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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leptin, a cytokine involved in the regulation of food intake, has been reported to be decreased in lung diseases such as chronic obstructive pulmonary disease and cystic fibrosis and increased in critically ill patients with sepsis. We investigated the role of leptin during hyperoxia in mice, which results in alveolar edema, severe weight loss, and death within 3-4 days. In oxygen-breathing mice, serum leptin was increased six- to sevenfold and its mRNA was upregulated in white adipose tissue. Leptin elevation could not be attributed to changes in circulating tumor necrosis factor-alpha but was completely dependent on endogenous corticosterone elevation because adrenalectomized mice did not exhibit any increase in leptin levels. Using leptin-deficient mice and wild-type mice treated with anti-leptin antibody, we demonstrate that weight loss was leptin independent. Lung damage was moderately attenuated in leptin-deficient mice but was not modified by anti-leptin antibody or leptin administration, suggesting that leptin does not play an essential role in the direct and short-term effects of oxygen-induced injury.
Am J Physiol Lung Cell Mol Physiol 2001 Nov
PMID:Hyperoxia increases leptin production: a mechanism mediated through endogenous elevation of corticosterone. 1159 6

Obesity is currently considered as a chronic metabolic disease, associated with a high risk of cardiovascular complications. Leptin, an adipocyte-derived hormone has a variety target cells influencing a wide range of processes. Possible counteractions of hyperleptinaemia are currently investigated. The Na(+)-H(+) exchanger (NHE 1) is involved in multiple cellular functions and its activation has been related to hypertension and obesity. NHE 1 is present on erythrocytes and can be stimulated by various hormones. Erythrocytes have on their surface a variety of receptors with mostly unknown function. In the present paper, the effect of leptin on erythrocytes NHE 1 activity has been investigated. For this reason, the intracellular pH and sodium influxes were measured before and after addition of leptin in erythrocyte suspensions from normal and obese individuals. Amiloride, a specific NHE 1 inhibitor, and staurosporine a protein kinase C inhibitor were used to inhibit erythrocyte NHE 1. For the binding study leptin was labeled with fluorescein isothiocyanate (FITC) and the binding on erythrocytes was estimated by Scatchard analysis. NHE 1 activity increased in the presence of leptin but significantly less in the obese than in the control group. Furthermore the concentrations of leptin binding sites on the surface of erythrocytes were lower in erythrocytes drawn from obese individuals than in erythrocytes drawn from normal subjects. Since NHE 1 activity has been associated with insulin resistance and hypertension, the activation of this antiport by leptin may represent a link between adipose tissue hypertrophy and cardiovascular complications of obesity.
Mol Cell Endocrinol 2001 Oct 25
PMID:The effect of leptin on Na(+)-H(+) antiport (NHE 1) activity of obese and normal subjects erythrocytes. 1160 19

Human and rat granulosa cells express receptors to leptin which synergies with glucocorticoid hormones in stimulation of ovarian steroidogenesis. To examine whether leptin affects follicular development and maturation, we injected recombinant ovine leptin (300 ng-10 microg/animal) daily to immature 21 day-old female rats. Non-treated rats reached puberty at 44.5+/-1.6 (n=9) days. In contrast, in leptin treated animals, puberty was reached at 34.5+/-1.6 (n=9) days. Ovarian sections revealed hypertrophy of granulosa cells in leptin treated animals. Moreover, the number of ovulations was 2-fold higher in the treated animals compared to controls (3-4 ovulations versus 7-8 on the first three estrous cycles, P<0.001). Leptin dramatically reduced incidence of follicular apoptosis measured by TUNEL, and was already evident after 7 days of leptin injection (12% of apoptosis in leptin treated group compared to 52% in controls, P<0.001). Maximal protection against apoptosis was achieved at 1-3 microg leptin/animal. The levels of FSH, LH, progesterone and the steroidogenic factors ADX and STAR were elevated earlier in development in the leptin treated animals compared to control animals which is in line with the achievement of early puberty in the leptin treated animals compared to non treated ones. To reveal whether modulation of death and survival genes is involved in leptin attenuation of follicular apoptosis, we examined the expression of the survival gene Bcl-2 and the death gene Bax in Western blots of ovarian homogenates. There was a pronounced elevation in Bcl-2 expression during 7-14 days of leptin injections up to 16.3-fold (P<0.001) compared to Bcl-2 expression in controls. Bax expression was elevated only 3.4 fold (P<0.001), leading to an increase in the Bcl-2/Bax ratio of 4.7 fold (P<0.001). Expression of the tumor suppressor gene p 53 and the oncogene Mdm2 did not change significantly. Our data suggests that leptin may be involved in accelerating follicular maturation by attenuating follicular atresia and increasing the ratio of Bcl-2/Bax.
Mol Cell Endocrinol 2001 Oct 25
PMID:Leptin attenuates follicular apoptosis and accelerates the onset of puberty in immature rats. 1160 38

Leptin, the 'obese' protein, is found in cultured granulosa cells derived from human pre-ovulatory follicles. However, the occurrence of leptin has not been studied in intact ovaries, either normal or polycystic, until now. Paraffin sections from 25 human ovaries of different cycle stages and 25 wedge resections of polycystic ovaries were investigated by means of immunochemistry. Additionally, three ovaries were available for reverse transcription-polymerase chain reaction analysis. Leptin-positive cells were located in the granulosa cells of pre-antral follicles, and distinctly in the thecal layer of intact and regressing antral follicles. In the corpus luteum (CL) in the developmental stage, the former epithelioid leptin-positive thecal cells became fibroblast-like in the septum. In the CL of the secretory stage, single leptin-positive cells were detected between luteal cells. In polycystic ovaries, leptin-positive cells were noted both in the hypertrophied thecal layer and in the luteinized granulosa layer. Our findings on leptin expression at the protein level were confirmed by a positive mRNA signal for leptin in granulosa cells and in the CL. Additionally, mRNA of the full-length leptin receptor OB-R and of the short isoforms B219.1-B219.3 was identified in granulosa cells and the CL, as well as in the cortex and medulla. We conclude that leptin is produced in the ovary and may act in autocrine and paracrine ways.
Mol Hum Reprod 2001 Dec
PMID:Evidence of leptin expression in normal and polycystic human ovaries. 1171 91

We have previously reported the expression of leptin mRNA and protein in adult rat brain and pituitary gland. We report here the presence of leptin and leptin receptor mRNA in neonatal female rat brain and pituitary using RT-PCR as well as leptin and leptin receptor immunoreactivity in neonatal rat brain. In addition, we describe age-related changes in leptin mRNA expression in female rat brain and pituitary from postnatal day 2 to 28, evaluated using semi-quantitative RT-PCR analysis. Age-related differences in leptin (ob) mRNA levels were tissue-dependent. The most striking developmental changes were noted in the pituitary and cerebral cortex. In the pituitary, ob mRNA levels were maximal during postnatal days 7-14 and fell sharply by postnatal day 22. In cortex, ob mRNA levels were low in neonatal pups (day 2-7) but increased significantly between postnatal days 14 and 28. Leptin mRNA was detectable at postnatal day 2 in hypothalamus and subcutaneous fat. No significant differences in the level of expression were observed between postnatal day 2 and 28. Serum leptin levels were highest at day 7-14 and decreased significantly by day 21-28, coincident with the fall in pituitary leptin expression. The high levels of leptin expression in the neonatal pituitary suggest that this gland may contribute to the circulating leptin levels during early postnatal development, when adipose deposits are minimal. These data indicate that regulation of leptin gene expression in the postnatal period is tissue-dependent, a finding, which suggests that local leptin expression may have important functional significance in the development of the brain-pituitary system.
Mol Cell Endocrinol 2001 Dec 20
PMID:Developmental regulation of leptin gene expression in rat brain and pituitary. 1173 5

Leptin is an adipose tissue-secreted hormone, which decreases caloric intake and increases energy expenditure. Some effects of leptin on energy balance seem to be mediated by the hypothalamo-pituitary-thyroid axis. The present study was designed to ascertain whether i) rat thyroid gland expresses the long form of leptin receptor (ObRb) and ii) the prolonged leptin administration (daily subcutaneous injections of 24 nmol/kg leptin for 6 consecutive days) affects thyroid-gland function in this species. Coupled RT-PCR, Western blotting and immunocytochemical findings demonstrated the expression of Ob-Rb as mRNA and protein in the thyroid gland of normal rats. Prolonged leptin treatment raised thyroid-gland weight, and morphometry showed that in the enlarged glands the volume of the follicle epithelium was increased, while that of colloid remained unchanged, so that epithelium/colloid ratio was markedly lowered. In leptin-administered rats, the plasma concentration of TSH was decreased, while those of thyroid hormones (free T3 and total T4) were notably raised. Collectively, these findings suggest that systemically administered leptin stimulates growth and secretion of thyroid gland in the rat, through a direct mechanism involving Ob-Rb.
Int J Mol Med 2002 Jan
PMID:Rat thyroid gland expresses the long form of leptin receptors, and leptin stimulates the function of the gland in euthyroid non-fasted animals. 1174 92

Leptin and tumor necrosis factor--alpha(TNF-alpha) are important mediators of insulin resistance in obese subjects through their over-expression in adipose tissue. Secretion of leptin into the circulation is a signal for the brain in patients with hyperinsulinemia. Regulation of TNF-alpha affects adipocyte insulin sensitivity and lipid accumulation. Exercise training has been suggested for the prevention and treatment of such disorders. However, how exercise modifies secretion of leptin and TNF-alpha is not known. We investigated leptin and TNF-alpha in a rat model of insulin resistance induced by sucrose. After 4 weeks of sucrose feeding, 4 weeks of voluntary wheel running significantly reduced the concentrations of leptin in mesenteric (MS) and subcutaneous fat (SC) when compared to sedentary sucrose-feeding rats. These results suggest that exercise controls cytokine regulation of leptin and TNF-alpha. The increased TNF-alpha in adipose tissue may activate cytolysis for energy consumption.
Res Commun Mol Pathol Pharmacol
PMID:Reciprocal changes in leptin and tumor necrosis factor-alpha with exercise in insulin resistant rats. 1175 69

The role of leptin in the control of obesity, insulin resistance and type II diabetes has been reported, however, the regulatory mechanism of leptin in animals affected by hormones is not clearly understood. In this study, the effects of insulin, epinephrine, growth hormone or dexamethasone on the expression of leptin was examined in mouse primary adipocytes. The leptin expression was also studied in the adipose tissue of the mouse treated with insulin or growth hormone (0.3 or 0.6 units/animal). Insulin (100 nM) or dexamethasone (100 nM) stimulated leptin mRNA transcription while epinephrine (100 nM) alleviated its transcription in mouse primary adipocytes. The level of leptin protein in cultured media of adipocytes treated with insulin or dexamethasone was higher than that of the control group but growth hormone or epinephrine treatment had no effect on them. Insulin administration (0.6 units/mouse) enhanced leptin mRNA as well as leptin protein in mouse adipose tissue but growth hormone administration (0.3 or 0.6 units/mouse) had no effect on them. Leptin protein level in sera of mice injected with insulin or growth hormone was not significantly different from that of control group. These results indicate that both insulin and dexamethasone stimulate leptin gene expression and secretion of its product, whereas, growth hormone has no effect on the expression of leptin gene in mouse adipocytes.
Exp Mol Med 2001 Dec 31
PMID:Regulation of leptin gene expression by insulin and growth hormone in mouse adipocytes. 1179 85

Developing rat lung lipofibroblasts express leptin beginning on embryonic day (E) 17, increasing 7- to 10-fold by E20. Leptin and its receptor are expressed mutually exclusively by fetal lung fibroblasts and type II cells, suggesting a paracrine signaling "loop." This hypothesized mechanism is supported by the following experimental data: 1) leptin stimulates the de novo synthesis of surfactant phospholipid by both fetal rat type II cells (400% x 100 ng(-1) x ml(-1) x 24 h(-1)) and adult human airway epithelial cells (85% x 100 ng(-1) x 24 h(-1)); 2) leptin is secreted by lipofibroblasts in amounts that stimulate type II cell surfactant phospholipid synthesis in vitro; 3) epithelial cell secretions such as parathyroid hormone-related protein (PTHrP), PGE(2), and dexamethasone stimulate leptin expression by fetal rat lung fibroblasts; 4) PTHrP or leptin stimulate the de novo synthesis of surfactant phospholipid (2- to 2.5-fold/24 h) and the expression of surfactant protein B (SP-B; >25-fold/24 h) by fetal rat lung explants, an effect that is blocked by a leptin antibody; and 5) a PTHrP receptor antagonist inhibits the expression of leptin mRNA by explants but does not inhibit leptin stimulation of surfactant phospholipid or SP-B expression, indicating that PTHrP paracrine stimulation of type II cell maturation requires leptin expression by lipofibroblasts. This is the first demonstration of a paracrine loop that functionally cooperates to induce alveolar acinar lung development.
Am J Physiol Lung Cell Mol Physiol 2002 Mar
PMID:Leptin mediates the parathyroid hormone-related protein paracrine stimulation of fetal lung maturation. 1183 33

The insect fat body is a dynamic tissue involved in maintaining homeostasis. It functions not only in energy storage and intermediary metabolism but also in detoxification, communication and the immune response. Some of these functions are confined to distinct groups of fat body cells. In Drosophila melanogaster, discrete precursor-cell clusters populate the fat body [Hoshizaki, D.K., Blackburn, T., Price, C., Ghosh, M., Miles, K., Ragucci, M. and Sweis, R. (1994) Embryonic fat-cell lineage in Drosophila melanogaster. Development 120: 2489-2499; Hoshizaki, D.K., Lunz, R., Ghosh, M. and Johnson, W. (1995) Identification of fat-cell enhancer activity in Drosophila melanogaster using P-element enhancer traps. Genome 38: 497-506; Riechmann, V., Rehorn, K.P., Reuter, R. and Leptin, M. (1998) The genetic control of the distinction between fat body and gonadal mesoderm in Drosophila. Development 125: 713-723]. Whether these clusters populate defined morphological regions or whether they represent the precursors to functionally similar groups of fat-body cells has not been formally demonstrated. We have identified a 2.1 kb enhancer region from serpent (srp), a GATA transcription factor gene that is sufficient to induce fat-cell formation. This enhancer region drives expression in specific groups of precursor-cell clusters, which we show give rise to defined regions of the mature embryonic fat body. We present evidence that srp expression in different precursor fat cells is controlled by independent cis-acting regulatory regions, and we have tested the role of trans-acting factors in the specification of some of these cells. We suggest that the different positional cues regulating srp expression, and therefore general fat-cell specification, might also be involved in the functional specialization of fat cells. This may be a common mechanism in insects to explain the origin of biochemically distinct regions of the larval/adult fat body.
Insect Mol Biol 2002 Feb
PMID:Identification of fat-cell enhancer regions in Drosophila melanogaster. 1184 4


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