sOB-R Levels Research Articles

Association between some Serum Parameters in Iraqi Women with Polycystic Ovary Syndrome and leptin receptor gene polymorphism

Polycystic ovarian syndrome (PCOS) is considered as a complex, heterogeneous disorder that impacts 5-10% of women at reproductive age. This study aimed to evaluate the association of leptin recepter gene polymorphism (Lys109Arg, rs1137100) and some serum parameters with PCOS in of Iraqi women. This case-control study was carried out during the period from July to October, 2022 at Infertility Care and IVF center of Kamal AL-Samaraay Hospital, Baghdad. The study included 120 Iraqi women as a sample size divided into two groups 60 PCOS patients and 60 apparently healthy control. PCOS patients were diagnosed by gynecologists according to Rotterdam criteria. The genotypes of leptin receptor gene at rs137100 SNP were determined by using HRM-PCR. The serum levels of leptin, soluble leptin receptor (sOB-R) and AMH were measured by using Elisa kits. Lipid profile parameters were measured by spin 200 full auto. LH, FSH, testosterone, estradiol, progesterone, TSH, T3 and T4 hormones were measured by cobas E411. Results revealed that BMI values were significantly increased (p≤0.01) in PCOS patients compared to controls (30.21±0.70 versus 24.28±0.617). Serum leptin and sOB-R levels were significantly (p˂0.05) higher in PCOS patients than controls (4303.28±71.55 versus 3854.84 ±213.96 pg /ml and 144.09 ±5.51 versus 122.16 ±7.64 ng/ml respectively). The frequency of AA genotypes was significantly (p˂0.05) lower in PCOS patients than in apparently healthy subjects (33.3 % versus 65.0% respectively) whereas the frequencies of AG and GG genotypes were significantly (p˂0.05) higher in PCOS patients versus controls (53.3% versus 26.6% and 13.4% versus 8.4% respectively).The A allele frequency was higher in apparently healthy subjects than in PCOS women (78.3% versus 60.0% respectively) while G allele frequency was significantly higher in PCOS patients versus controls (80.0% versus 21.7%, respectively). It was concluded that the leptin receptor polymorphism (rs1137100) is strongly linked to an increased risk of developing PCOS. Further, those with the A allele are less likely to develop PCOS.

Characterization of circulating leptin-receptor levels following acute sleep restriction: A pilot study on healthy adult females

BackgroundInsufficient sleep adversely affects energy homeostasis by decreasing leptin levels. The underlying physiological mechanisms; however, remain unclear. Circulating leptin is well described to be regulated by its soluble receptor (sOB-R). Intriguingly, the impact of short sleep duration on sOB-R levels has never been characterized. AimIn this study, we investigated, for the first time, the variation of sOB-R levels and its temporal relationship with circulating leptin upon acute sleep restriction. MethodsFive adult females were maintained on an 8-hour sleep schedule (bedtime at 00:00) for 1 week before restricting their sleep to 4.5 h (bedtime at 03:30) on 2 consecutive nights. Balanced meals were scheduled to specific hours and sleep was objectively measured. Four-hour blood samples were regularly collected during waking hours between 08:00 and 00:00. ResultsSleep restriction resulted in lower leptin (20.9 ± 1.7 vs 25.7 ± 1.7 ng/ml) and higher sOB-R concentrations (24.4 ± 1.2 vs 19.8 ± 1.6 ng/ml). Neither the discordant temporal relationship nor the pattern of leptin and sOB-R were altered in response to sleep restriction. ConclusionOur results suggest that sleep restriction may modulate circulating leptin levels and possibly metabolism via upregulating its soluble receptor. This observation may have valuable therapeutic implications when considering sOB-R as a potential target during the management of metabolic disturbances.

Metformin Affects Plasma Levels of Soluble Leptin Receptors in Type 2 Diabetes Mellitus and Metabolic Syndrome Patients

Background: Obesity and insulin resistance elevate plasma leptin, while it lowers plasma levels of soluble leptin receptors (sOB-R).Objectives: To measure the levels of sOB-R in patients with type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) and compare it to healthy controls. The study also aimed to investigate the influence of metformin on the levels of sOB-R in patients with T2DM and MetS. Materials and Methods: A cross-sectional study was conducted on 66 participants (33 patients and 33 controls). Patients were divided into two groups; Group I included 17 newly diagnosed T2DM patients, and Group II included 16 patients with MetS. Patients were studied before and 3 months after treatment with 850 mg metformin treatment. Group III included 33 non-obese healthy individuals as a control group. Measurements such as height, weight, waist circumference, hip circumference, blood pressure examination, and biochemical tests including fasting blood sugar, HbA1c, total cholesterol (Ch), triglyceride, high-density lipoprotein (HDL), insulin level, plasma sOB-R levels were performed. Ch/HDL ratio, non-HDL cholesterol, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), Waist Hip Ratio (WHR), and Body Mass Index (BMI) were calculated.Results: No statistically significant difference was found among the groups regarding sOB-R levels initially, but after metformin treatment, T2DM patients showed a significantly higher level (10.19 ng/ml). There was a significant increase in the levels of sOB-R after metformin treatment, as it increased from 7.82 ng/ml to 10.19 ng/ml in T2DM, and from 6.92 ng/ml to 7.82 ng/ml in MetS patients. Conclusion: Metformin significantly increases the plasma levels of sOB-R in T2DM patients but only slightly increases these levels in MetS patients.

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.

Insulin and Body Mass Index Decrease Serum Soluble Leptin Receptor Levels in Humans.

Serum soluble leptin receptor (sOb-R) may protect against future type 2 diabetes or serve as a marker for protective features, but how sOb-R is regulated is largely unknown. This work aimed to test how serum sOb-R is influenced by glucose, insulin, body fat, body mass index (BMI), food intake, and physical activity. We performed an epidemiological triangulation combining cross-sectional, interventional, and Mendelian randomization study designs. In 5 independent clinical studies (n = 24-823), sOb-R was quantified in serum or plasma by commercial enzyme-linked immunosorbent assay kits using monoclonal antibodies. We performed mixed-model regression and 2-sample Mendelian randomization. In pooled, cross-sectional data, leveling by study, sOb-R was associated inversely with BMI (β [95% CI] -0.19 [-0.21 to -0.17]), body fat (-0.12 [-0.14 to -0.10), and fasting C-peptide (-2.04 [-2.46 to -1.62]). sOb-R decreased in response to acute hyperinsulinemia during euglycemic glucose clamp in 2 independent clinical studies (-0.5 [-0.7 to -0.4] and -0.5 [-0.6 to -0.3]), and immediately increased in response to intensive exercise (0.18 [0.04 to 0.31]) and food intake (0.20 [0.06 to 0.34]). In 2-sample Mendelian randomization, higher fasting insulin and higher BMI were causally linked to lower sOb-R levels (inverse variance weighted, -1.72 [-2.86 to -0.58], and -0.20 [-0.36 to -0.04], respectively). The relationship between hyperglycemia and sOb-R was inconsistent in cross-sectional studies and nonsignificant in intervention studies, and 2-sample Mendelian randomization suggested no causal effect of fasting glucose on sOb-R. BMI and insulin both causally decreased serum sOb-R levels. Conversely, intensive exercise and food intake acutely increased sOb-R. Our results suggest that sOb-R is involved in short-term regulation of leptin signaling, either directly or indirectly, and that hyperinsulinemia may reduce leptin signaling.

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.

Racial/ethnic-specific associations of urinary phenols and parabens with adipokines in midlife women: The Study of Women's Health Across the Nation

BACKGROUND AND AIM: Environmental phenols have been associated with metabolic phenotypes. Adipokines, cytokines secreted by adipose tissue, may contribute to obesity-related metabolic disease. Growing evidence supports racial/ethnic difference in adipokine levels. We examined the ethnic-specific associations of urinary phenols and parabens with adipokines. METHODS: Urinary concentrations of 5 phenols (bisphenol-A, bisphenol-F, 2,4-diclorophenol, 2,5-diclorophenol, triclosan) and 4 parabens (Methyl-paraben, Ethyl-paraben, Butyl-paraben, Propyl-paraben) were measured in 2002-2003 among 1200 women of the Study of Women's Health Across the Nation Multi-Pollutant Study. Covariate-adjusted standardization approach was used for urine dilution adjustments of exposure concentrations. Serum adipokines included adiponectin, high molecular weight (HMW)-adiponectin, leptin, soluble leptin receptor (sOB-R), and adiponectin/leptin ratio (ALR). Linear regression models were used to estimate the percentage change in adiopokines per doubling of individual urinary phenols and parabens after adjusting for age, site, education level, physical activity score, smoking status, menopausal status, total caloric intake, and obesity status. RESULTS:Participants included white (52.5%), black (19.3%), and Asians (Chinese and Japanese, 28.1%) women. In white women, urinary bisphenol-F were associated with 6.79% (95% confidence interval: 0.58%, 13%) higher HMW-adiponectin and 2.9% (0.52%,5.27%) higher sOB-R levels. Urinary 2,4-dichlorophenol were associated with 3.92% (0.58%, 7.27%) higher adiponectin and 7.42% (1.79%,13.06%) higher HMW-adiponectin. Urinary methyl-paraben and propyl-paraben were associated with 5.56% (-9.07%, -2.06%) and 3.27% (95% CI: -6.01%, -0.53%) lower in leptin levels and 6.28% (1.75%,10.82%) and 4.09% (95% CI: 0.56%, 7.63%) higher ALR. In black women, urinary methyl-paraben was associated with 7.01% (2.09%,11.92%) higher leptin levels and 8.78% (-15.76%, -1.80%) lower ALR. No significant associations were observed in Asian. CONCLUSIONS:We found urinary bisphenol-F, 2,4-dichlorophenol and parabens were associated with favorable profiles of adipokines in white women whereas urinary methyl-paraben was associated with adverse profiles in black women. Our findings suggested that exposure to phenols and parabens were associated with adipokine profiles but the association could differ by race/ethnicity. KEYWORDS: Environmental epidemiology, Phenols, adipokines

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.

Population-based Study of the Effects of Adiponectin, Leptin and Soluble Leptin Receptor on Risks for Breast Cancer

To explore the individual or combined effects of adiponectin, leptin, and soluble leptin receptor (sOB-R) on risks for premenopausal and postmenopausal breast cancer, and to provide evidence for revealing the molecular mechanism between obesity and breast cancer. 469 newly-diagnosed breast cancer cases were sequentially recruited for the study and 469 age-frequency-matched healthy women were enrolled as the controls over the same period of time. The participant baseline information was collected with questionnaires, and plasmic levels of adiponectin, leptin and sOB-R were checked with ELISA. Multivariate unconditional logistic regression was conducted and the analyses were further stratified according to waist-to-hip ratio (WHR) and body mass index (BMI) to explore the effect of the indicators on the risks for premenopausal and postmenopausal breast cancer. A total of 480 premenopausal and 458 postmenopausal women were included in the study. Among the premenopausal subjects, 249 were breast cancer patients and 231 were controls. The median BMI was 22.9 kg/m 2and 23.2 kg /m 2, respectively, and the median WHR was 0.80 and 0.83, respectively. Among the postmenopausal subjects, 220 were breast cancer patients and 238 were controls. The median BMI was 23.4 kg/m 2 and 23.7 kg/m 2, respectively, and the median WHR was 0.82 and 0.86, respectively. Multivariate logistic regression analysis showed that before and after model adjustment, the increase in sOB-R and adiponectin levels was correlated to reduced risks of premenopausal and postmenopausal breast cancer ( P<0.05), while the increase in the leptin/sOB-R ratio (also known as free leptin index, FLI) and leptin/adiponectin (L/A) ratio was only correlated to increased risks of postmenopausal breast cancer. After further stratification by WHR and BMI, the association between adiponectin, FLI and postmenopausal breast cancer remained statistically significant in all subgroups. Among subjects with normal-BMI central obesity (18.5 kg/m 2≤BMI<24 kg/m 2 & WHR≥0.85) , higher L/A ratio was associated with an increased risk of postmenopausal breast cancer. No clear association between leptin and premenopausal and risks for postmenopausal breast cancer was found in the study. Postmenopausal women with decreased levels of sOB-R and adiponectin, and increased FLI and L/A, and premenopausal women with decreased levels of sOB-R and adiponectin were found to be at high risks for breast cancer.

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.

Urinary metals and adipokines in midlife women: The Study of Women's Health Across the nation (SWAN)

BackgroundInformation on the associations between metal exposures and adipokines in human populations is limited and results are inconsistent. We evaluated the associations between metals and adipokines. MethodsUrinary concentrations of 15 metals (arsenic, barium, cadmium, cobalt, cesium, copper, mercury, manganese, molybdenum, nickel, lead, antimony, tin, thallium, and zinc) were measured in 1999–2000 among 1228 women of the Study of Women's Health Across the Nation Multi-Pollutant Study. Serum adipokines including high molecular weight (HMW)-adiponectin, leptin, and soluble leptin receptor (sOB-R) were measured at the follow-up visit (2002–2003). Linear regression models with adaptive elastic-net (AENET) were fit to identify metals associated with adipokines and to compute estimated percent changes in adipokines for one standard deviation increase in log-transformed urinary metal concentrations. ResultsAfter adjustment for confounders, urinary molybdenum was associated with a 5.54% higher level (95% CI: 1.36%, 9.90%), whereas cadmium was associated with a 4.53% lower level (95% CI: −8.17%, −0.76%) of HMW-adiponectin. Urinary molybdenum was also associated with a 5.95% lower leptin level (95% CI: −10.15%, −1.56%) and a 2.98% (95% CI: 0.69%, 5.32%) higher sOB-R level. Urinary cesium and lead were associated with a 3.58% (95% CI: −6.06%, −1.03%) and a 2.53% (95% CI: −4.80%, −0.21%) lower level of sOB-R, respectively. ConclusionsOur findings suggest that molybdenum was associated with favorable profiles of HMW-adiponectin, leptin, and sOB-R. Exposures to cadmium, cesium, and lead were associated with adverse adipokine profiles.

Infant body composition relationship to maternal adipokines and fat mass: the PONCH study.

Infant adiposity is linked to both high maternal fat mass (FM) and excessive gestational FM gain, whereas the association with maternal adipokines is less clear. The aim was to determine how levels of maternal leptin, the soluble leptin receptor (sOB-R), adiponectin, and FM during pregnancy were linked to infant FM in normal-weight (NW) women and women with obesity (OB). Body composition and serum levels of leptin, adiponectin, and sOB-R were determined three times during pregnancy in 80 NW and 46 OB women. For infants, body composition was measured at 1 and 12 weeks of age. Maternal leptin and sOB-R levels increased during pregnancy. For NW women, infant FM at 1 week was inversely associated with changes in maternal leptin and at 12 weeks inversely associated with absolute maternal sOB-R levels throughout pregnancy, as well as changes in sOB-R levels in early pregnancy. For OB women, infant FM at both 1 and 12 weeks were best explained by maternal FM. Leptin and sOB-R, thought to regulate leptin bioavailability, are associated with fat accumulation in infants born to NW women. In OB women, maternal FM in early pregnancy is more important than leptin in determining infant fat accumulation. In normal-weight women, the regulation of maternal leptin bioavailability during pregnancy has a role in infant fat mass accumulation. In women with obesity, however, pre-pregnancy maternal fat mass seems more important for infant fat mass. This is the first study of maternal adipokines and fat mass including longitudinal measurements in both mothers and their children. Understanding the relationship between maternal factors and infant fat mass is of great importance as obesity is programmed over the generations, and it is important to learn what regulates this programming.

SAT-028 Leptin, Leptin Soluble Receptor and FLI in Healthy and Preeclamptic Pregnancies

ContextLeptin is an adipokine involved in many pleiotropic and key physiological actions and circulates free and active, or inactive bound to the leptin binding protein and sOB-r. Thus, the ratio Leptin/sOB-r or free leptin index (FLI) is commonly used as a marker of leptin sensitivity in different pathologies.ObjectiveEvaluate serum concentrations of leptin and sOB-r and determine FLI in healthy pregnant and mild pre – eclamptic women in the three trimesters of gestation.DesignA nested case-control study within a prospective cohort study of pregnant women, enrolled in the Department of Obstetrics and Gynecology of the School of Medicine at Universidad Nacional.Main Outcome Measure and MethodsFrom the initial cohort, 46 healthy pregnant women and 19 mild pre – eclamptic pregnant women were randomly selected. Anthropometric, biochemical and clinical parameters were determined during three stages of pregnancy [1st (11.3±2.3 weeks), 2nd (24.4±3.10 weeks) and 3rd (34.84±4.41 weeks) periods of gestation]. Data were presented as mean ± SD. A p value <0.05 was considered to be statistically significant.ResultsSerum leptin levels and sOB-r levels rose significantly throughout pregnancy in both healthy women [Leptin (1st 23.28±9.87 ng/mL; 2nd 34.58±18.45 ng/mL; 3rd 38.27±19.64 ng/mL trimester) (p=0.0001); sOB-r (1st 32.12±7.29 ng/mL; 2nd 43.26±9.25 ng/mL; 3rd 45.16±10.70 ng/mL trimester) (p<0.0000)] and preeclamptic women [Leptin (1st 29.91±9.91 ng/mL; 2nd 47.10±25.70 ng/mL; 3rd 63.00±3012 ng/mL trimester) (p<0.0000); sOB-r (1st 32.09±6.97 ng/mL; 2nd 37.54±6.33 ng/mL; 3rd 36.96±7.66 ng/mL trimester) (p=0.0380)].Serum leptin levels were significantly higher in preeclamptic pregnant women compared to healthy pregnant women at 2nd (p=0.029) and 3rd trimesters of pregnancy (p<0.000). Additionally, serum sOB-r levels were also significantly lower in pre - eclamptic pregnant women during the 2nd (p=0.017) and 3rd trimester (p=0.0036) of pregnancy compared to healthy pregnant women. As a result, the FLI index did not vary significantly during any of the three periods of pregnancy studied in healthy pregnant women [(1st 7.99±4.85; 2nd 8.72±6.5; 3rd 9.15±5.84 trimester) (p >0.05)], whereas, in contrast, this index markedly increased throughout pregnancy in pre - eclamptic women [(1st 8.69±4.96; 2nd 13.54±8.78; 3rd 18.06±10.35 trimester) (p=0.0044)]. Indeed, the FLI index was significantly higher at 2nd (p=0.0186) and 3rd (p<0.000) trimesters of pregnancy in pre - eclamptic women compared to healthy pregnant.ConclusionsThe present results demonstrate for the first time in a longitudinal study that FLI increases significantly in pre - eclamptic pregnant women towards the end of pregnancy. Hence, high FLI index values should be further explored as a potentially valuable indicator for the clinical manifestations of this pathology.

Correlations of serum leptin and leptin resistance with depression and anxiety in patients with type 2 diabetes.

The associations of serum leptin/soluble leptin receptor (sObR) and leptin resistance with symptoms of depression and anxiety were investigated in patients with type 2 diabetes (T2D). We report the results of two cross-sectional studies, performed 2 years apart, that included 216 and 237 T2D patients, respectively. Symptoms of depression and anxiety were assessed with specific questionnaires (Patient Health Questionnaire-9, Center for Epidemiologic Studies Depression Scale, and Generalized Anxiety Disorder-7, respectively). Laboratory data (including leptin and sObR) were collected, and free leptin index (FLI), as an estimate of leptin resistance, was calculated. One hundred forty patients had laboratory data available on both occasions, and were evaluated longitudinally. Simple and multiple correlations between depression/anxiety and parameters of interest were performed. In both studies, serum leptin levels were higher, whereas resting energy expenditure/leptin ratios were lower in T2D patients with depressive and moderate-severe anxiety symptoms. In the second study, patients with depressive symptoms had higher FLI and lower sObR levels, while those with moderate-severe anxiety only had higher FLI. Depression scores correlated with serum leptin (r = 0.29, [95%CI: 0.14-0.42]; r = 0.32, [95%CI: 0.18-0.45]) and FLI (r = 0.30, [95%CI: 0.15-0.43]; r = 0.32, [95%CI: 0.17-0.45]; P < 0.0001 for all). Multiple regression analyses identified leptin (β = 0.167; t ratio = 1.98) and FLI (β = 2.935, t ratio = 2.44) (P < 0.05 for both) as variables that significantly contributed to depressive symptoms. Depressive symptoms were present in significantly more patients with leptin levels in the highest versus the lowest quartiles on both evaluations (odds ratio: 5.98, 95%CI [1.76-20.32], P < 0.01). Depressive and moderate-severe anxiety symptoms were associated with high leptin concentrations and leptin resistance in T2D patients.

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.

Dietary protein restriction increases hepatic leptin receptor mRNA and plasma soluble leptin receptor in male rodents.

Leptin is an adipokine that regulates adipose tissue mass through membrane-anchored leptin receptor (Ob-R). Extracellular domain of Ob-R in plasma is called soluble leptin receptor (sOb-R), and is the main leptin-binding protein. Based on a previous DNA microarray analysis that showed induction of hepatic Ob-R mRNA in low-protein diet-fed mice, this study aimed to clarify the effect of dietary protein restriction on hepatic Ob-R mRNA and plasma sOb-R levels. First, the effect of protein restriction on hepatic Ob-R mRNA level was examined together with fasting and food restriction using male rats as common experimental model for nutritional research. Hepatic Ob-R mRNA level was increased by feeding low-protein diet for 7 d, although not significantly influenced by 12-h fasting and sixty percent restriction in food consumption. Then, effect of protein restriction on liver Ob-R and plasma sOb-R was investigated using male mice because specific sOb-R ELISA was more available for mice. Hepatic Ob-R mRNA level was also increased in protein restricted-mice although it did not increase in hypothalamus. Hepatic Ob-R protein was decreased, whereas plasma sOb-R was increased by protein restriction. Because the concentration of sOb-R increased without changing plasma leptin concentration, free leptin in plasma was significantly reduced. The direct effect of amino acid deprivation on Ob-R mRNA level was not observed in rat hepatoma cells H4IIE cultured in amino acid deprived medium. In conclusion, dietary protein restriction increased hepatic Ob-R mRNA, resulting in increased plasma sOb-R concentration, which in turn, reduces plasma free leptin level and may modulate leptin activity.

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.