The Association of Plasma Leptin, Soluble Leptin Receptor and Total and High-Molecular Weight Adiponectin With the Risk of Perioperative Neurocognitive Disorders.

BACKGROUND: Perioperative neurocognitive disorders (NCD) are poorly characterized in terms of their risk factor profiles. Leptin and adiponectin are adipose-tissue-derived hormones with a role in inflammation and atherosclerosis whose function in perioperative NCD is unclear. Here, we used a cohort of older adults to examine the association of preoperative plasma concentrations of these biomarkers with the risk of perioperative NCD. METHODS: Prospective analysis of 768 participants aged ≥ 65 years of the BioCog study. Blood was collected before surgery for measurement of plasma total and high-molecular-weight (hmw) adiponectin, leptin, and soluble leptin receptor (sOB-R). The free leptin index (FLI, leptin:sOB-R) was calculated. Postoperative delirium (POD) was assessed twice daily until postoperative day 7/discharge. Five hundred twenty-six patients (68.5%) returned for 3-month follow-up and provided data on postoperative cognitive dysfunction (POCD). POCD was defined as a decline on six neuropsychological tests that exceeded that of a nonsurgical control group. Logistic regression analyses examined the associations of each exposure with POD and POCD risk, in separate models adjusted for age, sex, fasting, surgery type, and body mass index (BMI). RESULTS: Of 768 patients, 152 (19.8%) developed POD. Of 526 attendants of the follow-up, 54 (10.3%) had developed POCD. Leptin, sOB-R, and total and hmw adiponectin were each not associated with POD. For POCD, we observed reduced risk in patients in FLI quartile 4 compared with quartile 1 (odds ratio, 0.26; 95% CI 0.08, 0.89). Sensitivity analyses for the outcome POD revealed statistically significant interaction terms of sOB-R and total adiponectin with obesity (BMI≥30kg/m2 versus BMI<30kg/m2). For the outcome POCD, a higher sOB-R was associated with an increased risk in the obese subgroup (odds ratio, 4.00; 95% CI 1.01, 15.86). CONCLUSIONS: We did not find consistent evidence for the role of leptin, its receptor, and total and hmw adiponectin in POD and POCD risk. Future research should be used to support or refute our findings and to fully characterize any differences in the associations of these hormones with POD/POCD between obese and nonobese individuals.

Exocrine Pancreatic Function in Girls with Anorexia Nervosa.

OBJECTIVES: To assess pancreatic exocrine function in patients with anorexia nervosa using a breath test with 13C-labeled mixed triglycerides (MTG-BT) and to determine the relationship between the test results and selected biochemical and hormonal parameters. MATERIAL AND METHODS: Anthropometric measurements, biochemical and hormonal parameters (serum leptin, soluble leptin receptor (sLR), acylated and desacylated ghrelin, free leptin index (FLI)), and MTG-BT were performed in a group of 31 girls with the restrictive type of AN, as well as 38 healthy girls (C). RESULTS: The average cumulative dose of 13C-triglycerides recovered with exhaled air (%CD) was similar in both study groups, while the average time from 13C-triglycerides administration to peak 13CO2 excretion in expired air (time to peak (TTP)) was significantly longer in patients with AN compared to C. In both groups, %CD correlated negatively with FLI. TTP correlated negatively with sLR and FLI in the AN and with serum insulin and HOMA-IR values in the C. CONCLUSIONS: In girls with AN, the pancreatic efficiency of lipase secretion was found to be normal, while the kinetics of this enzyme secretion were disturbed. These changes may result from disorders in the functioning of the adipose-insular and islet-acinar axes.

Pregnancy-specific Adaptations in Leptin and Melanocortin Neuropeptides in Early Human Gestation.

INTRODUCTION: Pregnancy is characterized by increased appetitive drive beginning early in gestation, yet the central mechanisms underlying this adaptation are poorly understood in humans. To elucidate central mechanisms underlying appetite regulation in early pregnancy, we examine plasma and cerebrospinal fluid (CSF) leptin and Agouti-related peptide (AgRP) as well as CSF proopiomelanocortin (POMC) as surrogates for brain melanocortin activity. METHODS: Plasma leptin, soluble leptin receptor, AgRP, and CSF leptin, POMC, and AgRP were collected from pregnant women before cerclage placement (16.6 ±â€…1.1 weeks; N = 24), scheduled cesarean section (39.2 ±â€…0.2 weeks; N = 24), and from nonpregnant controls (N = 24), matched for age and body mass index. RESULTS: Plasma leptin was 1.5 times higher in pregnancy vs controls (P = 0.01), but CSF leptin did not differ. CSF/plasma leptin percentage was lower in early pregnancy vs controls (0.8 ±â€…0.1 vs 1.7 ±â€…0.2; P < 0.0001) and remained unchanged at term (0.9 ±â€…0.1), supporting a decrease in leptin transport into CSF in pregnancy. Plasma AgRP, a peripheral biomarker of the orexigenic hypothalamic neuropeptide, was higher in early pregnancy vs controls (95.0 ±â€…7.8 vs 67.5 ±â€…5.3; P = 0.005). In early gestation, CSF AgRP did not differ from controls, but CSF POMC was 25% lower (P = 0.006). In contrast, at term, CSF AgRP was 42% higher vs controls (P = 0.0001), but CSF POMC no longer differed. Overall, the CSF AgRP/POMC ratio was 1.5-fold higher in early pregnancy vs controls, reflecting a decrease in melanocortin tone favoring appetitive drive. CONCLUSIONS: Pregnancy-specific adaptions in the central regulation of energy balance occur early in human gestation and are consistent with decreased leptin transport into brain and resistance to the effects of leptin on target melanocortin neuropeptides.

Fatty acid binding protein 4 (FABP4) and metabolic-related parameters in systemic lupus erythematosus active and non-active episode.

OBJECTIVE: To assess serum FABP4 and other metabolic-related parameters in Systemic Lupus Erythematosus (SLE) active and non-active episode. METHODS: Fifty-four SLE patients in Hasan Sadikin General Hospital, Bandung, Indonesia in 2018-2019 were recruited and serum samples were collected in their active and non-active episode status. Serum was analyzed for FABP4, leptin, glucose, and triglycerides. The clinical characteristics were analyzed from medical records. Disease activity was assessed with the SLEDAI-2K (≥4 defined as an active; <4 as non-active episode). RESULTS: Significantly correlation of Systolic Blood Pressure (SBP) (p = 0.001, r = 0.59) and C3 (p = 0.04, r = 0.47) between active and non-active episode. In non-active episode, there was significant correlation of FABP4 with Diastolic Blood Pressure (DBP) (p = 0.04, r = 0.26) and blood glucose (p = 0.01, r = -0.39). In active episode, there was significant correlation FABP4 with SBP (p = 0.04, r = -0.28) and triglyceride (p = 0.002, r = 0.55). CONCLUSION: FABP4 correlates with high DBP in the non-active and high triglyceride serum in the active episode.

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

OBJECTIVE: Binge 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. METHOD: We 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. RESULTS: In 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). CONCLUSION: This 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.

Circulating adipokine concentrations and risk of five obesity-related cancers: A Mendelian randomization study.

Obesity is considered a chronic inflammatory state characterized by continued secretion of adipokines and cytokines. Experimental and epidemiological evidence indicates that circulating adipokines may be associated with the development of obesity-related cancers, but it is unclear if these associations are causal or confounded. We examined potential causal associations of specific adipokines (adiponectin, leptin, soluble leptin receptor [sOB-R] and plasminogen activator inhibitor-1 [PAI-1]) with five obesity-related cancers (colorectal, pancreatic, renal cell carcinoma [RCC], ovarian and endometrial) using Mendelian randomization (MR) methods. We used summary-level data from large genetic consortia for 114 530 cancer cases and 245 284 controls. We constructed genetic instruments using 18 genetic variants for adiponectin, 2 for leptin and 4 for both sOB-R and PAI-1 (P value for inclusion<5 × 10-8 ). Causal estimates were obtained using two-sample MR methods. In the inverse-variance weighted models, we found an inverse association between adiponectin and risk of colorectal cancer (odds ratio per 1 µg/mL increment in adiponectin concentration: 0.90 [95% confidence interval = 0.84-0.97]; P = .01); but, evidence of horizontal pleiotropy was detected and the association was not present when this was taken into consideration. No association was found for adiponectin and risks of pancreatic cancer, RCC, ovarian cancer and endometrial cancer. Leptin, sOB-R and PAI-1 were also similarly unrelated to risk of obesity-related cancers. Despite the large sample size, our MR analyses do not support causal effects of circulating adiponectin, leptin, sOB-R and PAI-1 concentrations on the development of five obesity-related cancers.

Temporal Leptin to Determine Cardiovascular and Metabolic Fate throughout the Life.

Leptin links peripheral adiposity and the central nervous system (CNS) to regulate cardiometabolic physiology. Within the CNS, leptin receptor-expressing cells are a counterpart to circulating leptin, and leptin receptor-mediated neural networks modulate the output of neuroendocrine and sympathetic nervous activity to balance cardiometabolic homeostasis. Therefore, disrupted CNS leptin signaling is directly implicated in the development of metabolic diseases, such as hypertension, obesity, and type 2 diabetes. Independently, maternal leptin also plays a central role in the development and growth of the infant during gestation. Accumulating evidence points to the dynamic maternal leptin environment as a predictor of cardiometabolic fate in their offspring as it is directly associated with infant metabolic parameters at birth. In postnatal life, the degree of serum leptin is representative of the level of body adiposity/weight, a driving factor for cardiometabolic alterations, and therefore, the levels of blood leptin through the CNS mechanism, in a large part, are a strong determinant for future cardiometabolic fate. The current review focuses on highlighting and discussing recent updates for temporal dissection of leptin-associated programing of future cardiometabolic fate throughout the entire life.

Disordered leptin and ghrelin bioactivity in adolescent idiopathic scoliosis (AIS): a systematic review and meta-analysis.

BACKGROUND: Adolescents with scoliosis consistently demonstrate lower body weight, lean muscle mass, and bone mineral density than healthy adolescent counterparts. Recent studies have focused on understanding how leptin and ghrelin signaling may play a role in adolescent idiopathic scoliosis (AIS). In our current study, we aim to evaluate the serum levels of leptin, soluble leptin receptor (sOB-R), and ghrelin in AIS patients through systematic review and meta-analysis. METHODS: We conducted our systematic review by searching the keywords in online databases including PubMed, Embase, Cochrane, Elsevier, Springer, and Web of Science from the time of database inception to January 2020. Inclusion criteria were studies that measure leptin, soluble leptin receptor (sOB-R), and ghrelin levels in AIS patients. Selection of studies, assessment of study quality, and data extraction were performed by two reviewers independently. Then, data was analyzed to calculate the mean difference and 95% confidence interval (CI). RESULTS: Seven studies concerning leptin/sOB-R and three studies concerning ghrelin were qualified for meta-analysis (one study concerning both leptin and ghrelin). Serum leptin of patients with AIS were significantly lower when compared with healthy controls, with the weighted mean difference (WMD) of - 0.95 (95% CI - 1.43 to - 0.48, p < 0.0001) after reducing the heterogeneity using six studies for meta-analysis, while sOB-R and ghrelin level was significantly higher in AIS group when compared with control group, with the WMD of 2.64 (95% CI 1.60 to 3.67, p < 0.001) and 1.42 (95% CI 0.48 to 2.35, p = 0.003), respectively. CONCLUSION: Our current meta-analysis showed that serum level of leptin in AIS patients was significantly lower when compared with control subjects, while serum sOB-R and ghrelin levels were significantly higher in AIS patients. More clinical studies are still required to further validate the predictive value of leptin or ghrelin for the curve progression for AIS patients.

C-Peptide and leptin system in dichorionic, small and appropriate for gestational age twins-possible 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.

Circulating leptin level, soluble leptin receptor level and their gene polymorphism in patients with systemic lupus erythematosus: a systematic review and meta-analysis.

OBJECTIVES: Initial studies investigating peripheral levels of leptin and soluble leptin receptor (LepR) in systemic lupus erythematosus (SLE) patients have generated a number of controversial results. Thus, we conducted a meta-analysis to evaluate the circulating leptin level, soluble LepR level and related gene polymorphism in SLE patients. METHODS: We performed a meta-analysis comparing the circulating leptin level, LepR level and their gene polymorphism in patients with SLE to controls, and evaluate the relationship between leptin levels, LepR levels and SLE disease activity. Pubmed, Embase, Cochrane, CNKI, WanFang and VIP databases were searched systematically with no restriction to languages and years (up to Feb. 2020). Stata v. 14.0 was used to calculate statistical data. RESULTS: 34 articles involving 7337 SLE patients and 6866 healthy controls were included in this meta-analysis. Compared with the controls, SLE patients had a significantly higher level of leptin, in particular for active SLE patients, regardless of sample size, source, or assay method. The elevated leptin level was only found in the female SLE group, but not in the male SLE group. Apart from the South American subgroup, other ethnicity subgroups showed significantly higher levels of leptin in SLE patients. A marginally lower level of LepR in SLE patients was also observed. The LepR gene rs1137101 variant (i.e. AG+GG) was borderline significantly associated with the increased risk of SLE. CONCLUSIONS: Our meta-analysis revealed thta SLE patients had an elevated leptin level and decreased LepR level. LepR gene rs1137101 mutation might be associated with increased susceptibility to SLE.

Plasma leptin, but not adiponectin, is associated with cognitive impairment in older adults.

BACKGROUND: Leptin and adiponectin are adipose-tissue derived hormones primarily involved in glucose, lipid, and energy metabolism, inflammation, and atherosclerosis. Both adipokines may cross the blood-brain barrier but evidence on their roles in cognitive impairment is limited and conflicting. Here, we determined associations of plasma adipokine concentration with cognitive impairment in older adults. METHODS: Cross-sectional analysis of baseline data from 669 participants aged ≥65 years of the Biomarker Development for Postoperative Cognitive Impairment in the Elderly (BioCog) study were recruited 2014-2017 at study sites in Berlin, Germany and Utrecht, the Netherlands. Cognitive impairment was defined as the lowest tertile of a cognitive summary score derived from six neuropsychological tests. RESULTS: After adjustment for age, sex, fasting, BMI, diabetes, hypertension, cerebrovascular disease, and coronary heart disease, higher leptin concentrations and a higher leptin/adiponectin ratio (LAR) were associated with a higher odds of cognitive impairment (OR per 1 SD higher leptin concentration, 1.33; 95 % CI 1.05, 1.69; p = 0.02; OR per 1 SD higher LAR, 1.26; 95 % CI 1.01, 1.57; p = 0.04). Sensitivity analyses determined that these findings were driven by the non-obese group (BMI < 30 kg/m2), whereas leptin and LAR were not associated with cognitive impairment in the obese group (BMI ≥ 30 kg/m2). Soluble leptin receptor, leptin/soluble leptin receptor ratio, total adiponectin and high-molecular weight adiponectin concentrations were each not associated with impairment. CONCLUSIONS: With leptin as a known promoter of atherosclerosis and inflammation, our findings point to a pathogenic role of leptin in age-related cognitive impairment that may be limited to non-obese individuals and warrants further investigation.

Serum lipids, leptin, and soluble leptin receptor in alcohol dependence: A cross-sectional and longitudinal study.

OBJECTIVE: Alcohol dependence affects metabolic processes. Further research is needed to apply this knowledge clinically. In this study, possible differences in serum lipids and/or leptin activities between alcohol-dependent in-patients and healthy controls and possible associations with alcohol-related blood parameters and with prospective outcomes in alcohol dependence were assessed sex-specifically. METHOD: We measured and compared (median) serum lipids (triglycerides and total, HDL, and LDL cholesterol) and leptin activities (leptin, soluble leptin receptor [ObRe], and free leptin index) in 200 (males 56.5 %) early-abstinent alcohol-dependent in-patients and 240 (males 55.4 %) healthy controls and assessed alcohol-related readmissions during a 24 -month post-inclusion period. RESULTS: Male patients showed higher HDL cholesterol (61 versus 48 mg/dl), lower LDL/HDL ratios (2.06 versus 3.04), and lower free leptin index (0.30 versus 0.59) at study inclusion compared to healthy controls. In patients, ObRe levels were higher than in controls and decreased from inclusion to the second study-visit (at median 5 days later; males: 16.7-13.8 versus 11.0 ng/ml; females: 17.0-13.4 versus 12.1 ng/ml). The free leptin index increased between the two time points in females (0.80 versus 1.20). Lipids and leptin activities correlated with carbohydrate-deficient transferrin levels and liver enzyme activities. None of the serum parameters were significantly associated with alcohol-related readmissions. CONCLUSION: Our data support that serum lipid levels and leptin activities are involved in alcohol dependence. The parameters appear as possible indirect biomarkers for alcohol dependence.

Prospective Study of Long-Term Interrelationships Among Adiposity-Associated Biomarkers in Women.

OBJECTIVE: This study aimed to investigate the prospective interrelationships among biomarkers that may provide mechanistic insights into obesity-related diseases. METHODS: A total of 850 women in the Nurses' Health Study II with two fasting blood measurements (1996-1999 and 2010-2011) of adiponectin, leptin, soluble leptin receptor, insulin, retinol-binding protein 4, high-sensitivity C-reactive protein (hsCRP), and interleukin-6 were included. Biomarker interrelationships were examined in the following three ways: (1) cross-sectional associations at baseline and follow-up, (2) longitudinal associations of concurrent biomarker changes, and (3) prospective associations of each baseline biomarker with other biomarker changes. RESULTS: In cross-sectional analyses, most biomarkers were correlated after multivariable adjustment including BMI, with the strongest correlations observed between leptin and insulin and between hsCRP and interleukin-6. In longitudinal analyses, similar results were observed after multivariable adjustment including weight change. However, in prospective analyses, only three associations observed in cross-sectional and longitudinal analyses were consistently significant (P < 0.05). Every doubling in baseline adiponectin was associated with -9.0% insulin change. The corresponding estimate was 9.3% for baseline leptin and hsCRP change and 3.1% for baseline hsCRP and leptin change. CONCLUSIONS: Baseline adiponectin concentrations were inversely associated with subsequent insulin change, whereas baseline leptin concentrations were positively associated with hsCRP change and vice versa.

Expression of LEP, LEPR and PGC1A genes is altered in peripheral blood mononuclear cells of patients with relapsing-remitting multiple sclerosis.

Leptin (LEP) may contribute to the pathogenesis of multiple sclerosis (MS) by its immunomodulatory, proinflammatory and prooxidant effects. Therefore, plasma LEP levels and mRNA expression of five genes related to the LEP signaling pathway (LEP, LEP receptor (LEPR), peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC1A), superoxide dismutase 2, tumor necrosis factor-alpha) were investigated in relapsing-remitting MS. In patients (N = 64), compared to healthy subjects (N = 62), relative LEP mRNA levels were significantly increased (p = 0,01), while LEPR and PGC1A mRNA levels were decreased (p = 0,001 and p = 0,04, respectively). Significant positive correlation was observed between LEPR mRNA levels and clinical parameters of MS progression (EDSS, MSSS).

The effect of leptin on blood pressure considering smoking status: a Mendelian randomization study.

Studies on leptin and blood pressure (BP) associations have yielded inconsistent findings. The current study aimed to evaluate the effect of genetically determined leptin on BP and to explore whether smoking status modified this effect. We conducted a Mendelian randomization analysis using the baseline data of 3860 participants in the Framingham Heart Study 3rd generation cohort. Pairwise associations among leptin genetic risk score (GRS), log-transformed leptin (log-leptin), and BP were assessed by multivariate linear regression models. Age and sex were adjusted in the base model, and education, smoking, drinking, and physical activity were adjusted in the full model. The interaction between leptin GRS and smoking was evaluated by adding an interaction term, GRS × smoking, in the fully adjusted model. In the age- and sex-adjusted analyses, log-leptin was positively associated with systolic BP (SBP) (P = 2.35 × 10-79), diastolic BP (DBP) (P = 6.19 × 10-76), mean arterial pressure (MAP) (P = 1.10 × 10-90), and pulse pressure (P = 4.38 × 10-19). Leptin GRS significantly increased log-leptin (P = 0.00001). Leptin GRS was associated with reduced SBP (P = 0.04), DBP (P = 0.006), and MAP (P = 0.008) among current smokers. In the fully adjusted model, significant interactions between GRS and smoking were identified for SBP (P = 0.02), DBP (P = 0.002), and MAP (P = 0.003). Sensitivity analyses among participants not taking antihypertensive or glucose-lowering medications revealed similar associations. Our study provided evidence for a potentially causal relationship between leptin and BP among current smokers.

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

Purpose/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.

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.

Cortisol, leptin and free leptin index (FLI) in newborns in the first days of life and their importance for body weight programming.

BACKGROUND: Birth weight and leptin seem to be the factors responsible for early programming of body weight in later life. A marker for leptin action is free leptin index (FLI), which depends on soluble leptin receptor (Ob-Re) (FLI = leptin/Ob-Re). In the present article, we suggest that FLI is modulated partly by cortisol variations observed in newborns in the first days of life and is connected with their postnatal weight loss. METHODS: The study group consisted of 44 full-term newborns. Leptin, cortisol and Ob-Re concentrations were determined in the umbilical cord blood (UCB) and in the newborns' blood (NB) on the fourth day of life, free leptin index (FLI = leptin/Ob-Re) was calculated. Correlations between the assessed parameters and the somatic features of the newborns were examined. RESULTS: Birth weight, length and chest circumference of newborns were positively correlated with leptin concentration in the UCB but not with FLI in the UCB. Cortisol and leptin concentrations, as well as FLI values declined concomitantly with body weight, and were lower on the fourth day of life than on the first one; however, Ob-Re concentration increased (p < 0.0001). There was a positive correlation between the newborns' birth weight loss percentage evaluated on the fourth day of life and FLI in newborns (R = 0.39; p < 0.01). Positive correlations between cortisol and Ob-Re in UCB (R = 0.35; p < 0.02) and in NB (R = 0.36; p < 0.01), as well as a negative correlation between cortisol and FLI (R = -0.32; p < 0.03) in NB were noted. CONCLUSIONS: Our data suggest a possible relationship between cortisol and a soluble leptin receptor (Ob-Re), which changes free leptin index (FLI) and is connected with birth weight loss in newborns. Whether these observations are important for programming of future body weight of children requires further research.

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

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

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

AIM: 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). METHODS: 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. RESULTS: 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 (ß = 0.167; t ratio = 1.98) and FLI (ß = 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). CONCLUSION: Depressive and moderate-severe anxiety symptoms were associated with high leptin concentrations and leptin resistance in T2D patients.