Higher Leptin Levels Research Articles

Regional and ethnic factors of obesity and diabetes mellitus in women of re-productive age in the Pribaikal region

Introduction. Overweight is currently one of the leading global medical problems. Overweight and obesity contribute significantly to the development of diseases such as diabetes, cardiovascular disorder and can also cause premature death. Obesity has a negative impact on reproductive function; almost a quarter of women of childbearing age are overweight and about a third of them are obese.Aim. To study the characteristics of carbohydrate metabolism, hormonal indicators, and clinical-metabolic profiles, as well as to assess the potential risk of developing diabetes mellitus in women of fertile age with overweight and obesity residing in the Baikal region.Materials and methods. The study involved 60 overweight and obese women of reproductive age in the Pribaikalye region, including 33 women of Russian nationality (group 1) and 27 women of Buryat nationality (group 2). Anthropo-metric, sociodemographic and behavioural criteria were analysed, as well as questionnaires using the FINDRISC Scale. General clinical analyses of blood and urine were performed, lipid profile parameters, glucose, insulin, creatinine, transaminases, estradiol, thyroid hormone, leptin levels in blood plasma were studied. In addition, an oral glucose tolerance test was performed and the insulin resistance index (HOMA-IR) was calculated.Results. In the group of Buryat women with lower body weight as compared to Russians, higher levels of leptin, HOMA- IR index, and larger waist circumference are observed. In Buryat women, low physical activity makes a significant contribution to the development of overweight and obesity, while for Russian women, excessive caloric intake is more important. In accordance with the results of the FINDRISC scale survey, the greatest contribution to the potential development of diabetes mellitus in the Russian group is body mass index (weight), and in the Buryat group, in addition to these indicators, waist circumference and reduced physical activity.Conclusions. The results of the study will be of great help in the development of pro-grammes for the prevention of diabetes and obesity, taking into account regional and ethnic differences among the population.

Clinical and laboratory peculiarities in postmenopausal patients with benign ovarian tumors

Objective. To assess clinical and laboratory peculiarities of postmenopausal patients with benign ovarian tumors. Materials and methods. The data of a prospective study of concomitant somatic and gynecological pathology in postmenopausal patients with benign ovarian tumors (basic group, n = 40) and patients without pathologies (comparison group, n = 15) are presented. Clinical and laboratory data were evaluated in both groups as well. Results. Postmenopausal patients with benign ovarian tumors were frequently exposed to myomas, chronic salpingitis and chronic cervicitis, when women with no ovarian neoplasms did not have these pathologies. Patients of the main group had higher levels of FSG, leptin, GBP and lower levels of vitamin D, than patients of the comparison group. Conclusions. Postmenopausal patients with benign ovarian tumors frequently have concomitant gynecological pathology, pronounced vitamin D insufficiency and high levels of FSG, leptin and GBP in serum samples.

The Association between Leptin and Asprosin Levels in Female Patients with Type II Diabetes Mellitus

Background: Leptin and asprosin are adipokines secreted by white adipose tissue. The leptin and asprosin molecules have many functions in the central nervous system and other functions of the body: Appetite, glucose ‎metabolism, ‎insulin resistance, and cellular death. Objectives: The study aims to determine the potential relationship between leptin and asprosin hormones in female patients with type II diabetes mellitus. Methods: The present study was conducted in Al-Mahmodia Hospital / Baghdad and the laboratories of the College of Science for Girls / University of Baghdad / Iraq, for the period from 1/11/2023 to 1/2/ 2024. This study is a comparative analysis of several essential biomarkers ‎found in the sera of individuals with diabetes via estimating leptin, asprosin, fasting blood glucose, glycated ‎hemoglobin, body mass index, total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase in females with type II diabetes mellitus. The study consisted of 60 participants grouped into: Group I (30 females ‎with diabetes), and group II (30 healthy females). The Biochemical ‎parameters of every participant were ascertained. The quantification of leptin and asprosin in the serum was conducted using the enzyme-linked immunosorbent assay (ELISA). Results: The levels of leptin and asprosin were markedly high in the diabetic group [(‎5.1 ± 0.69‎‎), and (10.3 ± 1.07)] compared with the control group [(2.0 ± 0.48), and (1.6 ± 0.16)] respectively, with a significant difference. Conclusion: Despite the high levels of leptin and asprosin in female patients with Type II diabetes mellitus, the relationship between leptin and asprosin was a weak negative one.

Associations of Adipokine Levels With Levels of Remnant Cholesterol: The Multi-Ethnic Study of Atherosclerosis.

The metabolic syndrome phenotype of individuals with obesity is characterized by elevated levels of triglyceride-rich lipoproteins and remnant particles, which have been shown to be significantly atherogenic. Understanding the association between adipokines, endogenous hormones produced by adipose tissue, and remnant cholesterol (RC) would give insight into the link between obesity and atherosclerotic cardiovascular disease. We studied 1791 MESA (Multi-Ethnic Study of Atherosclerosis) participants who took part in an ancillary study on body composition with adipokine levels measured (leptin, adiponectin, and resistin) at either visit 2 or visit 3. RC was calculated as non-high-density lipoprotein cholesterol minus low-density lipoprotein cholesterol, measured at the same visit as the adipokines, as well as subsequent visits 4 through 6. Multivariable-adjusted linear mixed-effects models were used to assess the cross-sectional and longitudinal associations between adipokines and log-transformed levels of RC. Mean±SD age was 64.5±9.6 years; mean±SD body mass index was 29.9±5.0 kg/m2; and 52.0% were women. In fully adjusted cross-sectional models that included body mass index, diabetes, low-density lipoprotein cholesterol, and lipid-lowering therapy, for each 1-unit increment in adiponectin, there was 14.6% (95% CI, 12.2-16.9) lower RC. With each 1-unit increment in leptin and resistin, there was 4.8% (95% CI, 2.7-7.0) and 4.0% (95% CI, 0.2-8.1) higher RC, respectively. Lower adiponectin and higher leptin were also associated with longitudinal increases in RC levels over median follow-up of 5 (interquartile range, 4-8) years. Lower adiponectin and higher leptin levels were independently associated with higher levels of RC at baseline and longitudinal RC increase, even after accounting for body mass index and low-density lipoprotein cholesterol.

Unraveling the impact of hyperleptinemia on female reproduction: insights from transgenic pig model

BackgroundInfertility is a growing global health concern affecting millions of couples worldwide. Among several factors, an extreme body weight adversely affects reproductive functions. Leptin is a well-known adipokine that serves as an endocrine signal between adiposity and fertility. However, the exact mechanisms underlying the effects of high leptin level on female reproduction remain unclear.MethodsTransgenic pigs overexpressing leptin (♀) were produced by backcrossing and screened for leptin overexpression. The growth curve, fat deposition, reproductive performance, apoptosis, serum hormones and cholesterol production, RNA sequencing, and single-nucleus RNA sequencing (snRNA-seq) of the leptin-overexpressing pigs and wild-type group were evaluated.ResultsTransgenic pigs overexpressing leptin (♀) were obtained, which exhibited significantly reduced body weight, body size, and back fat thickness. These pigs manifested a late onset of puberty (330 ± 54.3 vs. 155 ± 14.7 days), irregular estrous behavior characterized by increased inter-estrous interval (29.2 ± 0 vs. 21.3 ± 0.7 days), and more number of matings until pregnancy (at least 3 times). This reproductive impairment in leptin pigs was related to hormonal imbalances characterized by increased levels of FSH, LH, prolactin, E2, P4, and TSH, altered steroidogenesis such as increased levels of serum cholesterol esters along with steroidogenic markers (StAR, CYP19A), and ovarian dysfunctions manifested by neutrophilic infiltration and low expression of caspase-3 positive cells in the ovaries. Moreover, bulk RNA sequencing of the ovaries also revealed neutrophilic infiltration followed by upregulation of inflammation-related genes. Furthermore, snRNA-seq reflected that leptin overexpression triggered immune response, suppressed follicle development and luteinization, resulting in metabolic dysfunction and hormone imbalance in the ovary.ConclusionsLow body weight in leptin overexpressing pigs adversely affects the reproductive performance, causing delayed puberty, irregular estrous cycles, and reduced breeding efficiency. This is linked to metabolic imbalances, an increased immune response, and altered ovarian functions. This study provides a theoretical basis for the complex mechanisms underlying leptin, and infertility by employing leptin-overexpressing female pigs.

The Role of Adiponectin and Leptin in Fibro-Calcific Aortic Valve Disease: A Systematic Review and Meta-Analysis.

Fibro-calcific aortic valve disease (FCAVD) is a progressive disorder characterized by the thickening and calcification of the aortic valve, eventually leading to aortic stenosis. Adiponectin and leptin, known for their anti-inflammatory and proinflammatory properties, respectively, have been implicated in cardiovascular diseases, but their associations with FCAVD are controversial. This meta-analysis aims to evaluate the relationships between adiponectin and leptin levels and FCAVD, particularly in patients with severe aortic stenosis (AS). A systematic search was conducted across the PubMed, Scopus, and Web of Science databases to identify studies on adiponectin and leptin levels in FCAVD. The methodological quality of each study was assessed using the Newcastle-Ottawa Scale. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated, and publication bias was evaluated using Egger's test and funnel plots. Out of 191 articles identified, 10 studies involving 2360 patients (989 with FCAVD and 1371 controls) were included. The analysis suggested trends in the associations of lower adiponectin levels (SMD = -0.143, 95% CI: -0.344, 0.057, p = 0.161) and higher leptin levels (SMD = 0.175, 95% CI: -0.045, 0.395, p = 0.119) with FCAVD. The association remained a trend for low adiponectin but showed a significant correlation with high leptin in severe AS patients (SMD = 0.29, 95% CI: 0.036, 0.543, p = 0.025). This meta-analysis indicates a potential association between elevated leptin levels and severe aortic stenosis, while the relationship with adiponectin levels remains inconclusive. These findings highlight the need for further and dedicated research to clarify the roles of these adipokines in the pathogenesis of FCAVD and their potential roles as biomarkers for disease progression.

Primary care perspectives on leptin and adiponectin in north Indian families with metabolic syndrome.

Urbanization, sedentary lifestyles, and dietary changes have all contributed to an increase in the prevalence of metabolic syndrome (MetS) in Indian populations during the past 10 years. Numerous markers have been investigated to determine if a person is at risk for developing MetS, with the bulk of them having to do with adipose tissue. Recently, adiponectin and leptin, two biomarkers with a high correlation to cardiometabolic health or disease, are of particular interest. In the general population of India, 100 persons were included. Body mass index (BMI), waist circumference, systolic and diastolic blood pressure, fasting blood glucose, plasma lipids, adiponectin, leptin, insulin, and the homeostasis model were measured to assess insulin resistance. We used binary logistic regression analysis to determine the connection between the researched factors and MetS and Spearman's analyses to evaluate correlations. In all, 200 participants (100 men and 100 women) were enrolled in the study. Men's and women's median ages were 53 and 48, respectively (P < 0.05). Men had significantly greater WHR, SBP, and DBP (P < 0.05, respectively). Women had significantly higher levels of triglycerides, LDL, insulin, adiponectin, leptin, and HOMA-IR (P < 0.05, respectively). Leptin-to-adiponectin ratio was significantly and positively correlated with BMI (r = 0.597, P < 0.001), waist circumference (r = 0.576, P < 0.001), triglycerides (r = 0.190, P = 0.001), insulin levels (r = 0.329, P < 0.000), and HOMA-IR (r = 0.301, P < 0.000). In this study, higher levels of LAR, together with higher levels of leptin and lower levels of adiponectin, were found to be significantly linked with MetS. To properly determine whether LAR can be a predictor of MetS, independent of confounding factors, research with adequate design must be conducted.

Combination of Blood Adiponectin and Leptin Levels Is a Predictor of Biochemical Recurrence in Prostate Cancer Invading the Surrounding Adipose Tissue.

Biochemical recurrence is a process that progresses to castration-resistant prostate cancer (CRPC) and prediction of biochemical recurrence is useful in determining early therapeutic intervention and disease treatment. Prostate cancer is surrounded by adipose tissue, which secretes adipokines, affecting cancer progression. This study aimed to investigate the correlation between blood adipokines and CRPC biochemical recurrence. We retrospectively analyzed the clinical data, including preoperative serum adipokine levels, of 99 patients with pT3a pN0 prostate cancer who underwent proctectomy between 2011 and 2019. The primary outcome was biochemical recurrence (prostate-specific antigen: PSA > 0.2). We identified 65 non-recurrences and 34 biochemical recurrences (one progressed to CRPC). The initial PSA level was significantly higher (p = 0.006), but serum adiponectin (p = 0.328) and leptin (p = 0.647) levels and their ratio (p = 0.323) were not significantly different in the biochemical recurrence group compared with the non-recurrence group. In contrast, significantly more biochemical recurrences were observed in the group with adiponectin < 6 μg/mL and Leptin < 4 ng/mL (p = 0.046), initial PSA > 15 ng/mL, clinical Gleason pattern ≥ 4, and positive resection margin. A significant difference was also observed in the multivariate analysis (hazard ratio: 4.04, 95% confidence interval: 1.21-13.5, p = 0.0232). Thus, low preoperative serum adiponectin and high leptin levels were significantly associated with biochemical recurrence in adipose tissue-invasive prostate cancer, suggesting that they may be useful predictors of biochemical recurrence. Further studies with larger cases are needed to increase the validity of this study.

Genetic polymorphisms (FTO rs9939609 and TMEM18 rs6548238), adipokines (leptin and adiponectin) and adiposity in children and adolescents with asthma

ObjectiveTo describe independent factors related to the interaction of FTO rs9939609, TMEM18 rs6548238, leptin, and adiponectin in children/adolescents with asthma, under the influence of obesity. MethodsThe authors performed a cross-sectional study with 57 children/adolescents, ages 8–19 years, at a tertiary hospital, from 2017 to 2018. Participants were classified by nutritional status, performed spirometry with a bronchodilator test and completed an asthma questionnaire, higher scores indicated more asthma symptoms. Two asthma groups were formed: Group 1(G1)-normal-weight; Group 2(G2)-overweight/obese. Serum was collected for adipokines (n = 32) and genetic polymorphisms (n = 53) dosages. ResultsAge and body mass index (BMI) correlated directly in normal-weight (p = 0.009) and obese participants (p = 0.004). Girls reported more asthma complaints (p = 0.044). Participants with negative bronchodilator responses presented lower BMI (14.55–17.16) than responders (19.4–26.84) (p = 0.049). Leptin dosages are related directly to BMI (5,34–40 ng/ml in obese × 0,54–42 ng/ml in nonobese) (p = 0.003). Levels were high in girls (4.78–17.55 µg/ml) (p = 0.029) and low in nonobese boys (0.54–6.92 µg/ml) (p = 0.006). In obese, low leptin levels (< 10 ng/ml) were found in small airway dysfunction carriers (p = 0.025); elevated adiponectin (> 5 µg/ml) correlated with FEV1/FVC > 80 % (p = 0.035) and positive bronchodilator tests (8.84–13 µg/ml) (p = 0.039); and FTO A allele correlated with low adiponectin 0–8.84 µg/ml (p = 0.021) and low FEV1/FVC (46 %-88 %) (p = 0.023). ConclusionBMI correlated directly with age and leptin levels. Obese participants presented high serum levels of leptin and FTO A allele correlated with low FEV1/FVC. Larger cohorts are necessary for better elucidation of the role of adipokines and polymorphisms in the pathophysiology of asthma and obesity.

70 Circulating leptin and immune-related transcriptomic patterns in clear cell renal cell carcinoma

Abstract Background Obesity has been associated with better outcomes in localized and metastatic clear cell renal cell carcinoma (ccRCC), as well as improved survival on immunotherapy treatment. However, the mechanisms underlying this association remain unclear. Leptin is an adipokine secreted by adipocytes, and circulating levels of leptin are higher in individuals with obesity. Additionally, leptin promotes inflammation and angiogenesis and has been proposed as pro-tumorigenic in colorectal and breast cancer. In this study, we examined how circulating leptin levels relate to both tumor and perinephric fat transcriptomic patterns in a cohort of ccRCC patients by evaluating the associations with body mass index (BMI), sex, and immune-related gene expression patterns. Methods We conducted a retrospective cohort study of 92 treatment-naïve ccRCC patients undergoing nephrectomy at Memorial Sloan Kettering Cancer Center. Available data included circulating leptin from fasting blood samples, clinical characteristics from medical records, and, in a subset of patients, RNA sequencing from tumor and perinephric fat specimens. We analyzed differentially expressed genes (DEG) according to circulating leptin levels using Gene Set Enrichment Analysis (GSEA) to describe pathways that were enriched in patients with high levels of leptin. We performed analysis for the whole cohort and stratified by sex based on differences in leptin levels. Results From the 92 patients with available peripheral leptin measurements, 51 and 44 had available tumor and perinephric fat RNA sequencing data, respectively. Of these, 64 (70%) were male, the median age was 60 years old, and most tumors were low grade and stage. Leptin distribution was significantly different in males than females, with circulating leptin levels of 7 ng/ml (IQR 4-14) and 22 ng/ml (IQR 9-52), respectively. Higher BMI was associated with higher leptin levels, with a correlation coefficient of 0.63 (p&amp;lt;0.001) in males and 0.77 (p&amp;lt;0.001) in females. GSEA of tumor DEGs by circulating leptin, showed upregulation of pathways related to adaptive immune activity in patients with higher leptin levels across sexes, although this association was attenuated in females. Strikingly, in the perinephric fat there were stark differences in opposite directions in female and male specimens, with females showing significantly enriched transcription of genes associated with B cell signaling, humoral and adaptive immune responses. Conclusions Higher leptin levels were associated with a modest increase of immune-related gene expression in the tumors in both males and females, but significantly different directional changes were observed in the perinephric fat. Circulating leptin may be involved in peritumoral immune responses which may link host factors to sex related tumor outcomes. Further studies should aim to address the relationship between leptin activity and the tumor and fat microenvironment. DOD CDMRP Funding: yes

Obesity and Early-Onset Breast Cancer and Specific Molecular Subtype Diagnosis in Black and White Women

Epidemiologic data suggest an association of obesity with breast cancer (BC); however, obesity's contribution to early onset and risk of diagnosis with specific molecular subtypes by race is uncertain. To examine the race-specific association of body mass index with early onset and diagnosis of specific molecular subtypes. This retrospective cohort study included patients with BC diagnosed between October 1, 2017, and March 31, 2022, at 3 University of South Alabama Mitchell Cancer Institute clinics. Participants were also prospectively enrolled for serum leptin measurement. The primary outcome was age at BC onset and specific subtype diagnosis. The secondary outcome was race-specific differences. Odds ratios (ORs) for associations of body mass index with age at onset and subtype were estimated using the Fisher exact test. Race was self-reported. Of the 1085 study patients, 332 (30.6%) were Black with a median age of 58 (IQR, 50-66) years, and 753 (69.4%) were White with a median age of 63 (IQR, 53-71) years. A total of 499 patients (46.0%) had obesity, with Black women with obesity receiving more frequent BC diagnosis than their White counterparts (OR, 2.40; 95% CI, 1.87-3.15; P < .001). In addition, Black women had a significantly higher incidence of early-onset disease (OR, 1.95; 95% CI, 1.33-2.86; P = .001) than White women, and obesity increased this risk significantly in Black women (OR, 2.92; 95% CI, 1.35-6.22; P = .006). Black women with obesity also had a significantly higher risk of luminal A BC (OR, 2.53; 95% CI, 1.81-3.56; P < .001) and triple-negative BC (TNBC) (OR, 2.48; 95% CI, 1.43-4.22; P = .002) diagnosis than White counterparts. Black women, with or without BC, had significantly higher serum leptin levels (median [IQR], 55.3 [40.3-66.2] ng/mL and 29.1 [21.1-46.5] ng/mL, respectively, P < .001) than White women (median [IQR], 33.4 [18.9-47.7] ng/mL and 16.5 [10.0-22.9] ng/mL, respectively), which was associated with higher odds of luminal A disease (OR, 5.25; 95% CI, 1.69-14.32, P = .003). Higher odds of early-onset disease (OR, 3.50; 95% CI, 0.43-23.15; P = .33 for trend), and TNBC diagnosis (OR, 6.00; 95% CI, 0.83-37.27; P = .14 for trend) were also seen, although these outcomes were not statistically significant. In this cohort study of patients with BC, obesity and high serum leptin levels were associated with an enhanced risk of early-onset BC and diagnosis of luminal A and TNBC subtypes in Black women. These findings should help in developing strategies to narrow the existing disparity gaps.

Impact of previous pregnancy and BMI on cellular and serum immune activity from early to late pregnancy

Immunological adaptions during pregnancy play a crucial role in healthy fetal development. Aberrant immune modifications however contribute to adverse pregnancy outcomes, which may be driven by maternal factors such as previous pregnancies and BMI. This secondary analysis of the MicrobeMom2 RCT investigates the changes to maternal inflammatory biomarkers derived from serum and stimulated peripheral blood mononuclear cells (PBMCs) during pregnancy, and the effects of previous pregnancies (parity) and BMI on maternal immune responses. Changes in immune and metabolic biomarkers from early (11–15 weeks’ gestation) to late (28–32 weeks’ gestation) pregnancy were compared using paired t-tests. Participants were then split by parity (nulliparous, parous) and BMI (BMI < 25, BMI > = 25), and the relationship between parity and BMI with immune biomarker levels was examined using independent t-tests, paired t-tests, ANCOVA, and linear regression. Equivalent non-parametric tests were used for skewed data. Recruited women (n = 72) were on average 31.17 (SD ± 4.53) years of age and 25.11 (SD ± 3.82) BMI (kg/m2). Of these, 51 (70.8%) had a previous term pregnancy. Throughout gestation, PBMC cytokines displayed contrasting trends to serum, with a dampening of immune responses noted in PBMCs, and enhanced production of cytokines observed in the serum. Significant decreases in PBMC derived TNF-α, IL-10 and IFN-γ were seen from early to late pregnancy. Serum C3, IL-17A, IL-6, TNF-α, CD163, GDF-15 and leptin increased throughout gestation. First pregnancy was associated with higher levels of leptin in late pregnancy, while parous women showed significant decreases in PBMC derived TNF-α, IL10, and IFN-γ with gestation. Differences in levels of C3, IL-17A, TNF-α, GDF-15 and leptin were observed across BMI groups. Overall, serum-derived cytokines exhibit contrasting levels to those derived from stimulated PBMCs. Maternal immune responses undergo significant changes from early to late pregnancy, which are influenced by parity and BMI. These differences aid our understanding as to why first-time mothers are at greater risk of placental disease such as pre-eclampsia and fetal growth restriction.

Amyloid-β peptide treatment reverses bone loss in the mandibular condyle via Wnt signalling pathway

ObjectiveTo explore the effect of amyloid-β peptide (Aβ) on mandibular condyle to develop a new treatment for postmenopausal women with Temporomandibular joint osteoarthritis. MethodsA murine bone loss model was established by ovariectomy. Microstructure parameters of the condyle were measured by microcomputed tomography before and after intraperitoneal injection with Aβ. Flow cytometry, Alizarin red staining, RT-qPCR assays, FITC/PI staining, Oil Red O staining and western blotting were used to evaluate the effect of Aβ on the osteogenic differentiation of mouse bone marrow stromal stem cells (mBMSCs). ResultsIn vivo, condylar microstructure parameters increased. Serum osteoprotegerin and procollagen type 1 N propeptide increased in a dose-dependent manner after the injection of Aβ, which were opposite the changes observed in c-terminal telopeptides of type I collagen, tumor necrosis factor-α and the high serum level of leptin. In vitro, Aβ promoted calcium nodule formation in the cells. The expression of ALP, Runx2, osteorix and osteocalcin increased significantly. The expression of mRNAs related to the Wnt signaling pathway was significantly upregulated, which could be blocked by DKK1. ConclusionAβ can reverse bone loss in the mandibular condyle in ovariectomized mice through promoting the osteogenic differentiation of mBMSCs via the Wnt pathway.

Changes in bone turnover markers 6–12 months after bariatric surgery

A rise in bone turnover markers (BTM) after bariatric surgery predicts poor bone health years later. This study explored factors associated with BTM and changes in BTM after bariatric surgery. Inclusion criteria were subjects 18 to 65 years of age with morbid obesity undergoing bariatric surgery. All data were measured before and 6 and 12 months after surgery. The study included 104 subjects: women/men: 83/21; mean age 43.1 (SD 8.4) years; BMI: 38.8 kg/m2 (SD 3.8). Surgery with Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) was performed in 84 (81%) and 20 (19%) subjects, respectively. From before to 6–12 months after surgery, procollagen type 1 N-terminal propeptid (P1NP) increased by 45.6 µg/L (95% CI 41.5–50.0, p < 0.001), and alkaline phosphatase (ALP) by 10 U/L (95% CI 7–14, p < 0.001). The increases were significantly larger after RYGB than after SG. The APOE- Ɛ3 allele was associated with low levels of BTM and high levels of leptin. There was an unfavourable increase in BTM after bariatric surgery. SG compared to RYGB and the presence of the APOE-Ɛ3 allele were associated with less unfavourable effects. The study emphasises the importance of optimal prophylactic interventions after bariatric surgery to prevent osteoporosis.

The role of leptin, resistin, and irisin levels as prognostic indicators of lung cancer in Iraqi patients

ABSTRACT Lung cancer is the most lethal malignancy and is often associated with a poor prognosis because of a lack of prognostic markers. Thus, this study aimed to determine whether irisin, resistin, and leptin could be useful biomarkers for lung cancer prognosis. The study is designed on 100 lung cancer patients, (66) patients with non-small cell lung cancer (NSCLC) and (34) patients with small cell lung cancer (SCLC). For the purpose of comparison, (66) samples as control group. Using the ELISA technique to estimate leptin, resistin, and irisin levels in patients and controls. The results indicate a significant increase in mean leptin in NSCLC and SCLC groups (10.71 ± 0.30 and 10.13 ± 0.51) ng/ml, respectively, in contrast to the control (8.26 ± 0.47) ng/ml. The mean of irisin and resistin had been significantly increased in SCLC group (5.86 ± 0.13 pg/ml and 7.25 ± 0.38 ng/ml, respectively) and NSCLC group (5.08 ± 0.09 pg/ml and 6.35 ± 0.13 ng/ml, respectively) in contrast to the control (4.13 ± 0.09 pg/ml and 3.96 ± 0.17 ng/ml, respectively). The higher levels of leptin in NSCLC patients could serve as a prognostic marker for NSCLC. The variations in Resistin and Irisin levels across different stages of lung cancer suggest that they might be useful in predicting the prognosis of lung cancer.

Impact of body mass index (BMI) on survival outcomes in patients with cancer treated with immune checkpoint inhibitors (ICPI): A systematic review and meta analysis.

2624 Background: With the increased adoption of ICPI in treating various cancers, there is active exploration of individual-level factors that could predict treatment responses. A high-body mass index (BMI) induces a chronic inflammatory state and could drive T-cell dysfunction through high leptin levels, which may confer better outcomes with ICPI usage. However, there are conflicting outcomes in different studies. We performed this systematic review and meta-analysis to evaluate survival outcomes with ICPI in patients with BMI ≥25 vs &lt;25 Kg/m2. Methods: A comprehensive search was conducted across PubMed, Embase, Scopus, and web of science databases. The original studies evaluating response [overall survival (OS) and progression free survival (PFS)], to ICPI-based therapies among adult cancer patients, stratified by BMI groups (high, BMI ≥25Kg/m2 or low, BMI &lt;25Kg/m2), were included. RevMan version 5.4.1 was used for statistical analysis. A random effect model with inverse variance as the statistical method was used for hazard ratio (HR) and 95% confidence interval (CI). Results: Of 1215 identified studies, 22 observational studies, comprising 5859 patients (60.3% males) met the inclusion criteria. ECOG performance score was reported as 0-1 for 40.3% patients, and ≥2 for 7.1% patients. In 12-studies only PD-1 and/or PD-L1 inhibitors were administered, but no CTLA-4 inhibitor. Most frequently reported cancers were non-small cell cancer of lung (40.9%), melanoma (36.6%), and renal cell cancer (31.8%) in advanced/metastatic stages. Higher BMI, compared to low BMI, favored significant improvement in PFS [HR 0.86; 95% CI (0.76, 0.99), P= 0.03, I2 47%], and OS [ HR 0.73; 95% CI (0.62, 0.85), P&lt; 0.0001, I2 53%] with any ICPI-based regimens. Similar findings were noted for patients treated with PD-1/PDL1 inhibitors [Table]. Conclusions: This study contributes to the evidence that BMI of 25 kg/m2 or higher exerts a beneficial impact on PFS and OS among cancer patients treated with ICPI. The favorable impact underscores the significance of considering BMI as a potential prognostic factor in ICPI therapy. However, the precise underlying mechanisms responsible for this observation warrant further investigation to deepen our understanding and potentially optimize therapeutic strategies in this patient population. [Table: see text]

The association between leptin, adiponectin levels and the ovarian reserve in women of reproductive age.

Reproduction ability requires a certain amount of body fat that is necessary for ovulation, menstruation and pregnancy. Fat tissue represents an endocrine organ with high metabolic activity as it produces adipokines such as leptin and adiponectin. Our aim is to examine potential associations between women of reproductive age's ovarian reserves and their levels of leptin and adiponectin. 74 women between 19 and 40 years of age consented to take part. Based on the patterns of their ovarian reserves, the women were divided into three main groups: women with adequate ovarian reserves (AOR - Group A, n=30), women with polycystic ovary syndrome (PCOS - Group B, n=31) and women with depleted ovarian reserves (DOR - Group C, n=13). Among these groups, several biochemical and demographic parameters were statistically compared. Compared to the other two groups, women with DOR had statistically higher age and follicle stimulation hormone (FSH) levels. For estradiol (E2) and thyroid-stimulating hormone (TSH), no statistically significant difference was seen between the groups. In addition, women with PCOS had higher body mass index (BMI), luteinizing hormone (LH), total testosterone (TT), 17 hydroxyprogesterone (17-OHP), dehydroepiandrosterone (DHEA), anti-Mullerian hormone (AMH), and antral follicle count (AFC) than the other two groups. In line with expectations, women with DOR also had lower levels of AMH and AFC than the other two groups. Women with PCOS had higher leptin levels than the other two groups, but there was no statistically significant difference. Women with PCOS had lower levels of adiponectin than the other groups, however the difference was not statistically significant. The way we classified women in our study according to their ovarian reserves is completely consistent with what has been published internationally. The ovarian reserve in women of reproductive age is not strongly correlated with leptin and adiponectin levels. For safe conclusions, more research including a greater number of samples is required.

Both endothelial mineralocorticoid receptor expression and hyperleptinemia are required for clinical characteristics of placental ischemia in mice.

One of the initiating events in preeclampsia (PE) is placental ischemia. Rodent models of placental ischemia do not present with vascular endothelial dysfunction, a hallmark of PE. We previously demonstrated a role for leptin in endothelial dysfunction in pregnancy in the absence of placental ischemia. We hypothesized that placental ischemia requires hyperleptinemia and endothelial mineralocorticoid receptor (ECMR) expression to induce PE-associated endothelial dysfunction in pregnant mice. We induced placental ischemia via the reduced uterine perfusion pressure (RUPP) procedure in pregnant ECMR-intact (ECMR+/+) and ECMR deletion (ECMR-/-) mice at gestational day (GD) 13. ECMR+/+ RUPP pregnant mice also received concurrent leptin infusion via miniosmotic pump (0.9 mg/kg/day). RUPP increased blood pressure via radiotelemetry and decreased fetal growth in ECMR+/+ pregnant mice. Both increases in blood pressure and reduced fetal growth were abolished in RUPP ECMR-/- mice. Placental ischemia did not decrease endothelial-dependent relaxation to acetylcholine (ACh) but increased phenylephrine (Phe) contraction in mesenteric arteries of pregnant mice, which was ablated by ECMR deletion. Addition of leptin to RUPP mice significantly reduced ACh relaxation in ECMR+/+ pregnant mice, accompanied by an increase in soluble FMS-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PLGF) ratio. In conclusion, our data indicate that high leptin levels drive endothelial dysfunction in PE and that ECMR is required for clinical characteristics of hypertension and fetal growth restriction in placental ischemia PE. Collectively, we show that both ECMR and leptin play a role to mediate PE.NEW & NOTEWORTHY Leptin is a key feature of preeclampsia that initiates vascular endothelial dysfunction in preeclampsia characterized by placental ischemia. Endothelial mineralocorticoid receptor (ECMR) deletion in placental ischemia protects pregnant mice from elevations in blood pressure and fetal growth restriction in pregnancy. Increases in leptin production mediate the key pathological feature of endothelial dysfunction in preeclampsia in rodents. ECMR activation contributes to the increase in blood pressure and fetal growth restriction in preeclampsia.

Leptin gene Polymorphism and Leptin protein levels in Pediatric Autoimmune Hepatitis

ABSTRACT Background Leptin plays a role in regulating energy balance, immunity, and inflammation. Studies suggest higher leptin levels might be associated with various autoimmune diseases. Most of them were in adult. To our knowledge, our study is one of the few that describe serum leptin level and leptin gene polymorphism in children with autoimmune hepatitis (AIH). Objective Our study aims to explore the association between serum leptin level and genetic variations in leptin gene with the likelihood of AIH in children. Patients and methods Thirty-one children with AIH and 29 healthy children serving as a control group were included. Serum leptin levels were measured by ELISA assays. Leptin rs2167270 genotyping was done using the real time-PCR. The relationship of serum leptin level and leptin gene polymorphism with patients’ data was studied. Patients follow up to assess treatment response. Results Children with AIH had significantly higher levels of leptin compared to healthy controls. GG genotype was significantly more prevalent in the AIH group compared to controls. Conclusion High serum leptin levels and leptin gene polymorphism may play a role in AIH development. It is worthy to recognize if leptin can serve as diagnostic and/or therapeutic target in AIH in children.

MiR-21, miR-221, miR-29 and miR-34 are distinguishable molecular features of a metabolically unhealthy phenotype in young adults.

Discrepancies between the measurement of body mass index (BMI) and metabolic health status have been described for the onset of metabolic diseases. Studying novel biomarkers, some of which are associated with metabolic syndrome, can help us to understand the differences between metabolic health (MetH) and BMI. A group of 1469 young adults with pre-specified anthropometric and blood biochemical parameters were selected. Of these, 80 subjects were included in the downstream analysis that considered their BMI and MetH parameters for selection as follows: norm weight metabolically healthy (MHNW) or metabolically unhealthy (MUNW); overweight/obese metabolically healthy (MHOW) or metabolically unhealthy (MUOW). Our results showed for the first time the differences when the MetH status and the BMI are considered as global MetH statures. First, all the evaluated miRNAs presented a higher expression in the metabolically unhealthy group than the metabolically healthy group. The higher levels of leptin, IL-1b, IL-8, IL-17A, miR-221, miR-21, and miR-29 are directly associated with metabolic unhealthy and OW/OB phenotypes (MUOW group). In contrast, high levels of miR34 were detected only in the MUNW group. We found differences in the SIRT1-PGC1α pathway with increased levels of SIRT1+ cells and diminished mRNA levels of PGCa in the metabolically unhealthy compared to metabolically healthy subjects. Our results demonstrate that even when metabolic diseases are not apparent in young adult populations, MetH and BMI have a distinguishable phenotype print that signals the potential to develop major metabolic diseases.