Soluble Leptin Receptor Levels Research Articles

Association of plasma leptin levels and soluble leptin receptor with breast cancer

Objective: To explore the association between plasma leptin (LEP) levels, soluble leptin receptor(SLR), free leptin index and breast cancer. Methods: 245 new female cases of primary breast cancer confirmed by histopathology examination were sequentially recruited into the study. A total of 245 age-matched healthy women were enrolled as controls during the same period. A standardized questionnaire was used to collect the demographic information of the subjects. Blood samples were collected and the levels of LEP and SLR in plasma were measured by enzyme linked immunosorbent assay. The differences of LEP, SLR and FLI expression between control and cases group, as well as different breast cancer subtypes and TNM stages were compared using t-test and ANOVA after stratification by menopause status. Multivariate logistic regression was used to explore the contributions of the three indexes to the risk of breast cancer. Results: Females in both cases and control group were (50.7 ± 9.4) years old. The level of SLR and FLI (P(50)(P(25),P(75))) in premenopausal women were 18.4 (11.2, 28.7), 0.5 (0.4, 0.6) μg/L in case group and 27.7 (19.2, 43.4), 0.3 (0.3, 0.4) μg/L in control group (P<0.001). While the level of postmenopausal women in case group were 20.3 (12.8, 31.8), 0.5 (0.4, 0.6) μ g/L (P<0.001), and 30.1 (18.8, 40.5), 0.3 (0.3, 0.5) μg/L in control group (P<0.001), respectively. After adjustment for confounding factors and BMI, the relationship between FLI and breast cancer remained significant for both pre- and postmenopausal women while the association between SLR and breast cancer was significant only in premenopausal women. Compared with the lowest level of SLR, higer levels of SLR is associated with a reduced risk of breast cancer (premenopausal women, OR=0.10, 95% CI: 0.04-0.29, P(trend)<0.001). Compared with the lowest level of FLI, FLI at higher levels is associated with an increased risk of breast cancer (premenopausal women, OR=7.14, 95% CI: 2.86-17.83, P(trend)<0.001; postmenopausal women, OR=8.10, 95% CI: 2.85-22.98, P(trend)<0.001). No significant association between LEP and breast cancer or association between the three indexes and breast cancer subtypes and TNM stages was found (P>0.05). Conclusion: SLR may be a protective factor for breast cancer while FLI may increase the risk of breast cancer.

Central and peripheral leptin and agouti-related protein during and after pregnancy in relation to weight change.

To study changes of neuropeptides and adipokines in cerebrospinal fluid (CSF) and serum from pregnancy to postpregnancy in relation to weight changes, fat mass and glucose metabolism. With high postpartum weight retention being a risk factor in future pregnancies and of lifelong obesity, we evaluated neuropeptide and adipokine changes in women who either gained weight or were weight stable. Women were followed for 5±1years after pregnancy and divided into two groups, weight stable and weight gain, by weight change from start of pregnancy. Twenty-five women (BMI 27±5kg/m2 ) recruited at admission for elective caesarean section. CSF and serum levels of agouti-related protein (AgRP), leptin and insulin, and serum levels of adiponectin and soluble leptin receptor were measured during and after pregnancy. These measurements were further related to fat mass and insulin sensitivity (HOMA-IR). S-AgRP levels during pregnancy were lower in the weight stable group and a 1 unit increase in s-AgRP was associated with 24% higher odds of pertaining to the weight gain group. After pregnancy, s-AgRP increased in the weight stable group but decreased in the weight gain group. Decreased transport of leptin into CSF during pregnancy was reversed by an increased CSF:serum leptin ratio after pregnancy. In women who returned to their prepregnancy weight, serum adiponectin increased after pregnancy and correlated negatively with HOMA-IR. S-AgRP concentration in late pregnancy may be one factor predicting weight change after pregnancy, and circulating AgRP may be physiologically important in the long-term regulation of body weight.

Comparison of body composition and adipokine levels between thin and normal‐weight prepubertal children

ObjectiveThinness can have substantial consequences for child development and health. Adipokines, including leptin and adiponectin, play a significant role in the regulation of important metabolic functions. The aim of this study was to investigate associations between body composition and serum leptin and adiponectin levels in thin and normal‐weight children. MethodsThe authors examined 100 healthy prepubertal children, who were divided into two subgroups: thin (n=50) and normal‐weight children (n=50). Body composition was assessed by dual‐energy X‐ray absorptiometry. Serum concentrations of adipokines were determined by immunoenzymatic assays. ResultsThin children had a similar body height but significantly lower (p<0.0001) body weight, body mass index, fat mass, lean mass, and bone mineral content compared with normal‐weight children. Serum concentrations of leptin were about 2‐fold lower (p<0.0001) in thin vs. normal‐weight subjects. Serum levels of total adiponectin, adiponectin multimers, and soluble leptin receptor (sOB‐R) were similar in both groups. The leptin/soluble leptin receptor ratio and leptin/adiponectin ratios were lower (p<0.0001) in thin vs. normal‐weight children. In both groups of children, it was found that body composition parameters were positively related with leptin but not with adiponectin levels. Additionally, bone mineral content was positively related with body mass index, fat mass, lean mass, and leptin level in thin and normal‐weight children. ConclusionsPrepubertal thin children have disturbances in body composition and adipokine profile. Early recognition of thinness and determination of body composition parameters and adipokine levels can be useful in medical and nutritional care of thin children for the optimization of bone mineral accrual.

LEPR Gene Polymorphism and Plasma Soluble Leptin Receptor Levels are Associated with Polycystic Ovary Syndrome in Han Chinese Women

To investigate the association of LEPR polymorphisms and plasma leptin and soluble leptin receptor (sOB-R) levels with polycystic ovary syndrome (PCOS) in Chinese women. LEPR Lys109Arg (rs1137100) and Gln223Arg (rs1137101) polymorphisms of PCOS patients and the controls were genotyped. Plasma leptin and sOB-R levels of two groups were measured. The genotypic distributions of Lys109Arg (rs1137100) differed between the PCOS and control groups. Plasma sOB-R levels increased significantly in PCOS patients and were associated with PCOS independent of BMI. Furthermore, luteinizing hormone, triglyceride and fasting blood glucose correlated significantly to PCOS patients' sOB-R levels. LEPR Lys109Arg (rs1137100) was associated with PCOS susceptibility and genotype AA was deduced to be a protective factor for PCOS; sOB-R levels might be recognized as a new indicator for the severity of PCOS.

Содержание лептина, растворимых рецепторов лептина и индекса свободного лептина у больных с метаболическим синдромом

Aim . To assess the levels of leptin, its soluble receptor, and index of the formation of free leptin in metabolic syndrome (MS). Materials and methods . The study included 110 individuals with obesity and overweight. The group 1 consisted of 70 patients with MS (IDF, 2005), the average body mass index (BMI) 38.4 ± 4.4 kg/m 2 , aged 48.2 ± 2.4 years, with arterial hypertension (AH) 1–2 degree, without regular antihypertensive therapy. Group 2 – obesity accounted for 40 patients aged 38.4 ± 6.2 years, BMI 36.0 ± 5.5 kg/m 2 without hypertension and metabolic disorders. Group 3 consisted of 30 healthy persons, BMI 27.1 ± 1.3 kg/m2. All patients were evaluated for insulin, HOMA index, leptin, leptin receptor, leptin free index (calculated as the ratio of leptin (ng/ml) to the leptin receptor (ng/ml), multiplied by 100). Results : In patients with MS as compared to other two groups there were higher levels of HOMA IR index, leptin and free leptin index. Values of leptin receptor in groups 1 and 2 did not differ significantly and were lower than in healthy persons. The free leptin index was significantly higher in MS group relative to the group 2 and 15 times higher than in the healthy individuals. Free leptin index correlated with values of BMI (R = 0.32; p = 0.02), blood pressure (R = 0.3; p = 0.04), uric acid (R = 0.27; p = 0.04), triglycerides (R = 0.42; p = 0.02), index HOMA-IR (R = 0.45; p = 0.02). Conclusions : Reduction of soluble leptin receptor, depending on the degree of abdominal obesity, may cause progression of leptin resistance in patients with MS. The levels of leptin and soluble leptin receptor appears to have dramatical gender differences. Calculation of free leptin index should be used for the objective evaluation of leptin resistance, regardless of gender, degree of obesity, and other metabolic parameters.

Leptin, soluble leptin receptor, and free leptin index in patients with metabolic syndrome

Aim. To assess the levels of leptin, its soluble receptor, and index of the formation of free leptin in metabolic syndrome (MS).&#x0D; Materials and methods. The study included 110 individuals with obesity and overweight. The group 1 consisted of 70 patients with MS (IDF, 2005), the average body mass index (BMI) 38.4 4.4 kg/m2, aged 48.2 2.4 years, with arterial hypertension (AH) 12 degree, without regular antihypertensive therapy. Group 2 "healthy" obesity accounted for 40 patients aged 38.4 6.2 years, BMI 36.0 5.5 kg/m2 without hypertension and metabolic disorders. Group 3 consisted of 30 healthy persons, BMI 27.1 1.3 kg/m2. All patients were evaluated for insulin, HOMA index, leptin, leptin receptor, leptin free index (calculated as the ratio of leptin (ng/ml) to the leptin receptor (ng/ml), multiplied by 100).&#x0D; Results: In patients with MS as compared to other two groups there were higher levels of HOMA IR index, leptin and free leptin index. Values of leptin receptor in groups 1 and 2 did not differ significantly and were lower than in healthy persons. The free leptin index was significantly higher in MS group relative to the group 2 and 15 times higher than in the healthy individuals. Free leptin index correlated with values of BMI (R = 0.32; p = 0.02), blood pressure (R = 0.3; p = 0.04), uric acid (R = 0.27; p = 0.04), triglycerides (R = 0.42; p = 0.02), index HOMA-IR (R = 0.45; p = 0.02).&#x0D; Conclusions:&#x0D; &#x0D; Reduction of soluble leptin receptor, depending on the degree of abdominal obesity, may cause progression of leptin resistance in patients with MS. &#x0D; The levels of leptin and soluble leptin receptor appears to have dramatical gender differences. &#x0D; Calculation of free leptin index should be used for the objective evaluation of leptin resistance, regardless of gender, degree of obesity, and other metabolic parameters.

Plasma soluble leptin receptor levels are associated with pancreatic β-cell dysfunction in patients with type 2 diabetes.

Aims/IntroductionA soluble form of the leptin receptor (soluble Ob‐R) in the circulation regulates leptin's bioactivity, and is inversely associated with body adiposity and circulating leptin levels. However, no study has examined the clinical impact of soluble Ob‐R on glucose metabolism in diabetes. The present study aimed to investigate the association of plasma soluble Ob‐R levels with insulin resistance and pancreatic β‐cell function in patients with type 2 diabetes.Materials and MethodsA total of 289 Japanese patients with type 2 diabetes were included in the present study. Fasting plasma soluble Ob‐R levels and plasma leptin levels were measured by enzyme‐linked immunosorbent assay. Insulin resistance and pancreatic β‐cell function were estimated by homeostasis model assessment of insulin resistance, homeostasis model assessment of β‐cell function and fasting C‐peptide index.ResultsThe median plasma soluble Ob‐R level and plasma leptin level were 3.4 ng/mL and 23.6 ng/mL, respectively. Plasma soluble Ob‐R levels were negatively correlated with homeostasis model assessment of insulin resistance, homeostasis model assessment of β‐cell function and the C‐peptide index, whereas plasma leptin levels were positively correlated with each index in univariate analyses. Multivariate analyses including plasma soluble Ob‐R levels, plasma leptin levels and use of sulfonylureas, along with age, sex, body mass index and other covariates, showed that soluble Ob‐R levels were independently and negatively associated with homeostasis model assessment of β‐cell function and the C‐peptide index, but not significantly associated with homeostasis model assessment of insulin resistance.ConclusionsPlasma soluble Ob‐R levels are independently associated with pancreatic β‐cell function, but not with insulin resistance, in patients with type 2 diabetes. The present study implicates the role of soluble Ob‐R in pancreatic β‐cell dysfunction in type 2 diabetes.

Examining the Causal Role of Leptin in Alzheimer Disease: A Mendelian Randomization Study

Background: Observational evidence regarding the role of leptin in Alzheimer disease (AD) is conflicting. We sought to determine the causal role of circulating leptin and soluble plasma leptin receptor (sOB-R) levels in AD using a separate-sample Mendelian randomization study. Methods: Single nucleotide polymorphisms (SNPs) independently and solely predictive of log-transformed leptin (rs10487505 [LEP], rs780093 [GCKR], rs900400 [CCNL1], rs6071166 [SLC32A1], and rs6738627 [COBLL1]) and of sOB-R (rs1137101 [LEPR], rs2767485 [LEPR], and rs1751492 [LEPR]) levels (ng/mL) were obtained from 2 previously reported genome-wide association studies. We obtained associations of leptin and sOB-R levels with AD using inverse variance weighting with fixed effects by combining Wald estimates for each SNP. Sensitivity analyses included using weighted median and MR-Egger methods and repeating the analyses using only SNPs of genome-wide significance. Results: Using inverse variance weighting, genetically predicted circulating leptin levels were not associated with AD, albeit with wide confidence intervals (CIs): odds ratio (OR) 0.99 per log-transformed ng/mL; 95% CI 0.55-1.78. Similarly, the association of sOB-R with AD was null using inverse variance weighting (OR 1.08 per log-transformed ng/mL; 95% CI 0.83-1.41). Results from our sensitivity analyses confirmed our findings. Conclusions: In this first Mendelian randomization study estimating the causal effect of leptin on AD, we did not find an effect of genetically predicted circulating leptin and sOB-R levels on AD. As such, this study suggests that leptin is unlikely to be a major contributor to AD, although the wide CIs preclude a definitive assessment.

Comparison of body composition and adipokine levels between thin and normal-weight prepubertal children

ObjectiveThinness can have substantial consequences for child development and health. Adipokines, including leptin and adiponectin, play a significant role in the regulation of important metabolic functions. The aim of this study was to investigate associations between body composition and serum leptin and adiponectin levels in thin and normal-weight children. MethodsThe authors examined 100 healthy prepubertal children, who were divided into two subgroups: thin (n=50) and normal-weight children (n=50). Body composition was assessed by dual-energy X-ray absorptiometry. Serum concentrations of adipokines were determined by immunoenzymatic assays. ResultsThin children had a similar body height but significantly lower (p<0.0001) body weight, body mass index, fat mass, lean mass, and bone mineral content compared with normal-weight children. Serum concentrations of leptin were about 2-fold lower (p<0.0001) in thin vs. normal-weight subjects. Serum levels of total adiponectin, adiponectin multimers, and soluble leptin receptor (sOB-R) were similar in both groups. The leptin/soluble leptin receptor ratio and leptin/adiponectin ratios were lower (p<0.0001) in thin vs. normal-weight children. In both groups of children, it was found that body composition parameters were positively related with leptin but not with adiponectin levels. Additionally, bone mineral content was positively related with body mass index, fat mass, lean mass, and leptin level in thin and normal-weight children. ConclusionsPrepubertal thin children have disturbances in body composition and adipokine profile. Early recognition of thinness and determination of body composition parameters and adipokine levels can be useful in medical and nutritional care of thin children for the optimization of bone mineral accrual.

Correlation between the expressions of leptin and its receptors (ObR,sObR) in gastric cancer / Mide kanserinde leptin ve reseptörlerinin (ObR, sObR) ekspresyonları arasındaki korelasyon

Abstract Objective: The expressions of leptin and its receptor (ObR) have been observed in human gastric cancer (GC) tissue. Leptin can promote the proliferation of GC cells. However, the correlation between leptin and ObR expressions in GC and the role of gastric ObR protein levels in patients with GC is still unclear. This study aimed to evaluate the relationship between leptin, gastric ObR protein and soluble leptin receptor (sObR) levels and whether their possible role of indicator in GC. Methods: Serum leptin, gastric leptin and serum sObR concentrations were determined in 30 male patients with GC and 25 male dyspeptic subjects by enzyme linked immunosorbent assay. We analysed the expression of gastric ObR levels in endoscopically obtained biopsy samples by using Western Blotting method. Results: Compared with controls, patients had lower serum leptin and higher gastric tissue leptin levels. sObR protein concentrations of patients were detected significantly higher, gastric ObR protein expression were lower than subjects in control group. Conclusion: Leptin in gastric cancerous region and sObR in circulation are overexpressed in GC. Their expressions are associated with malignancy. Decreased leptin levels, induces the sObR signal in circulation. This negative feedback regulation is also seen in gastric tissue: increased gastric tissue leptin levels inhibits gastric ObR protein expression. Thus,leptin and ObR may be important indicators in GC.

Lower Muscle Mass and Body Fat in Adolescent Idiopathic Scoliosis Are Associated With Abnormal Leptin Bioavailability.

This was a case-control study. This study aimed to investigate the body composition and its correlation with leptin and soluble leptin receptor (sOB-R) levels in girls with adolescent idiopathic scoliosis (AIS) and compared with healthy controls. Patients with AIS are associated with lower body weight, taller stature, lower body mass index (BMI), and deranged bone quality. Despite the widely reported lower BMI and body weight in girls with AIS, the body composition of these patients was not thoroughly studied with sufficient sample size. Leptin is an important factor in regulating energy and bone metabolism, and has been postulated as one of the etiologic factors of AIS. One hundred forty-eight AIS and 116 control girls aged 12 to 14 were recruited. Body composition was measured with bioelectrical impedance analysis. Caloric intake and physical activity level were assessed by food frequency and Baecke questionnaires respectively. Serum total leptin and sOB-R levels were measured with enzyme-linked immunosorbent assay, and free leptin index was calculated. AIS girls had lower body weight and BMI, other anthropometric and sexual maturity parameters were comparable with controls. There were no difference in caloric intake and physical activity levels. After adjustment for physical activity level, AIS girls had lower skeletal muscle mass, lower body fat, and %body fat. Higher sOB-R and lower free leptin index were found in AIS girls after adjusted for age and body weight. Weaker correlations between serum total leptin, FLI, and body composition parameters were observed in AIS girls. Results suggested that the lower body weight in AIS girls was contributed by both lower skeletal muscle mass and lower body fat. Altered leptin bioavailability also exists in AIS girls and could lead to lower body weight, lower BMI, and abnormal body composition that were manifested in AIS simultaneously. 4.

Human breast milk and adipokines – A potential role for the soluble leptin receptor (sOb-R) in the regulation of infant energy intake and development

Concentrations of different adipokines in human breast milk are thought to be able to affect energy intake of the infant. Leptin is a hormone synthesized by adipose tissue and the human placenta and favors satiety. The availability of leptin in breast milk is influenced by epithelial cells of the mammary gland that are known to be able to produce leptin, as well as leptin from maternal circulation that is transported to the breast milk, and which can thus in turn reach neonatal blood after absorption. Research so far as mainly focused on leptin concentrations in breast milk. However, evidence suggests that in addition to leptin concentrations levels of the so-called soluble leptin receptor (sOb-R), the main high-affinity binding protein for leptin in humans, are necessary in order to calculate the free leptin index (FLI) and to assess function of the leptin axis. FLI is calculated from the ratio of leptin to the sOb-R, and serves as the main parameter for assessing function of the leptin axis throughout maturation and development. Here we propose that assessing sOb-R levels in addition to leptin concentrations in breast milk could serve as a valuable tool to investigate effects of the leptin axis in breast milk because sOb-R concentrations can impact available leptin levels, and which in turn can have significant implications for infant energy intake and related development.

Identifying clues to molecular etiology of multiple sclerosis in South Indian patients

BackgroundEnvironmental risk factors have a dominant role in the pathogenesis of multiple sclerosis (MS). Unhealthy lifestyle can predispose people to autoimmune diseases. MS was a rare disease in Kerala, but now, we notice frequent cases of MS at the city neurology clinic. Changing lifestyle and associated changes in the level of proinflammatory biomolecules like: leptin, soluble leptin receptor (SLR) and free fatty acids (FA) could be contributing to rise in MS incidence. ObjectiveTo identify variations in the levels of bio-molecules: leptin, SLR and FA, between MS patients and matched healthy control. Method: Leptin and SLR levels in the blood serum, were estimated using ELISA, while total FA levels, were estimated using an enzyme based calorimetric assay. ResultMean serum FA levels in MS patients (31.39±4.83nmole/100μl) were 2.7 fold higher than controls (11.54±2.66nmoles/100μl) at more than 99% CI. The differences in mean leptin and SLR levels were not statistically significant. ConclusionMS patients had high level of total FA in their blood. High FA in blood may have a role in MS pathogenesis. More in-depth study is required to understand the precise mechanism by which FA rise in MS blood sample can contribute to pathogenesis.

Plasma leptin level is associated with cardiac autonomic dysfunction in patients with type 2 diabetes: HSCAA study.

BackgroundIt has been shown that visceral fat accumulation is associated with autonomic dysfunction, though the precise mechanism remains unclear. A recent basic study found that leptin can directly modulate autonomic function through the dorsomedial hypothalamus in relation to obesity. Here, we investigated the mutual relationships among plasma leptin, visceral fat accumulation, and cardiac autonomic dysfunction in patients with type 2 diabetes.MethodsThis cross-sectional study included 100 diabetic patients, and 100 age- and gender-matched non-diabetic patients with cardiovascular risk factors. Plasma leptin and soluble leptin receptor levels, visceral fat area (VFA), and heart rate variability (HRV) were determined in addition to classical cardiovascular risk factors.ResultsIn the type 2 diabetic patients, VFA was significantly (p < 0.05) and inversely associated with HRV parameters (SDNN: r = −0.243; SDANN5: r = −0.238), while the plasma level of leptin, but not soluble leptin receptor, was also significantly (p < 0.05) and inversely associated with HRV parameters (SDNN: r = −0.243; SDANN5: r = −0.231). Multiple regression analysis showed that plasma leptin was significantly associated with SDNN and SDANN5 independent of other factors, including age, gender, presence of hypertension and dyslipidemia, duration of diabetes, HbA1c, and eGFR. Furthermore, the relationship of leptin with SDNN and SDANN5 (β = −0.279 and −0.254, respectively) remained significant (p < 0.05) after adjustment for VFA. In patients without diabetes, no significant associations were observed between leptin and any of the HRV parameters.ConclusionsHyperleptinemia may be involved in cardiac autonomic dysfunction in patients with type 2 diabetes and visceral obesity.

Plasma leptin levels and free leptin index in women with Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by irreversible and progressive loss of memory and other cognitive functions. Controversies still exist on the precise mechanisms contributing to neurodegeneration. Obesity and disturbances in metabolic homeostasis are thought to be AD risk factors. Adipokine leptin has receptors in the brain, also in the regions related to AD. Leptin may protect against AD. The aim was to assess leptin and soluble leptin receptor levels in plasma as well as free leptin index (FLI) in correlation with metabolic status of women diagnosed with Alzheimer's disease. Eighteen women with moderate to severe stage of AD, 40 women with AD at early stage, and 42 female controls, matched for age and body mass index, participated in the study.Leptin and soluble leptin receptor levels were measured with RIA and IRMA, respectively. Then, FLI was calculated. In addition, metabolic parameters (lipid profile, glucose and insulin concentrations, HOMA-IR) were estimated. Clinical and anthropometric data were collected. The Mini-Mental State Examination (MMSE) as a cognitive impairment measurement was performed. Correlations with both leptin and FLI, and MMSE, clinical and biochemical parameters were evaluated.Leptin levels and FLI were significantly lower and leptin receptor concentrations were higher in AD subjects when compared with the controls. In AD group leptin, soluble leptin receptor and FLI correlated with selected metabolic parameters but not with MMSE.We conclude that alterations in leptin, leptin receptor, and FLI were the most intensified in advanced AD. However, these results did not correlate with dementia stage measured with MMSE. Therefore, further intensive research is needed to explain the mechanisms involved in this phenomenon.

Serum Leptin Levels, Leptin Receptor Gene (LEPR) Polymorphism, and the Risk of Systemic Lupus Erythematosus in Kashmiri Population

The study is conducted to evaluate relationship between LEPRQ223R (Gln > Arg) polymorphism, serum leptin levels, soluble leptin receptor (SOb-R) levels and SLE risk in Kashmiri population.LEPR genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 100 unrelated SLE patients and equal number of healthy control subjects. Leptin and SOb-R levels were measured by ELISA assays. The present study showed higher frequency of variant genotype (AG + GG) in cases compared to controls [OR = 2.52, CI = 1.18–5.35, p = 0.03]. Moreover the rare (G) allele was significantly more predominant in cases than controls [OR = 1.49, p = 0.04]. Interestingly a positive association between the variant genotype and the development of arthritis [OR = 11.8, CI = 1.6–85.1, p = 0.002] and an inverse association with cardiac disorder [OR = 0.09, CI = 0.02–0.46, p = 0.001] was observed in this study. Furthermore the study showed significant differences of leptin levels in SLE patients and controls (23.9 ± 19.5 vs 14.8 ± 10.4, p < 0.001). SLE patients in the highest quartile leptin levels (≥32.5 ng/mL) were significantly more likely to have higher BMI (p = 0.001) and increased risk of developing arthritis (p = 0.02). Furthermore positive association was observed between the variant genotype(AG + GG) and leptin levels (p = 0.001) in SLE patients. Thus, it is evident from our study that LEPRQ223R polymorphism and elevated leptin levels are associated with increased susceptibility of SLE in Kashmiri population.

Effects of a short-term reduction in brain serotonin synthesis on the availability of the soluble leptin receptor in healthy women.

Serotonin (5-HT) and the hormone leptin have been linked to the underlying neurobiology of appetite regulation with evidence coming from animal and cellular research, but direct evidence linking these two pathways in humans is lacking. We examined the effects of reduced brain 5-HT synthesis due to acute tryptophan depletion (ATD) on levels of soluble leptin receptor (sOb-R), the main high-affinity leptin binding protein, in healthy adults using an exploratory approach. Women, but not men, showed reduced sOb-R concentrations after ATD administration. With females showing reduced baseline levels of central 5-HT synthesis compared to males diminished brain 5-HT synthesis affected the leptin axis through the sOb-R in females, thereby potentially influencing their vulnerability to dysfunctional appetite regulation and co-morbid mood symptoms.

Effect of leptin receptor Q223R polymorphism on breast cancer risk.

Leptin receptor (LEPR) is a member of the class I cytokine receptor super-family that is known implicated in the initiation and progression of breast cancer. We have investigated the effect of Q223R polymorphism on the breast cancer susceptibly in a sample of Iranian subjects. We utilized a polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) method to investigate the association of LEPR Q223R polymorphism with breast cancer risk in a case control study consisting of 100 breast cancer cases and 100 controls without breast cancer. Serum levels of leptin and soluble leptin receptor (sOB-R) were measured by ELISA method. The genotype (QQ, QR, and RR) distributions were 25, 56, and 19 % in breast cancer cases and 54, 40, and 6% in controls, respectively. The frequency of 223 RR genotype was significantly elevated in breast cancer cases as compared to controls (χ(2)= 20.072, P<0.001). Similar significance differences were also found in allele frequencies for Q and R between two groups (χ(2)= 19.027, P< 0.001). Additionally, there were significant association between Q223R genotypes and breast cancer risk; homozygotes for RR genotype (OR= 6.840; 95% confidence interval [CI] = 2.434-19.218), heterozygotes for QR (OR=3.024; 95% CI = 1.620-5.644, P = 0.001), and QR+RR genotype (OR= 3.522; 95% CI = 1.934-6.414, P < 0.001), respectively. Our results showed that the LEPR Q223R polymorphism is associated with increased breast cancer risk as well as tumor grade in a sample of Iranian subjects.

The relation of leptin and soluble leptin receptor levels with metabolic and clinical parameters in obese and healthy children

We investigated the relation of serum leptin, soluble leptin receptor (sLR) and free leptin index (FLI) with metabolic and anthropometric parameters in obese and healthy children. Height, weight, waist circumference (WC), fasting serum glucose, insulin, lipid profile, leptin and sLR levels of 35 obese children and 36 healthy children were measured and FLI was calculated as the ratio of leptin to sLR. In obese children, serum leptin and FLI were found significantly higher, while sLR level was significantly lower than the healthy children. Comparison of obese children regarding the insulin resistance showed significantly higher serum leptin and FLI in the insulin resistant group; however sLR level was not different between the insulin resistant and non-resistant obese children. In obese children, sLR was not correlated with any of the metabolic parameters except total cholesterol, while FLI was significantly and positively correlated with BMI, WC, TC, fasting insulin, and HOMA-IR. However, regression analysis confirmed that the HOMA-IR was the only independent variable significantly correlated with FLI in obese children. Findings of this study suggest that in obese children and adolescents (i) serum leptin and FLI were found significantly higher, while sLR level was significantly lower than the healthy children, (ii) increased FLI might be a compensatory mechanism for increasing leptin effect in peripheral tissue, (iii) FLI is a more accurate marker to evaluate leptin resistance than leptin or sLR alone, and (iv) increased FLI may contribute toward the development of hyperinsulinemia and insulin resistance.

Continuous 24-Hour Leptin, Proopiomelanocortin, and Amino Acid Measurements in Human Cerebrospinal Fluid: Correlations With Plasma Leptin, Soluble Leptin Receptor, and Amino Acid Levels

In order to characterize diurnal changes in central leptin and its target neuropeptide, proopiomelanocortin (POMC), we measured leptin and POMC in cerebrospinal fluid (CSF) as related to changes in plasma leptin and soluble leptin receptor (sOB-R) levels. CSF and plasma levels of 20 amino acids (AA) were also measured because AA can affect brain POMC. Stored CSF and plasma samples obtained from eight healthy subjects who served as controls for a previous study were evaluated. CSF was collected hourly over 33 h via indwelling subarachnoid catheter. Leptin, sOB-R, and POMC were measured by sensitive ELISA and AA by gas chromatography-mass spectrometry. There was a diurnal rhythm for plasma leptin with a peak at 2200 h (144% of baseline) and there was a similar diurnal rhythm for CSF leptin with a peak (117%) 3-5 h after the plasma peak. Plasma sOB-R was lowest at 0300 h and correlated negatively with plasma and CSF leptin. A diurnal rhythm for POMC in CSF was also detected with a peak (125%) at 0100 h. A positive correlation existed between CSF POMC and leptin in individual subjects over time. CSF levels of many AA increased at night. There was a significant correlation between CSF POMC and 10 AA, including leucine, isoleucine, tryptophan, and tyrosine. Diurnal changes occur in leptin and POMC in human CSF that likely reflect changes in central leptin and melanocortin activity. Our results suggest that nocturnal elevations in leptin, AA, and POMC may help to suppress appetite and feeding at night.