipocytes. Leptin was also present on the cell membranes of endothelial cells and macrophages. We conclude that the expression of the Ob-R in human white adipose tissue is not restricted to adipocytes but is present in resident endothelial and immune cells. Ultrastructural localization studies revealed an association of leptin with cell membranes and small vesicles. The cellular and subcellular distribution of leptin and its receptor suggests an important autocrine and paracrine role for leptin in human adipose tissue.
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PMID:Immunohistochemical and ultrastructural localization of leptin and leptin receptor in human white adipose tissue and differentiating human adipose cells in primary culture. 1087 Nov 89

Leptin, the adipocyte-derived hormone, is secreted into the blood and regulates body weight via its receptors in the hypothalamus. Leptin receptors are also present in many peripheral tissues implicating leptin in the regulation of other body functions, including reproduction, liver and enteric metabolism, hematopoiesis, and immunity. Four splice variants of the leptin receptor have been identified in humans: the long isoform that has full intracellular signaling capacity and 3 shorter isoforms that differ in the length of their cytoplasmic tail. Here, we report the quantification by reverse transcriptase-polymerase chain reaction (RT-PCR) of the relative expression levels of the 2 major leptin receptor splice variants, the long (OB-RL) and the shortest membrane bound variant (OB-RS) in mononuclear cells from peripheral blood of 15 healthy human subjects (9 women and 6 men), with a body mass index (BMI) that ranged from 19.7 to 41.6. Both OB-RL and OB-RS were coexpressed in all mRNAs tested. However, the expression of the short form (OB-RS), was on average 8-fold higher than the expression of the long form (OB-RL) (120.8 +/- 12.9 v 14.6 +/- 3.0 relative intensity units, P < .001). The predominance of the short splice variant over the long one was apparent in all samples and ranged from 4- to 27-fold. There was no significant difference in the expression of either isoform between men and women. However, the relative expression of both OB-RS and OB-RL isoforms was significantly lower in the overweight (BMI > 26), compared with the lean subjects (BMI < 25) (78.8 +/- 9.1 and 6.2 +/- 1.1 v148.8 +/- 14.4 and 18.9 +/- 4.0 relative intensity units, respectively, P < .03) and was inversely correlated with the BMI and plasma leptin levels (P < .01). In conclusion, the expression of OB-RS and OB-RL leptin receptor isoforms appears to be reduced in human peripheral blood mononuclear cells from obese individuals, with OB-RS remaining the predominant leptin receptor isoform. This might have implications for the bioavailability and/or action of circulating leptin not only on these cells, but also on other target tissues.
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PMID:Expression of the long and short leptin receptor isoforms in peripheral blood mononuclear cells: implications for leptin's actions. 1114 13

Leptin, the product of the ob gene, regulates food intake, energy expenditure, and other physiological functions of the peripheral tissues. Leptin receptors have been identified in the hypothalamus and in extrahypothalamic tissues. Increased circulating leptin levels have been correlated with cardiovascular disease, obesity, aging, infection with bacterial lipopolysaccharide, and high-fat diets. All these conditions have also been correlated with increased vascular calcification, a hallmark of atherosclerotic and age-related vascular disease. In addition, the differentiation of marrow osteoprogenitor cells is regulated by leptin. Thus, we hypothesized that leptin may regulate the calcification of vascular cells. In this report, we tested the effects of leptin on a previously characterized subpopulation of vascular cells that undergo osteoblastic differentiation and calcification in vitro. When treated with leptin, these calcifying vascular cells had a significant 5- to 10-fold increase in alkaline phosphatase activity, a marker of osteogenic differentiation of osteoblastic cells. Prolonged treatment with leptin enhanced the calcification of these cells, further supporting the pro-osteogenic differentiation effects of leptin. Furthermore, the presence of the leptin receptor on calcifying vascular cells was demonstrated using reverse transcriptase polymerase chain reaction, immunocytochemistry, and Western blot analysis. We also identified the presence of leptin receptor in the mouse artery wall, localized to subpopulations of medial and adventitial cells, and the expression of leptin by artery wall cells and atherosclerotic lesions in mice. Taken together, these results suggest that leptin regulates the osteoblastic differentiation and calcification of vascular cells and that the artery wall may be an important peripheral tissue target of leptin action.
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PMID:Leptin enhances the calcification of vascular cells: artery wall as a target of leptin. 1134 6

Expression of the long form of the leptin receptor was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting in the human liver cell line WRL68. Leptin (50-200 nM) significantly increased tyrosine phosphorylation of STAT cytoplasmic transcription factors STAT3 and STAT5b in a dose-dependent manner and produced a gel-shift with STAT3- and STAT5-specific oligonucleotides. WRL68 cells therefore provide the first human in vitro hepatocyte system in which to study leptin receptor-mediated signalling and to elucidate the role of leptin in liver.
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PMID:Leptin receptor long-form signalling in a human liver cell line. 1144 22


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