Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Leptin”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMed2001

Leptin administration prevents spontaneous gestational diabetes in heterozygous Lepr(db/+) mice: effects on placental leptin and fetal growth.

Gestational diabetes mellitus (GDM) results from an interaction between susceptibility genes and the diabetogenic effects of pregnancy. During pregnancy, mice heterozygous for the lepin receptor (db/+) gain more weight, are glucose intolerant, and produce macrosomic fetuses compared with wild-type (+/+) mothers, suggesting that an alteration in leptin action may play a role in GDM and fetal overgrowth. To investigate whether leptin administration or pair-feeding can reduce adiposity and thereby prevent GDM and neonatal overgrowth, we examined energy balance, glucose and insulin tolerance, and fetal growth in pregnant db/+ and +/+ mice treated with recombinant human leptin-IgG during late pregnancy. Leptin reduced food intake and adiposity in pregnant db/+ mice to levels similar to pregnant +/+ mice and significantly reduced maternal weight gain. Maternal glucose levels were markedly lower during glucose and insulin challenge tests in leptin-treated db/+ mice relative to db/+ and pair-fed controls. Despite reduced energy intake and improved glucose tolerance, leptin administration did not reduce fetal overgrowth in offspring from db/+ mothers. Fetal and placental leptin levels were 1.3- to 1.5-fold higher in offspring from db/+ mothers and remained unchanged with leptin administration, whereas leptin treatment in +/+ mothers or pair-feeding decreased placental leptin concentration and reduced fetal birth weight. Our results provide evidence that leptin administration during late gestation can reduce adiposity and improve glucose tolerance in the db/+ mouse model of spontaneous GDM. However, fetal and placenta leptin levels are higher in db/+ mothers and are subject to reduced negative feedback in response to leptin treatment. These data suggest that alterations in placenta leptin may contribute to the regulation of fetal growth independently of maternal glucose levels.

Animals↗
PubMed2005

Leptin and soluble leptin receptor levels in obese children in fasting and satiety states.

AIM: To investigate the role of soluble leptin receptors in leptin resistance in obese children. METHODS: Thirty-one obese children (16 boys and 15 girls) with a median age of 12.1 years and 15 age- and sex-matched controls were included in the study. Leptin and soluble leptin receptor levels were measured in fasting and satiety states. RESULTS: Serum leptin levels were significantly higher and soluble leptin receptor levels were significantly lower in obese children compared to controls in fasting and satiety states. In obese children, there was a high and inverse correlation between leptin levels and soluble leptin receptor levels after fasting. Prepubertal obese children had lower leptin and higher soluble leptin, receptor levels compared to pubertal children in both states. CONCLUSION: In this study, being the first to consider both fasting and satiety states, obese children were found to have higher leptin, but lower soluble leptin receptor levels, compared to controls. With these findings, it can be postulated that leptin resistance in obese children originates from a defect of soluble leptin receptor production.

Adolescent↗
PubMed2005

Seasonal changes in serum leptin of the feral raccoon (Procyon lotor) determined by canine-leptin-specific ELISA.

Several reports have been published on blood leptin concentrations in feral animals, including members of the Carnivora, using a commercially available multi-species radioimmunoassay (RIA) kit with anti-human leptin antibody. However, we observed weak immunoreactivity between recombinant canine leptin and anti-human leptin antibody, suggesting a limitation in the applicability of the RIA kit for leptin assays in Carnivora species. We tested the applicability of RIA and sandwich enzyme-linked immunosorbent assay (ELISA) with anti-canine leptin antibody to assay blood leptin in the dog (Canis familiaris) and the raccoon (Procyon lotor). When RIA was used for recombinant canine leptin and dog sera, values were much lower than those determined by ELISA at higher concentrations (>10 ng/ml), while rather higher at lower concentrations (<2 ng/ml). A similar discrepancy between the two methods was found for serum leptin concentrations in raccoons. Clear seasonal variations were observed by ELISA, but not by RIA, with high values in autumn (3.46+/-0.45 ng/ml) and low values in spring and summer (0.71+/-0.07 ng/ml). Serum leptin concentrations in raccoons correlated positively with their body weight (r=0.753) and body mass index (r=0.755), corroborating our previous findings of a strong positive correlation between serum leptin concentrations and body fat content in dogs. Thus, the canine leptin ELISA is useful for assays of dog and raccoon leptin, and blood leptin is a good marker of nutritional condition in the species of Carnivora assayed in this study.

Animals↗
PubMed2003

Leptin signaling in the hypothalamus: emphasis on energy homeostasis and leptin resistance.

Leptin, the long-sought satiety factor of adipocytes origin, has emerged as one of the major signals that relay the status of fat stores to the hypothalamus and plays a significant role in energy homeostasis. Understanding the mechanisms of leptin signaling in the hypothalamus during normal and pathological conditions, such as obesity, has been the subject of intensive research during the last decade. It is now established that leptin action in the hypothalamus in regulation of food intake and body weight is mediated by a neural circuitry comprising of orexigenic and anorectic signals, including NPY, MCH, galanin, orexin, GALP, alpha-MSH, NT, and CRH. In addition to the conventional JAK2-STAT3 pathway, it has become evident that PI3K-PDE3B-cAMP pathway plays a critical role in leptin signaling in the hypothalamus. It is now established that central leptin resistance contributes to the development of diet-induced obesity and ageing associated obesity. Central leptin resistance also occurs due to hyperleptinimia produced by exogenous leptin infusion. A defective nutritional regulation of leptin receptor gene expression and reduced STAT3 signaling may be involved in the development of leptin resistance in DIO. However, leptin resistance in the hypothalamic neurons may occur despite an intact JAK2-STAT3 pathway of leptin signaling. Thus, in addition to defective JAK2-STAT3 pathway, defects in other leptin signaling pathways may be involved in leptin resistance. We hypothesize that defective regulation of PI3K-PDE3B-cAMP pathway may be one of the mechanisms behind the development of central leptin resistance seen in obesity.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1998

Serum leptin levels and leptin expression in growth hormone (GH)-deficient and healthy adults: influence of GH treatment, gender, and fasting.

Growth hormone (GH) treatment is associated with a reduction in fat mass in healthy and GH-deficient (GHD) subjects. This is mainly mediated via a direct GH action on adipose cells and stimulation of lipolysis. Leptin is secreted from adipose tissue and may be involved in signaling information about adipose tissue stores to the brain. Hormonal regulation of leptin is still not fully elucidated, and in the present study, we investigated both the long-term (4-month) and short-term (28-hour) GH effects on serum leptin and leptin gene expression in subcutaneous adipose tissue. In GHD adults (n = 24), leptin correlated with most estimates of adiposity (r = .62 to .86), as previously found in healthy subjects. However, no correlation was observed with intraabdominal fat determined by computed tomographic (CT) scan (INTRA-CT). GH treatment for 4 months had no independent effect on either serum leptin or leptin gene expression. In a short-term study, we found that fasting gradually reduced leptin levels in both healthy men and GHD adults, with a maximum reduction of 58% to 60% (P < .01) after 31 hours. No independent effect of GH suppression or GH substitution on serum leptin was found during fasting. Adipose tissue leptin mRNA correlated with serum leptin (r = .51, P < .01) and the body mass index ([BMI] r = .55, P < .05). Serum leptin levels and gene expression were significantly higher in women compared with men (26.6 +/- 5.8 v 10.0 +/- 1.30 ng/mL, P < .05). However, in regression analysis accounting for the gender differences in subcutaneous femoral adipose tissue (FEM-CT), the difference in serum leptin disappeared, indicating that subcutaneous femoral fat or factors closely related to femoral fat (eg, sex hormones) may be causal factors for the gender difference in leptin.

Adipose Tissue↗
PubMed2000

Free serum leptin but not bound leptin concentrations are elevated in patients with end-stage renal disease.

BACKGROUND: Leptin is a 16-kDa protein that is thought to be a regulator of food intake and body weight. Although total serum leptin levels have been reported to be elevated in obese and normal weight patients with end-stage renal disease (ESRD), it is not known whether serum-free leptin concentrations are also increased in patients with ESRD with no apparent nutritional problems. Furthermore, there are no data on how different dialysis modes (high-flux haemodiafiltration and low-flux dialysis) influence serum leptin subfractions. METHODS: We measured fasting serum free and bound leptin levels in three groups of male subjects: patients on haemodiafiltration with high flux dialysers (n=11), patients on haemodialysis with low-flux dialysers (n=17) and healthy age (61+/-8 years) and BMI (23.8+/-3.1 kg/m(2)) matched control subjects (n=28). Both leptin components were determined before and after a single dialysis session. RESULTS: Body mass indices were correlated with serum free leptin levels in both patients (r=0.69, P<0.001) and controls (r=0.77, P<0.001). Mean (SD) serum free leptin levels were significantly higher in ESRD patients than in control subjects (91+/-33 vs 41+/- 21 pmol/l; P<0.01). Bound leptin levels did not differ in both groups (0.67+/-0.12 vs 0.56+/-0.11 nmol/l, NS). Elevated serum-free leptin levels in ESRD patients could be reduced by haemodiafiltration with high-flux membranes, but not with low-flux haemodialysis membranes. The former led to a reduction of initial serum free leptin values to 76+/-17% (P<0.01), whereas bound leptin remained unaffected. CONCLUSION: Serum-free leptin levels are elevated in ESRD without any apparent effect on body weight. In contrast, serum bound leptin levels remain stable, thus central feedback regulation via the bound form of the hormone may serve as an alternative explanation in the regulation of food intake and energy expenditure in chronic patients on haemodialysis with no apparent nutritional problems.

Body Mass Index↗
PubMed2006

Leptin antagonist reveals that the normalization of caloric intake and the thermic effect of food after high-fat feeding are leptin dependent.

High-fat (HF) feeding induces a transient increase in caloric intake and enhances energy expenditure. We hypothesized that leptin is necessary for homeostatic restoration of the HF-enhanced caloric intake and may mediate the increase in uncoupling protein-1 (UCP1) in brown adipose tissue (BAT). We employed a leptin antagonist to examine the role of leptin in these biological processes. Simultaneous central administration of leptin and increasing doses of the leptin antagonist revealed a dose-dependent inhibition of leptin-induced hypothalamic signal transducer and activator of transcription-3 phosphorylation, and 7 days of infusion of the leptin antagonist produced the predicted increase in food intake and weight gain. When delivered with exogenous leptin in a 7-day infusion, the leptin antagonist blocked leptin-mediated anorexic effects as well as the increase in BAT UCP1 protein and signal transducer and activator of transcription-3 phosphorylation. Rats were then fed an HF diet (60% kcal as fat) or chow and simultaneously infused with antagonist (25 microg/day into the lateral ventricle) for 7 days and compared with vehicle-infused chow-fed rats. Daily caloric intake of both HF groups peaked on day 2. HF feeding elevated caloric intake, which nearly normalized by day 7, whereas in the presence of the antagonist, caloric intake remained elevated. Moreover, the HF-mediated augmentation in UCP1 in BAT was prevented by the antagonist. These results demonstrate that leptin is essential for the homeostatic restoration of caloric intake after HF feeding and that this leptin antagonist is able to block central leptin signaling and leptin-mediated UCP1 elevation.

Adipose Tissue, Brown↗
PubMed1998

Gender differences in both spontaneous and stimulated leptin secretion by human omental adipose tissue in vitro: dexamethasone and estradiol stimulate leptin release in women, but not in men.

Leptin is a hormone secreted by the adipocytes to serve as a signal to the central nervous system to regulate energy homeostasis. Circulating leptin mainly reflects both total fat mass and the size of constituent adipocytes, although other ancillary hormonal factors may contribute to its blood concentration. Relevant gender differences in leptin concentrations have been reported, but it is not clear whether the elevated leptin levels in women are an intrinsic property of their adipocytes or merely reflect a greater amount of fat reserves. To clarify these points, a systematic study with organ culture from human omental adipose tissue either stimulated or not with steroid hormones was undertaken in samples obtained at surgery from 67 nonobese donors (33 women and 34 men). The assay was standardized in periods of 24 h ending at 96 h, with no apparent tissue damage. Each adipose tissue sample from a single donor was incubated in triplicate, and leptin results are expressed as the mean +/- SEM of the integrated secretion to the medium (area under the curve; nanograms of leptin per g tissue/48 h). Control nonstimulated samples showed a steady leptin secretion along the 96 h studied, with the peak of secretory activity reached at 48 h; afterward, the in vitro secretion reached a plateau state. Spontaneous leptin secretion in samples from 33 women (3904 +/- 347) was significantly higher (P < 0.05) than that in samples from 34 men (2940 +/- 323). Coincubation of adipose tissue with 1 mumol/L dexamethasone induced a clear-cut leptin increase (P < 0.05) in samples from women (5848 +/- 624; n = 12), but did not change the spontaneous release of leptin in samples from men (3353 +/- 741; n = 6). Similarly, coincubation of adipose tissue with 1 mumol/L estradiol induced a notable leptin increase (P < 0.05) in samples from women (5698 +/- 688; n = 9), whereas it did not alter the secretion in the male samples (3373 +/- 444; n = 6). In samples from both sexes, coincubation with 1 mumol/L estrone or progesterone had no effect, whereas 1 mumol/L forskolin significantly (P < 0.05) reduced leptin release. In conclusion, leptin secretion from omental adipose tissue in vitro 1) is significantly higher in samples from women than in samples from men, 2) is stimulated by dexamethasone and estradiol in women but not in men, 3) is not modified by progesterone or estrone in both sexes, and 4) is inhibited by forskolin in both genders. This different response to the stimulation of adipose tissue may be the biological basis for the gender differences observed in circulating levels of human leptin.

Adipose Tissue↗
PubMed2001

Prenatal leptin production: evidence that fetal adipose tissue produces leptin.

In the adult, circulating leptin is highly correlated to adipose tissue mass. Whether such a relationship exists prenatally is unknown, because the actual source of fetal leptin has not been determined. In the present study, we have assessed the placental contribution to fetal and maternal circulating leptin concentrations and determined whether fetal adipose tissue produces leptin. The rate of leptin production in dually perfused human placenta was 0.036 ng/min.g. Ninety-five percent of the leptin released was delivered into the maternal circulation, vs. only 5% on the fetal side. Leptin messenger RNA and protein were detected in adipose tissue biopsies of 20-38 week human fetuses. However, leptin concentration was twice lower in fetal (0.22 +/- 0.11 ng/mg protein, n = 6) than in adult (0.49 +/- 0.12 ng/mg protein, n = 8) adipose tissue. Umbilical leptin levels closely reflected ponderal index at birth over a wide range of birth weights (1.6--4.1 kg). In sharp contrast, maternal and placental leptin concentrations were increased in pregnancies associated with fetal growth retardation. We conclude that umbilical leptin levels are independent of placental leptin production and can be taken as a marker of fat mass in human fetuses. By contrast, placental leptin production makes a substantial contribution to maternal circulating leptin levels during pregnancy.

Adipose Tissue↗
PubMed2000

Breast milk leptin concentrations in initial and terminal milk samples: relationships to maternal and infant plasma leptin concentrations, adiposity, serum glucose, insulin, lipid and lipoprotein levels.

Leptin has recently been shown to be present in human milk and is produced by mammary epithelial cells. We studied leptin concentrations in human milk and its relationships with maternal and infant plasma leptin concentrations, adiposity, serum glucose, insulin, lipid and lipoprotein levels. We also compared the initial and terminal milk leptin concentrations to investigate whether leptin acts as a satiety factor. Venous blood samples were obtained from 18 healthy lactating women aged from 17-42 years and their 3-120 day-old infants. Breast milk samples were collected just before and immediately after suckling, when the infant had self-terminated sucking. Leptin mean values in breast milk were lower than in maternal plasma (p<0.001). Breast milk log leptin concentrations positively correlated with both maternal and infant plasma log leptin concentrations (p<0.001 and p=0.001, respectively) and negatively correlated with maternal serum total cholesterol and low-density lipoprotein cholesterol levels (p<0.001 and p<0.01, respectively), but did not correlate with maternal and infant adiposity, serum glucose and insulin levels, maternal serum HDL-C, triglyceride levels and infants' lipid and lipoprotein concentrations (p>0.05). Using stepwise multiple regression analysis, maternal plasma log leptin and serum HDL-C concentrations were related to breast milk log leptin concentration (R2=0.82; p<0.0001 and p<0.001, respectively). There was no significant difference between initial and terminal milk leptin levels (p>0.05). We concluded that maternal leptin may be transferred to the infant via milk and may exert biological effects; there may be factors other than adiposity affecting breast milk leptin levels, and that leptin might not contribute to the development of satiation at the end of suckling.

Adipose Tissue↗
PubMed2000

Leptin in cerebrospinal fluid from children: correlation with plasma leptin, sexual dimorphism, and lack of protein binding.

BACKGROUND: Previous studies in adults have established that leptin is present at very low concentrations in cerebrospinal fluid (CSF), but few data exist concerning CSF leptin in children. Current evidence suggests that CSF leptin concentrations interact with hypothalamic centers controlling food intake. Serum leptin concentrations manifest a sexual dimorphism that arises during puberty. METHODS: Leptin concentrations were determined in CSF from 42 pre- and postpubertal children who had been objectively classified into non-neurological disease or aseptic meningitis groups. Multivariate analysis of the dependence of CSF leptin on gender, pubertal state, body mass index (BMI), presence of aseptic meningitis, and CSF protein concentration was performed. RESULTS: CSF leptin concentrations correlated with log-transformed plasma leptin concentrations in concomitantly collected samples (r = 0.582; P = 0.029). BMI and gender were significant determinants of CSF leptin in postpubertal children, but only BMI was significant in prepubertal children. Analysis with HPLC to separate protein-bound and free forms of leptin found only free leptin in CSF. CONCLUSIONS: CSF leptin concentrations in children reflect plasma leptin concentrations, including the advent of sexual dimorphism at puberty. Only free leptin is detectable in CSF, suggesting that it is the biologically active form.

Adolescent↗
PubMed2000

Elevated circulating leptin levels in arterial hypertension: relationship to arteriovenous overflow and extraction of leptin.

Leptin, a peptide hormone produced mainly in fat cells, appears to be important for the regulation of metabolism, insulin secretion/sensitivity and body weight. Recently, elevated plasma leptin levels have been reported in patients with arterial hypertension. Because a change in circulating leptin concentrations in such patients could be caused by altered rates of production or disposal, or both, the aim of the present study was to identify regions of leptin overflow into the bloodstream and of leptin extraction. Patients with arterial hypertension (n=12) and normotensive controls (n=20) were studied during catheterization with elective blood sampling from different vascular beds (artery, and renal, hepatic, iliac and cubital veins). Plasma leptin was determined by a radioimmunoassay. Patients with hypertension had significantly elevated levels of circulating leptin (12.8 ng/l, compared with 4.1 ng/l in the controls; P<0.001), and this was also the case when adjusted for body mass index (BMI) [0.435 and 0.167 ng/l per unit BMI (kg/m(2)) respectively; P<0.001]. Circulating leptin was directly related to arterial blood pressure (r=0.38-0.62, P</=0.05-0.005) and immunoreactive insulin (r=0.51, P<0.62), but not to plasma renin activity. A significant renal extraction ratio for leptin was seen in the hypertensive patients, but this was not significantly lower than that in the controls (0.09 compared with 0. 16; P=0.1). The hypertensive patients had a significantly higher hepatic venous/arterial leptin ratio than the controls (1.02 compared with 0.93; P<0.02), and this ratio was correlated directly with the BMI (r=0.38, P=0.05) and immunoreactive insulin (r=0.43, P<0.05). In both hypertensive patients and controls there was a significant spillover of leptin into the iliac vein, but not into the cubital vein. In conclusion, the high concentration of circulating leptin in patients with arterial hypertension is probably caused by increased release of leptin from abdominal (especially mesenteric and omental) and gluteal adipose tissue stores, and renal extraction is slightly reduced. Leptin kinetics in arterial hypertension require further investigation.

Adult↗
PubMedDate not supplied

Maternal serum leptin concentrations do not correlate with cord blood leptin concentrations in normal pregnancy.

OBJECTIVE: To determine whether there is a difference in maternal leptin concentration and cord blood concentration, consistent with the hypothesis of a noncommunicating, two-compartement model of fetoplacental leptin regulation. METHODS: Blood samples were collected from 139 women, identified as having an uncomplicated pregnancy, from an antecubital vein at delivery. Cord blood samples were taken from the umbilical vein. Leptin was measured by radioimmunoassay, and its relationship to fetal and maternal anthropometrics was assessed by Spearman correlation. Differences in maternal and cord blood leptin levels between male and female infants were tested with the Mann-Whitney Utest. Maternal and cord blood leptin were compared by the Wilcoxon signed rank test. The outcome measures were maternal and cord blood leptin at delivery, fetal birth weight, length, weight/length ratio, and ponderal index, maternal prepregnancy body mass index, pregnancy weight gain, relative weight gain, and body mass index at delivery. RESULTS: No correlations were found between maternal and cord blood leptin concentrations. Fetal leptin level correlated with birth weight (rho = 0.665; P <.0001), length (rho = 0.490; P <.0001), ponderal index (rho = 0.260; P =.002), and weight/length ratio (rho = 0.625; P <.0001). Median leptin concentrations were higher in female (9.3 ng/mL, range 1.5-34.4 ng/mL) than in male (8.2 ng/mL, range 1.6-38.3 ng/mL) neonates, but this difference was statistically not significant. Logistic regression analysis showed a significant influence on umbilical venous leptin concentration for birth weight (P <.0001) but not for gender. Maternal leptin concentrations were significantly higher than cord leptin concentrations (P <.0005 for the male and female neonates and the entire group). CONCLUSION: There was no correlation between maternal and cord leptin, which supports the hypothesis of a noncommunicating, two-compartment model of fetoplacental leptin regulation.

Birth Weight↗
PubMed2005

[Expression of leptin mRNA in luteinized granulosa cells and leptin levels in serum and follicular fluid of non-obese infertile patients with polycystic ovary syndrome].

OBJECTIVE: To investigate the expression of leptin mRNA in luteinized granulose cells and the leptin level in serum and follicular fluid of non-obese patients with polycystic ovary syndrome (PCOS). METHODS: Granulosa cells were collected from the puncture fluid of follicle of 16 obese infertile patients with PCOS to undergo external fertilization. Fasting venous blood was collected while collecting the ova. RT-PCR was used to detect the expression of leptin mRNA in the granulosa cells. ELISA was used to detect the leptin level in the serum and follicular fluid. Twenty normal women undergoing external fertilization because of male infertility of their husbands were used as controls. RESULTS: The expression of leptin mRNA (A value) was 1.5 +/- 0.4 in the obese infertile patients with PCOS and was 1.8 +/- 0.6 (P > 0.05) in the controls. Both the leptin levels of serum and follicular fluid were not different between the obese infertile patients with PCOS and controls (both P > 0.05). The leptin level in follicular fluid was significantly correlated with both the serum leptin level in the obese infertile patients with PCOS (r(s) = 0.838, P = 0.000) and the control group (r(s) = 0.712, P = 0.000). The expression level of leptin mRNA in the luteinized was not correlated with the leptin level of follicular fluid in both the obese infertile patients with PCOS and the control group (both P > 0.05). The fertility rate was not different between the obese infertile patients with PCOS (7/16) and the controls (9/24) (P = 0.693). CONCLUSION: The expression of leptin mRNA is normal in the follicular fluid of the obese infertile patients with PCOS. The leptin levels in serum and follicular fluid of the obese infertile patients with PCOS are similar to those of normal women. The leptin level in follicular fluid depends mainly on the circulating leptin level.

Adult↗
PubMed2006

High expression of leptin receptor mRNA in breast cancer tissue predicts poor prognosis for patients with high, but not low, serum leptin levels.

The association of mRNA expression levels of leptin receptors (long isoform: Lep-R(L) and short isoform: Lep-R(S)) in breast cancer tissue with patient prognosis was studied with special reference to the serum leptin level or the leptin mRNA level in tumor tissue. Lep-R(L), Lep-R(S) and leptin mRNA levels in breast cancer tissue (n = 91) were determined with a real-time PCR assay, and serum leptin levels in breast cancer patients (n = 67) with an enzyme-linked immunosorbent assay. Neither Lep-R(L) nor Lep-R(S) mRNA levels in tumor tissue were significantly associated with patient prognosis, but both intratumoral Lep-R(L) and Lep-R(S) mRNA high tumors were significantly (p < 0.01) associated with a poor prognosis. Multivariate analysis showed that a high level of both Lep-R (L) and Lep-R (S) mRNA in tumor tissue was a significant risk factor, independent of other risk factors. The subset analysis demonstrated that both intratumoral Lep-R(L) and Lep-R(S) mRNA high tumors were significantly associated with a poor prognosis for the subset of patients with high serum leptin or high intratumoral leptin mRNA levels but not in the subset of patients with low serum leptin or low intratumoral leptin mRNA levels. The association between both intratumoral Lep-R(L) and Lep-R(S) mRNA high tumors and a poor prognosis in the presence of high serum leptin or high intratumoral leptin mRNA levels seems to suggest that the leptin and Lep-R(L)/Lep-R(S) pathways are implicated in the growth stimulation of breast tumors. The well-established finding that obesity serves as a risk factor for relapse in breast cancer patients may thus be partially explained by the high serum leptin level seen in obese women.

Adult↗
PubMed2001

Soluble leptin receptor represents the main leptin binding activity in human blood.

In human blood leptin circulates both free and bound to high molecular weight proteins. Hypothesising that these proteins may modulate ligand bioavailability and bioactivity of leptin, we investigated their molecular nature. Therefore, leptin binding activity was partially purified from human plasma using a leptin affinity column. Subjecting this preparation to size exclusion chromatography (SEC) we observed a coelution of leptin binding activity with levels of the soluble leptin receptor (sOB-R) determined by a newly developed ligand immunofunctional assay. In Western blot analysis the partially purified leptin binding activity exhibited sOB-R immunoreactivity in two bands of 110 and 140 kD. Following N-deglycosylation these bands were replaced by two bands with the molecular weight of 90 and 60 kD, suggesting two isoforms which are capable of leptin binding, as determined by cross-linking. Furthermore, different ratios of these isoforms were detectable in fractions of the leptin binding activity after separation by SEC. These findings indicate the formation of heterodimers and homodimers complexed with and without leptin. As the two sOB-R bands from Western blot analysis correspond to only two specific bands in cross-linking experiments with 125l-leptin, the role of both isoforms as leptin binding proteins appears to be exclusive. Therefore, our results indicate that sOB-R is the major leptin binding protein in the circulating human blood.

Blotting, Western↗
PubMed2001

Insulin inhibits leptin receptor signalling in HEK293 cells at the level of janus kinase-2: a potential mechanism for hyperinsulinaemia-associated leptin resistance.

AIMS/HYPOTHESIS: Leptin resistance in obese humans seems to be predominantly caused by signalling abnormalities at the post receptor level. Leptin resistance in obese individuals is frequently associated with insulin resistance and pronounced hyperinsulinaemia indicating a negative crosstalk of the insulin and leptin signalling chain. METHODS: This hypothesis was tested using a cell model of peripheral leptin signalling, i. e. insulin-secreting cell lines (RINr1046-38). Mechanisms for a crosstalk between the insulin and leptin signalling pathway were also studied in rat-1 and HEK293 cells overexpressing elements of the insulin and leptin signalling chain. RESULTS: The effects of leptin on insulin secretion are completely cancelled by a 4-h preincubation with 1 nmol/l insulin, supporting the hypothesis of a negative crosstalk of insulin and leptin signalling. We investigated the potential molecular mechanisms in more detail in HEK293 cells and Rat-1 fibroblasts that overexpressed proteins of the insulin and leptin signalling chain. Leptin (60 ng/ml) stimulated autophosphorylation of JAK-2 in HEK 293 cells. This leptin effect could be inhibited by simultaneous treatment of cells with insulin. Furthermore, overexpression of the insulin receptor in HEK 293 cells clearly reduced JAK-2 phosphorylation and led further downstream to a diminished phosphatidylinositol 3-kinase activity. The inhibitory effect of the insulin signal could be partially prevented by transfection of the cells with an inactive mutant of the tyrosine phosphatase SHP-1. CONCLUSION/INTERPRETATION: In summary, our data suggest that the insulin receptor signalling pathway interferes with leptin signalling at the level of JAK-2. Inhibition of JAK-2 phosphorylation might occur through SHP-1-dependent pathways, indicating that hyperinsulinaemia contributes to the pathogenesis of leptin resistance.

Animals↗
PubMed2006

Serum adiponectin, leptin and soluble leptin receptor in pre-eclampsia.

OBJECTIVES: To delineate the changes in serum levels of adiponectin, leptin and soluble leptin receptor, and in the free leptin index in women with pre-eclampsia. METHODS: Blood samples were collected from 38 pregnant women with pre-eclampsia and 42 normotensive pregnant women as controls. Serum concentrations of adiponectin, leptin and soluble leptin receptor were determined by enzyme-link immunosorbent assay and the free leptin index was calculated as the ratio of serum leptin to soluble leptin receptor for each sample. RESULTS: No significant differences were observed between the groups regarding maternal age, gestational age and body mass index. Women with pre-eclampsia had significantly higher levels of serum adiponectin and leptin, and a higher free leptin index than controls (P<0.01, P<0.001 and P<0.001, respectively). There were no significant differences between the two groups in serum levels of soluble leptin receptor (P>0.05). CONCLUSIONS: The study demonstrated elevated serum levels of adiponectin and leptin as well as a higher free leptin index in women with pre-eclampsia, suggesting these as important factors contributing to this complication of pregnancy.

Adiponectin↗