scholarly journals Association of leptin receptor gene polymorphisms and meta-inflammation markers with metabolically unhealthy obesity in children

2021 ◽  
Vol 23 (5) ◽  
pp. 696-702
Author(s):  
А. Е. Abaturov ◽  
A. O. Nikulina
Keyword(s):  
Leptin Receptor ◽  
Receptor Gene ◽  
Strong Association ◽  
Main Group ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Inflammation Markers ◽  
Obese Children ◽  
Lepr Gene ◽  
Metabolically Unhealthy Obesity

The aim: to study the contribution of single-nucleotide polymorphisms (SNP) of the leptin receptor (LEPR) gene and meta-inflammation markers to the formation of metabolically unhealthy obesity (MUO) in children. Materials and methods. A total of 109 obese children aged 6–18 years were examined. Based on the recommendations of the National Heart, Lung, and Blood Institute (NHLBI), 2 observation groups were formed. The main group (n = 56) was represented by patients with MUO. The control group (n = 53) comprised children with metabolically healthy obesity (MHO). Serum levels of interleukin-1β (IL-1β) were measured using a chemiluminescent immunoassay (CLIA) method, interleukin-6, leptin, adiponectin – by enzyme-linked immunosorbent assay (ELISA) and the serum level of C-reactive protein were quantified by latex turbidimetric method (Synevo, Ukraine). The method of next-generation sequencing (NGS) (CeXGat, Germany) was used to identify LEPR SNP. Statistical methods were used: analysis of variance, Spearman’s correlation analysis and multiple discriminant analysis. Results. In obese children aged 6 to 18 years, there was an increase in pro-inflammatory adipokines IL-6 and leptin and a decrease in anti-inflammatory adiponectin. Statistically significant changes in these indicators were more expressed in the main group: IL-6 – 7.4 ± 0.5 pg/ml (ρ = 0.65; P ≤ 0.001); adiponectin – 3.9 ± 0.8 μg/ml (ρ = -0.27; P = 0.007) among all the children examined, leptin in girls – 47.8 ± 4.4 ng/ml (ρ = -0.28; P = 0.003) compared with the results of patients in the control group: IL-6 – 4.3 ± 0.3 pg/ml, adiponectin – 7.7 ± 2.4 μg/ml, leptin in girls – 32.5 ± 4.3 ng/ml, P ≤ 0.05. The most important in the development of MUO were the following SNP of the LEPR gene: rs3790435 (CiMUO = 0.939), rs2186248 (CiMUO = 0.862), P < 0.05. A strong correlation was found between MUO and serum IL-6 level (ρ = 0.7), LEPR SNP rs3790435 (ρ = 0.7), basal hyperinsulinemia (ρ = 0.72); Р ≤ 0.001. The risk of IL-6-dependent meta-inflammation in the presence of SNP rs3790435 of the LEPR gene: OR = 17.11; 95 % CI 2.8–20.4. Conclusions. Meta-inflammation in MUO is IL-6-dependent. Among the 10 SNPs of the LEPR gene that we identified, SNP rs3790435 of the LEPR gene has a strong association with the formation of MUO. SNP rs2186248 LEPR was described by us for the first time when it was found in 94.1 % of obese children, but it was characterized by the presence of a weak association with MUO.

scholarly journals Obesity in Children with Leptin Receptor Gene Polymorphisms

2021 ◽  
Vol 64 (3) ◽  
pp. 158-164
Author(s):  
Aleksandr Abaturov ◽  
Anna Nikulina
Keyword(s):  
Discriminant Analysis ◽  
Sequential Analysis ◽  
Leptin Receptor ◽  
Receptor Gene ◽  
Bioinformatic Analysis ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Multiple Discriminant Analysis ◽  
Obese Children ◽  
Nominal Data

Introduction: The study of single nucleotide polymorphisms (SNPs) of the leptin receptor gene (LEPR) based on next generation genomic sequencing (NGS) data is becoming an increasingly important aspect of diagnosis, treatment and prevention of both metabolically healthy (MHO) and metabolically unhealthy obesity (MUO) phenotypes. Material and methods: 35 obese children 6-18 years old were examined by the NGS method with bioinformatic analysis. The main group (n = 18) was formed by children with MUO, according to the recommendations of the expert group of the National Heart, Lung, and Blood Institute. The control group (n = 17) was represented by children with MHO. Statistical methods were used: analysis of variance, Wald’s sequential analysis, Spearman’s correlation analysis, analysis of nominal data and multiple discriminant analysis. Results: 10 types of non-synonymous SNPs (rs3790435, rs1137100, rs2186248, rs70940803, rs79639154, rs1359482195, rs1137101, rs1805094, rs13306520, rs13306522) of the LEPR gene in obese children have been identified. Multiple discriminant analysis demonstrated that the following LEPR SNPs are of greatest importance in the development of MUO: rs3790435, rs13306522, rs13306520. Analysis of nominal data revealed significant differences in the groups for Copy number variation (CNV) rs3790435 of the LEPR gene. Wald’s analysis allowed us to identify 6 important predictors of MUO (І ≥ 0.5): 2 CNV rs3790435 (Relative Risk, RR = 2, Prognostic coefficient, PC = +2.76); male gender of the child (RR = 1.3, PC = +1.35); rs3790435 (RR = 1.9, PC = +2.76); hyperleptinemia more than 40.56 ng/ml (RR = 2, PC = +3); CNV rs1359482195 ≥ 3 (RR = 1.9, PC = +5.8); SNP of the LEPR gene ≥4 (RR = 3.8, PC = +5.8). Conclusion: Children with the genotype rs3790435 gene LEPR had signs of MUO more often.

Association between leptin receptor gene polymorphism and quality of both meat and back fat in large white pigs of ukrainian breeding

2016 ◽  
Vol 3 (2) ◽  
pp. 42-48
Author(s):  
V. Balatsky ◽  
I. Bankovska ◽  
A. Saienko
Keyword(s):  
Gene Polymorphism ◽  
Leptin Receptor ◽  
Receptor Gene ◽  
Intramuscular Fat ◽  
Large White ◽  
Pig Breeds ◽  
Lepr Gene ◽  
Large White Breed ◽  
White Breed

Leptin receptor is one of the components of the system of regulating energy homeostasis of the organism. Leptin receptor gene (LEPR) polymorphism is associated with pig carcass index of the content of intramus- cular fat in its valuable parts, which is particularly important when assessing the quality of their carcasses for processing. Intramuscular fat is associated with meat fl avor characteristics and partly determines its tenderness, juiciness, and other parameters. Aim. To analyze LEPR gene (SNP NM001024587.1, p. 1987 C > T) polymor- phism in populations of various pig breeds and to establish its relationship with the quality of both meat and fat of pigs of Large White breed of Ukrainian breeding. Methods. Genetic-population analysis of nine pig breeds, associative analysis on the search connection of LEPR gene polymorphism with quality of both meat and fat of pigs of Large White breed of Ukrainian breeding. LEPR locus genotyping was performed by High Resolution Melting (HRM). Results. All the studied breeds are characterized by polymorphism of the leptin receptor gene (SNP NM001024587.1, p. 1987 C > T), signifi cant breed specifi city in the distribution of frequencies of alleles was established. Statistically confi rmed effect (p < 0.05) of genotypes LEPR on the content of intramuscular fat, total dry matter and moisture in the meat, as well as the moisture content in the back fat of pigs of Ukrainian Large White breed was revealed. Higher content of intramuscular fat was found in the animals with genotype TT, while a smaller amount of intramuscular fat and more moisture in fat was revealed in heterozygotes. Conclusions. Genetic marker LEPR SNP NM001024587.1, p. 1987 C > T can be used in the marker-assisted selection to predict and improve the performance quality of the meat of pigs of Large White breed of the Ukrainian breeding. These results suggest that porcine leptin receptor gene controls the quality of fat comp- lex – inside muscles and in the dorsal part of the carcass.

Impact of leptin and leptin-receptor gene polymorphisms on serum lipids in Japanese obese children

2010 ◽  
Vol 99 (8) ◽  
pp. 1213-1217 ◽  
Author(s):  
T Okada ◽  
T Ohzeki ◽  
Y Nakagawa ◽  
S Sugihara ◽  
O Arisaka ◽  
...  
Keyword(s):  
Gene Polymorphisms ◽  
Serum Lipids ◽  
Leptin Receptor ◽  
Receptor Gene ◽  
Obese Children ◽  
Receptor Gene Polymorphisms

scholarly journals Wen-Dan Decoction Improves Negative Emotions in Sleep-Deprived Rats by Regulating Orexin-A and Leptin Expression

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Fengzhi Wu ◽  
Yuehan Song ◽  
Feng Li ◽  
Xin He ◽  
Jie Ma ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Blood Serum ◽  
Leptin Receptor ◽  
Negative Emotions ◽  
Field Tests ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Orexin A ◽  
Therapeutic Mechanisms ◽  
Leptin Expression

Wen-Dan Decoction (WDD), a formula of traditional Chinese medicine, has been clinically used for treating insomnia for approximately 800 years. However, the therapeutic mechanisms of WDD remain unclear. Orexin-A plays a key role in the sleep-wake cycle, while leptin function is opposite to orexin-A. Thus, orexin-A and leptin may be important factors in sleep disorders. In this study, 48 rats were divided into control, model, WDD-treated, and diazepam-treated groups. The model of insomnia was produced by sleep deprivation (SD) for 14 days. The expressions of orexin-A, leptin, and their receptors in blood serum, prefrontal cortex, and hypothalamus were detected by enzyme-linked immunosorbent assay, immunohistochemistry, and real time PCR. Open field tests showed that SD increased both crossing movement (Cm) and rearing-movement (Rm) times. Orexin-A and leptin levels in blood serum increased after SD but decreased in brain compared to the control group. mRNA expressions of orexin receptor 1 and leptin receptor after SD were decreased in the prefrontal cortex but were increased in hypothalamus. WDD treatment normalized the behavior and upregulated orexin-A, leptin, orexin receptor 1 and leptin receptor in brain. The findings suggest that WDD treatment may regulate SD-induced negative emotions by regulating orexin-A and leptin expression.

scholarly journals Leptin Receptor Gene Variant rs11804091 Is Associated with BMI and Insulin Resistance in Spanish Female Obese Children: A Case-Control Study

2017 ◽  
Vol 18 (8) ◽  
pp. 1690 ◽  
Author(s):  
Josune Olza ◽  
Azahara Rupérez ◽  
Mercedes Gil-Campos ◽  
Rosaura Leis ◽  
Ramón Cañete ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Leptin Receptor ◽  
Case Control Study ◽  
Receptor Gene ◽  
Case Control ◽  
Gene Variant ◽  
Obese Children ◽  
Control Study

scholarly journals Genetic aspects of metabolic disorders in pregnant women with pathological weight gain

2019 ◽  
Vol 10 (3) ◽  
pp. 271-275
Author(s):  
S. O. Ostafiichuk
Keyword(s):  
Weight Gain ◽  
Pregnant Women ◽  
Leptin Receptor ◽  
Metabolic Diseases ◽  
Receptor Gene ◽  
Insulin Level ◽  
Late Pregnancy ◽  
Serum Levels ◽  
Leptin Resistance ◽  
Enzyme Linked Immunosorbent Assay

Polymorphism of the leptin receptor gene (LEPR) has been shown to be linked to obesity-related metabolic markers and phenotype. Therefore, we hypothesized that the Gln233Arg LEPR polymorphism is related to metabolic changes in pregnancy and the risk of excessive gestational weight gain (GWG). A total of 97 pregnant women with a singleton gestation were enrolled from April 2016 until December 2018. Genetic variants of LEPR were analyzed by real-time polymerase chain reaction, leptin by enzyme-linked immunosorbent assay, lipid profile, and carbohydrate status were assessed in the first, and third trimesters of pregnancy. The recommended GWG was diagnosed in 34.0%, insufficient in 19.6%, and excessive in 46.4% patients. Statistical analysis revealed that 20.6% patients were with AA genotype, 50.5% – AG genotype, and 28.9% – GG genotype. The frequency of GG-alleles carriers of the LEPR Gln233Arg gene in the group of excessive GWG patients was 3 times higher compared to recommended GWG patients. Thus, the inheritance of pathological G-homozygotes increases the risk of excessive weight gain by 7 times, compared to carriers of the AA genotype. LEPR GG polymorphism was significantly associated with high levels of triglycerides, total cholesterol, lipoprotein low and very low density, and leptin compared to homozygous А-carriers in the third trimester of pregnancy. In pregnant women with GG polymorphism, the glucose level, insulin level, and HOMO-IR index were significantly increased compared to women with AA genotype in late pregnancy. In the group with excessive GWG, the presence of GG-alleles of the LEPR gene was accompanied by a higher level of hyperleptinemia, compared to carriers of AA-genotype. Inheritance of pathological G-homozygotes was associated with hyperlipidemia, leptin resistance with high leptin serum levels, and increased insulin resistance, which was especially manifested in excessive GWG. In our opinion, excessive GWG can be seen as a marker of the mother's genotype and genetic predisposition to the development of metabolic diseases after delivery.

Serum leptin levels during pregnancy in multiple sclerosis

2009 ◽  
Vol 15 (8) ◽  
pp. 907-912 ◽  
Author(s):  
RF Neuteboom ◽  
E Verbraak ◽  
JSA Voerman ◽  
M van Meurs ◽  
EAP Steegers ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Leptin Receptor ◽  
Late Pregnancy ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Third Trimester ◽  
Serum Leptin ◽  
The Third ◽  
Healthy Women

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.

scholarly journals Clinical efficacy of a screening approach to the differentiated prescription of antibiotic therapy in children with acute tonsilopharyngitis

2020 ◽  
Vol 101 (6) ◽  
pp. 805-811
Author(s):  
O I Pikuza ◽  
A M Zakirova ◽  
T B Moroz
Keyword(s):  
Antibiotic Therapy ◽  
Respiratory Infections ◽  
Main Group ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Practical Implementation ◽  
Microbial Culture ◽  
Hemolytic Streptococcus ◽  
Screening Approach ◽  
Group A

Aim. To assess the effectiveness of the screening approach by prescribing a streptotest to verify the etiological cause of tonsillopharyngitis in children. Methods. We observed 67 patients aged 7 to 11 with a history of recurrent respiratory infections. The incidence of acute respiratory infections varied from 8 to 12 times during the year preceding the examination. The main group consisted of 36 children who had tonsillopharyngitis with severe inflammation of the tonsils and plaque on the tonsils. The control group included 31 patients with acute tonsillopharyngitis with inflammatory changes in the tonsils and the absence of plaque. The observation and control groups were comparable and did not have statistically significant differences in gender and age. All patients underwent a common clinical, laboratory, and instrumental examination. Along with microbial culture, the special examinations included an express test (Dectra Pharm, France) for the presence of group A -hemolytic streptococcus. Results. All children underwent an etiological examination. The presence of a viral antigen was confirmed in 71.64% of children. 27.49% of patients in the control group and 30.72% of patients in the main group had positive results of the express test for group A -hemolytic streptococcus, taking into account the requirements for assessing this reaction. It was revealed a reliable direct relationship between the detected viral infection and the negative results of the streptatest test (r=0.86; p=0.03) for the control group, and a positive correlation of the confirmed presence of group A -hemolytic streptococcus in the main group as with both C-reactive protein (r=0.78; p=0.04) and with inflammatory markers in the general blood test. A combination of positive fluorescence of viral antigens based on the results of immunofluorescence and a positive enzyme-linked immunosorbent assay (ELISA) for group A -hemolytic streptococcus was recorded in 7.46% of all patients. Clinical examples are given the justification of practical implementation of the express test for the quick diagnostic information. Conclusion. Differentiated etiological diagnosis of acute tonsillopharyngitis based on clinical symptoms and the levels of markers of bacterial inflammation is extremely difficult therefore laboratory criteria should be the justification for prescribing antibiotic therapy; currently, the most accessible is the streptatest for the detection of group A -hemolytic streptococcus, which allows confirming or denying the presence of group A -hemolytic streptococcus within a few minutes, which means that it is correct to prescribe antibacterial drugs to patients.

scholarly journals Genome-wide analyses reveal a strong association between LEPR gene variants and body fat reserves in ewes

2021 ◽  
Author(s):  
Tiphaine Macé ◽  
Eliel Gonzalez-Garcia ◽  
Didier Foulquié ◽  
Fabien Carrière ◽  
Julien Pradel ◽  
...  
Keyword(s):  
Leptin Receptor ◽  
Body Condition Score ◽  
Receptor Gene ◽  
Strong Association ◽  
Significant Snps ◽  
Chromosome 1 ◽  
Nucleotide Polymorphisms ◽  
Fat Reserves ◽  
Genome Wide ◽  
Pregnancy And Lactation

Among the adaptive capacities of animals, the management of energetic body reserves (BR) through the BR mobilization and accretion processes (BR dynamics, BRD) has become an increasingly valuable attribute for livestock sustainability, allowing animals to cope with more variable environments. BRD has previously been reported to be heritable in ruminants. In the present study, we conducted genome-wide studies (GWAS) in sheep to determine genetic variants associated with BRD. BR levels and BR changes over time were obtained through body condition score measurements at eight physiological stages throughout each productive cycle in Romane ewes (n=1034) and were used as phenotypes for GWAS. After quality controls and imputation, 48,513 single nucleotide polymorphisms (SNP) were included in the GWAS. Among the QTLs identified, a major QTL associated with BR levels during pregnancy and lactation was identified on chromosome 1. In this region, several significant SNPs mapped to the leptin receptor gene (LEPR), among which one SNP mapped to the coding sequence. The point mutation induces the p.P1019S substitution in the cytoplasmic domain, close to tyrosine phosphorylation sites. The frequency of the SNP associated with increased BR levels was 32%, and the LEPR genotype explained up to 5% of the variance of the trait. These results provide strong evidence for involvement of LEPR in the regulation of BRD in sheep and highlight it as a major candidate for improving adaptive capacities.

scholarly journals Severe Early-Onset Obesity in Three Adult Patients Harboring Inactivating Mutations of the Leptin Receptor Gene

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A37-A37
Author(s):  
Carolina Marques Chaves ◽  
Teresa Kay ◽  
Joao Anselmo
Keyword(s):  
Early Onset ◽  
Leptin Receptor ◽  
Reference Range ◽  
Receptor Gene ◽  
Pubertal Development ◽  
Genetic Diagnosis ◽  
The Body ◽  
Homozygous Mutation ◽  
Genetic Sequencing ◽  
Lepr Gene

Abstract Background: Leptin is secreted by white adipocytes in response to fat storage and binds to leptin receptors (LEPR) expressed all over the body particularly in hypothalamic neurons. This hormone regulates several physiologic functions including energy expenditure and appetite. Clinical Case: We describe the clinical and hormonal findings in 3 adult brothers with body mass index (BMI) of 36.7, 50.7, and 46.1 kg/m2, respectively. There is no history of consanguinity in the family and none of the patients exhibited dysmorphic features. A rapid weight gain was noticed during their first few months of life, associated with permanent hyperphagia. At 2 years old, their BMI was already above 25 kg/m2 (&gt; +3SD), and at 10 years old, it was over 40 kg/m2 (&gt; +3SD). The linear growth was within the expected target heights for their parents. They did not seem to present cognitive impairment. The pubertal development began at 16 to 18 years old, and since then they maintained levels and FSH and LH above the upper limit of normal (15.6±3.7mUI/mL and 12.3±2.2mUI/mL, reference range 1.5–12.4 and 1.7–8.6, respectively), but with normal sexual steroids (estradiol 36.4±16.1pg/mL and total testosterone 445±401ng/dL, reference range 11–44 and 249–836, respectively). The thyroid function was normal and none of the patients suffered from dyslipidemia or diabetes, despite high serum insulin levels 26.4±15.8 mU/L (normal 5–10). Genetic sequencing identified a homozygous mutation of the leptin receptor gene in the 3 brothers: c.2357T&gt; C, p. (Leu786Pro). Their parents were heterozygous for the mutation as well as the patients’ daughters. Homozygous carriers of the mutation presented a significantly higher BMI than their heterozygous family members, 44.5±7.1 Kg/m2 vs 32.2±1.7 Kg/m2 (p=0.023), a significantly increased leptin levels, 80±36.4 ng/ml vs 26.3±9.3 ng/ml (p=0.028), and significantly higher weight, 134.6±16.9 vs 89.2±15,2 kg (p=0.021), respectively. Women had higher BMI than men (42.0 ±12.2 Kg/m2 vs 37.9±7.5 Kg/m2, p=0.496) and also higher percentage of fat (46.4±3.1% vs 34.9±6.8%, p=0.108). Serum levels of leptin in homozygous patients were not significantly higher than those measured in 10 patients with adult-onset morbid obesity, 80± 36.4 ng/ml vs 53.8±24.1 ng/ml, respectively (p=0.149). Therefore, serum leptin is not a useful discriminative maker of LEPR gene mutations. Conclusion: Patients with severe early-onset obesity should have a genetic diagnosis workup. Firstly, because clinical trials with MC4R-agonists have raised expectations regarding the treatment of patients with mutations of the LEPR gene. Secondly, and in contradiction to other reports in the literature, our patients were fertile. Therefore, identification of the mutation allows genetic counseling of these patients and their families, including the possibility of Pre-Natal Diagnosis or Pre-Implantation Genetic Diagnosis.

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