Leptin Receptor Concentrations Research Articles

Identification of leptin resistance in patients with coronary artery disease and heart defects

Aim. To compare the incidence of leptin resistance (LR) in patients with acute and chronic coronary artery disease (CAD) and patients with acquired heart defects (AHD).Material and methods. The study included 234 patients: 114 patients with acute myocardial infarction (MI) and 120 patients with chronic CAD. The comparison group consisted of 48 patients with degenerative non-rheumatic AHD — aortic stenosis (AS). The control group consisted of 40 healthy volunteers. On the 1st day of hospitalization, the concentration of leptin and leptin receptor was measured, and the free leptin index (FLI) was assessed. LR was recorded at leptin >6,45 ng/ ml and FLI >25. Statistical data processing was carried out using the software package Statistica 10.0 and SPSS 17.0 for Windows.Results. Initially, LR in MI, chronic CAD and non-coronary disease was revealed in 64%, 56,2% and 25%, respectively. Significant differences in the incidence of LR were observed between patients with MI and chronic CAD relative to patients with AHD (p=0,02 and p=0,03, respectively), while no differences were found between patients with coronary pathology (p=0,82). Equation of patients for body mass index (BMI) did not affect the incidence of LR. High incidence of LR remained for patients with acute and chronic CAD, and amounted to 63% and 57,3%, respectively, while for patients with AS — 25%.Conclusion. Patients with acute and chronic CAD are characterized by a high LR incidence, in contrast to patients with AHD. The number of LR cases in patients with coronary pathology did not depend on BMI values, which indicates possible alternative leptin sources contributing the development of hyperleptinemia. In addition, studying the mechanisms underlying the leptin receptor decrease in CAD is necessary for adequate leptin effects and the prevention of LR.

ЛЕПТИНОРЕЗИСТЕНТНОСТЬ И ЕЕ КЛИНИКО-ПРОГНОСТИЧЕСКУЮ ЗНАЧИМОСТЬ ВО ВЗАИМОСВЯЗИ С МЕТАБОЛИЧЕСКИМИ НАРУШЕНИЯМИ В ГОСПИТАЛЬНОМ ПЕРИОДЕ ИНФАРКТА МИОКАРДА

Introduction. Leptin resistance (LR) is characterized by a weakening of the positive metabolic effect of leptin, despite its elevated level, while maintaining some of the pleiotropic effects, including those on the cardiovascular system. However, since most of the data have been obtained in cellular and animal models, the role of LR in cardiovascular diseases remains unclear. The lack of precise diagnostic criteria for assessing LR limits the study of this phenomenon. As a result, data on the incidence and contribution of LR in MI are critically scarce today, in addition, they are extremely contradictory. Purpose: to evaluate the prevalence of LR and its clinical and prognostic significance in conjunction with metabolic disorders in the hospital period of myocardial infarction (MI). Materials and methods. The study included 114 men with an established diagnosis of ST elevation MI. Patients on the 1st and 12th day of MI measured the concentration of leptin, the leptin receptor. The free leptin index (FLI) was calculated as the ratio of leptin concentration (ng/mL) to the concentration of soluble leptin receptor (ng/mL) multiplied by 100. LR was recorded at leptin > 6.45 ng/mL and LL >25. Assessment of glucose, lipid spectrum (total cholesterol, TAG, LDL-C, VLDL-C, HDL-C, FFA) in blood serum was performed using standard test systems from Thermo Fisher Sientific on an automatic biochemical analyzer Konelab 30i (Finland) , the content of C-peptide and insulin were determined using enzyme immunoassay (Monobind, USA) according to the protocol established by the manufacturer. To determine insulin resistance (IR), the QUICKI index was calculated, the severity of IR was assessed according to A. Katz et al. A comparative analysis of clinical and anamnestic characteristics and cardiovascular prognosis between patients with and without PR was carried out. Data analyzed using Statistica 10.0. Results. In patients with MI in the whole group in the hospital period, there was an increased content of leptin relative to the reference interval of 2.0-5.6 ng/ml. On the 1st and 12th days of the disease, the leptin concentration in patients with MI was 11.6 [6.6;20.5] ng/ml and 11.5 [5.4;13.9] ng/ml, respectively. . The content of the leptin receptor did not go beyond the established reference interval. LSI on the 1st day of the disease was 32.7 [14.3; 70.5], on the 12th day - 31.9 [16.2; 64.5]. The prevalence of LR in the hospital period for MI was 64%. LR was associated with CVD risk factors - hereditary burden for cardiovascular pathology (p=0.02), arterial hypertension (p=0.01), dyslipidemia (p=0.001), obesity (p=0.001). When assessing the metabolic profile, a statistically significant increase in the content of glucose (p=0.02), insulin (p=0.02) and C-peptide (p=0.03) on the 1st day of MI, insulin (p=0 .01) and C-peptide (p=0.03) on the 12th day of the disease, a decrease in the QUICKI index (p=0.03) throughout the hospital period in patients with PR compared with patients without PR. In the group of patients with PR, 45 people (61.8%) had a moderate and severe degree of IR, in patients without PR - in 12 patients (29.2%). When conducting a correlation analysis, a significantly significant direct relationship was found between the level of insulin on the 12th day of MI and LSI (r=0.509, p=0.02), as well as an inverse correlation between the QUICKI index on the 12th day and LSI (r= -0.367, p=0.01). Among the studied parameters of lipid metabolism, only the content of FFA on the 1st day of the disease in the group of patients with LR was higher than in the group without LR (p=0.03). Patients with LR were more often prone to early postinfarction angina (p=0.03), recurrent MI (p=0.001), rhythm and conduction disturbances (p=0.03) during the hospital period of MI. Prognostic significance in relation to the risk of adverse cardiovascular events in the hospital period of MI, according to logistic regression analysis, had LSI both on the 1st and 12th days of the disease, as well as FFA levels on the 1st day of the disease. Conclusion. Patients with MI are characterized by a high prevalence of LR in the hospital period. LR is associated with CVD risk factors, metabolic disorders, and IR formation. The identified features in the presence of LR can probably contribute to the development of adverse cardiovascular events in the hospital period of MI.

Adipocyte-Derived Adipokines and Other Obesity-Associated Molecules in Feline Mammary Cancer.

Obesity has been identified as a serious health concern in domestic cats. Feline mammary cancer (FMC) is also a concern, as it is highly prevalent and aggressive. Considering the identified connection between obesity and breast cancer, it is worthwhile to investigate the potential obesity-cancer relationship in FMC. This review investigated the association between adipokines and other obesity-associated molecules and FMC, with the aim of identifying gaps in the current literature for future research. Based on the reports to date, it was found that tissue concentrations of leptin, serum concentrations of leptin receptor, serum amyloid A, and estrogen correlate positively with FMC, and serum concentrations of leptin correlate negatively with FMC. The roles of adiponectin and prolactin in FMC development were also investigated, but the reports are either lacking or insufficient to suggest an association. Numerous research gaps were identified and could be used as opportunities for future research. These include the need for studies on additional cohorts to confirm the association of leptin/leptin receptor and serum amyloid A with FMC, and to address the role of adiponectin and prolactin in FMC. It is also important to investigate the genetic determinants of FMC, evaluate the use of molecular-targeted therapies in FMC, and exploit the enrichment of the triple-negative immunophenotype in FMC to address current clinical needs for both human triple-negative breast cancer and FMC. Finally, mechanistic studies with any of the molecules reviewed are scarce and are important to generate hypotheses and ultimately advance our knowledge and the outcome of FMC.

High free leptin index as the risk factor for childhood obesity in Indonesia: A case-control study.

Identifying the risk factors is critical in preventing childhood obesity. Leptin concentration is elevated in obesity. High serum leptin levels are believed to reduce soluble leptin receptor (sOB-R) concentrations and are associated with leptin resistance. The free leptin index (FLI) is a biomarker of leptin resistance and the status of leptin action. This study aims to investigate the association between leptin, sOB-R, and FLI with measurements to diagnose obesity in children, such as BMI, waist circumference and waist-to-height ratio (WHtR). We conducted a case-control study in 10 elementary schools in Medan, Indonesia. The case group was children with obesity, while the control group was children with normal BMI. Leptin and sOB-R levels were measured from all the subjects using the ELISA method. Logistic regression analysis was employed to determine which factors were predictor variables of obesity. A total of 202 children between 6 and 12 years old were recruited for this study. Children with obesity showed significantly higher leptin levels and FLI and lower SOB-R levels FLI (p < .05) than control. The cut-off for WHtR in this study was 0.499 (sensitivity 90% and specificity 92.5%). Children with higher leptin levels had a higher risk of obesity based on BMI, waist circumference, and WHtR values.

Effect of Tithonia diversifolia Leaf Extract on Leptin, Adiponectin, and Insulin Receptor Levels in Diabetic Rats

This study aimed to evaluate the effect of Tithonia diversifolia extract (TDE) on leptin, adiponectin, and insulin receptor (IR) concentrations in diabetic rats. Twenty-four Wistar rats were divided into a control and treatment groups (n=6 per group). The control group received normal saline, and the treatment groups received 0.25% sodium carboxymethyl cellulose, TDE at 100 mg/kg body weight (bw), and catechin at 10 mg/kg bw for 7 days. On day 8, the rats were sacrificed, blood samples were obtained, and leptin, adiponectin, and insulin concentrations were measured using avidinhorseradish peroxidase sandwich-enzyme-linked immunosorbent assay. A calorimetric method was used to measure blood glucose (BG) and total serum cholesterol concentrations. The pancreas and kidneys were collected for the measurement of renal IR and macrophage cluster of differentiation (CD)14 levels using immunohistochemical staining. Acute type 2 diabetes mellitus (T2DM) with elevated BG and total serum cholesterol concentrations was observed in the treatment groups administered streptozotocin. The administration of TDE at 100 mg/kg bw significantly decreased leptin and increased adiponectin concentrations (P≤0.05). Furthermore, TDE treatment significantly increased renal IR and decreased macrophage CD14 levels (P<0.05). Therefore, TDE decreased leptin and BG concentrations by increasing IR levels. TDE also suppressed the necrosis of pancreatic tissues by inhibiting macrophage CD14 expression in diabetic rats. However, further research is necessary to determine the effect of TDE on interleukin and IR levels in the related tissues of patients with T2DM.

Dietary Fibre Supplementation Improves Semen Production by Increasing Leydig Cells and Testosterone Synthesis in a Growing Boar Model.

Testicular development is imperative to spermatogenesis, and pre-puberty is the key period for testis development. This study, therefore, investigated the effects of fibre supplementation on testis development and its possible mechanism in a growing boar model. Thirty Yorkshire boars were randomly divided into a control group (Control) and a fibre group (Fibre) from day 0 to 90 after weaning, with three pigs per pen and five pens per treatment. Blood and testes were collected for analysis. Dietary fibre supplementation had no significant effect on growth performance, testicular volume, or libido but increased the semen production of boars. Boars fed with fibre had lower serum cholesterol (CHO) and low-density lipoprotein (LDL) levels compared to those on the Control diet; however, testicular CHO, triglyceride (TG), and LDL concentration in the Fibre group were significantly higher than the Control group (P < 0.01). Testicular histological analysis showed that seminiferous tubules and testicular germ cells of 120-day-old boars were densely arranged in the Fibre group, and the number of Leydig cells was significantly higher than that of the Control group (P < 0.001). Furthermore, the diet supplemented with fibre significantly decreased leptin, leptin receptor (Leptor), and luteinising hormone (LH) concentrations in boar serum (P < 0.05), whereas follicle-stimulating hormone (FSH) and testosterone concentrations were significantly increased (P < 0.05). Meanwhile, the expression of AMH, AMHR2, and SYCP3 genes related to proliferation and differentiation, and hormone-related genes STAR and SOCS3, were significantly up-regulated (P < 0.05). OCCLUDIN expression was up-regulated, whereas CDH2 expression was down-regulated. In conclusion, increased fibre intake during the pre-puberty period in growing boar is crucial for Leydig cell proliferation, up-regulating the expression of genes related to hormone synthesis and thereby promoting the secretion of testosterone and semen production.

Quantile-specific heritability of sibling leptin concentrations and its implications for gene-environment interactions

“Quantile-dependent expressivity” occurs when the effect size of a genetic variant depends upon whether the phenotype (e.g., leptin) is high or low relative to its distribution. Leptin concentrations are strongly related to adiposity, whose heritability is quantile dependent. Whether inheritance of leptin concentrations is quantile dependent, and whether this explains the greater heritability in women than men in accordance with their greater adiposity, and explains other gene-environment interactions, remains to be determined. Therefore, leptin and leptin receptor concentrations from 3068 siblings in 1133 sibships from the Framingham Heart Study Third Generation Cohort were analyzed. Free leptin index (FLI) was calculated as the ratio of leptin to soluble leptin receptor concentrations. Full-sib (βFS) regression slopes were robustly estimated by quantile regression with nonparametric significance assigned from 1000 bootstrap samples. The analyses showed βFS increased significantly with increasing percentiles of the offspring’s age- and sex-adjusted leptin distribution (Plinear = 0.0001), which was accelerated at the higher concentrations (Pquadratic = 0.0003). βFS at the 90th percentile (0.418 ± 0.066) was 4.7-fold greater than at the 10th percentile (0.089 ± 0.032, Pdifference = 3.6 × 10−6). Consistent with quantile-dependent expressivity, the βFS was greater in female sibs, which was attributable to their higher leptin concentrations. Reported gene-environment interactions involving adiposity and LEP, LEPR, MnSOD, PPARγ, PPARγ2, and IRS-1 polymorphisms were consistent with quantile-dependent expressivity of leptin concentrations. βFS for leptin receptor concentrations and free leptin index also increased significantly with increasing percentiles of their distributions (Plinear = 0.04 and Plinear = 8.5 × 10−6, respectively). In conclusion, inherited genetic and shared environmental effects on leptin concentrations were quantile dependent, which likely explains male–female differences in heritability and some gene-environment interactions.

The Effects of Laparoscopic Sleeve Gastrectomy on the Parameters of Leptin Resistance in Obesity.

Obesity is a growing public health problem worldwide. Bariatric surgical procedures achieve the most sustainable and efficacious outcomes in the treatment of morbid obesity. However, little is known about the underlying molecular pathways modulated by these surgical interventions. Since leptin resistance is implicated in the pathogenesis of obesity, we herein report the effects of laparoscopic sleeve gastrectomy (LSG) on the serum levels of leptin and leptin receptor, in addition to its overall effect on leptin resistance. This was an interventional and follow-up clinical study. In the first part, patients attending the general surgery outpatient clinics at our university hospital were first stratified according to their Body-Mass Index (BMI) into cases (n = 38) with BMI ≥ 35 who were scheduled to undergo LSG, and controls (n = 75) with a normal BMI. Serum leptin and leptin receptor levels were measured by sandwich ELISA technique. A leptin resistance index was estimated by adjusting leptin to BMI ratio to leptin receptor concentration. In the second part of the study, cases who underwent LSG were followed up one year postoperatively to assess their BMI and serum leptin and leptin receptor levels. Leptin to BMI ratio was significantly higher, while serum leptin receptor was significantly lower, in obese patients compared to controls. This translated into a significantly higher leptin resistance index in obese patients. LSG resulted in a significant reduction of BMI, leptin to BMI ratio, and leptin resistance index, as it significantly increased leptin receptor levels. In conclusion, LSG showed significant decrease in leptin resistance in obese patients after one year. Further studies are needed to determine the clinical impact of this finding on LSG outcomes.

Metabolic effects of leptin receptor knockdown or reconstitution in adipose tissues

The relative contribution of peripheral and central leptin signalling to the regulation of metabolism and the mechanisms through which leptin affects glucose homeostasis have not been fully elucidated. We generated complementary lines of mice with either leptin receptor (Lepr) knockdown or reconstitution in adipose tissues using Cre-lox methodology. Lepr knockdown mice were modestly lighter and had lower plasma insulin concentrations following an oral glucose challenge compared to controls, despite similar insulin sensitivity. We rendered male mice diabetic using streptozotocin (STZ) and found that upon prolonged leptin therapy, Lepr knockdown mice had an accelerated decrease in blood glucose compared to controls that was associated with higher plasma concentrations of leptin and leptin receptor. Mice with transcriptional blockade of Lepr (LeprloxTB/loxTB) were obese and hyperglycemic and reconstitution of Lepr in adipose tissues of LeprloxTB/loxTB mice resulted in males reaching a higher maximal body weight. Although mice with adipose tissue Lepr reconstitution had lower blood glucose levels at several ages, their plasma insulin concentrations during an oral glucose test were elevated. Thus, attenuation or restoration of Lepr in adipocytes alters the plasma insulin profile following glucose ingestion, modifies the glucose-lowering effect of prolonged leptin therapy in insulin-deficient diabetes, and may modulate weight gain.

Human Obesity: A Noxious Sequel of Inverse Intents of Ligands and Receptors

Diabetes and cardiovascular disease are the two most common deleterious side effects in the first line complications of chronic human obesity. Hyperleptinemia, hyperinsulinemia and hypercholesterolemia are the reported proximal outbreaks in progressive human obesity. Leptin, insulin and LDL remain interacted through their cognate receptors. A phase matched comparison has been conducted in present study between expressions of cognate receptors and plasma profile of their respective ligands in three human male groups viz. normal (18.5&lt; BMI &lt; 25), obese (25&lt; BMI &lt;40) and morbid obese (BMI &gt; 40). Our study shows a declined leptin receptor concentration on peripheral blood mononuclear cells (PBMC) with a meagre change in its soluble counterpart (sOR/ OB-Re) in blood circulation, averring the outbreak of hyperleptinemia with obesity. Simultaneously, a cumulative decline of concentrations of LDL receptor (LDLR) and insulin receptor (IR) in PBMC are the reasons behind hypercholesterolemia and hyperinsulinemia cum insulin resistance in human obesity.

Serum leptin and leptin resistance correlations with NAFLD in patients with type 2 diabetes.

Leptin/leptin resistance has been suggested to play a role in nonalcoholic fatty liver disease (NAFLD), and therefore we investigated the correlation of leptin/leptin-receptor system with markers of hepatic steatosis (HS) and fibrosis (HF) in patients with type 2 diabetes (T2D). In 159 T2D subjects with disease duration of 6.0 (0.0-27.0) years, HS was evaluated by semi-quantitative ultrasonographic scores and by clinical/biochemical variables: Fatty liver index and Hepatic steatosis index. HF was evaluated by NAFLD fibrosis score (NAFLD-FS). Serum leptin and leptin receptor (sObR) concentrations were measured and leptin resistance estimated by Free Leptin Index (FLpI). Both simple and multiple correlations between the HS and HF with the three parameters of interest were examined. Leptin levels and FLpI correlated with diabetes duration (0.25 [95%CI: 0.09-0.39] and 0.24 [95%CI: 0.08-0.39]; P<0.01 for both). 76.1% of T2D patients had HS and 29% had HF. The univariate analysis indicated positive correlations of HS indexes with serum leptin, FLpI, and negative correlations with serum sObR (P<0.0001 for all). In the multiple regression analysis leptin, sObR, FLpI, waist-to-hip ratio, HbA1c, lipids, and HOMA-IR correlated independently with HS (P<0.0001 for all). Although the univariate analyses indicated weak correlations of NAFLD-FS with leptin, sObR, and FLpI, in the multiple regression analyses, only age and waist independently predicted HF. In patients with T2D, HS correlated positively with serum leptin and leptin resistance, and negatively with sObR, along with variables of adiposity and metabolic control, but neither of them made a significant contribution to HF.

Estimation of Leptin and Leptin Receptor Concentrations in Seminal Plasma of Primary Infertile Men

Background: There are many sources for Leptin secretion, and it is activated by binding with its receptor known as leptin receptor, that play a role in male infertility.Objective: To assess the levels of leptin and leptin receptors in seminal plasma among primary infertile men and its impact on semen parameters.Patients and Methods: A case control study of 75 primary infertile males and 40 healthy individuals who were enrolled in this study during March 2013 to May 2013. Estimation of age, body mass index (BMI), semen analysis, seminal plasma leptin, leptin receptor and testosterone hormone concentration were done for all study subjects.Results: Highly significant difference found in mean of semen parameters of infertile male compared with healthy controls. Mean concentration of seminal plasma leptin and leptin receptor of infertile men were significantly were elevated, while serum testosterone concentration significantly decreased compared with healthy control.Conclusion: There is emerging evidence that the leptin concentration negatively impacts fertility through its correlation with age, BMI, testosterone hormone and semen parameters.

قدير تركيزالليبتين ومستقبل اللبتين في بلازما السائل المنوي للذكور ذو العقم الأولي

الخلفيه العلميه: الليبتين، عبارة عن بروتين يفرز من مصادر متعددة، وتقوم بدورها من خلال ارتباطها بمستقبلات خاصة لها تسمى بمستقبلات الليبتين، وتلعب دوراً مهم في العقم لدى الذكور . الهدف من الدراسه: تقييم مستوى الليبتين ومستقبلات اللبتين في السائل المنوي للذكور ذو العقم الاولي وتاثيرها على نوعيه السائل المنوي. طرق العمل :&nbsp; تضمنت الدراسة 75 مريضاً من الذكور الذين يعانون من العقم الاولي و40 شخصاً من الاصحاء الخصبين، أخضعوا جميعهم لتقيم العمر ومؤشر كتلة الجسم وتحليل السائل المنوي وتركيز البلازما المنوية لليبتين ومستقبلات الليبتين ومصل الدم لهرمون التستوستيرون. النتائج:&nbsp; وجد فرق معنوي عالي في معدل مستوى نوعية السائل المنوي للذكور العقيمين مقارنة بالأصحاء الخصبين. ووجد أرتفاع ملحوظ في معدل تريكز اللبتين في السائل المنوي و مستقبل الليبتين، في حين وجد انخفاض ملحوظ في معدل تركيز هرمون التستوستيرون في مصل الدم للمرضى المصابين بالعقم الأولي مقارنة مع الأصحاء الخصبين. الاستنتاجات:يظهر اللبتين و مستقبل الليبتين دور مهم في حالات العقم والتي تنعكس على مؤشرات السائل المنوي.

Relationship between α-MSH, soluble leptin receptor, MC4R polymorphism and BMI in Thai children and adolescents

In order to evaluate the mechanism of disturbance of melanocortin signaling in different groups of Thai children and adolescents classified according to body mass index (BMI) pe rcentile for age by The Centers for Disease Control and Prevention (CDC) growth charts, and �-melanocortin stimulating hormone (�-MSH), soluble leptin receptor and melanocortin 4 receptor (MC4R) polymorphism were studied. 149 male and 127 female children and adolescent Thai subjects with age range between 5-19 years were selected. Statistically significant differ ence of serum leptin receptor concentration between under weight (< 5th percentile), possible at risk for underweight (between 5th and 15th percentile), probably healthy (between 15th and 85th percentile); at risk for overweight (between the 85th and 95th percentile) and overweight (over the 95th percentile) were found. The levels of �-MSH were not significantly different when comparing the gro ups. Heterozygous of MC4R polymorphism (Val103Ile) were found in underweight, possible at risk for underweight and probably healthy group which might have been the cause of lower BMI for age even they have had normal serum �-MSH concentration. Using the logistic regression analysis, the group of risk for being overweight and overweight was statistically significant with �-MSH. This study supported a positive correlation between �-MSH and BMI with ages of Thai children and adolescents group.

Complementary Effects of Genetic Variations in LEPR on Body Composition and Soluble Leptin Receptor Concentration after 3-Month Lifestyle Intervention in Prepubertal Obese Children.

In obese individuals, weight loss might be affected by variants of the adipokine-encoding genes. We verified whether selected functional single nucleotide polymorphisms in LEP, LEPR and ADIPOQ are associated with changes in serum levels of the respective adipokines and weight loss in 100 prepubertal obese (SDS-BMI > 2) Caucasian children undergoing lifestyle intervention. Frequencies of the -2548G > A LEP, Q223R LEPR, K656N LEPR, -11377C > G and -11426A > G ADIPOQ polymorphisms were analyzed by restriction fragment length polymorphism. Serum adipokine and soluble leptin receptor (sOB-R) concentrations were measured using the ELISA method. Among the analyzed polymorphisms, only LEPR polymorphisms were associated with changes of SDS-BMI or sOB-R concentrations in children after therapy. Carriers of the wild-type K665N and at least one minor Q223R allele had the greatest likelihood of losing weight (OR = 5.09, p = 0.006), an increase in sOB-R (ptrend = 0.022) and decrease in SDS-BMI correlated with the decrease of fat mass (p < 0.001). In contrast, carrying of the wild-type Q223R and at least one minor K665N allele were associated with a decrease in sOB-R concentrations and a decrease in SDS-BMI correlated with a decrease in fat-free mass (p = 0.002). We suggest that the combination of different LEPR variants, not a single variant, might determine predisposition to weight loss in the prepubertal period.

Serum Concentrations of Insulin, Ghrelin, Adiponectin, Leptin, Leptin Receptor and Lipocalin-2 in Children with Celiac Disease Who Do and Do Not Adhere to a Gluten-Free Diet.

Background/AimsThe roles of the many bioactive peptides in the pathogenesis of celiac disease remain unclear. To evaluate the serum concentrations of insulin, ghrelin, adiponectin, leptin, leptin receptor, and lipocalin-2 in children with celiac disease who do and do not adhere to a gluten-free diet (GFD, intermittent adherence).MethodsPrepubertal, pubertal, and adolescent celiac children were included in this study (74 girls and 53 boys on a GFD and 80 girls and 40 boys off of a GFD).ResultsInsulin levels in prepubertal (9.01±4.43 μIU/mL), pubertal (10.3±3.62 μIU/mL), and adolescent (10.8±4.73 μIU/mL) girls were higher than those in boys (5.88±2.02, 8.81±2.88, and 8.81±2.26 μIU/mL, respectively) and were neither age-dependent nor influenced by a GFD. Prepubertal children off of a GFD exhibited higher ghrelin levels than prepubertal children on a GFD. Adiponectin levels were not age-, sex- nor GFD-dependent. Adherence to a GFD had no effect on the expression of leptin, leptin receptor, and lipocalin-2.ConclusionsAdherence to a GFD had no influence on the adiponectin, leptin, leptin receptor, and lipocalin-2 concentrations in celiac children, but a GFD decreased highly elevated ghrelin levels in prepubertal children. Further studies are required to determine whether increased insulin concentrations in girls with celiac disease is suggestive of an increased risk for hyperinsulinemia.

GENDER PECULIARITIES OF LEPTIN, SOLUBLE LEPTIN RECEPTORS AND RESISTIN LEVELS IN PATIENTS SUFFERING FROM ARTERIAL HYPERTENSION ASSOCIATED WITH OBESITY

Aim. At present, the problem of obesity as a risk factor for cardiovascular diseases remains actual. The aim of the work was to assess the gender peculiarities of the levels of adipokin and soluble leptin receptors in patients suffering from arterial hypertension (AH) associated with obesity. Materials and methods. The study enclosed 70 patients with AH. The parameters: mean body mass index (BMI) - 38,0 ± 9 kg/m2, mean age - 48,2 ± 2,4 years. There were 40 patients with obesity without AH and metabolic disorders and 30 practically healthy persons comparable by sex and age. Results. Leptin and resistin levels were reliably higher, but soluble leptin receptor concentration was lower in the group of AH patients with obesity. In the group of women, higher concentrations of leptin and resistin, and lower concentrations of soluble leptin receptors were observed than in the group of men. Correlation analysis indicated direct correlation of leptin and resistin with BMI, HOMA and TH indices, DAP level and reverse correlation of soluble leptin receptors with HOMA index. Conclusions. Thus, hormonal status of adipose tissue in women suffering from AH associated with obesity is characterized by higher leptin and resistin levels than in men. The cause of leptin resistance can be a low level of soluble leptin receptors.

Circulating Adipokines and Vascular Function: Cross-Sectional Associations in a Community-Based Cohort.

Adipokines may be potential mediators of the association between excess adiposity and vascular dysfunction. We assessed the cross-sectional associations of circulating adipokines with vascular stiffness in a community-based cohort of younger adults. We related circulating concentrations of leptin and leptin receptor, adiponectin, retinol-binding protein 4, and fatty acid-binding protein 4 to vascular stiffness measured by arterial tonometry in 3505 Framingham Third Generation cohort participants free of cardiovascular disease (mean age 40 years, 53% women). Separate regression models estimated the relations of each adipokine to mean arterial pressure and aortic stiffness, as carotid femoral pulse wave velocity, adjusting for age, sex, smoking, heart rate, height, antihypertensive treatment, total and high-density lipoprotein cholesterol, diabetes mellitus, alcohol consumption, estimated glomerular filtration rate, glucose, and C-reactive protein. Models evaluating aortic stiffness also were adjusted for mean arterial pressure. Mean arterial pressure was positively associated with blood retinol-binding protein 4, fatty acid-binding protein 4, and leptin concentrations (all P<0.001) and inversely with adiponectin (P=0.002). In fully adjusted models, mean arterial pressure was positively associated with retinol-binding protein 4 and leptin receptor levels (P<0.002 both). In fully adjusted models, aortic stiffness was positively associated with fatty acid-binding protein 4 concentrations (P=0.02), but inversely with leptin and leptin receptor levels (P≤0.03 both). In our large community-based sample, circulating concentrations of select adipokines were associated with vascular stiffness measures, consistent with the hypothesis that adipokines may influence vascular function and may contribute to the relation between obesity and hypertension.

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

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

Body composition parameters and adipokines levels in relation to bone mineral density in patients with malignant bone tumors after treatment

Recent data support the concept that adipokines, which are secreted by fat cells, are important modulators of bone metabolism. The aim of this study was to assess the relationships between body composition parameters, adipokines (leptin, adiponectin) and bone mineral density (BMD) in patients with malignant bone tumors after anticancer therapy. The study included 35 patients (median age 14.8 years) with diagnosed malignant bone tumors treated according to obligatory protocols. Total fat mass, lean mass, bone mineral content (BMC) and BMD measurements were performed after treatment completion by dual energy-ray absorptiometry (DXA). Serum concentrations of leptin, leptin receptor and adiponectin were determined using immunoenzymatic assays. The control group consisted of 28 healthy children (median age 14.3 years). Patients with bone tumor after chemotherapy had significantly higher fat mass (P < 0.01), increased ratio of fat mass/lean mass (P < 0.001), and a decrease (P < 0.001) in total body and lumbar spine BMD compared with controls. We observed higher serum leptin concentration (P < 0.01) and lower soluble leptin receptor (P < 0.001) and adiponectin (P = 0.01) in patients than in controls. The ratios of leptin/leptin receptor and leptin/adiponectin were about three-fold higher in patients compared with the control group (P = 0.001). We found a significant positive correlation between BMD and body composition and a negative correlation between BMD and adiponectin in the patients group. Changes in body composition parameters coexisting with disturbed adipokine levels, especially higher levels of leptin and lower levels of adiponectin, might be associated with bone status in patients treated for malignant bone tumors.