Soluble Leptin Receptor Levels Research Articles

Peripheral Biomarkers of Anorexia Nervosa: A Meta-Analysis.

The pathogenesis of anorexia nervosa (AN) has been hypothesized to involve several biological systems. However, reliable biomarkers for AN have yet to be established. This study was aimed to identify statistically significant and clinically meaningful peripheral biomarkers associated with AN. A systematic literature search was conducted to identify studies published in English from inception until 30 June 2022. We conducted two-level random-effects meta-analyses to examine the difference between AN and comparison groups across 52 distinct biomarkers and found that acylated ghrelin, adrenocorticotropic hormone (ACTH), carboxy-terminal collagen crosslinks (CTX), cholesterol, cortisol, des-acyl ghrelin, ghrelin, growth hormone (GH), obestatin, and soluble leptin receptor levels were significantly higher in cases of AN compared with those in non-AN controls. Conversely, C-reactive protein (CRP), CD3 positive, CD8, creatinine, estradiol, follicle-stimulating hormone (FSH), free thyroxine, free triiodothyronine, glucose, insulin, insulin-like growth factor 1 (IGF-1), leptin, luteinizing hormone, lymphocyte, and prolactin levels were significantly lower in AN compared with those in non-AN controls. Our findings indicate that peripheral biomarkers may be linked to the pathophysiology of AN, such as processes of adaptation to starvation. Scientific investigation into peripheral biomarkers may ultimately yield breakthroughs in personalized clinical care for AN.

Полиморфные варианты генов LEP и LEPR у пациентов с инфарктом миокарда: связь с уровнем лептина и его растворимым рецептором в сыворотке крови

Aim: to determine the association between the rs7799039, rs1137100, and rs1137101 polymorphic variants of the LEPR gene and serum leptin and its soluble receptor levels in patients with myocardial infarction (MI) and obesity. Patients and Methods: the study included 146 patients (108 men and 38 women) with an established MI, with a mean age of 57 (51; 64) years. The control group consisted of 300 conditionally healthy individuals (110 men and 190 women). The levels of leptin and its soluble receptor were measured by solid phase enzyme immunoassay Genetic analysis was performed using genomic DNA isolated from whole blood Polymorphic variants (rs7799039, rs1137100, rs1137101) of LEP and LEPR genes were genotyped by PCR with fluorescein-labeled probes Results: carrying the G allele of the polymorphic variant rs1137100 of the LEPR gene increases the risk of MI by 7 times in the recessive inheritance (odds ratio/OR=7.62, 95% confidence interval/CI 4.14-14.02). The rs1137101 variant of the LEPR gene has a protective effect in terms of the risk of MI. Furthermore, there were no significant differences in genotype rate between the groups of patients without obesity and with obesity The study found that individuals with the A/G and G/G genotypes of the rs1137100 variant of the LEPR gene had significantly higher levels of soluble leptin receptor (39.57 (30.59; 54.53) ng/mL) compared to those with the A/A genotype (24.29 (19.49; 34.70) ng/mL). Conclusion: the G allele of the LEPR gene is associated with an increased risk of MI and higher serum levels of soluble leptin receptor. These phenomena may be associated with a more unfavorable course of the cardio-metabolic continuum in these patients, particularly in those who are obese. KEYWORDS: myocardial infarction, leptin, polymorphic variant, leptin receptor, LEP, LEPR FOR CITATION: Hryachkova O.N., Khutornaya M.V., Sinitskaya A.V., Sinitskiy M.Yu., Kashtalap V.V. Polymorphic variants of LEP and LEPR genes in patients with myocardial infarction: association with serum leptin and its soluble receptor levels. Russian Medical Inquiry. 2024;8(1):4–8 (in Russ.). DOI: 10.32364/2587-6821-2024-8-1-1.

An Important Problem in AdV-36 Seropositive Obesity Patients: Leptin Resistance

Adenoviruses are naked viruses with an icosahedral nucleocapsid containing a 36 kb linear double-stranded DNA genome that encodes 30-40 proteins. The word "obesity" in Latin means "because of feeding". Obesity is an energy metabolism pathology that paves the way for physical and psychological problems with excessive fat accumulation that can impair health. Body mass index (BMI), unaffected by gender and age, is the most useful indicator of overweight and obesity at the population level. The concept of infectobesity was first introduced in 1978 after the data showed that viruses might also play a role in obesity cases. In the same year, adenovirus 36 (AdV-36) was isolated from the stool of a six-year-old girl with diabetes who was admitted to the hospital with the complaint of enteritis. One of the adipokines important for obesity is leptin. Leptin regulates food intake and energy metabolism by having a "negative feedback" effect on the hypothalamus. Leptin acts as a sensor that acutely regulates energy metabolism by creating hunger and satiety signals and it also regulates the amount of body fat and the required weight of the person by adjusting its concentration in the plasma according to the nutritional status. Changes in body weight and metabolic status are often associated with acute or chronic inflammatory processes. Human cells infected by AdV-36 showed greater differentiation and higher lipid accumulation than uninfected control cells, which increases the prevalence of obesity. There are two fractions of serum leptin, protein-bound and free form. The balance between these two fractions depends on serum leptin and soluble leptin receptor (sLR) plasma concentration, which is adversely affected by BMI. AdV-36 infection reduces norepinephrine and leptin levels. These two effects contribute to obesity by increasing appetite and food intake. In this study, it was aimed to determine the presence of immunoglobulin G against AdV-36 in the blood serum of obesity patients (BMI≥ 30) and healthy weight individuals (18.5≤ BMI≤ 25), and also aimed to determine and compare the leptin and soluble leptin receptor levels of these individuals. In this study, 10 ml of blood was collected on an empty stomach from obese individuals (n= 101; BMI≥ 30) and healthy individuals (n= 96; 18.5≤ BMI≤ 25) between the ages of 18-55. All participants consisted of who were not taking any medication and were not immunosuppressed. Blood samples separated into their serum were analyzed for AdV-36 IgG, leptin, and soluble leptin receptor levels. Mean, standard deviation, and percentage values were calculated by descriptive statistical analysis. The data with normal distribution were evaluated with the paired and independent sample t-test and data with abnormal distribution were evaluated with the paired and independent sample Mann-Whitney U test. Findings with a p-value less than 0.05 were considered statistically significant. In conclusion, leptin levels in obese individuals who were not infected with Adv-36 were found to be low, in line with the principle that "insufficient leptin synthesis has a role in the pathophysiology of obesity". When AdV-36 infection is added to the obesity picture, it may be due to the fact that it increases leptin synthesis in patients and the level of soluble leptin receptors increases in response to the increased leptin level, that AdV-36 suppresses the binding of the leptin molecule to its receptor, which leads to leptin resistance.

Measurement of leptin and soluble leptin receptor levels in patients with endometrial hyperplastic processes

Objective. To measure leptin and soluble leptin receptor levels in patients with endometrial hyperplastic processes.Materials and methods. 90 patients were included in the study, 70 with hyperplastic endometrial processes made up the main group, 20 with morphologically normal endometrium were included in the comparison group. The concentration of leptin and the soluble leptin receptor in the blood serum was measured by the method of enzyme immunoassay, the clinical and anamnestic characteristics of the disease were studied Results. There were no significant differences between the groups when comparing serum leptin levels: in the study group, the hormone level was 6,01 (3,64;7,50) ng/ml, in the comparison group — 6,44 (3,55;10,11) ng/ml (z = 0,61, p = 0,54). The level of soluble leptin receptor was significantly lower in patients in the main group and was 8531 (5697; 15895) ng/ml, and 16181 (10696; 20251) ng/ml in the comparison group (z = 2.614, p = 0.008).Conclusion. Patients with endometrial hyperplastic processes are characterized by a decreased level of the soluble leptin receptor, whereas a leptin level has no significant differences compared to those in patients without endometrial pathology. The identified condition causes a defect in the signal transmission from the leptin receptor and a decrease in the hormone transport, leading to a disruption of the biological action of leptin. The established level of soluble leptin receptor < 14769 pg/ml, in combination with ultrasound examination, will increase the efficiency of diagnostic measures to detect endometrial hyperplastic processes.

1594-P: Interorgan Insulin-Leptin Signal Cross Talk Originating in the Liver Enhances Survival under Food-Shortage Conditions

The liver can store energy and distribute it to other tissues/organs, according to the energy states involving hepatic insulin action. In addition, we and others have shown that the liver transmits metabolic information to other organs, via neuronal and humoral mechanisms. Herein, we demonstrate a novel form of inter-organ crosstalk originating in the liver, which links hepatic insulin action with hypothalamic leptin signaling and promotes survival during food shortage. We first observed that tamoxifen-inducible liver insulin receptor (IR) knockout (iLIRKO) mice ate more and consumed less oxygen with decreased hypothalamic leptin action, thereby gaining body weight. Circulating soluble leptin receptor (sLepR) levels were elevated in iLIRKO mice. We then produced tamoxifen-inducible liver leptin receptor (LepR) and IR double-knockout (iLLepRIRKO) mice. In iLLepRIRKO mice, sLepR elevations were not seen. Moreover, increased body weights, hyperphagia and decreased whole-body oxygen consumption seen in iLIRKO mice were reversed, indicating the importance of hepatic sLepR production in the liver-hypothalamus crosstalk. Human hepatic lepr and circulating sLepR levels also correlated negatively with hepatic insulin action indices. Additionally, we restricted food intake in wild type mice. Food restriction decreased hepatic insulin action and whole-body oxygen consumption with increased circulating sLepR. We furthermore performed food restriction in tamoxifen-inducible liver LepR knockout (iLLepRKO) mice. Notably, in iLLepRKO mice, the decreases in basal metabolic rates were blunted and mortality was markedly increased during food restriction. Collectively, the liver translates metabolic cues regarding energy-deficient status, which is reflected by decreased hepatic insulin action, into sLepR, thereby suppressing energy dissipation. This novel inter-organ crosstalk may assure survival of individuals facing food shortages in nature. Disclosure K.Takahashi: Speaker's Bureau; Taisho Pharmaceutical Holdings Co., Ltd. T.Yamada: Speaker's Bureau; MSD, Mitsubishi Tanabe Pharma Corporation, Eli Lilly Japan K.K., Boehringer Ingelheim Japan, Inc., Novo Nordisk, Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Abbott Japan Co., Ltd. H.Katagiri: None. Funding Japan Society for the Promotion of Science (21K08522, 22H03126, 20H05694); Japan Science and Technology Agency (JPMJPS2023)

The association between variant rs9939609 in the FTO gene with free leptin index and the risk of obesity in the Indonesian children population

BackgroundSeveral studies have reported that fat mass and obesity-associated gene (FTO), especially the rs9939609 polymorphism, are associated with obesity and high leptin levels. The free leptin index (FLI) is known to be accurate in determining the function of leptin. The aim of this study was to determine the association between the rs9939609 variant in the FTO gene and FLI and the risk of obesity among children living in Medan, Indonesia.MethodsThis case–control study included 212 children aged 6–12 years who were genotyped for variants of the rs9939609 FTO gene. The case group consisted of children with obesity who were < 6 years old, and the control group had a normal body mass index and came from the Bataknese or Chinese ethnicities. Anthropometric measurements were performed. Serum leptin and soluble leptin receptor (sOB-R) levels were measured. Odds ratio and 95% confidence intervals were calculated to determine the risk of having obesity associated with the risk allele.ResultsIn this study, there was no significant association between leptin, soluble leptin receptor, or free leptin index and the rs9939609 FTO gene; however, the risk allele (A) of FTO rs9939609 had a significant association with obesity in Chinese ethnicity subjects (p < 0.05). The AA/AT genotype had an increased risk of FLI 5.889 times compared to the TT genotype. Multivariate analysis showed that the rs9939609 polymorphism in the FTO gene played a role in obesity through the FLI.ConclusionIt was concluded that the rs9939609 polymorphism played a significant role in obesity through FLI. Further studies are still needed.

Examining the Causal Inference of Leptin and Soluble Plasma Leptin Receptor Levels on Schizophrenia: A Mendelian Randomization Study.

Background: Observational studies that have supported the role of the leptin level in schizophrenia (SCZ) risk are conflicting. Therefore, we performed a two-sample Mendelian randomization (MR) analysis to investigate whether the circulating leptin and soluble plasma leptin receptor (sOB-R) levels play a causal role in SCZ risk.Methods: We first selected five independent single-nucleotide polymorphisms (SNPs) associated with the circulating leptin level and three independent SNPs associated with the sOB-R level from two genome-wide association studies (GWASs) of European individuals. Then, we extracted their associations with SCZ using a large-scale GWAS that consisted of 40,675 patients with SCZ and 64,643 controls of European ancestry. We performed an MR analysis using the inverse variance-weighted (IVW) method to examine the causal effect of leptin on SCZ risk. Moreover, we performed sensitivity analyses to verify our MR results using the weighted median and MR-Egger methods.Results: According to the IVW method, genetically predicted circulating leptin levels were not associated with SCZ risk (OR = 1.98, for per 1-SD unit increase in leptin level; 95% CI, 0.87–4.53; p = 0.10). In addition, the sOB-R level showed no causal effect on the SCZ risk using IVW (OR = 0.98 for per 1-SD unit increase in sOB-R level; 95% CI, 0.97–1.00; p = 0.06). Our sensitivity analysis results confirmed our MR findings.Conclusions: By estimating the causal effect of leptin on SCZ risk using the MR methods, we identified no effect of genetically predicted circulating leptin or the sOB-R level on SCZ. As such, our study suggests that leptin might not be a risk factor for SCZ.

The role of soluble leptin receptor in the pathogenesis of coronary heart disease

Introduction. The participation of soluble leptin receptor (SLR) in the formation of hyperleptinemia and leptin resistance in patients with coronary artery disease (CAD) in combination with obesity is discussed. Aim. Study of the role of SLR in the pathogenesis of ischemic heart disease. Materials and methods. A cohort study of 744 patients was performed: 465 patients with CAD (56 years old, Q1=44; Q3=62), 270 patients without CAD (52 years old, Q1=44; Q3=56). Methods: EchoCG, heart computed tomography, coronary angiography. In the blood serum, the lipids, glucose, creatinine, uric acid, and c-reactive protein were assessed using a highly sensitive method (HF-CRP). Concentrations of SLR, leptin (LN), adiponectin (total and high molecular weight), fatty acid binding protein-4 (FABP-4) tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), serum insulin were determined by enzyme immunoassay. Results. The level of SLR in blood serum in men and women with CAD is lower than in men without CAD (p &lt;0.001). In CAD patients, obesity was associated with a low SLR level in the blood serum and a high free LN index. At a serum SLR concentration of &lt;7.5ng/ml in men with CAD, the incidence of obesity was higher simultaneously with signs of visceral obesity of the heart, the presence of atherosclerotic plaques in the common carotid arteries, high glycaemic levels, insulin, IL-6, and LN in serum, serum LN/adiponectin ratio and a high HOMA-IR index. Diabetes mellitus, visceral obesity, high levels of hs-CRP, TNF-α, FABP-4, serum insulin, and HOMA-IR index were more often detected in women with coronary artery disease with SLR &lt;10.2 ng/ml. In men and women with CAD, there were no differences in SLR concentration depending on the extent of coronary atherosclerosis. Conclusion. An increase in the free LN index indicates the disruption of connections in the leptin-receptor system and reflects the mechanisms of compensation for overcoming the resistance of peripheral tissues to leptin, which is confirmed by a noticeable negative relationship between the levels of SLR and leptin in the serum of men with coronary artery disease. A low concentration of SLR in patients with CAD is associated with obesity, pro-atherogenic and pro-inflammatory markers of cardiovascular diseases.

Association of leptin G2548A and leptin receptor Q223R polymorphisms and their serum levels with infertility and recurrent pregnancy loss in Iranian women with polycystic ovary syndrome.

BackgroundAdipokine leptin plays a crucial role in metabolic and reproductive functions. Leptin receptor has a soluble form that binds to leptin, thus modulating its level in the circulation. It has been indicated that the levels of leptin and leptin receptor and also LEP rs7799039 and LEPR rs1137101 polymorphisms are associated with metabolic disorders. In the present study, we assessed the levels of leptin and soluble leptin receptor (sOB-R), and also the frequency of rs7799039 and rs1137101 polymorphisms in healthy fertile women and patients with polycystic ovary syndrome (PCOS), inclusive of PCOS-infertile and PCOS-recurrent pregnancy loss (RPL) subjects.MethodsA total of 324 PCOS patients- including 199 infertile cases and 125 patients with a history of RPL- and 144 healthy controls were enrolled in this study. Biochemical parameters and plasma leptin and sOB-R levels were measured by ELISA and the genotypes of rs7799039 and rs1137101 polymorphisms were determined using PCR- RFLP.ResultsPlasma leptin and sOB-R levels were significantly higher and lower in PCOS, PCOS-infertile and PCOS RPL groups, respectively. The GG genotype frequencies of rs7799039 and rs1137101 polymorphisms were significantly different between PCOS-infertile women and non-PCOS subjects (P = 0.043, OR = 0.47, 95% CI = 0.22–0.97, and P = 0.01, OR = 0.31, 95% CI = 0.12–0.75, respectively). Increased LEP levels were associated with the risk of PCOS and RPL in women with PCOS (P = 0.039, OR = 1.203, 95%CI = [1.009–1.435] and P = 0.012, OR = 1.267, 95% CI = [1.054–1.522], respectively).ConclusionPolymorphisms rs7799039 and rs1137101 and circulating leptin and sOB-R levels were associated with infertility in Iranian women with PCOS. Further studies are needed to reveal the role of leptin in PCOS pathogenesis.

Circulating Level of Soluble Leptin Receptor and its Association with Cardiometabolic Risk Factors among Obese Subjects in Kerala, South India

Background and Aims: Leptin, the peptide hormone secreted mainly by adipose tissue is reported to play the central role in the pathogenesis of obesity. Leptin exerts its biological effects through specific receptor molecules present in target tissues. Among the different isoforms of leptin receptor, the Soluble Leptin Receptor (SLR) is the major leptin binding protein seen in circulation which modulates the bioavailability of leptin. Our objectives were to analyse the level of circulating SLR among obese subjects and its association with biomarkers of obesity, serum leptin, insulin and cardiometabolic risk factors in comparison with healthy age and sex matched control subjects.&#x0D; Methods: About 173 study participants of both genders were selected and grouped as case (n=102) and control (n=71) with a cut off point of BMI 25kg/m2. Waist to hip ratio (WHR) and body fat percentage (BF%) were calculated from anthropometric measurements. Leptin, insulin, soluble leptin receptor were estimated in fasting blood samples by sandwich ELISA method. Fasting plasma glucose and lipid profile were measured by standard enzymatic methods in autoanalyzer. Homeostasis Model Assessment of Insulin resistance (HOMA-IR) was calculated. Comparison between groups was done by independent sample ‘t’ test. P values &lt;.05 were considered statistically significant.&#x0D; Results: The SLR level was found to be increased in obese group in comparison with control group(P =.001). A significant increase in serum leptin and insulin level was observed in obese group when compared to control (P =.001). Obese group showed more than two fold increase in insulin resistance expressed as HOMA-IR when compared to control subjects (P =.001). But no significant difference in the synthesis of insulin expressed as HOMA-beta between the groups. No significant difference in serum lipoprotein levels was observed between the two groups.&#x0D; Conclusion: Increased level of circulating soluble leptin receptor has been observed in obese subjects in comparison with control subjects and is associated with hyperleptinemia, hypertension and insulin resistance.

Body mass index and serum levels of soluble leptin receptor are sex-specifically related to alcohol binge drinking behavior

ObjectiveBinge drinking is a highly prevalent behavior in adolescents and young adults and a risk factor to develop alcohol use disorder. Body mass index (BMI) and blood levels of leptin peptide and its soluble receptor have been implicated in alcohol use disorder; however, their role in binge drinking remains to be investigated. MethodWe studied associations of BMI, serum levels of soluble leptin receptor (ObRe) and leptin as well as the free leptin index with binge drinking in 93 male and 99 female young adults. ResultsIn men, binge drinkers showed significantly higher BMI (kg/m2) than non-binge drinkers (23.67 vs. 22.08) and higher BMI correlated significantly with more severe binge drinking episodes (ρ = 0.251). In women, we found significantly higher ObRe (ng/ml) / BMI (kg/m2) values in binge drinkers than in non-binge drinkers (0.52 vs. 0.44) and ObRe/BMI values correlated significantly with more severe binge drinking episodes (ρ = 0.210). ConclusionThis study confirms that higher BMI associates with binge drinking in men and shows for the first time a role of ObRe/BMI in binge drinking in women. Our data emphasize the importance of further research in the field of metabolic markers and implications in neurobiological processes of binge drinking.

CB1R regulates soluble leptin receptor levels via CHOP, contributing to hepatic leptin resistance.

The soluble isoform of leptin receptor (sOb-R), secreted by the liver, regulates leptin bioavailability and bioactivity. Its reduced levels in diet-induced obesity (DIO) contribute to hyperleptinemia and leptin resistance, effects that are regulated by the endocannabinoid (eCB)/CB1R system. Here we show that pharmacological activation/blockade and genetic overexpression/deletion of hepatic CB1R modulates sOb-R levels and hepatic leptin resistance. Interestingly, peripheral CB1R blockade failed to reverse DIO-induced reduction of sOb-R levels, increased fat mass and dyslipidemia, and hepatic steatosis in mice lacking C/EBP homologous protein (CHOP), whereas direct activation of CB1R in wild-type hepatocytes reduced sOb-R levels in a CHOP-dependent manner. Moreover, CHOP stimulation increased sOb-R expression and release via a direct regulation of its promoter, while CHOP deletion reduced leptin sensitivity. Our findings highlight a novel molecular aspect by which the hepatic eCB/CB1R system is involved in the development of hepatic leptin resistance and in the regulation of sOb-R levels via CHOP.

C-Peptide and leptin system in dichorionic, small and appropriate for gestational age twins\u2014possible link to metabolic programming?

Children born small for gestational age (SGA) are at increased risk of future glucose intolerance and type 2 diabetes, possibly after due intrauterine metabolic programming. Soluble leptin receptor (SLR) limits leptin access to signal-transducing membrane receptors. The present study examines whether SGA and appropriate for gestational age (AGA) twins differ with regard to their C-peptide, glucose and leptin systems. The markers C-peptide, glucose, fetal leptin, and SLR in cord blood were assessed in children from dichorionic twin pregnancies at delivery. In 32 cases, weight differed by >15% between twins: one demonstrated Intrauterine Growth Retardation (IUGR) (<10th percentile-SGA), while the other did not (AGAI). The other 67 pairs presented appropriate weight for gestational age (AGAII). Placental leptin and placental leptin receptor content were also assessed. Despite the same concentrations of glucose, the SGA twins maintained a higher level of C-peptide [44.48 pmol/l vs. 20.91 pmol/l, p < 0.05] than the AGAI co-twins, higher HOMA index, calculated as [C-peptide] x [Glucose] (p = 0.045), in cord blood, and a higher level of SLR [SGA vs AGAI—mean: 28.63 ng/ml vs. 19.91 ng/ml, p < 0.01], without any differences in total leptin (p = 0.37). However, SGA placentas demonstrated higher leptin level [130.1 pg/100 g total protein vs 83.8 pg/100 g total protein, p = 0.03], without differences in placental leptin receptor (p = 0.66). SGA/IUGR twins demonstrate relative insulin resistance accompanied by decreased fetal and increased placental leptin signaling. We speculate that relative insulin resistance and changes in the leptin system might be the first evidence of processes promoting deleterious metabolic programming for post-natal life.

Leptin in adolescent idiopathic scoliosis – A meta-analysis

To compare the serum levels of leptin and soluble leptin receptor (sOB-R) with adolescent idiopathic scoliosis (AIS) girls and controls through meta-analysis. The MEDLINE via PubMed, Cochrane, Scopus, and EMBASE database, from the earliest available date of indexing between January 2010 and January 2019, were searched for comparative studies evaluating serum levels of leptin and sOB-R in AIS girls. Two authors performed the data extraction independently. Any discrepancies were resolved by a consensus. Six comparative studies were identified. There was no statistically significant difference in terms of leptin between AIS girls and control [p = 0.19, WMD = −2.06 (−5.14, 1.03) ng/mL]. However, the sOB-R level was significantly higher [p < 0.00001, WMD = 2.85 (1.81, 3.88) ng/mL] and the free leptin index was significantly lower [p = 0.0006, WMD = −0.12 (−0.19, −0.05)] in AIS girls than those of healthy control girls. The body mass index was significantly lower in AIS girls [p = 0.03, WMD = −1.53 (−2.95, −0.12) kg/m2]. The current meta-analysis showed that the level of sOB-R is higher in AIS patients than controls, while the concentration of leptin remains unchanged in AIS patients. Further well-designed studies would be necessary to substantiate our results.

Effects of Metformin Treatment on Soluble Leptin Receptor Levels in Women with Polycystic Ovary Syndrome

The effects of metformin treatment on soluble leptin receptor (sOB-R) levels in women with polycystic ovary syndrome (PCOS) were investigated. This prospective and open-label study was conducted by the Department of Obstetrics & Gynecology at Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, China. Fifty-five women with PCOS and insulin resistance (IR) were treated with metformin for 6 months. According to body mass index (BMI), the patients were divided into two groups: lean PCOS group (BMI <23 kg/m2, n=34) and overweight or obese PCOS group (BMI ≥23 kg/m2, n=21). Before and after treatment, serum luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHEAS), insulin and sOB-R levels were determined. Thirty-one BMI-matched ovulatory women served as controls. The results showed: (1) The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), androgen levels and hirsutism scores were higher, and sOB-R levels were lower in PCOS groups than in control group. A subgroup analysis of lean and overweight or obese PCOS patients revealed there was significant difference in sOB-R level between lean PCOS group and overweight or obese PCOS group. There were no significant differences in anthropometric parameters between lean PCOS patients and BMI-matched controls. However, sOB-R level was significantly lower in lean PCOS women than in controls. (2) There was no correlation between sOB-R level and BMI, waist and hip circumference, total testosterone, androstendione, DHEAS, LH or hirsutism scores in PCOS patients, but there was a significant negative correlation between sOB-R and HOMA-IR. (3) After treatment with metformin for 6 months, serum insulin levels decreased, and sOB-R levels increased significantly (P<0.01). It was suggested that considering low sOB-R levels supposedly compensate diminished leptin action, PCOS per se might cause leptin resistance. It is likely that reduction of hyperinsulinemia produced by metformin effectively improves the sOB-R levels in PCOS.

Are Omentin Rs2274907 and Vaspin Rs2236242 Gene Polymorphisms Related to Body Composition, Lipid Profile and Other Adipokines in Prepubertal Healthy Children?

ABSTRACTPurpose/Aim: So far no research concerning the omentin-1 (ITLN1) rs2274907 and vaspin (SERPINA12) rs2236242 polymorphisms has been carried out in a healthy pediatric population. We analyzed associations of these polymorphisms with anthropometric parameters, lipid profile, as well as adiponectin, leptin and soluble leptin receptor (sOB-R) levels in prepubertal healthy children, to search for their possible role in the risk of obesity and obesity-related disorders.Materials and Methods: Frequencies of these polymorphisms were analyzed by the restriction fragment length polymorphism in 89 normal-weight children. The body composition was measured by dual-energy X-ray absorptiometry. Serum levels of adipokines were measured using ELISA methods.Results: We observed differences in values of HDL-cholesterol (p = 0.002) and triglycerides (p = 0.039) in children carrying different genotypes of the ITLN1 rs2274907 polymorphism. In children carrying different genotypes of the SERPINA12 rs2236242 polymorphism differences in BMI (p =0.025) and BMI Z-score (p = 0.01) values were found. Significant relations between anthropometric parameters and levels of HDL-cholesterol and triglycerides were associated with minor alleles of the studied polymorphisms. In addition, leptin/sOB-R ratio was related to HDL-cholesterol (p = 0.004) and triglycerides (p = 0.03) levels in children carrying minor allele of the SERPINA12 rs2236242 SNP.Conclusions: We suggest that both ITLN1 rs2274907 and SERPINA12 rs2236242 polymorphisms influence body composition and lipid profile in prepubertal healthy children. Relations between anthropometric parameters, lipid and adipokine levels may be associated with minor alleles of the studied polymorphisms. The possible role of these polymorphisms in the modulation of the risk of obesity and obesity-related disorders in the later life might be considered.

Impact to short-term high intensity intermittent training on different storages of body fat, leptin and soluble leptin receptor levels in physically active non-obese men: A pilot investigation

Studies have postulated High Intensity Intermittent Training (HIIT) as a superior strategy to reduce body fat. The purpose of this study was to compare the effects HIIT and steady-state training (SST) on body composition, leptin, soluble leptin receptor (sOB-R) levels, and hunger perception in physically active non-obese men. Twenty men performed five weeks of HIIT (5km - 1min running at 100% speed correspondent to VȩO2peak - v VȩO2peak - interspersed with 1-min passive recovery; n=10) or SST (5km at 70% of vVȩO2peak continuously; n=10) three times a week. Body composition, and hunger perception were assessed at pre- and post-training and were compared by a two-way analysis (group and training period) with repeated measures in the second factor. A fasting time-course (baseline, 24h, and 48h after an experimental session of exercise) of leptin and sOB-R levels were measured at pre- and post-five weeks of training and assessed by a three-way analysis (group, period and time of measurement) with repeated measures in the second and third factors. There was no effect on body composition and hunger perception. Leptin was reduced in both groups, while sOB-R was increased post-five weeks of training in HIIT but not in the SST. Although both training groups exerted alterations in leptin levels, only HIIT was able increased sOB-R levels, this suggest a superior impact on central responses in physically active non-obese men.

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

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

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

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

Association of plasma leptin levels and soluble leptin receptor with breast cancer

Objective: To explore the association between plasma leptin (LEP) levels, soluble leptin receptor(SLR), free leptin index and breast cancer. Methods: 245 new female cases of primary breast cancer confirmed by histopathology examination were sequentially recruited into the study. A total of 245 age-matched healthy women were enrolled as controls during the same period. A standardized questionnaire was used to collect the demographic information of the subjects. Blood samples were collected and the levels of LEP and SLR in plasma were measured by enzyme linked immunosorbent assay. The differences of LEP, SLR and FLI expression between control and cases group, as well as different breast cancer subtypes and TNM stages were compared using t-test and ANOVA after stratification by menopause status. Multivariate logistic regression was used to explore the contributions of the three indexes to the risk of breast cancer. Results: Females in both cases and control group were (50.7 ± 9.4) years old. The level of SLR and FLI (P(50)(P(25),P(75))) in premenopausal women were 18.4 (11.2, 28.7), 0.5 (0.4, 0.6) μg/L in case group and 27.7 (19.2, 43.4), 0.3 (0.3, 0.4) μg/L in control group (P<0.001). While the level of postmenopausal women in case group were 20.3 (12.8, 31.8), 0.5 (0.4, 0.6) μ g/L (P<0.001), and 30.1 (18.8, 40.5), 0.3 (0.3, 0.5) μg/L in control group (P<0.001), respectively. After adjustment for confounding factors and BMI, the relationship between FLI and breast cancer remained significant for both pre- and postmenopausal women while the association between SLR and breast cancer was significant only in premenopausal women. Compared with the lowest level of SLR, higer levels of SLR is associated with a reduced risk of breast cancer (premenopausal women, OR=0.10, 95% CI: 0.04-0.29, P(trend)<0.001). Compared with the lowest level of FLI, FLI at higher levels is associated with an increased risk of breast cancer (premenopausal women, OR=7.14, 95% CI: 2.86-17.83, P(trend)<0.001; postmenopausal women, OR=8.10, 95% CI: 2.85-22.98, P(trend)<0.001). No significant association between LEP and breast cancer or association between the three indexes and breast cancer subtypes and TNM stages was found (P>0.05). Conclusion: SLR may be a protective factor for breast cancer while FLI may increase the risk of breast cancer.