Soluble Leptin Receptor Levels Research Articles

Leptin Exacerbates Sepsis-Mediated Morbidity and Mortality

The adipose-derived hormone leptin is well known for its contribution to energy metabolism and satiety signaling in the hypothalamus. Previous studies suggested that obesity is an independent risk factor for sepsis morbidity and mortality, and it is associated with elevated baseline levels of circulating leptin in normal, nonseptic patients. In mouse endotoxemia and cecal ligation puncture models of sepsis, we observed elevated levels of leptin and soluble leptin receptor (sLR). Exogenously administered leptin increased mortality in endotoxemia and cecal ligation puncture models and was associated with increased expression of adhesion and coagulation molecules, macrophage infiltration into the liver and kidney, and endothelial barrier dysfunction. Conversely, longform leptin receptor-deficient mice were protected from sepsis morbidity and mortality and had less endothelial dysfunction. Furthermore, an in vitro study revealed that leptin-induced endothelial dysfunction is likely mediated, at least in part, by monocytes. Moreover, administration of an sLR conferred a survival benefit. Human septic patients have increased circulating sLR concentrations, which were correlated with disease severity indices. Together, these data support a pathogenic role for leptin signaling during sepsis.

Identification of the nasal mucosa as a new target for leptin action

The aim of this study was to examine systemic and local nasal leptin and leptin receptor expression in patients with nasal polyposis and healthy controls. Serum leptin and soluble leptin receptor levels were examined by enzyme-linked immunosorbent assay (ELISA). The presence of leptin and leptin receptor mRNA was investigated using reverse transcriptase-polymerase chain reaction (RT-PCR), and tissue leptin and leptin receptor protein expression was analysed by immunohistochemistry and ELISA. Serum levels of biologically active leptin were significantly elevated in patients with nasal polyps compared with control subjects. These serum leptin levels were strongly correlated with the levels found in tissue in both study groups, although leptin was not significantly elevated in nasal polyp tissue. Using RT-PCR, we showed that both leptin and its receptors were produced in nasal mucosa. Finally, immunohistochemistry showed that leptin and leptin receptor protein were expressed in several cells of the normal and inflamed nasal mucosa. Leptin receptors and their biological ligand leptin are expressed in the nasal mucosa, suggesting a possible role in upper airway immunology.

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.

Increased circulating adiponectin levels and decreased leptin/soluble leptin receptor ratio throughout puberty in female ballet dancers: association with body composition and the delay in puberty

Ballet dancers (BDs) have a negative energy balance related to physical training that results in alterations in body composition, sexual development, and adipokine secretion. Our aims were to study anthropometric parameters, body composition, and their relationship with adipokines throughout pubertal development. We carried out a prospective follow-up study of 22 female Caucasian BDs (Tanner II stage) followed throughout puberty. Nutritional status was determined by measurement of height, weight, and body mass index (BMI). We calculated growth velocity, bone maturity, and body composition at Tanner stages II, III, and V by dual energy X-ray absorptiometry. Circulating leptin, adiponectin, and soluble leptin receptor (sObR) levels were determined. BDs presented a delay in skeletal maturation during puberty, without affectation of final height. Energy intake was deficient according to their physical exercise, and they had a delay of 1 year in the mean age of menarche. Leptin levels were decreased, whereas sObR and adiponectin levels were increased throughout puberty. The percentage of trunk fat, total fat mass, and fat of the extremities was decreased throughout the study period (P<0.01). Lean mass was increased in the lower extremities, and bone mineral density was normal. A negative energy balance together with maintained physical exercise induced modifications in body composition in BDs. Changes in leptin and adiponectin levels appear to be more related to total fat content than to BMI. Furthermore, the onset and delayed progress of puberty may be related with an inadequate energy balance due to increased exercise.

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.

Serum leptin levels during pregnancy in multiple sclerosis

Background Disease activity in patients with multiple sclerosis (MS) is suppressed during pregnancy, whereas attack frequency increases after delivery. It is yet unclear, which immuno – endocrinological processes mediate these disease fluctuations. Leptin has been identified as a hormone that can influence inflammatory activity. Objective The aim of this study was to investigate whether pregnancy-induced fluctuations of serum leptin levels differed between patients with MS and controls and whether serum leptin levels correlate with periods of enhanced and diminished disease activity. Methods Women with MS and healthy women were prospectively followed during and after pregnancy. The MS group could be studied already at a timepoint before pregnancy. Serum leptin and soluble leptin receptor (SLR) levels were measured using enzyme-linked immunosorbent assay. Results Pre-pregnancy serum leptin levels were (mean ± SD) 22.9 ± 12.8 ng/ml in the MS group. These levels increased in the third trimester to 28.5 ± 15.0 ng/ml (P = 0.007). The third trimester serum leptin levels in healthy women were comparable, 29.4 ± 19.0 ng/ml. Serum leptin levels after delivery dropped to 18.5 ± 12.8 ng/ml in women with MS (P < 0.001) and to a lesser extend (22.0 ± 17.5 ng/ml) in healthy women (P = 0.04). SLR levels showed the same pattern. Remarkably, women with the highest relative decrease in serum leptin levels after delivery had more often a postpartum relapse (P = 0.008). Conclusion In women with MS, leptin increased during late pregnancy. A postdelivery drop in leptin levels was observed in both the MS and control group. The postdelivery drop was associated with the occurrence of postpartum relapse.

Long term effects of high fat and sucrose diets on obesity and lymphocyte proliferation in mice

ObjectiveTo clarify the effect of prolonged feeding of a high-fat and sucrose, and to clarify the effect of sucrose instead of other carbohydrate on obesity and immunity in C57BL/6J mice. MethodsWe investigated the development of obesity and immune cell function in four groups of mice fed high-fat, high-fat plus high-sucrose, high-sucrose, and control diet for 7 months. ResultsMice fed high-fat and high-fat plus high-sucrose groups developed severe obesity. Body weight, adipose tissue weight, serum leptin, blood glucose, and insulin were significantly higher, while the level of serum soluble leptin receptor was significantly lower in mice fed high-fat and high-fat plus high-sucrose diets than in mice fed the control or high-sucrose diets. Splenocyte proliferation stimulated by T-cell mitogen (PHA, ConA, and anti-CD 3 antibody) and B-cell mitogen (LPS) was significantly lower in both obese, high-fat and high-fat plus high-sucrose groups than in control and high-sucrose groups. However, these parameters did not differ between high-fat and high-fat plus high-sucrose groups. ConclusionsLong-term feeding of high-fat diet and high-fat plus high-sucrose diet similarly induced severe obesity in C57BL/6J mice. Not only T-cell, but also B-cell function may be impaired in mice made severely obese by the high-fat or high-fat plus high-sucrose diets.

The effects of PACAP and related peptides on leptin, soluble leptin receptor and resistin in normal condition and LPS-induced inflammation

Leptin and resistin are adipokines considered as pro-inflammatory factors related to metabolic syndrome, inflammatory and/or autoimmune conditions. Pituitary adenylate cyclase activating peptide (PACAP) is a pleiotropic neuropeptide with anti-inflammatory properties. We investigated the influence of PACAP on the serum level of leptin, soluble leptin receptor (SLR) and resistin in ordinary and LPS-induced inflammatory conditions using PACAP38 and a series of selective agonist for each PACAP receptor types. It was found that PACAP exerted opposite effects on the leptin:SLR ratio and the serum resistin level. In ordinary condition, PACAP acted as a pro-inflammatory factor by increasing the leptin:SLR ratio and serum resistin level. But in LPS-induced acute inflammatory condition, PACAP not only antagonized the effects of LPS, but also even reversed the effects of LPS. In mice treated with LPS, co-treatment with PACAP decreased the serum leptin and resistin levels and increased the serum soluble leptin receptor level significantly. It was also found that, in ordinary condition, treatment with PAC1 agonist maxadilan induced marked increase in serum leptin, leptin:SLR ratios and resistin levels; while in LPS-induced inflammation, VPAC1 mediated much more anti-inflammatory and reversing-LPS effects of PACAP on leptin and resistin than PAC1 and VPAC2. It is concluded that different receptors mediates different effects of PACAP on leptin, SLR and resistin in non-inflammatory and LPS-induced inflammatory conditions.

In Vivo and ex Vivo Regulation of Visfatin Production by Leptin in Human and Murine Adipose Tissue: Role of Mitogen-Activated Protein Kinase and Phosphatidylinositol 3-Kinase Signaling Pathways

Visfatin is an adipogenic adipokine with increased levels in obesity, properties common to leptin. Thus, leptin may modulate visfatin production in adipose tissue (AT). Therefore, we investigated the effects of leptin on visfatin levels in 3T3-L1 adipocytes and human/murine AT, with or without a leptin antagonist. The potential signaling pathways and mechanisms regulating visfatin production in AT was also studied. Real-time RT-PCR and Western blotting were used to assess the relative mRNA and protein expression of visfatin. ELISA was performed to measure visfatin levels in conditioned media of AT explants, and small interfering RNA technology was used to reduce leptin receptor expression. Leptin significantly (P < 0.01) increased visfatin levels in human and murine AT with a maximal response at leptin 10(-9) M, returning to baseline at leptin 10(-7) M. Importantly, ip leptin administration to C57BL/6 ob/ob mice further supported leptin-induced visfatin protein production in omental AT (P < 0.05). Additionally, soluble leptin receptor levels rose with concentration dependency to a maximal response at leptin 10(-7) M (P < 0.01). The use of a leptin antagonist negated the induction of visfatin and soluble leptin receptor by leptin. Furthermore, leptin-induced visfatin production was significantly decreased in the presence of MAPK and phosphatidylinositol 3-kinase inhibitors. Also, when the leptin receptor gene was knocked down using small interfering RNA, leptin-induced visfatin expression was significantly decreased. Thus, leptin increases visfatin production in AT in vivo and ex vivo via pathways involving MAPK and phosphatidylinositol 3-kinase signaling. The pleiotropic effects of leptin may be partially mediated by visfatin.

Serum concentrations of adipocyte fatty acid binding protein in patients with anorexia nervosa

Serum adipocyte fatty acid-binding protein (FABP) concentrations are linked to human obesity and other features of metabolic syndrome. Whether FABP associates with metabolic alterations in chronic malnutrition is unknown. In the present study, we measured fasting serum levels of FABP, leptin, soluble leptin receptor, adiponectin, resistin, C-reactive protein (CRP), insulin, glucose, cholesterol and triglycerides in 19 patients with a restrictive type of anorexia nervosa (AN) and in 16 healthy age-matched control women (C). Body mass index, serum leptin, and CRP concentrations were significantly lower, while serum adiponectin and soluble leptin receptor levels were significantly higher in AN relative to C group. Serum insulin, glucose, cholesterol and triglyceride levels did not differ between the groups studied. Serum FABP levels were unchanged in patients with AN and were not related to any of parameters studied. We conclude that, in contrast to patients with obesity where FAPB is a prominent marker of metabolic alterations, chronic malnutrition in AN does not significantly affect its serum levels.

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.

Obesity in psoriasis: leptin and resistin as mediators of cutaneous inflammation

Obesity is a significant risk factor for psoriasis and body mass index (BMI) correlates with disease severity. Objectives To investigate the relationship between obesity and psoriasis, focusing on the role of adipokines such as leptin and resistin. Patients with psoriasis (n = 30) were recruited and their BMI, waist circumference and disease severity [Psoriasis Area and Severity Index (PASI)] were recorded. Fasting serum samples were obtained on enrolment and after a course of ultraviolet (UV) B treatment. Age-, sex- and BMI-matched healthy controls were also recruited. On enrolment, serum leptin and soluble leptin receptor levels were not raised compared with the controls. However, resistin, interleukin (IL)-1beta, IL-6, and chemokines CCL2, CXCL8 and CXCL9 were all significantly elevated in the patient group and serum resistin correlated with disease severity (r = 0.372, P = 0.043). Improvement after UVB treatment was accompanied by decreased serum CXCL8. In vitro, both leptin and resistin could induce CXCL8 and tumour necrosis factor-alpha production by blood monocytes, and leptin could additionally induce IL-1beta and IL-1 receptor antagonist production. Leptin also dose dependently increased secretion of the growth factor amphiregulin by ex vivo-cultured lesional psoriasis skin. These data support the view that leptin and resistin may be involved in the pathogenesis of psoriasis in overweight individuals, possibly by augmenting the cytokine expression by the inflammatory infiltrate.

Leptin, Soluble Leptin Receptor, Lipid Profiles, and LEPR Gene Polymorphisms in Thai Children and Adolescents

To evaluate the relationships between leptin, soluble leptin receptor, lipid profiles, and LEPR gene polymorphisms in child and adolescent Thai subjects. Cross-sectional study of Thai children and adolescents. 116 male and 65 female at risk for overweight/overweight child and adolescent Thai subjects, and 33 male and 62 female healthy child and adolescent Thai subjects (age: 5-19 years). Leptin levels, soluble leptin receptor levels, lipid profiles, LEPR gene polymorphisms. Significantly higher levels of cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), and leptin levels were observed in at risk for overweight/overweight group. On the other hand, high-density lipoprotein cholesterol (HDL-C) and soluble leptin receptor levels were significantly lower in the same group. Serum soluble leptin receptor levels were significantly negatively correlated with leptin. The at risk for overweight/overweight subjects with the Lys656Lys homozygous wild type LEPR gene had significantly higher cholesterol and LDL-C levels than those with Lys656Asn heterozygous and Asn656Asn homozygous mutant type. In contrast, subjects with Lys656Lys homozygous wild type had significantly lower leptin levels than those with Lys656Asn heterozygous and Asn656Asn homozygous mutant type. There was a statistically significant association between body mass index (BMI) and hyperleptinemia (odds ratio; OR = 2.49, p = 0.000) and females had more increased risk of hyperleptinemia than males (OR = 15.74, p = 0.004) in adolescent Thai subjects. The present study is the first report of Lys656Asn polymorphism of the LEPR gene associated with cholesterol, LDL-C, and leptin levels in Thai children and adolescents. Serum leptin levels were significantly higher in the at risk for overweight/overweight. In contrast, there were significantly lower soluble leptin receptor levels in the same group. In addition, there was a statistically significant association between BMI, sex, and hyperleptinemia in adolescent Thai subjects.

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.

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.

Metformin treatment does not affect total leptin levels and free leptin index in obese patients with polycystic ovary syndrome

Leptin, particularly in its free form, is deeply involved in the regulation of energy balance. Insulin was suggested to influence plasmatic leptin levels and soluble leptin receptor in humans. However, this study indicates that metformin treatment, although improving insulin levels, does not exert a significant effect on either total leptin level or free leptin index in obese women with hyperinsulinemia and PCOS.

The Soluble Leptin Receptor of Regular Exercisers

This study examined the concentrations and the relationships of soluble leptin receptor (sLR) and leptin levels among both physically active people and lean sedentary persons. Information collected for this study came from twelve joggers (JOG), ten weight trainers (WET) and eleven lean sedentary persons (CON). Regular exercisers were defined as those who consistently participated in jogging or weight training 30 minutes a day, at least four times a week, for a period of no less than three years prior to the study. The CON group was defined as exercising, at most, one time per week, less than 20 minutes each time if at all. Leptin and sLR were analyzed using enzyme-linked immunosorbent assay. The results show the BMI of the WET group to be higher than the other groups, yet their percent body fat was not significantly different. Although sLR levels of the JOG group were higher than the WET and CON groups, their free leptin index (FLI) did not show a significant difference. The sLR levels for joggers were higher than the weight trainers. The sLR concentration or the ratio of sLR to fat mass may be an alternative index to FLI for comparing physically active and lean people.

Distinct roles of free leptin, bound leptin and soluble leptin receptor during the metabolic‐inflammatory response in patients with liver cirrhosis

Alteration of the leptin system appears to play a role in the inflammatory-metabolic response in catabolic diseases such as chronic liver diseases. To investigate the association between leptin components, inflammatory markers and hepatic energy and substrate metabolism. We investigated in vivo hepatic substrate and leptin metabolism in 40 patients employing a combination of arterial and hepatic vein catheterization techniques and hepatic blood flow measurements. In addition to metabolic, inflammatory and neuroendocrine parameters, circulating levels of free leptin, bound leptin and soluble leptin receptor were determined. Compared with controls, bound leptin and soluble leptin receptor levels were significantly elevated in cirrhosis, while free leptin did not increase. In cirrhosis bound leptin was correlated with soluble leptin receptor (r = 0.70, P < 0.001). Free leptin was positively correlated with metabolic parameters such as energy storage (body fat mass; r = 0.36, P < 0.05), insulin and insulin resistance (r = 0.48; r = 0.46, P < 0.01) as well as with hepatic glucose and energy release (r = 0.35 and r = 0.40, P < 0.05). In contrast, bound leptin and soluble leptin receptor were linked to proinflammatory cytokines and sympathetic activity (r = 0.61 and r = 0.56, P < 0.01). The components of the leptin system (free leptin, bound leptin and soluble leptin receptor) have distinct roles in metabolic and inflammatory processes in patients with liver cirrhosis. The better understanding of this metabolic and inflammatory tissue-repair response may lead to innovative new therapeutic strategies in liver disease as well as in various other catabolic diseases.

Free Leptin Index in a State of High Insulin Resistance and Advanced Fibrosis in NAFLD/NASH

Purpose: Soluble leptin receptor (SLR) serves as a major leptin binding protein, but the SLR and the free leptin index (FLI) have not been studied yet in humans with nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH). Since the measured leptin in the previous studies represented total serum leptin, our goal was to test the hypothesis that SLR and/or FLI correlates better with steatosis, inflammation, and/or fibrosis in human NAFLD/NASH. Methods: Sixty-one patients who were listed for bariatric surgery were enrolled in this cohort study. Data including demographics and risk factors for the metabolic syndrome {BMI, diabetes mellitus type 2 (DM2), hypertension, and lipid profile} were obtained. Fasting blood was drawn at 1100h preoperatively, and the EDTA-plasma was analyzed for glucose, insulin, total leptin, and SLR. All patients had intraoperative liver biopsies read by a hepatopathologist. Results: Of 61 patients, 39 patients had sufficient liver specimens (size >1.5 cm and >10 portal tracts) and their serum was collected appropriately. Their demographics were: 10 male, 29 female and mean ages of 44.9 ± 1.5. Their mean BMI was 45.7 ± 0.9. Twenty patients had hypertension, 14 had DM2, and 20 had hyperlipidemia. Thirty-six of 39 had various degrees of steatosis: 5 had less than 10%, 15 had 10–29%, 13 had 30–60%, and 3 had greater than 60%. According to Brunt's scoring system, 14 patients had grade 0, 20 had grade 1, and 2 had grade 2 NASH. Twenty-five had stage 0, 8 had stage 1 and 3 had stage 3 fibrosis. Spearman correlation with two-tailed test showed that FLI was negatively correlated with advanced fibrosis (stage > = 3) (p= 0.007), Homeostasis Model Assessment (HOMA) score (p < 0.001) and DM2 (p= 0.003). In contrast, SLR was positively correlated with HOMA score (p < 0.001). NASH grading was not significantly correlated with SLR or FLI. Serum total leptin was positively correlated with the BMI (p= 0.006). Conclusions: Serum total leptin is increased in obesity, but the state of insulin resistance may promote high levels of SLR thus decreasing the amount of serum free leptin. The low free leptin index seen in advanced fibrosis in NASH in this population is a novel finding and needs validation with larger studies.

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

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