sOB-R Levels Research Articles

Race–ethnic differences in adipokine levels: the Study of Women's Health Across the Nation (SWAN)

Differences in adipose tissue secretory profile, as measured by adipokine levels, may play a role in race–ethnic disparities in cardiovascular disease (CVD). We examined race–ethnic differences in adipokine levels in a group of mid-life Caucasian, African American (AA), Chinese and Japanese women, after accounting for adiposity. Data on 1876 women from the Study of Women’s Health Across the Nation were analyzed. In multivariable adjustment, including total fat mass, differences in total and high molecular weight (HMW) adiponectin, leptin and soluble leptin receptor (sOB-R) levels were examined. Despite intermediate levels of adiposity, Caucasian women had higher levels of both total and HMW adiponectin, when compared to both AA and Chinese and Japanese women. After multivariable adjustment, compared to Caucasian women, AA women had significantly lower total (β: −3.40; 95% CI: −4.29, −2.52; P<.001) and HMW adiponectin (β: −0.53; 95% CI: −0.64, −0.43; P<.001) levels, higher leptin levels (β: 3.26; 95% CI: 1.36, 5.16; P<.001) and lower sOB-R levels (β: −0.07; 95% CI: −0.11, −0.03; P<.001). Compared to Caucasian women, both Chinese and Japanese women had lower total (Chinese: β: −5.50; 95% CI: −7.07, −3.93; P<.001; Japanese: β: −5.48; 95% CI: −6.95, −4.02; P<.001) and HMW adiponectin (Chinese: β: −0.57; 95% CI: −0.75, −0.38; P<.001; Japanese: β: −0.61; 95% CI: −0.78, −0.44; P<.001) levels and lower sOB-R levels (Chinese: β: −0.13; 95% CI: −0.20, −0.06; P<.001; Japanese: β: −0.09; 95% CI: −0.15, −0.02; P=.008). Significant race–ethnic differences exist in circulating adipokines, even after accounting for adiposity. Further research is needed to explicitly determine if such differences contribute to known racial differences in CVD risk.

Soluble leptin receptor and leptin are associated with baseline adiposity and metabolic risk factors, and predict adiposity, metabolic syndrome, and glucose levels at 2-year follow-up: the Cyprus Metabolism Prospective Cohort Study

We examined the relationship between serum levels of leptin-binding protein (soluble leptin receptor [sOB-R]) and leptin with metabolic parameters at baseline and prospectively at 2-year follow-up in young healthy men. A total of 916 eighteen-year-old men were examined at baseline, with a subgroup of 91 participants examined again 2 years later. Anthropometric and metabolic measurements were performed at baseline and at follow-up. In the cross-sectional study, levels of sOB-R were significantly inversely correlated with all baseline measures of obesity and metabolic risk factors (blood pressure, total and low-density lipoprotein cholesterol, and fasting glucose), and significantly positively correlated with high-density lipoprotein cholesterol. After correcting for age, smoking status, and waist-to-hip ratio, the inverse correlation remained statistically significant for all measures of adiposity, fasting glucose, and the metabolic syndrome score. Correlations for leptin were similar in magnitude but opposite in direction to correlations for sOB-R. In prospective analyses, baseline levels of sOB-R were predictive at 2-year follow-up of fasting glucose, the metabolic syndrome score, and measures of adiposity in both unadjusted and adjusted models. Similarly, leptin was predictive of fasting glucose, the metabolic syndrome score, adiposity, and systolic blood pressure. We confirm correlations of leptin and sOB-R levels with measures of adiposity and metabolic risk factors at baseline, and demonstrate for the first time prospectively the role of sOB-R as an independent, although weak, predictor of metabolic syndrome and fasting glucose in young men.

Genome-wide association study identifies polymorphisms in LEPR as determinants of plasma soluble leptin receptor levels

Plasma soluble leptin receptor (sOB-R) levels were inversely associated with diabetes risk factors, including adiposity and insulin resistance, and highly correlated with the expression levels of leptin receptor, which is ubiquitously expressed in most tissues. We conducted a genome-wide association study of sOB-R in 1504 women of European ancestry from the Nurses' Health Study. The initial scan yielded 26 single nucleotide polymorphisms (SNPs) significantly associated with sOB-R levels (P < 5 x 10(-8)); all mapping to the leptin receptor gene (LEPR). Analysis of imputed genotypes on autosomal chromosomes revealed an additional 106 SNPs in and adjacent to this gene that reached genome-wide significance level. Of these 132 SNPs (including two non-synonymous SNPs, rs1137100 and rs1137101), rs2767485, rs1751492 and rs4655555 remained associated with sOB-R levels at the 0.05 level (P = 9.1 x 10(-9), 0.0105 and 0.0267, respectively) after adjustment for other univariately associated SNPs in a forward selection procedure. Significant associations with these SNPs were replicated in an independent sample of young males (n = 875) residing in Cyprus (P < 1 x 10(-4)). These data provide novel evidence revealing the role of polymorphisms in LEPR in modulating plasma levels of sOB-R and may further our understanding of the complex relationships among leptin, leptin receptor and diabetes-related traits.

Leptin and Soluble Leptin Receptor Levels in Plasma and Risk of Type 2 Diabetes in U.S. Women

OBJECTIVEWe prospectively examined plasma levels of leptin and soluble leptin receptor (sOB-R), as well as their interactions with other diabetes risk factors, in relation to type 2 diabetes to elucidate the complex relation between these two biomarkers and diabetes risk.RESEARCH DESIGN AND METHODSOf 32,826 Nurses' Health Study participants who provided blood samples during 1989–1990, 1,054 incident case subjects of type 2 diabetes were identified and confirmed during 1990–2004 and 1,254 matched control subjects were selected. Plasma leptin and sOB-R levels were measured among these participants.RESULTSAfter multivariate adjustment for BMI, lifestyle practices, and dietary factors, sOB-R levels were significantly associated with a lower risk of type 2 diabetes. In comparison with women in the lowest quintile, the ORs (95% CI) of developing type 2 diabetes were 0.73 (0.55–0.96), 0.51 (0.38–0.68), 0.42 (0.31–0.57), and 0.39 (0.28–0.54; P for trend < 0.0001) for women in the second to fifth quintiles of sOB-R levels, respectively. In contrast, plasma leptin levels were not significantly associated with the risk of type 2 diabetes: The OR (95% CI) was 0.82 (0.62–1.10; P for trend = 0.46) comparing the highest with the lowest quintile of leptin levels. sOB-R levels were consistently associated with a decreased risk of type 2 diabetes at various levels of leptin or high-molecular-weight adiponectin.CONCLUSIONSThese data suggest a strong inverse association between plasma sOB-R levels and risk of type 2 diabetes, independent of BMI, leptin, and adiponectin levels.

The Effect Of One Single Acute Exercise On Serum Soluble Leptin Receptor And Leptin Concentrations

PURPOSE: This study was to examine the effect of one single acute exercise on sOB-R and FLL, the ratio of leptin to sOB-R. METHODS: Male participants (n=15, 21.5 ±1.8 years, 21.2 ±1.5kg/m2) engaged in the maximal oxygen consumption VO2max test (54.3 ± 3.8 ml·kg-1·min-1) in a randomized fashion. Their blood was collected for determining serum sOB-R, leptin and insulin levels by an enzyme-linked immunosorbent assay (ELISA) and body weight and percent body fat were measured before and after exercise. RESULTS: After exercise, sOB-R, leptin concentrations and FLI did not differ significantly when compared with the baseline levels although post-insulin concentration was lower than pre-insulin. In addition, there was no significant difference in percent body fat and weight and no significant correlationships among the changes of sOB-R, leptin, body weight, energy expenditure from exercise between before and after VO2max test. CONCLUSIONS: When maintained daily energy steadily, regular exercisers' sOB-R levels and FLI do not change in short-term energy expenditure from a single acute aerobic exercise.

Comparison of maternal ghrelin and leptin in healthy mothers and mothers with Type 1 diabetes

Maternal leptin affects placental growth hormone (GH), whereas ghrelin, a natural ligand of the growth-hormone-secretagogue receptor, modulates GH action. Both hormones may affect fetal growth, and dysregulation in diabetes may lead to fetal growth disturbances. The aim was to investigate changes in maternal ghrelin during pregnancy with diabetes and to establish reference leptin levels. Twelve healthy non-diabetic (ND) and 12 pregnant women with Type 1 diabetes (T1DM) were recruited. Age and body mass index (BMI) [ND: age 29.9 +/- 4.7 years (mean +/- sd), BMI 25.2 +/- 3.7 kg/m2; T1DM: age 31 +/- 5.5 years, BMI 27 +/- 3.1 kg/m2] were similar in the groups. HbA1c in T1DM was 6.2 +/- 1.1% at 20 weeks, 6.3 +/- 1.1% at 30 weeks' gestation and 7.8 +/- 2.1% postpartum. Fasting plasma ghrelin, total leptin, free leptin (FL) and soluble leptin receptor (sOB-R) levels were measured at 20 and 30 weeks' gestation and postpartum and determined by radioimmunoassay. All pregnancies resulted in full-term singleton births with no differences in birth weight between groups [T1DM: 3.4 +/- 0.56 kg (mean +/- SE); ND: 3.6 +/- 0.3 kg, P = NS]. Ghrelin levels were lower in T1DM when corrected for age and mothers' weight (T1DM: 458 +/- 36 pg/ml and 432.9 +/- 26.6 pg/ml; ND: 562 +/- 52 pg/ml and 515.8 +/- 63 pg/ml at 20 and 30 weeks, respectively, P < 0.05). T1DM mothers had higher levels of sOB-R and FL levels declined at 30 weeks' gestation in T1DM (P = 0.04) but not in ND. In a population of pregnant women with expected changes in leptin levels as previously reported, ghrelin levels were lower in T1DM pregnancies at 20 and 30 weeks. This may have implications for fetal development and requires further study in diabetes, particularly in pregnancies that result in macrosomia.

Does an altered leptin axis play a role in obesity among children and adolescents with classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency?

Congenital adrenal hyperplasia (CAH) patients are at a higher risk to develop obesity. The role of leptin in CAH is still controversial. Our study aimed to evaluate serum levels of leptin, the soluble leptin receptor (sOB-R), and the sOB-R: leptin molar ratios in a cohort of CAH children and adolescents, and their associations with clinical and metabolic parameters. We studied 51 CAH patients, aged 5.6-19.6 years (median 11.8, n=30 females) cross-sectionally. All patients had genetically proven CAH and received standard steroid substitution therapy. Blood specimens were taken after overnight fasting between 0800 and 1000 h. For the analyses of leptin and sOB-R, matched pairs were built with healthy Caucasian patients for sex, Tanner stage (TS), chronologic age (CA), and body mass index (BMI). BMI and SDS were significantly elevated compared with the reference population. Leptin levels were not different between matched pairs, whereas sOB-R levels were significantly lower in CAH. Consequently, the sOB-R: leptin molar ratios were significantly decreased in CAH. Correlation analyses in CAH patients revealed significant relationship between leptin and CA, TS, BMI, and homeostasis model assessment of insulin resistance. Similar results were obtained for the matched control group. For sOB-R, we found no significant correlation for CA, TS, or BMI in CAH, but we did in the controls. There were significant correlations for androgens within the CAH group. Additional analyses revealed no correlation with steroid medication or metabolic control. Our data show that an altered leptin axis with normal serum leptin concentrations but decreased sOB-R serum levels may contribute to the increased risk of overweight and obesity in CAH.

Relationship between plasma leptin or soluble cleaved leptin-receptor concentrations and glucocorticoid sensitivity of peripheral blood mononuclear cells in patients with nephrotic syndrome

Leptin is a small peptide hormone which centrally regulates weight. Leptin receptor (OB-R) is expressed in hematopoietic cells, the central nervous, and immune systems. OB-R bears a homology similar to members of the class Ι cytokine family, and therefore, leptin appears to modulate immune responses. The aim of this study was to examine the effect of plasma leptin, soluble OB-R (sOB-R), and the free leptin index (FLI), the ratio between leptin and sOB-R levels, on the sensitivities of peripheral blood mononuclear cells (PBMCs) to prednisolone and cyclosporine in 16 healthy subjects and seven nephrotic syndrome (NS) patients. The NS patients had significantly higher serum sOB-R and lower FLI, compared with the healthy subjects (respectively, P = 0.0026, P = 0.0383). Whereas, the NS patients had significantly lower PBMC sensitivity to prednisolone ( P = 0.0049). PBMCs sensitivity to cyclosporine was not significantly different between the healthy subjects and the NS patients. In addition, when the data from all subjects were analyzed, there was a significantly positive correlation between plasma sOB-R concentrations and the IC 50 values of prednisolone ( P = 0.0478). In contrast, plasma leptin concentrations and FLIs did not correlate significantly with the prednisolone and cyclosporine IC 50 values. From these observations it can be suggested that plasma leptin has little effect on PBMC sensitivity to immunosuppressive drugs in NS patients. Molecular background(s) for the influence of sOB-R on the PBMC sensitivity to glucocorticoids remain(s) to be elucidated.

Leptin, soluble leptin receptor, adiponectin and resistin in relation to OGTT in overweight/obese postmenopausal women

ObjectiveIn obese postmenopausal women with normal glucose metabolism (NGT) and impaired glucose tolerance (IGT) we assessed serum leptin, adiponectin, resistin, soluble leptin receptor (sOB-R) during oral glucose tolerance test (OGTT) in order to investigate their response to acute changes in glucose and insulin in the abnormal glucose metabolism, as it is early detected by IGT. MethodsThirty in total, overweight/obese postmenopausal women, were included in the study: 15with NGT and 15 with IGT as it was diagnosed by OGTT. Serum glucose and insulin levels were measured at 30min intervals, leptin, sOB-R, adiponectin and resistin at 60min intervals during the 120min OGTT. ResultsIn fasting state, leptin, adiponectin, resistin and sOB-R levels did not differ between the two groups. In women with NGT, leptin was positively correlated with BMI, insulin and HOMA, and negatively correlated with QUICKI and with sOB-R; adiponectin was negatively correlated with insulin and HOMA and positively correlated with QUICKI. In women with IGT, resistin was positively correlated with BMI and waist circumference. In both groups, sOB-R was negatively correlated with insulin. During OGTT, in both groups, leptin concentration increased significantly and fasting glucose predicts significantly serum leptin change; there was no change in adiponectin, resistin and sOB-R concentrations. ConclusionIn overweight/obese postmenopausal women fat distribution does not affect leptin and adiponectin production. Abnormal glucose metabolism is not accompanied by disturbance in adipokines production. Leptin secretion is acutely regulated by glucose levels in insulin presence.

Serum leptin and soluble leptin receptor in non-alcoholic fatty liver disease

To determine the role of leptin system in non-alcoholic fatty liver disease (NAFLD) development by delineating the changes in serum levels of leptin and soluble leptin receptor (sOB-R). Blood samples were collected from 30 consecutive patients with liver-biopsy-proven NAFLD and 30 patients with cholecystolithiasis (stationary phase) as controls. Serum leptin levels were determined by radioimmunoassay and concentration of sOB-R was measured by ELISA. Body mass index (BMI) was calculated for all subjects, and serum insulin, C-peptide, and lipoprotein levels were also detected. Mean serum leptin level and BMI in the NAFLD group were significantly higher than in the controls (both P < 0.001), but mean sOB-R level was lower in the NAFLD group when compared to the controls. Both men and women in the NAFLD group had higher mean serum leptin levels and lower sOB-R levels than did the men and women in the control group (all P < 0.001). There was a significant negative correlation between serum leptin and sOB-R levels (r = -0.725, P < 0.001). Multivariate analysis showed that the percentage of hepatocyte steatosis, sex, BMI, and homeostasis model assessment of insulin resistance (HOMA IR) were independently related to serum leptin levels. Elevated serum leptin seems to be a feature of steatosis, and serum leptin seems to increase as hepatocyte steatosis develops. An enhanced release of leptin is accompanied by an decrease in sOB-R concentration, which suggests higher resistance of peripheral tissues towards the action of leptin.

LEPTIN AND LEPTIN RECEPTOR IN SERUM AND URINE FROM CHILDREN WITH NEPHROTIC SYNDROME ACCOMPANYING HYPERLIPIDEMIA

INTRODUCTION: Hyperlipidemia may cause glomerulosclerosis in children with nephrotic syndrome (NS). OBJECTIVE: Our goal was to observe the role of soluble leptin receptor (sOBR) and leptin in serum and urine on the mechanism of hyperlipidemia in children with NS. METHODS: Twenty-three children with untreated NS and 15 age-, gender-, and BMI-matched healthy controls were enrolled onto the study. Leptin and sOBR in serum and urine were measured by enzyme-linked immunosorbent assay, and plasma lipid and insulin levels were detected by automatic biochemistry analyzer and radioimmunoassay, respectively. sOBR messenger RNA and membrane protein expression in peripheral blood mononuclear cells were detected by reverse-transcription polymerase chain reaction and immunocytochemistry. RESULTS: Low-density lipoprotein, total cholesterol, triglyceride, and apolipoprotein A levels were increased. sOBR messenger RNA and membrane protein expression by peripheral blood mononuclear cells were significantly lower in the patient group compared with controls. The ratio of serum leptin versus sOBR (free leptin index) was significantly higher in the NS group. Urinary leptin in the patient group was higher than that in the control group. The free leptin index showed no correlation with BMI or total cholesterol, triglyceride, or apolipoprotein B levels in both groups but did show a correlation with plasma albumin, low-density lipoprotein, high-density lipoprotein, apolipoprotein A, and insulin levels in the patient group. CONCLUSIONS: The reduced sOBR level, which enhanced the biologically active form of leptin in children with NS, might be correlated partly with serum lipid parameters, albumin, and insulin. Increased free leptin in serum might be a complementary mechanism against hyperlipidemia in children with NS.

High Circulating Leptin Receptors with Normal Leptin Sensitivity in Liver-specific Insulin Receptor Knock-out (LIRKO) Mice

Liver-specific insulin receptor knock-out (LIRKO) mice display hyperinsulinemia, abnormal glucose metabolism, and progressive liver dysfunction. In addition, circulating leptin levels appear to be increased more than 10-fold. However, food intake, body weight, and adipose mass are not significantly altered in LIRKO mice compared with wild-type littermates. Using a ligand immunofunctional assay, we found that the apparent increase in circulating leptin in LIRKO mice is because of an 80-fold increased serum level of soluble leptin receptor. Gene expression analysis by microarray and real time PCR reveals the liver as the source of soluble leptin receptor in LIRKO mice, with an increase in expression of the short (Ob-Ra), long (Ob-Rb), and soluble (Ob-Re) forms of the leptin receptor. Direct control of leptin receptor expression by insulin could also be demonstrated in isolated hepatocytes from normal mice. Despite the markedly increased levels of leptin receptor in their circulation, LIRKO mice exhibit normal or even enhanced leptin sensitivity, as assessed by their physiological and molecular responses to exogenous leptin administration and their lower base-line hypothalamic levels of SOCS3 mRNA. Thus, insulin signaling in the liver plays an important role in control of leptin receptor expression and shedding. In the LIRKO mouse, this is lost, leading to markedly increased leptin receptors into the circulation. These high levels of circulating leptin receptor bind leptin and likely alter its clearance, but do not inhibit leptin action and may actually potentiate leptin action. In this manner, insulin signaling in liver plays an important role in leptin homeostasis and fine modulation of leptin action.

Metabolic decompensation in children with type 1 diabetes mellitus associated with increased serum levels of the soluble leptin receptor

Type 1 diabetes mellitus (T1DM) leads to increased serum levels of the soluble leptin receptor (sOB-R) by an as yet unknown cellular mechanism. The aim of our study was to investigate potential metabolic factors that may be associated with the induction of the sOB-R release from its membrane receptor. Twenty-five children (aged between 1.5 and 17.0 years) were studied at the onset of T1DM. Blood samples were collected before (n = 25), during the first 18 h (mean +/- S.D. 11.1 +/- 4.3 h, n = 16) and 92 h (47.5 +/- 22.5 h; n = 14) after beginning insulin therapy. Serum sOB-R and leptin levels were determined by in-house immunoassays. The sOBR-level and the molar sOB-R/leptin ratio were significantly higher before than after starting insulin treatment (P < 0.05). In contrast, leptin levels were significantly lower (P < 0.05) before insulin therapy. The correlation between sOB-R and blood glucose (r = 0.49; P < 0.05), as well as sOB-R with parameters of ketoacidosis, such as pH (r = -0.72), base excess (r = -0.70), and bicarbonate (r = -0.69) (P < 0.0001) at diagnosis of T1DM remained significant during the first 18 h of insulin treatment. Multiple regression analysis revealed that base excess predicted 41.0% (P < 0.001), age 16.4% (P < 0.05), and height SDS 13.9% (P < 0.01) of the sOB-R variance. Metabolic decompensation in children with new onset T1DM is associated with dramatic changes of the leptin axis; serum levels of sOB-R are elevated and of leptin are reduced. The molar excess of sOB-R over leptin (median 11.3) in this condition may contribute to leptin insensitivity. Upregulation of the soluble leptin receptor appears to be a basic mechanism to compensate for intracellular substrate deficiency and energy-deprivation state.

Serum soluble leptin receptor levels and free leptin index in women with polycystic ovary syndrome: relationship to insulin resistance and androgens

To evaluate levels of soluble receptor (sOB-R) and free leptin in women with polycystic ovarian syndrome (PCOS) and note any relationships with insulin resistance, adiposity, and androgens. Leptin is an adipokine that circulates in a free form and bound to an sOB-R. Only free leptin is biologically active. Prospective, case-control study. University-based reproductive endocrinology practice. Forty women with PCOS and severe insulin resistance and 15 body mass index (BMI)-matched ovulatory controls. Measurements of serum insulin, leptin, sOB-R at fasting and during a standard oral glucose tolerance test (OGTT), and measurements before and after treatment with rosiglitazone. Fasting glucose, insulin, leptin, sOB-R, T, and DHEAS levels in women with PCOS and controls were measured to investigate the relationship of sOB-R and the free leptin index (FLI) to insulin, adipocity, and androgens and to investigate the effect of acute hyperinsulinemia during OGTT and the effect of improvement of insulin resistance with rosiglitazone on the leptin system. FLI was calculated by dividing leptin levels by sOB-R. Total leptin and FLI correlated significantly with BMI in both patients with PCOS and in controls. There was a significant negative correlation between DHEAS and sOB-R in PCOS. Leptin, sOB-R, and FLI were not significantly different in the two groups, and neither sOB-R nor FLI correlated with insulin or glucose levels. The sOB-R levels increased significantly 3 hours after oral glucose ingestion, resulting in a significant decline in FLI. [1] Adiposity rather than insulin resistance appears to be the main determinant of leptin levels and FLI. [2] Acute increase in insulin levels during OGTT is associated with an increase in levels of sOB-R. [3] DHEAS may play a role in leptin bioavailability by modulating sOB-R levels.

Differential distribution of adipokines between serum and synovial fluid in patients with osteoarthritis. Contribution of joint tissues to their articular production

To analyze the distribution of leptin, adiponectin and resistin between paired serum and synovial fluid (SF) samples of patients with osteoarthritis (OA) and to determine the potential sources of these adipokines in the joint. The active free form of leptin was also examined by evaluating the level of the soluble leptin receptor (sOb-R). Levels of adipokines and sOb-R were measured by a sandwich enzyme-linked immunosorbent assay in serum and SF collected from OA patients. The levels of adipokines were also determined in conditioned media from cultured joint tissues (synovium, infrapatellar fat pad, meniscus, osteophyte, cartilage and bone). The adipokines exhibited different patterns of distribution between the joint and the circulating compartment. Serum levels of resistin and adiponectin exceeded those in the paired SF. Conversely, leptin SF concentrations were similar or higher than those measured in serum counterparts. Leptin and adiponectin in SF may derive from each joint tissue examined, whereas resistin was not detected in conditioned media of cultured explants. Synovium and infrapatellar fat pad were the major sources of adipokines, but osteophytes released also large amounts of leptin. The sOb-R deficiency found in SF further increased the difference in the bioactive leptin levels between serum and SF. A gender-specific difference was observed with women exhibiting the highest level of free leptin in the joint. These data demonstrated that adipokines serum levels are not predictive values for SF determination. The joint cavity is a special space where each adipokine undergoes specific regulatory pathways, strengthening the hypothesis that adipokines may have local effects in the joint and may account for the high prevalence of OA in women.

Decreased soluble leptin receptor levels in women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is associated with insulin resistance and a high incidence of obesity. Leptin, the product of the ob gene, is involved in the regulation of energy balance and obesity and circulates in both free and bound forms. The soluble leptin receptor (sOB-R) is the most important leptin-binding protein, thus influencing the biologically active free leptin level. We assessed the correlation of metabolic and endocrine parameters with leptin and sOB-R levels in 122 PCOS women (aged 27 +/- 5.7 years) and 81 healthy controls (aged 25 +/- 4.0 years). Leptin and sOB-R levels were measured using ELISA kits. In addition, anthropometric variables, body fat and endocrine parameters were evaluated and a glucose tolerance test performed to assess indices of insulin resistance and glucose metabolism. In PCOS patients, no correlation was found between leptin or sOB-R and parameters of hyper-androgenism. However, as expected, body mass index (BMI), body fat, waist circumference and indices of insulin resistance were significantly correlated with leptin in PCOS subjects and controls. In a subgroup analysis of lean, overweight and obese PCOS patients, significant differences were found in leptin (29.7 +/- 20.7 vs 45.4 +/- 25.0 vs 67.7 +/- 28.8 ng/ml, P < 0.0001) and sOB-R (8.0 +/- 3.4 vs 6.4 +/- 2.5 vs 5.7 +/- 2.3 ng/ml, P < 0.05). Compared with BMI-matched controls, lean PCOS patients had lower sOB-R levels (8.0 +/- 3.4 vs 12.7 +/- 4.7 ng/ml, P < 0.0001) and higher free leptin indices (4.5 +/- 3.9 vs 2.8 +/- 2.2, P = 0.0285). Taking into account that low sOB-R levels supposedly compensate diminished leptin action, PCOS per se might cause leptin resistance.

Influence of Nutritional Recovery on the Leptin Axis in Severely Malnourished Children

Leptin might be more important as a starvation hormone than as a satiety signal. The role of the soluble leptin receptor (sOB-R) and its regulation in children with protein energy malnutrition (PEM) is poorly understood. We elucidated the effect of intensive nutritional support on the leptin axis in 26 severely malnourished toddlers who received infant milk-based formula for 2 wk via continuous enteral tube feeding followed by 2 wk ad libitum feeding. Serum levels of leptin, sOB-R, IGF-I, and IGF-binding protein-3 as well as anthropometric measurements were determined at the beginning of the study and at 2-wk intervals. The control group consisted of 13 well-nourished children. The following were changes in the PEM toddlers after the nutritional support. Leptin increased significantly (P < 0.001), reaching 166% of levels observed in control group. sOB-R decreased significantly (P < 0.001), and a 142-fold molar excess of sOB-R over leptin was found. There were significant correlations between leptin and IGF-I after 2 wk and IGF-binding protein-3 during the whole study. sOB-R was not correlated with any anthropometric data, whereas IGF-I was a predictor of sOB-R variance in the PEM toddlers (19.9%, P = 0.022). It can be concluded that sOB-R has a modulatory effect on leptin in PEM children during nutritional recovery and participates in their adaptive survival mechanisms. Leptin and the molar excess of sOB-R over leptin are better biomarkers of nutritional status than IGF-I in PEM children during nutritional recovery.

Circulating soluble leptin receptor, leptin, and insulin resistance before and after weight loss in obese children

To study the relationships between leptin, soluble leptin receptor (sOB-R), and insulin resistance in obese children before and after weight reduction. We determined fasting serum leptin, sOB-R, and insulin resistance index (Homeostasis model assessment (HOMA)) in 36 obese children at baseline and 1 y later and compared them to 72 lean children matched for age, gender, and pubertal stage. The changes of leptin (Deltaleptin) and sOB-R (DeltasOB-R) over the 1 y period were correlated to the changes of HOMA (DeltaHOMA), the changes of weight status, and the changes of percentage body fat (Delta%BF) based on skinfold measurements. Multiple linear regression analyses were conducted for the dependent variables Deltaleptin and DeltasOB-R, including DeltaBMI and DeltaHOMA as independent variables adjusted for age, gender, and pubertal stage. Changes of leptin and sOB-R levels were analyzed in 11 obese children after they had lost weight substantially (decrease SDS-BMI>0.5) and compared to 11 obese children without substantial weight loss matched for age, gender, and pubertal stage. Obese children showed significantly (P<0.001) higher leptin and lower sOB-R levels. Deltaleptin correlated significantly to DeltaSDS-BMI (r=0.28, P<0.05), Delta%BF (r=0.44, P<0.05), and DeltaHOMA (r=0.42, P<0.01), while DeltasOB-R correlated significantly to DeltaSDS-BMI (r=-0.42, P<0.01) and Delta%BF (r=-0.47, P<0.01), but not to DeltaHOMA. In contrast to DeltasOB-R, Deltaleptin correlated significantly to DeltaHOMA (P=0.02) in multiple linear regression analysis. Substantial weight loss led to a significant increase in sOB-R (P=0.02) and to a decrease in HOMA (P=0.02). In children without substantial weight loss, there were no changes in sOB-R, while HOMA (P=0.04) and leptin (P=0.02) increased significantly. The decrease of sOB-R and the increase of leptin levels in obese children normalized after weight loss. Therefore, these changes are consequences rather than the cause of overweight. In contrast to sOB-R, leptin levels are associated with insulin resistance.

Relationship between serum concentrations of leptin, soluble leptin receptor, testosterone and IGF-I, and growth during the first year of postnatal life in the male rhesus monkey, Macaca mulatta

Subnormal leptin levels in low birth weight infants may allow for catch-up growth during infancy. Scant data are available that relate growth with circulating leptin during normal infancy in primates. The current study objective was to examine the association between serum leptin, its soluble receptor (sOB-R), testosterone and IGF-I concentrations, and body weight during infancy in male rhesus monkeys. Hormone levels were assessed longitudinally in animals (n = 7) from birth until 1 year of age. Body weight increased during the first 6 months of life and was strongly correlated with rising IGF-I levels and, as IGF-I plateaued and then declined during the second half of the year, body weight gain decelerated. In contrast, leptin levels declined gradually with age during the first year of life in conjunction with increasing body weight. There was no association between body weight gain and serum leptin levels or between serum testosterone and leptin values. Since sOB-R levels also declined with leptin values, it does not appear that levels of bioavailable leptin changed during infancy. The data do not support the contention that leptin regulates growth during infancy, but the close association between IGF-I levels and body weight suggested that this hormone may regulate growth in infant male monkeys. The failure to observe an association between serum testosterone and leptin concentrations suggested that leptin is not involved in the activation of the hypothalamic-pituitary -testicular axis during this developmental period.

Leptin and soluble leptin receptor levels in patients with the polycystic ovary syndrome: influence of metabolic and endocrine parameters

Polycystic ovary syndrome (PCOS), which affects about one million women in Germany, is associated with insulin resistance and a high incidence of obesity. Leptin, the product of the ob gene, is involved in the regulation of energy balance and obesity and circulates in both, free and bound forms. The soluble leptin receptor (sOB-R) is the most important leptin binding protein, thus influencing free leptin levels in humans. We assessed the association of metabolic or endocrine parameters and leptin or sOB-R levels in 52 PCOS women (28±5.8 years). Leptin and sOB-R levels were measured using ELISA kits (dsl, Sinsheim, Germany). In addition, endocrine parameters (testosterone, free andogen index –FAI-, androstendione, LH/FSH ratio) were evaluated and a 3-h glucose tolerance test (OGTT) was performed to assess indices of insulin resistance (HOMA-IR, fasting insulin, AUC-insulin). Body fat was measured using a bio-impedance analyser. In PCOS patients no correlation was found between leptin or sOB-R and endocrine features or indices of insulin resistance. However, as expected, body fat, BMI, waist and hip circumference were positively correlated with leptin levels (r=0.76, 0.74, 0.62 and 0.72, respectively). A better inverse correlation of leptin and sOB-R was found in lean women than in the entire PCOS cohort (r=0.66 and 0.37, respectively). In a subgroup analysis of lean, overweight and obese patients significant differences were found in: leptin (20.8±19.4 vs. 37.2±25.2 vs. 68.5±21.4 ng/ml, p<0.001), sOB-R (9.4±3.6 vs. 9.8±4.4 vs. 7.0±3.2 ng/ml, p=0.046) and HOMA-IR (1.2±0.5 vs. 2.3±0.8 vs. 6.0±3.5). In conclusion, in PCOS women obesity and insulin resistance are associated with high leptin and low sOB-R levels, suggesting that the decrease in sOB-R, by increasing the degree of unbound leptin, might be a compensatory mechanism of leptin resistance in obesity.