sOB-R Levels Research Articles

Acupuncture Treatment Reduces Body Weight Possibly by Down-regulating Insulin and Leptin Resistance, and Up-regulating Soluble Leptin Receptor Level in Prediabetic Patients

To observe the effect of acupuncture of Feishu (BL 13), Pishu (BL 20), etc. on body weight, blood lipid, leptin (LP) and soluble leptin receptor (sOB-R) levels in prediabetic patients, so as to explore its mechanisms underlying treatment and prevention of prediabetes. A total of 100 prediabetic patients were randomly assigned to medication (Metformin) group (n＝35), acupuncture group (n＝35) and simple lifestyle intervention group (n＝30) with random number table method. All the patients of the 3 groups were treated with lifestyle intervention (reasonable diet and moderate physical exercise) and ordered to stop administration of any hypoglycemic drugs during the treatment period. Bilateral Feishu (BL 13), Pishu (BL 20), Weishu (BL 21), Shenshu (BL 23), Zusanli (ST 36) and Sanyinjiao (SP 6) were punctured with filiform needles which were manipulated by lifting, thrusting and twirling repeatedly for about 2 min every 5 min during 30 minutes' needle retaining. The acupuncture treatment was conducted once every other day for 12 weeks. Patients of the medication group were ordered to orally take Metformin tablets (0.5 g/time, twice a day) for continuous 12 weeks. Body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), 2 h-postprandial blood glucose (2 h-PBG), fasting blood glucose (FBG), glycosyla-ted hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), fasting insulin (FINS), serum LP and sOB-R levels were measured before and after the treatment. After the treatment, the BMI in the acupuncture group, and BMI, WC and WHR in the medication group were significantly decreased relevant to their own pre-treatment in each group (P<0.05, P<0.01). Following the treatment, the levels of FBG, 2 h-PBG, HbA1C, TC, TG, FINS, HOMA-IR and LP in both acupuncture and medication groups, and FBG in the simple lifestyle intervention group were significantly decreased in comparison with their own pre-treatment in each group (P<0.01, P<0.05), and the levels of FBG, 2 h-PBG, HbA1C, TC and TG, HOMA-IR and LP in both acupuncture and medication groups were all considerably lower than those of the simple lifestyle intervention group (P<0.01，P<0.05). The level of FINS in the medication group was significantly lower than that of the simple lifestyle intervention group (P<0.05). Additionally, following the treatment, serum sOB-R contents in both acupuncture and medication groups were obviously increased compared with their own pre-treatment in each group and also relevant to the simple lifestyle intervention group (P<0.01). No significant changes were found in the simple lifestyle intervention group in all the above-mentioned blood indexes except FBG (P>0.05). Acupuncture can induce body weight loss, down-regulate FINS, insulin resistance and LP resistance, and up-regulate sOB-R content in prediabetic patients, displaying a positive role in the treatment of prediabetes.

Low Plasma Leptin and High Soluble Leptin Receptor Levels Are Associated With Mild Cognitive Impairment in Type 2 Diabetic Patients.

Background: Metabolic disturbances, such as hyperglycemia, hyperlipidemia, and obesity, are thought to be risk factors for Alzheimer's disease.Objective: This study aimed to investigate whether adipokine leptin and soluble leptin receptor (sOBR) levels are correlated with mild cognitive impairment (MCI) and metabolic status of the patients of type 2 diabetes mellitus (T2DM).Methods: Total of 169 T2DM patients were recruited and divided according to the Montreal Cognitive Assessment (MoCA) score. Their cognition and metabolic parameters were extensively assessed. Plasma leptin and sOBR levels were determined by RIA and ELISA, respectively. Free leptin index (FLI) was calculated.Results: Of 124 enrolled T2DM patients, 61 were diagnosed with MCI (MoCA < 26). In MCI group and female subgroup, leptin levels and FLI were significantly lower and sOBR concentrations were higher when compared with their respective health cognition controls (all p < 0.05). Leptin levels and FLI were positively associated with the most cognitive domains and their Waist-to-Hip Ratio (WHR), a traditional index of central obesity. Leptin, sOBR, and WHR were independent variables of MCI in all individuals (all p < 0.05). For the females, MoCA was also positively correlated with leptin (β = 0.893, p < 0.001) and negatively correlated with WHR (β = −0.363, p = 0.014). Leptin was positively correlated only with WHR (β = 0.441, p = 0.025).Conclusions: This study showed that a high level of leptin and low level of sOBR are associated with the improved cognitive function in T2DM patients and more significantly in female individuals, while WHR, as an indicator of the visceral obesity, contributes to cognitive deficits.Trial registration: Advanced Glycation End Products Induced Cognitive Impairment in Diabetes: BDNF Signal Meditated Hippocampal Neurogenesis ChiCTR-OCC-15006060; http://www.chictr.org.cn/showproj.aspx?proj=10536.

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.

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.

Soluble Leptin Receptor and Risk of Gestational Diabetes in a Multiethnic Population: A Prospective Cohort Study.

Soluble leptin receptor (sOb-R), a potential marker of leptin resistance, is inversely associated with risk of type 2 diabetes, independently of leptin concentrations. We have previously shown that ethnic difference in leptin concentration may partly explain the increased risk of gestational diabetes (GDM) in South Asians. Our objective was to investigate whether sOb-R concentrations are associated with risk of GDM, whether concentrations of sOb-R differ across ethnic groups, and whether ethnic differences in sOb-R explain the ethnic differences in GDM risk. The STORK Groruddalen study; a prospective cohort study of pregnant women living in Oslo, Norway, between May 2008 and May 2010. Of the total sample (n = 823), 680 (47.1% Europeans) had sOb-R measured in pregnancy week 15 and an oral glucose tolerance test performed in week 28. GDM was diagnosed according to World Health Organization 2013 criteria. sOb-R was inversely associated with GDM (odds ratio, 0.76 [95% confidence interval, 0.69-0.83] per ng/ml increase in sOb-R, P < .001) in crude analysis. The association was attenuated after adjustments for covariates and leptin (0.85 [0.77-0.95], P = .004). Compared to women with sOb-R higher than 5 ng/ml, the odds ratio of GDM was 0.29(0.11-0.78; P = .014) among women with sOb-R greater than 10 ng/ml and 0.59 (0.37-0.94; P = .026) among women with sOb-R 5-10 ng/ml, in adjusted analysis. sOb-R levels did not differ across ethnic groups, and sOb-R did not explain ethnic differences in GDM risk. There was an independent, inverse association between sOb-R and GDM, with the lowest risk of GDM observed among higher sOb-R concentrations.

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.

Metformin increases hepatic leptin receptor and decreases steatosis in mice.

In addition to the ascertained efficacy as antidiabetic drug, metformin is increasingly being used as weight-loss agent in obesity, and as insulin sensitizer in nonalcoholic fatty liver disease (NAFLD). However, the mechanisms underlying these effects are still incompletely understood. Emerging evidence suggest metformin as leptin sensitizer to mediate the weight-loss effect in the brain. In this study, we investigated effects of metformin on expression of leptin receptors in liver and kidney in mice. C57BL/6 mice were fed with chow diet (CD) or high-fat diet (HF) for 5months. Afterward, mice were treated with metformin (50mg/kg or 200mg/kg) for 15days. Metabolic parameters and hepatic gene expression were analyzed at the end of the treatment. We also tested the effects of metformin on plasma-soluble leptin receptor (sOB-R) levels in newly diagnosed type 2 diabetes mellitus (T2DM) patients, and assessed its effect on hepatosteatosis in mice. Results showed that metformin upregulates the expression of leptin receptors (OB-Ra, -Rb, -Rc, and -Rd) in liver but not kidney. The stimulation effect is dose-dependent in both chow and HF mice. Upregulation of OB-Rb, long signaling isoform, needs a relatively higher dose of metformin. This effect was paralleled by increased sOBR levels in mice and T2DM patients, and decreased hepatic triglyceride (TG) content and lipogenic gene expression, including sterol regulatory element-binding protein 1c (SREBP-1c), fatty acid synthase (FAS) and acetyl-CoA carboxylase-1 (ACC-1). Taken together, these data identify hepatic leptin receptor as target gene being upregulated by metformin which may enhance leptin sensitivity in liver to alleviate steatosis.

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.

Evaluating Growth Regulating Hormones in Rural Gambian Children

ObjectivesTo evaluate the hormonal status in malnourished children during nutritional rehabilitation in order to identify markers of nutritional recovery.MethodsChildren 6‐24 months of age were recruited from the Medical Research Council‐ Keneba clinic. Anthropometric measurements done at baseline and on alternate days. Children were assigned to a group based on their WHO weight/height z scores (WHZ): WHZ&lt;‐2 “malnourished” and WHZ&gt;‐2 “well‐nourished”(WN). Children received WHO F‐75 test meal at baseline. Malnourished children received milk‐based formulas and/or supplementation with ready‐to‐use therapeutic food. We used Quantakine ELISA kits to measure the plasma hormonal levels.ResultsSixty one children were recruited. Median age was 15.4 months. There were significant differences in the levels of leptin, sOBR, IGF‐1, IGFBP3 between malnourished and WN children, (P&lt;0.005). Nutritional supplementation increased WHZ in the malnourished children and induced increases in the levels of leptin, IGF‐1, IGFBP3 and decreases in the levels of (sOBR) and the sOBR: Leptin molar ratio. The levels of leptin at Day 28 in the malnourished children remained below those of the WN, (p&lt;0.005). However, the sOBR, sOBR: Leptin molar ratio, IGF‐1, IGFPB3 and IGF‐1:IGFPB3 molar ratios in the malnourished children on Day 28 were similar to the levels in the WN.ConclusionOur findings suggest that in rural Gambian children leptin alone is not be a good biomarker for nutritional recovery. The sOBR, sOBR: leptin molar ratio, IGF‐1, IGFPB3 and IGF‐1:IGFPB3 molar ratios appear to be better biomarkers.

Morphological and bone strength indices in girls with adolescent idiopathic scoliosis and their correlations with leptin and soluble leptin receptor

Results Compared with controls, AIS subjects had higher sOB-R level (p=0.006), higher SMI value (p=0.020) reflecting more rod-like structures within the trabecular compartment, and numerically lower stiffness (-2.03%) and estimated failure load (-3.07%). Significant negative correlation was found between SMI and serum total leptin level in AIS (r=-0.325; p=0.003) but not in controls (p=0.533). Significant positive correlations were found between stiffness, estimated failure load, and serum total leptin in both AIS (r=0.278, p=0.003; r=0.268, p=0.004 respectively) and controls (r=0.462, p<0.001; r=0.468, p<0.001 respectively). Conclusion

Association of Serum Adiponectin and Leptin Levels with Breast Cancer in Iraqi Women

Obesity has been associated with an increased risk of cancer especially postmenopausal breast cancer. Adipokines have been hypothesized to underlie this association. Adiponectin and leptin are adipocyte-secreted hormones that opposite each other not only in their biological activities but also in their effects on breast neoplastic cells. in addition, Leptin receptor, found in both membrane-bound isoforms and a soluble form (sOB-R), sOB-R bind to leptin in circulation and correlate with its activity. The aim of this study was to investigate the relationship between serum levels of adiponectin, leptin and sOB-R with breast cancer. Methods: In a case-control study Serum adiponectin, leptin and sOB-R levels were measured by enzyme-linked Immunosorbent assay in 48 women with histologically confirmed breast cancer and compared with 41 age and BMI matched women without breast cancer as control groups. Control groups were divided into; Control group 1 (C1) contains 26 healthy women and control group 2(C2) contains 15 women with breast benign diseases. Results: The mean serum levels of adiponectin in both controls (C1 and C2) were significantly higher than that in breast cancer cases (25.08±5.59and 22.49±3.49) versus (15.84±6.21) respectively. Conversely, the mean serum levels of leptin in both controls (C1 and C2) were significantly lower than that in breast cancer cases (27.98±6.85 and 34.50±10.59) versus (48.97±24.56) respectively. Higher circulating levels of sOB-R (140.21±74.20) were significantly associated with an increased risk of breast cancer as compared to controls (47.13±38.30 and 27.68±23.58) for C1 and C2 respectively. In addition, the association of BMI with breast cancer was non-significant. Conclusion: These data suggest that dysregulation in hormones (adipokines) secreted by adipose tissue may be associated with breast cancer independently of BMI. Further prospective studies examining the role of adipokines in the etiology of breast cancer are warranted.

Circulating IGF-axis protein levels and their relation with levels of plasma adipocytokines and macronutrient consumption in women

ObjectiveCirculating free insulin-like growth factor (IGF)-I and its binding proteins, most notably, IGFBP-1 and IGFBP-2, have been prospectively associated with incident type 2 diabetes in women. However, little is known regarding the factors that may influence these IGF-axis protein levels. The aim is to study the relation of IGF-axis protein levels with adipcytokines, macronutrient consumption, and other factors related to diabetes. DesignFasting plasma from 558 controls enrolled in a nested case–control study within the Nurses' Health Study of incident type 2 diabetes in women was tested for: IGF-axis proteins (free and total IGF-I, IGFBP-1, IGFBP-2, IGFBP-3), adipocytokines (leptin, adiponectin, resistin), soluble leptin receptor (sOB-R), inflammatory factors (IL-18 and C-reactive protein (CRP)), insulin, and glycated hemoglobin (HbA1C). ResultsIn multivariate models, each 1% increase in sOB-R (mean 34.9ng/mL, standard deviation (SD) ±11.3) was associated with −0.20% total IGF-I (P=0.0003) and −0.42% free IGF-I (P=0.002), as well as 0.73% higher IGFBP-1 (P<0.0001) and 0.27% IGFBP-2 (P=0.003). For example, a one SD change from the mean sOB-R level was associated with 11% lower free IGF-I. Insulin levels (mean 6.8μU/mL±5.3) were inversely and adiponectin (mean 18.3μg/mL±7.4) positively associated with IGFBP-1 and IGFBP-2 (all P<0.01). Consumption of dairy protein, monounsaturated fats, and saturated fats, was also correlated with IGF-axis protein levels (all P<0.05). ConclusionsSeveral molecular factors and macronutrients were independently associated with plasma IGF-axis protein levels. Which of these, if any, reflect biologic relationships that can be intervened upon to influence IGF-axis protein concentrations warrants further investigation.

Are Volumetric Bone Mineral Density and Bone Micro-Architecture Associated with Leptin and Soluble Leptin Receptor Levels in Adolescent Idiopathic Scoliosis? – A Case-Control Study

BackgroundAdolescent idiopathic scoliosis (AIS) is associated with low bone mineral density (BMD). The underlying etiology and how it may relate to the development of osteopenia remains unknown. Leptin has been postulated as one of the etiologic factors of AIS because of its profound effects on bone metabolism and pubertal growth. Its modulator, soluble leptin receptor (sOB-R), may affect leptin bioavailability and signaling. This study aimed to investigate whether serum leptin and sOB-R levels may be associated with bone quality, and whether these relationships may differ between young adolescent girls with and without AIS.MethodsThis was a case-control study involving 94 newly diagnosed AIS girls (Cobb angle 12–48°) aged 12 to 14 years old and 87 age and gender-matched normal controls. Subjects with BMI>23.0 Kg/m2 were excluded. Anthropometric measurements including body weight, height, arm span and sitting height were taken. Serum total leptin and sOB-R were assayed with ELISA. Non-dominant distal radius was scanned with High Resolution pQCT for assessing bone quality in terms of bone morphometry, volumetric BMD (vBMD) and trabecular bone micro-architecture.ResultsCompared with normal controls, AIS girls had numerically higher sOB-R (p = 0.006), lower average vBMD (p = 0.048), lower cortical vBMD (p = 0.029), higher cortical bone perimeter (p = 0.014) and higher trabecular area (p = 0.027), but none remained statistically significant after the Hochberg-Benjamini procedure. Correlation analysis on serum leptin level indicated that distinctive correlations with trabecular bone parameters occurred only in AIS.ConclusionThis study showed that bone quality in AIS girls was deranged as compared with controls. In addition, the distinct differences in correlation pattern between leptin and trabecular bone parameters indicated possible abnormalities in bone metabolism and dysfunction of the leptin signaling pathway in AIS.

Effects of an acute bout of exercise on serum soluble leptin receptor (sOB-R) levels

We investigated the effects of an acute bout of exercise on serum soluble leptin receptor (sOB-R) concentrations. Eighteen male participants completed two different exercise sessions with intensities of 25% and 65% maximal aerobic capacity (VO2max). In addition to the energy expenditure during exercise sessions being measured, blood samples were collected before exercise, and immediately, at 24 h, and at 48 h post-exercise to analyse sOB-R, leptin and insulin levels. At 24 h post-exercise, sOB-R and leptin concentrations at the 65% VO2max were significantly different from those at the 25% VO2max. Leptin levels at 48 h post-exercise were also significantly lower for the 65% VO2max than for the 25% VO2max (P < 0.01). In the 65% VO2max session, the energy expenditure during exercise was significantly associated with leptin concentrations at 24 h and 48 h and sOB-R concentrations at 24 h post-exercise. However, no correlations were found between sOB-R and leptin at the three post-exercise time points. In conclusion, an acute bout of exercise with 920 kcal of output resulted in an increase in sOB-R levels at 24 h post-exercise. However, the changes in sOB-R levels due to an acute bout of exercise might not contribute to the delayed decrease observed for leptin.

Role of leptin in legg–calvé–perthes disease

Obesity is considered a clinical risk sign for Legg-Calvé-Perthes disease (LCPD). Leptin is primarily secreted by adipocytes, and it regulates adipose tissue mass and body weight. Furthermore, obesity is clearly associated with increased leptin levels. We investigated the roles of leptin and the soluble leptin receptor (sOB-R) in LCPD. This matched case-control study included 38 male and 3 female patients with LCPD, and an equal number of age-(range was 4-12) and sex-matched control patients with healthy fractures. Serum leptin and sOB-R levels were quantified with ELISA. The free leptin index (FLI) was defined as the ratio of leptin to sOB-R levels. Serum leptin levels, sOB-R, and FLI were compared between groups. The relationship between leptin, disease severity, and treatment outcomes were analyzed in the LCPD group. There were no significant differences between groups in terms of age, sex, and body mass index (BMI) percentile. Mean leptin levels (p = 0.042), sOB-R levels (p = 0.003), and FLI (p = 0.013) differed significantly between groups. In the LCPD group, the serum leptin levels, sOB-R levels, and FLI differed significantly between the lateral pillar and Stulberg classification groups (p < 0.05). Also, the leptin levels and FLI increased significantly according to the lateral pillar and Stulberg classifications even after adjusting for age and BMI percentile (p < 0.05). Circulating leptin and FLI were significantly higher in the LCPD group. Furthermore, leptin, disease severity, and treatment outcomes were associated. This correlation suggests that leptin might play an important role in LCPD pathogenesis.

Associations of testosterone and sex hormone binding globulin with adipose tissue hormones in midlife women.

Regulators of adipose tissue hormones remain incompletely understood, but may include sex hormones. As adipose tissue hormones have been shown to contribute to numerous metabolic and cardiovascular disorders, understanding their regulation in midlife women is of clinical importance. Therefore, we assessed the associations between testosterone (T) and sex hormone binding globulin (SHBG) with leptin, high molecular weight (HMW) adiponectin, and the soluble form of the leptin receptor (sOB-R) in healthy midlife women. Cross-sectional analyses were performed using data from 1,881 midlife women (average age 52.6 (±2.7) years) attending the sixth Annual follow-up visit of the multiethnic Study of Women's Health Across the Nation. T was weakly negatively associated with both HMW adiponectin and sOB-R (r = -0.12 and r = -0.10, respectively; P < 0.001 for both), and positively associated with leptin (r = 0.17; P < 0.001). SHBG was more strongly and positively associated with both HMW adiponectin and sOB-R (r = 0.29 and r = 0.24, respectively; P < 0.001 for both), and more strongly and negatively associated with leptin (r = -0.27; P < 0.001). Adjustment for fat mass, insulin resistance, or waist circumference only partially diminished associations with HMW adiponectin and sOB-R, but attenuated associations with leptin. In conclusion, in these midlife women, lower SHBG values, and to a lesser extent, higher T levels, were associated with lower, or less favorable, levels of adiponectin and sOB-R, independent of fat mass. These data suggest that variation in these adipose hormones resulting from lower SHBG levels, and possibly, though less likely, greater androgenicity, may contribute to susceptibility for metabolic and cardiovascular outcomes during midlife in women.

The association of adipokine levels in plasma and synovial fluid with the severity of knee osteoarthritis

We sought to determine the association between plasma and SF levels of leptin and adiponectin in patients with knee OA. Plasma and SF levels of adipokines and soluble leptin receptor (sOB-R) were determined by ELISA in 96 patients with knee OA at different stages, according to Ahlback's classification. Levels of adiponectin, leptin, sOB-R and free leptin in plasma and SF did not differ significantly across categories of OA severity. However, the ratio of SF to plasma leptin was significantly lower in the advanced OA stage compared with early stages of the disease (P = 0.02). After adjustment for sex and BMI, plasma leptin positively correlated with categories of OA severity (r = 0.23, P = 0.02), whereas SF/plasma leptin negatively correlated with OA stage (r = -0.27, P = 0.01). Cluster analysis showed that all men were included in one cluster and distributed in different stages of OA, whereas women formed three clusters with similar BMI, but those who were older and had the highest plasma leptin levels suffered from advanced OA. Plasma leptin positively correlated with the severity of knee OA. The ratio of SF to plasma leptin might be a marker related to the severity of knee OA. Further studies should investigate whether similar associations exist in other joints affected by OA.

Novel Regulatory Mechanisms for Generation of the Soluble Leptin Receptor: Implications for Leptin Action

BackgroundThe adipokine leptin realizes signal transduction via four different membrane-anchored leptin receptor (Ob-R) isoforms in humans. However, the amount of functionally active Ob-R is affected by constitutive shedding of the extracellular domain via a so far unknown mechanism. The product of the cleavage process the so-called soluble leptin receptor (sOb-R) is the main binding protein for leptin in human blood and modulates its bioavailability. sOb-R levels are differentially regulated in metabolic disorders like type 1 diabetes mellitus or obesity and can, therefore, enhance or reduce leptin sensitivity.Methodology/Principal FindingsTo describe mechanisms of Ob-R cleavage and to investigate the functional significance of differential sOb-R levels we established a model of HEK293 cells transiently transfected with different human Ob-R isoforms. Using siRNA knockdown experiments we identified ADAM10 (A Disintegrin And Metalloproteinase 10) as a major protease for constitutive and activated Ob-R cleavage. Additionally, the induction of lipotoxicity and apoptosis led to enhanced shedding shown by increased levels of the soluble leptin receptor (sOb-R) in cell supernatants. Conversely, high leptin concentrations and ER stress reduced sOb-R levels. Decreased amounts of sOb-R due to ER stress were accompanied by impaired leptin signaling and reduced leptin binding.ConclusionsLipotoxicity and apoptosis increased Ob-R cleavage via ADAM10-dependent mechanisms. In contrast high leptin levels and ER stress led to reduced sOb-R levels. While increased sOb-R concentrations seem to directly block leptin action, reduced amounts of sOb-R may reflect decreased membrane expression of Ob-R. These findings could explain changes of leptin sensitivity which are associated with variations of serum sOb-R levels in metabolic diseases.

Abnormal Leptin Bioavailability in Adolescent Idiopathic Scoliosis

This was a cross-sectional study. The present study aimed to explore the differences in leptin bioavailability between adolescent idiopathic scoliosis (AIS) and healthy age-matched girls in a Chinese Han population. AIS is a common spinal deformity mainly occurring in girls during the peripubertal period. The development of scoliosis is related to relative anterior spinal overgrowth. AIS girls also have associated lower body mass index (BMI) and lower bone mineral status. Leptin, together with soluble leptin receptor (sOB-R), was shown to play an important role in the regulation of bone and energy metabolism in children. It was hypothesized that leptin and sOB-R are abnormal and associated with deranged growth and anthropometric phenotypes in AIS girls. Serum leptin and sOB-R were measured together with documentation of anthropometric parameters and clinical data in 95 AIS girls and 46 healthy matched controls (age 11-16 years). Serum leptin and sOB-R concentrations were measured by enzyme-linked immunosorbent assay and correlated with the different measured parameters. AIS girls had significantly lower BMI and longer arm span than healthy controls. AIS girls were found to have significantly higher sOB-R levels and lower free leptin index (FLI) after adjusting for age and body weight in multivariate regression analysis. Significant correlation was found between sOB-R, FLI, and curve severity in AIS girls. This is the first study demonstrating the presence of abnormal leptin bioavailability in AIS girls that might play an important role in the etiopathogenesis of AIS. Further investigation is required to provide a better understanding of the underlying mechanisms, with the aim to explore the potential clinical application as a biomarker for predicting curve initiation or progression in AIS.