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

To investigate the role of leptin during pregnancy, we assessed leptin production by pure cultured human cytotrophoblastic cells (CTB), its regulation by cytokines and 17beta-oestradiol and its effects on human chorionic gonadotrophin (HCG) secretion. Purified CTB from first trimester placenta were incubated in duplicates in the presence or absence of cytokines or 17beta-oestradiol. Medium was harvested on day 2 and the culture stopped on day 4. Results were corrected for protein content of each individual well and expressed as percent of controls per day (mean +/- SEM). Basal CTB leptin production was 25.2 +/- 2.6 (ng/mg prot). In comparison with controls, leptin production was stimulated to 320 +/- 16% (P < 0.0001) and 195 +/- 3.2% (P < 0.0004) by 3 and 10 ng/ml of interleukin-1alpha respectively. 17beta-oestradiol 10(-6) to 10(-9) mol/l increased basal leptin production 5-9-fold, while 10(-5) mol/l had no such effect. Basal CTB HCG secretion was 5722 +/- 1055 (mIU/mg prot). There was a dose-dependent leptin-induced increase in HCG secretion (P = 0.0039) reaching a 5-fold increase with a leptin concentration of 1 microg/ml (P < 0.006). Gonadotrophin-releasing hormone (GnRH) 8.5 x 10(-8) mol/l significantly increased HCG secretion to 140 +/- 21% of controls (P = 0.031). Cetrorelix (0.1 microg/ml) inhibited leptin-induced HCG secretion (P = 0.0028).
Mol Hum Reprod 1999 Nov
PMID:Modulation of human cytotrophoblastic leptin secretion by interleukin-1alpha and 17beta-oestradiol and its effect on HCG secretion. 1054 71

Agonist-induced activation of peroxisome proliferator-activated receptor gamma (PPAR gamma) is known to cause adipocyte differentiation and insulin sensitivity. The biological role of PPAR gamma was investigated by gene targeting. Homozygous PPAR gamma-deficient embryos died at 10.5-11.5 dpc due to placental dysfunction. Quite unexpectedly, heterozygous PPAR gamma-deficient mice were protected from the development of insulin resistance due to adipocyte hypertrophy under a high-fat diet. These phenotypes were abrogated by PPAR gamma agonist treatment. Heterozygous PPAR gamma-deficient mice showed overexpression and hypersecretion of leptin despite the smaller size of adipocytes and decreased fat mass, which may explain these phenotypes at least in part. This study reveals a hitherto unpredicted role for PPAR gamma in high-fat diet-induced obesity due to adipocyte hypertrophy and insulin resistance, which requires both alleles of PPAR gamma.
Mol Cell 1999 Oct
PMID:PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance. 1054 91

Leptin has recently been implicated as having a role in sexual maturation and reproduction. This review describes recent findings regarding the putative reproductive functions of leptin within the context of the attainment of sufficient long-term fuel reserves to sustain and support pregnancy and lactation. The review considers the evidence, within the context of the development of hyperleptinaemia during pregnancy, that leptin has an important function to modulate maternal nutrient partitioning in order to optimise the provision of nutrients for fetal growth and development. It is suggested that, through modulation of maternal insulin secretion and hepatic metabolism, leptin integrates maternal nutrient storage to the nutrient requirements of the fetus. The importance of the placenta as a site of leptin synthesis and the potential role(s) of placentally derived leptin are evaluated in relation to maternal-fetal interactions during intrauterine development. The review also examines whether intrauterine growth retardation due to nutritional restriction reflects dysregulation of such cross-talk. Finally, the review describes emerging evidence for participation of leptin in lactation and neonatal growth.
Mol Cell Endocrinol 1999 Nov 25
PMID:Current concepts concerning the role of leptin in reproductive function. 1061 93

Leptin regulates energy homeostasis via binding to receptors in the hypothalamus and peripheral tissues. We have investigated the signaling pathways and effects of leptin on glucose transport in C2C12 muscle cells. Long and short forms of leptin receptor are expressed in differentiated C2C12 myotubes. Leptin enhanced the DNA-binding activity of the transcription factor STAT3 and extracellular signal-regulated kinase 2 (ERK2) activity was stimulated by leptin after 15 min. Leptin increased glucose uptake and GLUT4 recruitment to the cell surface after 30 min, whereas no changes in GLUT1 was observed. PD98059, an ERK2 kinase-1 inhibitor, and wortmannin, an inhibitor of phosphatidylinositol 3-kinase blocked the leptin-induced increase in glucose uptake and GLUT4 recruitment to the cell surface. In contrast, insulin-stimulated glucose transport and GLUT4 translocation was inhibited by wortmannin, but not by PD98059. Our results suggest that leptin may regulate glucose metabolism by acting directly on skeletal muscle and that the signaling pathways involved may be different from that activated by insulin.
Mol Cell Endocrinol 1999 Nov 25
PMID:Leptin stimulates glucose uptake in C2C12 muscle cells by activation of ERK2. 1061 3

Orexins-A and B are two novel hypothalamic peptides, which, like leptin and neuropeptide-Y (NPY), are involved in the central regulation of feeding. Since leptin and NPY were found to modulate adrenal function, we have examined whether orexins are able to directly affect rat adrenal steroid secretion. Both orexin-A and orexin-B raised basal corticosterone secretion of dispersed rat zona fasciculata-reticularis (ZF/R) cells, their maximal effective concentration being 10(-8) M. In contrast, orexins did not affect either maximally ACTH (10(-9) M)-stimulated corticosterone production by ZF/R cells or the basal and agonist-stimulated aldosterone secretion of dispersed zona glomerulosa cells. The ACTH-receptor antagonist corticotropin-inhibiting peptide (10(-6) M) annulled corticosterone response of ZF/R cells to ACTH (10(-9) M), but not to orexins (10(-8) M). Orexins (10(-8) M) enhanced cyclic-AMP release by ZF/R cells, and the selective inhibitor of protein-kinase A (PKA) H-89 (10(-5) M) abolished corticosterone responses to both ACTH (10(-9) M) and orexins (10(-8) M). A subcutaneous injection of both orexins (5 or 10 nmol/kg) evoked a clear-cut increase in the plasma concentration of corticosterone (but not aldosterone), the effect of orexin-A being significantly more intense than that of orexin-B. Collectively, these findings suggest that orexins exert a selective and direct glucocorticoid secretagogue action on the rat adrenals, acting through a receptor-mediated activation of the adenylate cyclase/PKA-dependent signaling pathway.
J Steroid Biochem Mol Biol
PMID:Orexins stimulate corticosterone secretion of rat adrenocortical cells, through the activation of the adenylate cyclase-dependent signaling cascade. 1062 6

Sulpiride (SUL, 20 mg kg-1 day-1) induces weight gain, hyperphagia, hyperprolactinemia, hypogonadism, and perhaps increased insulin sensitivity in rats. Leptin seems to signal the brain about the size of body fat stores and nutrient metabolism. We evaluated the basal serum leptin levels in rats after acute (1 h) or prolonged SUL or vehicle administration (10, 20 and 30 days). At days 10 and 30 leptin was also assessed during a glucose overload test. As the maximal weight gain during SUL administration is observed at days 10-15 of treatment, leptin was measured in a comparison group of insulin-treated rats (5 IU day-1 for 10 days). SUL-treated rats significantly gained weight. However, leptin levels were not significantly increased at any time-point of treatment. SUL did not affect insulin levels either. By contrast, leptin levels were significantly elevated after insulin administration, along with weight gain and hyperinsulinemia. An opposite correlation was also observed at day 10: leptin and insulin correlated negatively in the SUL group and positively in the insulin group. In addition, leptin and the magnitude of weight gain tended to correlate positively after SUL treatment, but negatively after insulin administration. SUL-treated rats, thus, appear to exhibit an unusual type of weight gain, characterized by normal circulating leptin and insulin levels. Such a particular leptin profile may be related to hyperprolactinemia, hypogonadism or lack of hyperinsulinemia. Molecular Psychiatry (2000) 5, 70-76.
Mol Psychiatry 2000 Jan
PMID:Antipsychotic drug-induced obesity in rats: correlation between leptin, insulin and body weight during sulpiride treatment. 1067 71

The acute and chronic effects of tumour necrosis factor-alpha (TNF-alpha) on leptin production by human preadipocytes, differentiated preadipocytes, and mature adipocytes have been examined by competitive RT-PCR of leptin mRNA and by western blotting. In preadipocytes, secreted leptin was detectable after 5-day incubation in differentiation medium and this increased 4-fold by day 20. TNF-alpha blocked leptin synthesis during differentiation. In differentiated preadipocytes and mature adipocytes, TNF-alpha treatment resulted in time-dependent decreases in mRNA for leptin and glycerol-3-phosphate dehydrogenase (G3PD). In contrast, TNF-alpha (4-8-h treatment) resulted in a 4-fold increase in leptin release. This effect was lost at 24 h and leptin accumulation in culture medium was decreased 24-48 h after TNF-alpha addition. We conclude that TNF-alpha stimulates the release of preformed leptin from human mature adipocytes and existing differentiated preadipocytes, which may contribute to obesity/infection-linked hyperleptinemia, and that TNF-alpha inhibits leptin synthesis via inhibition of preadipocyte differentiation and induction of adipocyte dedifferentiation.
Mol Cell Endocrinol 2000 Jan 25
PMID:Tumour necrosis factor-alpha exerts dual effects on human adipose leptin synthesis and release. 1068 54

Cytokines regulate the proliferation and differentiation of cells through their interaction with specific receptors on the surface of target cells which are coupled to intracellular signal transduction pathways. The cytokine receptor class I superfamily, characterized by structural homology in the extracellular domain, includes receptors for many interleukins and hematopoietic growth factors, but also those of growth hormone, leptin, ciliary neurotrophic factor (CNTF), oncostatin M (OSM), leukemia inhibitory factor (LIF) and cardiotrophin-1 (CT-1). The receptors for interferons are structurally distinct and have therefore been categorized separately (class II cytokine receptors). The discovery of the JAK/STAT pathway in the early 1990s has been an important step forward in deciphering cytokine mediated signaling. This pathway connects activation of the receptor complexes directly to transcription of genes. Studies of humans and mice, deficient for one of the JAKs or STATs, have revealed crucial roles of these molecules in embryonic development, blood cell formation and immune responses. In addition, recent studies have revealed some of the mechanisms that control the activation of the JAKs and STATs, which contribute to signal intensity and specificity. In this review we will summarize these recent insights and discuss their implications for a variety of pathological conditions.
Mol Cell Endocrinol 2000 Feb 25
PMID:Signaling mechanisms of cytokine receptors and their perturbances in disease. 1071 33

Leptin is a hormone which controls fat metabolism. Leptin plasma levels and adipose tissue mRNA expression were measured in cancer patients. Plasma levels were correlated with TNM staging, cachexia parameters, tumour markers and hormones. Breast and colorectal cancer patients showed blood plasma levels of insulin, TNF-alpha and tumour markers higher than controls. Breast cancer patients, but not colorectal cancer patients, had plasma levels and adipose tissue expression of leptin significantly higher than controls associated with elevated values of estrogen- and progesterone-receptors. These data suggest the possible use of leptin as a clinical marker.
Int J Mol Med 2000 Apr
PMID:Leptin expression in colorectal and breast cancer patients. 1071 61

This paper reviews the general mechanisms by which leptin acts as a regulator of lipid reserves through changes in food intake, energy expenditure and fuel selection, with an emphasis on its direct effects on cellular lipid metabolism. Briefly, when leptin levels increase, food consumption decreases via modulation of hypothalamic neuropeptides. As well, normal decreases in energy expenditures (e.g. with diurnal cycles or reduced caloric intake) do not occur. This is probably caused by an increase in mitochondrial proton leak mediated by leptin via increases in sympathetic nervous system stimulation and thyroid hormone release. The decrease in caloric input coupled with relatively higher energy expenditure, therefore, leads to negative energy balance. Leptin also changes the fuel source from which ATP is generated. Fuel preference switches from carbohydrate (glucose) to lipid (fatty acids). This effect arises through stimulation of triacylglycerol catabolism by leptin. In vitro studies show that leptin is a potent stimulator of lipolysis and fatty acid oxidation in adipocytes and other cell types. Consequently, leptin is also a regulator of cellular triacylglycerol content. Hormonal regulation of leptin, as well as its role in fasting and seasonal weight gain and energy expenditure are also briefly discussed.
Comp Biochem Physiol A Mol Integr Physiol 2000 Mar
PMID:Leptin: an essential regulator of lipid metabolism. 1079 58


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