Serum Leptin Levels Research Articles

Spontaneous nonsense mutation in the tuftelin 1 gene is associated with abnormal hair appearance and amelioration of glucose and lipid metabolism in the rat.

Recently, we have identified a recessive mutation, an abnormal coat appearance in the BXH6 strain, a member of the HXB/BXH set of recombinant inbred (RI) strains. The RI strains were derived from the spontaneously hypertensive rat (SHR) and Brown Norway rat (BN-Lx) progenitors. Whole genome sequencing of the mutant rats identified the 195875980 G/A mutation in the tuftelin 1 (Tuft1) gene on chromosome 2, which resulted in a premature stop codon. Compared with wild-type BXH6 rats, BXH6-Tuft1 mutant rats exhibited lower body weight due to reduced visceral fat and ectopic fat accumulation in the liver and heart. Reduced adiposity was associated with decreased serum glucose and insulin and increased insulin-stimulated glycogenesis in skeletal muscle. In addition, mutant rats had lower serum monocyte chemoattractant protein-1 and leptin levels, indicative of reduced inflammation. Analysis of the liver proteome identified differentially expressed proteins from fatty acid metabolism and β-oxidation, peroxisomes, carbohydrate metabolism, inflammation, and proteasome pathways. These results provide evidence for the important role of the Tuft1 gene in the regulation of lipid and glucose metabolism and suggest underlying molecular mechanisms.NEW & NOTEWORTHY A new spontaneous mutation, abnormal hair appearance in the rat, has been identified as a nonfunctional tuftelin 1 (Tuft1) gene. The pleiotropic effects of this mutation regulate glucose and lipid metabolism. Analysis of the liver proteome revealed possible molecular mechanisms for the metabolic effects of the Tuft1 gene.

Potential use of cowpea protein hydrolysate as a dietary supplement in broiler chickens: effects on growth, intestinal morphology, muscle lipid profile, and immune status

In the current study, we tested the effects of dietary cowpea protein hydrolysate (CPH) on broilers’ growth, carcase traits, intestinal histomorphology, The fatty acid profile of breast muscle, blood biochemical parameters, and immune status. Three-day age male Ross-308 broilers (n = 300, average weight 86.72 g ± 0.20) were distributed into five groups and fed on five diets supplied with five levels of CPH at 0, 2, 4, 6, and 8 g kg−1 for 35 days. The results revealed that dietary CPH did not change (P < 0.05) the broilers’ growth performance or carcase traits, except for a quadratic decrease (P < 0.05) in FCR at concentrations 2 and 4 g kg−1 during the finisher period. The villus heights (VH) and goblet cell count (GCC) were increased (P < 0.05) in the duodenum and jejunum; however, the villus width decreased (P < 0.05) in the duodenum without showing changes (P < 0.05) in the jejunum and ileum. Dietary supplementation with 6 g CPH kg−1 increased (P < 0.05) the duodenal crypt depth (CD). Dietary supplementation with 8 g CPH kg −1 increased the VH: CD in the duodenum compared to the control; nevertheless, a quadratic (P < 0.05) change was reported in the jejunum. The VH: CD did not change (P < 0.05) in the ileum; however, dietary supplementation with 6 CPH kg−1 increased (P < 0.05) the ileal VH and GCC. The inclusion of CPH led to a linear (P < 0.05) increase in the total n-3 polyunsaturated fatty acids (PUFA), n-6 PUFA, and n-3/n-6 PUFA in broilers’ breast muscle. An increase in the assessed metabolic and immune status indices was reported, as evidenced by increases (P < 0.05) in thyroid hormones, growth hormone, total protein, albumin, globulin, lysozymes, interferon-gamma, interleukin10, and complement 3 serum levels. However, the serum glucose and leptin levels did not show significant (p > 0.05) changes in response to dietary CPH. Moreover, the dietary CPH levels 4–8 g kg−1 upregulated the immunostaining of IgG in the spleen of these groups. These findings suggested that including CPH in broiler diets could be an effective candidate for modulating the chickens’ metabolic and immune status; however, it had no increased effect on broiler growth.

T2D triggers distinct cardiac transcriptomic signatures in patients with severe aortic stenosis

Abstract Type 2 diabetes (T2D) is often associated to left ventricular (LV) pressure overload, as in aortic stenosis (AS). We reported, on DIAPASON cohort, that T2D increases adverse cardiac remodelling and dysfunction in patients with severe AS referred for aortic valve replacement. We aimed to study the underlying molecular mechanisms by a transcriptomic approach. We realised a transcriptomic analysis of LV cardiac biopsies obtained during aortic valve surgery from 17 T2D and 30 non-diabetic patients. Principal component analysis (PCA), on the 1029 significantly differentially expressed genes, shows a general segregation between T2D and non-diabetic patients. Functional enrichment maps reveal that 4 major biological processes are upregulated in T2D patients: regulation of inflammation, adaptation to cardiac hypertrophy, regulation of endothelial function/angiogenesis, and organisation of extracellular matrix. Decreased gene expression by T2D gathers 4 major biological processes: regulation of cardiac muscle contraction, mitochondrial organization, organization of mitochondrial respiratory chain and amino acid metabolism. After adjustment with other T2D comorbidities (age, sex, hypertension, BMI or the 4 combined), T2D effect remains mainly significant on the upregulated biological processes whereas the downregulation of amino acid metabolism, regulation of cardiac muscle contraction and mitochondrial transport processes seems to depend on hypertension and age. As an overlap was still present between T2D and non-diabetics transcriptomes in the PCA, we decided to use Factor Analysis of Mixed Data to identify potential subgroups of patients among the whole cohort. 84 patients have been clustered into 3 groups. Cluster 1 is associated with a patient profile without T2D and displaying a mild cardiac dysfunction, contrary to cluster 3 which includes mainly male T2D patients with a pronounced structural and functional cardiac alteration. Cluster 2 is only composed of female patients with higher BMI and leptin serum level, diastolic alteration and a moderately increased hypertrophy. Biological processes were differently affected between cluster 1 and cluster 2 or 3. Cluster 2 presents a decrease in gene expression involved in histone and protein demethylation. As for cluster 3, the expression of genes involved in immune response processes is increased while the one for the regulation of cardiac muscle organisation is decreased. To conclude, T2D is specifically associated with a reduction of gene expression involved in mitochondrial function, and an upregulation of angiogenesis, inflammation, and organisation of extracellular matrix. The unsupervised analysis revealed different clusters with specific gene expression and more specifically an association of female sex and metabolic syndrome with demethylation processes, and an association of T2D in men with inflammation and dysregulation of cardiac muscle contraction processes.Biological process in T2D patients

Network analysis identifies circulating miR-155 as predictive biomarker of type 2 diabetes mellitus development in obese patients: a pilot study

Obesity is the main risk factor for many non-communicable diseases. In clinical practice, unspecific markers are used for the determination of metabolic alterations and inflammation, without allowing the characterization of subjects at higher risk of complications. Circulating microRNAs represent an attractive approach for early screening to identify subjects affected by obesity more at risk of developing connected pathologies. The aim of this study was the identification of circulating free and extracellular vesicles (EVs)-embedded microRNAs able to identify obese patients at higher risk of type 2 diabetes (DM2). The expression data of circulating microRNAs derived from obese patients (OB), with DM2 (OBDM) and healthy donors were combined with clinical data, through network-based methodology implemented by weighted gene co-expression network analysis. The six circulating microRNAs overexpressed in OBDM patients were evaluated in a second group of patients, confirming the overexpression of miR-155-5p in OBDM patients. Interestingly, the combination of miR-155-5p with serum levels of IL-8, Leptin and RAGE was useful to identify OB patients most at risk of developing DM2. These results suggest that miR-155-5p is a potential circulating biomarker for DM2 and that the combination of this microRNA with other inflammatory markers in OB patients can predict the risk of developing DM2.

Association of Adipocytokines and Vitamin D Status in Tuberculosis

Leptin and Adiponectin are considered principal indicators of tuberculosis (TB). They are critical parts of the pathophysiological processes to which treatment can be applied. Thus, this research aimed at finding out the role of Adipocytokines and 25-dihydroxy vitamin D in the aetiology of tuberculosis. The research sample included (90) participants divided into (50) tuberculosis patients and (40) healthy subjects representing the control group who were age and sex-matched. Circulating levels of adipocytokines and 25- dihydroxy vitamin D were analysed by using ELISA techniques. Compared to the subjects of control group, tuberculosis subjects had significantly (P&lt;0.0001) lower levels of serum leptin (5.84±1.83 pg/mL) and vitamin D (2.77±0.52 ng/mL). However, compared to their control counterparts, tuberculosis patients had significantly (P&lt;0.0001) higher levels of adiponectin (16.30±1.23 ng/mL). The ROC curve analysis of Leptin, Adiponectin, and 25-dihydroxy vitamin D indicated a high diagnostic value in predicting the risk of tuberculosis. The present study findings revealed that elevated serum adiponectin with decreased serum leptin levels and hypovitaminosis D are strongly correlated with the pathogenesis and state of tuberculosis.

Case report: clinical improvements observed in first off-label metreleptin treatment of a patient with atypical anorexia nervosa

Off-label metreleptin treatment resulted in cognitive, emotional and behavioral improvements of patients with anorexia nervosa, who presented with hypoleptinemia. We now report a case study of a 16-year-old female patient with atypical anorexia nervosa who was treated off-label with metreleptin for 11 days. She had lost 21 kg over 6 months. Her body mass index at referral for inpatient treatment was 20 kg/m2, her serum leptin level was just within the normal range (2.4 ng/ml). Dosing resulted in prominent improvements of mood and weight phobia entailing a comparatively brief inpatient treatment. The observed improvements are similar to those observed in patients with AN, suggesting overlapping mechanisms with respect to clinical effects induced by elevations of absolute or relative hypoleptinemia. Randomized controlled trials are warranted for both eating disorders.

Alterations in Adipose Tissue Distribution, Cell Morphology, and Function Mark Primary Insulin Hypersecretion in Youth With Obesity.

Excessive insulin secretion independent of insulin resistance, defined as primary hypersecretion, is associated with obesity and an unfavorable metabolic phenotype. We examined the characteristics of the adipose tissue in youths with primary insulin hypersecretion and the longitudinal metabolic alterations influenced by the complex adipo-insular interplay. In a multiethnic cohort of non-diabetic adolescents with obesity, primary insulin hypersecretors had enhanced model-derived β-cell glucose sensitivity and rate sensitivity, but worse glucose tolerance, despite similar demographics, adiposity, and insulin resistance measured by both OGTT and euglycemic-hyperinsulinemic clamp. Hypersecretors had greater intrahepatic and visceral fat depots at abdominal MRI, hypertrophic abdominal subcutaneous adipocytes, higher FFA and leptin serum levels per fat mass, and faster in vivo lipid turnover assessed by a long-term 2H2O labeling protocol. At 2-year follow up, hypersecretors had greater fat accrual and 3-fold higher risk for abnormal glucose tolerance, while individuals with hypertrophic adipocytes or higher leptin levels showed enhanced β-cell glucose sensitivity. Primary insulin hypersecretion is associated with marked alterations in adipose tissue distribution, cellularity, and lipid dynamics, independent of whole-body adiposity and insulin resistance. Pathogenetic insight into the metabolic crosstalk between β-cell and adipocyte may help identify individuals at risk for chronic hyperinsulinemia, body weight gain, and glucose intolerance.

The role of adiposity, adipokines and polymorphisms of leptin and adiponectin in myelodysplastic syndromes.

The aim of the present study was to investigate the relationship between leptin and adiponectin gene polymorphisms, circulating levels of leptin and adiponectin, adiposity and clinical markers in patients with myelodysplastic syndrome (MDS). This cross-sectional study was conducted with 102 adults and elderly MDS patients and 102 age- and sex-matched controls. Clinical characteristics, co-morbidities, anthropometric data, laboratory evaluation and genetic analysis (polymorphisms -2548G > A/rs7799039 of the LEP gene and +276G > T/rs1501299 of the ADIPOQ gene) were investigated. Serum leptin was higher and adiponectin lower in MDS when compared with controls. There was a significant positive correlation between serum leptin levels and BMI (r = 0·264, P = 0·025), waist circumference (r = 0·235, P = 0·047), body fat percentage (BF %) (r = 0·373, P = 0·001) and the fat mass index (FMI) (r = 0·371, P < 0·001). A lower mean adiponectin was found among patients with high BF %, higher visceral adiposity index and metabolic syndrome. A significant association was found between the AA genotype (mutant) of the LEP polymorphism rs7799039 and male sex and blast excess (≥ 5 %). In addition, a significant association was observed between the TT genotype (mutant) of the ADIPOQ rs1501299 polymorphism and Fe overload. These results demonstrate the importance of a comprehensive and systematic evaluation in patients with MDS in order to identify and control negative factors not related to the disease at an early stage.

Leptin Rs7799039 polymorphism is associated with type 2 diabetes mellitus Egyptian patients

Background Leptin (LEP) is an anti-obesity hormone that regulates food intake, energy expenditure, and glucose metabolism. The genetic variants in LEP and the LEP receptor (LEPR) gene may play an important role in the pathogenesis of type 2 diabetes mellitus (T2DM) and obesity. The current study aimed to investigate the association of serum LEP levels, and LEP polymorphisms in LEP (rs7799039, 2548 G/A) with T2DM in Egyptian patients. Methods A total of 205 subjects were included in the present case-control study, consisting of 100 T2DM patients and 105 healthy controls. The anthropometric, psychometric, and biochemical measurements were taken from all the subjects. The genotyping of LEP gene variants was carried out by polymerase chain reaction TaqMan technology. Serum LEP levels were measured by the ELISA technique. Results T2DM patients had significantly elevated levels of glycated haemoglobin (HbA1c), fasting blood sugar (FBS), postprandial blood sugar (PPBS), international normalisation ratio (INR), creatinine, urea, cholesterol, triglyceride (TG), and low-density lipoproteins (LDL) and significantly decreased high-density lipoprotein (HDL) compared to healthy subjects. serum LEP levels were significantly decreased p (<0.001) as compared to the control group. LEP gene SNP rs7799039 was associated with an increased diabetic risk with A allele being more frequent in T2DM patients than control subjects. The distribution of the AA genotype and GA genotype of LEP SNP rs7799039 was higher in the diabetic group than control one. In addition, AA + GA genotype carriers had significantly elevated HbA1c, FBS, PPBS, TG, and LDL levels and on the contrary, decreased serum LEP levels compared to GG homozygotes. Conclusion The genetic polymorphism rs7799039 showed a highly significant correlation with blood LEP. The co-dominant and dominant models of the LEP genetic polymorphism (rs7799039, 2548 G/A) were shown to have a significant correlation with complicated and uncomplicated diabetes individuals, but we have found that serum LEP levels were inversely related with control and diabetes patients. A positive significant association was found between LEP genetic polymorphism (rs7799039, 2548 G/A) and serum LEP in patients and controls. LEP levels and its rs7799039 genetic variant may play a vital role in increasing T2DM susceptibility.

Association of Leptin with Glucose Intolerance and Gestational Diabetes Mellitus in Pregnant Women: Prospective Analytical Case-Control Study.

This study aimed to investigate the use of leptin as a marker for gestational diabetes by analyzing any correlation between serum leptin levels versus oral glucose tolerance tests (at 24 to 28weeks of pregnancy) and increased body weight (during pregnancy). A total of 110 female cases (81 pregnant and 29 non-pregnant) were included in the study. The 81 pregnant cases were divided into 3 groups according to their oral glucose tolerance test results. A chi-square test was used for categorical variables. The distribution of numerical variables was tested with the Shapiro-Wilk test. ANOVA and a post-hoc Bonferroni test was used for parametric data. Kruskal-Wallis variance analysis was used for non-parametric data. The Mann-Whitney U-test was used for pairwise comparisons. Spearman correlation analysis and multivariate regression analysis were performed for the evaluation of the correlation analysis between the parameters. Oral glucose tolerance test results were compared with leptin levels with a cut-off value of 11.43 for leptin. The ROC curve demonstrated an 83.3% sensitivity and 72.1% specificity for leptin. Leptin may play a role in the pathophysiology of gestational diabetes mellitus. However, the relationship between leptin levels and maternal weight gain during pregnancy is still unknown.

Adipokines in rheumatoid arthritis patients suffering glomerulonephritis

Background: Beside their eminent role in metabolic syndrome, white adipose tissue (WAT) derived adipokines might have a distinguished role in autoimmune and rheumatic diseases. In addition, increased level of many adipokines is observed in patients suffering glomerulonephritis. The status of adipokines was not studied in rheumatoid arthritis patients (RA) suffering glomerulonephritis (GN). Objective: To study serum level of adiponectin, leptin, and Visfatin in RA patients suffering GN in a trial to elucidate if they play a role on metabolic or endothelial function. Cases and methods: In this cross-sectional case control observational study, we compared serum level of adiponectin, leptin, and Visfatin in fifty RA patients (group I) in coparison to fifty RA cases suffering chronic GN (group II) and fifty normal control subjects. In addition, we looked for kidney function tests and 24 urine protein (UP), serum calcium, phosphorus, alkaline phosphatase (AP), 25 hydroxy vitamin D (25 OH vit. D), parathyroid hormone (PTH), C-reactive protein (CRP), interleukin 6(IL6), lipid profile, and Homa insulin resistanc (Homa IR). RA cases were further investigated for rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) carotid arteries intima media thickness (IMT), brachial artery flow mediated Dilation (BA-FMD), health assessment questionnaire (HAQ), disease activity score calculator (DASC), simple disease activity index (SDAI), and clinical disease activity index (CDAI). Percutaneous kidney biopsies were obtained in group II patients. Results: Serum adiponectin and Visfatin are significantly higher and serum leptin is significantly lower in Group II compared to group I and the control group (20.3 vs. 18.6 and 12.3, 24,5 vs. 20.9 and 9.8, and 3.6 vs. 4.6 and 7.8 ng/mL for median serum adiponectin, visfatin, and leptin in group II vs group I and control group respectively, P&lt;0.001 in all). Serum level of 25 (OH) vit D is significantly lower, while serum AP, PTH and Homa IR are significantly higher in group I compared to control subjects (18 vs. 37 ng/mL, 140.5 vs, 57 u/L, 63 vs 47.8 ng/mL, and 13.2 vs 4 respectively, P&lt;0.001 in all) whilst there is no significant difference in these parameters between the RA groups. BA-FMD is significantly lower in group II vs group I (3% vs 4%, P=0.02) but there are no significant differences between these two groups in IMT of carotid arteries, HAQ, DASC, SDAI or CDAI. Moreover, there is no difference in any of the studied parameters within patients of group II according to renal histopathology. Conclusion: Studied adipokines have no relation to metabolic or vascular complications of RA. Changes of serum adipokines in GN patients are unrelated to inflammation. This pilot study would stimulate further research looking for the possible role of different adipokines in GN complicating RA.

Serum Leptin Receptor and the rs1137101 Variant of the LEPR Gene Are Associated with Bladder Cancer.

Globally, bladder cancer (BC) is one of the ten most common tumors. Obesity is a worldwide problem associated with an increased BC risk. Considering that levels of leptin and/or its receptor are often deregulated in obese individuals, we hypothesized that they could contribute to BC. To test this hypothesis, we utilized a case-control study in which 116 patients with a confirmed diagnosis of BC and 116 controls were recruited. The serum levels of leptin and leptin receptor were measured. Patients and controls were also genotyped for SNPs in the LEP (rs7799039, rs791620, and rs2167270) and LEPR genes (rs1137100, rs1137101, and rs1805094). The univariate analysis indicated that BC patients had significantly higher levels of leptin and lower levels of leptin receptor (p < 0.05). Moreover, rs7799039 of LEP and rs1137101 of LEPR were associated with BC (p < 0.05). In the multivariate analysis, leptin receptor levels were protective (OR: 0.98, 95% CI = 0.97-0.99, p = 0.002) while the GG genotype of rs1137101 of LEPR increased BC risk (OR: 3.42, 95% CI = 1.27-9.20, p = 0.02). These findings highlight that lifestyle changes could be useful in preventing BC and that disturbances in energy metabolism could play a role in the pathobiology of BC.

Circulating Levels of Leptin and Lipocalin-2 in Patients With X-Linked Hypophosphatemia.

Individuals with X-linked hypophosphatemia (XLH) are at greater risk for being overweight or obese. Whether there are underlying metabolic abnormalities that put patients with XLH at greater risk for excessive weight gain is largely unknown. Lipocalin-2 (LCN2) has recently received attention as a factor regulating energy consumption and specifically is postulated to be anorexigenic and to improve insulin sensitivity. In a retrospective study, circulating levels of LCN2, leptin, and insulin were measured in 32 patients with XLH, ages 2-60 years, all of whom were being treated with burosumab, and 38 control subjects. Control subjects were chosen who were close in age to those with XLH, with a similar number of participants of each sex. Subjects were analyzed in 3 age cohorts, 2-10 years, 11-18 years, and 20-60 years. In all age groups LCN2 levels were lower in the patients with XLH than in controls but when adjusted for weight class (normal, overweight, obese) the differences were not significant. In contrast, serum leptin levels were significantly lower in children with XLH compared to controls in the 2-10 years age cohort. Serum levels of insulin were also significantly lower in the 2-10-year-old children with XLH when compared with controls. We conclude that changes in expression of lipocalin-2 in children and adolescents with XLH is unlikely to contribute to their risk for obesity in adulthood. It is unclear if lower circulating levels of leptin in these children plays a role in the higher prevalence of obesity among adults with XLH.

Obesity as a risk factor for chronic kidney disease: a contemporary view on the problem. Review

The review article is devoted to an actual clinical problem of participation of obesity in development and progression of chronic kidney disease (CKD). Some pathogenic links due to which a negative renal effect of obesity is mediated including in particular, dyslipidemia (DLP), endothelial dysfunction (ED) of renal vessels, activation of renin‑angiotensin‑aldosterone system (RAAS), arterial hypertension (AH), a production of adipose tissue mediators with renal injuring properties such as leptin, tumor necrosis factor‑α, interleukines 1,6,8 are discussed. The data about the main factors of progression of renal damage associated with obesity included insulin resistance (IR), hyperinsulinemia, DLP, systemic and renal hemodynamic disorders caused by activation of RAAS (AH, intraglomerular hypertension) are given. The role of metabolic syndrome and its components in pathogenesis of CKD as well as a role of diabetes mellitus (DM) frequently combined with obesity in development of diabetic kidney disease (diabetic nephropathy) is generalized. Among adipokines a special attention in the present review is paid for pathogenic role of leptin and adiponektin in obesity with its conditions promoted renal damage. The participation of resistance to leptin in the pathogenesis of CKD through such links as IR, ED, oxidative stress and inflammation is discussed. The role of ED and glomerular hyperfiltration in pathogenesis of microalbuminuria is elucidated. The significance of injury of kidney tubular cell structures so called podocytes in pathogenesis of CKD in obesity is uncovered. The clinical significance of early revealing of renal pathology as well as body weight, glycemia level, arterial blood pressure control and following of healthy mode of life in reduction of risk development of CKD associated with obesity, DM and other metabolic disorders is generalized. It’s emphasized that evaluation of lipid and carbohydrate exchange parameters, serum leptin level, IR indices is considered to be perspective for diagnostics of renal damage in obesity.

Mahanine mediated therapeutic inhibition of estrogen receptor-α and CDK4/6 expression, decipher the chemoprevention-signaling cascade in preclinical model of breast cancer

Ethnopharmacological relevanceMahanine (MH), a naturally occurring carbazole alkaloid, isolated from Ayurvedic medicinal plant Murraya koenigii (L.) Spreng, has been shown to have various pharmacological properties, including its inhibitory activity against different breast cancers (BC) subtypes. Aim of the studyWhile MH triggers apoptosis in BC cells regardless of subtype, the specific mechanism of MH action is not fully understood. In this study, we show the effect of MH in preventing BC progression by inducing apoptosis in relation to estrogen receptor-α (ERα) and cell cycle regulatory proteins. Materials and methodsTo assess the pharmacological activity in various in vitro and in vivo tests, isolated and pure MH was used. To conclude the study, cutting edged molecular biology techniques including Western blot analysis, enzyme-linked immunosorbent assay (ELISA), molecular simulation study, and other related software analysis were employed. ResultsMH demonstrated dose dependent cell viability against drug sensitive (MCF-7 and MDA-MB-231) and paclitaxel resistant (MCF-7TR and MDA-MB-231TR) BC cells. MH also exhibited synergistic activity with tamoxifen (TAM) against estrogen receptor positive (ER+) BC cells by inhibiting ERα expression in MCF-7 cells and N-Methyl-N-nitrosourea (MNU)-induced mammary tumor in a dose-dependent manner while having no effect on vinculin expression. In addition, MH inhibited cell cycle regulatory genes namely CDK1/CDK4/CDK6/CDC25A and neo-angiogenesis through downregulation of CD31/PECAMs in MCF-7, MDA-MB-231 cells and mammary tumors from MNU-induced rats. MH therapy has been shown to be significantly able to lower the serum leptin level and to be beneficial against the initiation of tumor development in SD rats for up to 12 weeks. Molecular modeling study revealed that MH has antagonized the effectiveness of several types of estrogen those bind to the ERα and has comparable binding efficacy to TAM. ConclusionOverall, the current investigation showed the ability of MH to modify cell cycle genes especially CDK4 and CDK6 might be responsible for its anticancer activity against different breast cancer subtypes. Additionally, this study will aid in advancing MH translational research to the clinical trial stage.

Association of Overweight and Obesity with Semen Parameters and Metabolic and Hormonal Status in Young Men.

We evaluated possible associations of overweight and obesity with semen parameters, sperm DNA fragmentation (SDF), and different indicators of metabolic and hormonal status in young men (n=226, mean age 22.5 years). Overweight and obese men were found to have a significant deterioration of metabolic health, reduced total sperm count and concentration, serum testosterone, and inhibin B levels, and increased serum leptin and seminal zinc levels in comparison with men with normal weight, although sperm DNA fragmentation, motility, and morphology did not change. In overweight and obese men, increased seminal zinc content appears to perform a protective function via reduction of oxidative stress caused by excess body fat. It is assumed that in the absence of individual lifestyle correction and weight loss for a long time, obese subjects are not protected from the development of reproductive comorbidities, in particular, subfertility and infertility.

DIET, EXERCISEREGIMENS AND MEDICATIONSTHAT ALTER BLOOD LEPTIN, ADIPONECTIN LEVELS AND ADIPONECTIN/LEPTIN RATIO TO PREVENT AND CONTROL CARDIO METABOLIC DISEASES DEVELOPMENT AND PROGRESSION

Objectives: High adiponectin and low leptin levels in serum are associated with less risk of insulin resistance, hypertension, atherosclerosis and a favorable lipid profile. In this systematic review, our objective was to determine effective diet changes, exercise and medications to achieve a favorable adiponectin/leptin ratio that decrease the risk of cardio metabolic conditions. Methods: After searching the literature in PubMed, MEDLINE, Google scholar and Cochrane library, we included randomized controlled trials and observational studies done on human participants regardless of age, BMI, sex and co-morbid conditions and studies that compared or assessed effects of interventions like diet, exercise or medications for more than two weeks on blood leptin and adiponectin levels. Follow up studies, animal studies and the studies in which adiponectin and leptin levels were not specified were excluded from the review. We screened 118 studies, data was retrieved from 70 studies out of which 36 studies were eligible for quality assessment. We used Cochrane risk of bias tool for randomized controlled trials and new castle Ottawa scale for observational studies for their quality assessment. Finally, we included 22 randomized controlled trials and 2 observational studies. Findings: The supplements, diet and exercise regimens and medications that were studied, many of them showed desirable changes in adipokine levels. Some of these regimens have not shown changes from baseline. Conclusions: Exercise, diet modifications and medications like Orlistat, Resveratrol, Pioglitazone should be used to target the adipokine levels to reduce cardiometabolic disease risk and progression.

Benefit of Adiponectin And Leptin For Monitoring Exercise Effect On Adipose Function In Metabolic Syndrome

Introduction: The Prevalence of metabolic syndrome (MetS) in Indonesia is increasing, with the highest age in the 45 – 54 years old, and high mortality and morbidity rates complications and cost. Biomarkers such as adiponectin, leptin, and their ratios may be useful in monitoring and quantifying patient's body fat tissue function improvement after exercise training. This study aims to determine adiponectin, leptin, and their ratios benefits in monitoring physical exercise effects on adipose tissue function in pre-elderly (45-59 years old) and elderly (&gt; 60 years old) patients with MetS.Methods: Literature review through hand searching and pubmed database related to the benefits of leptin and adiponectin test in monitoring physical exercise effect on adipose function in the pre-elderly and/or elderly population with MetS.Results: Physical exercise significantly increased adiponectin levels (mean difference (MD): 0.42 µg/mL; 95% CI 0.23, 0.60, p &lt; 0.0001), and reduced leptin levels (MD: -1.89 ng /ml; 95% CI, -2.64, -1.14, p&lt;0.0001). High-intensity aerobic exercise can even reduce serum leptin levels by 6.29 ng/ml (p &lt; 0.001), and increase serum adiponectin levels by 0.74 μg/ml (p = 0.04). This significant change mainly occurs in men with a Body Mass Index (BMI) of 30 kg/m2 and 25.0-29. 9 kg/m2.Conclusion: Adiponectin/leptin ratio examination has potential future benefits in MetS management as an evaluation physiological biomarkers related to exercise interventions. There are only a few capable laboratories, and expensive cost, so that its current implementation is mostly devoted to research. Adopting a healthy lifestyle, balanced nutrition, physical activity habits and regular physical exercise are still the best suggestions for preventing MetS.

The Correlations Between Level of Zonulin, Leptin and Anthropometric Indicators in Patients with Metabolic-associated Fatty Liver Disease in Combination with Type 2 Diabetes mellitus

The objective: to analyze the correlations between the level of zonulin, leptin and anthropometric parameters in patients with metabolically associated fatty liver disease (MAFLD) in combination with type 2 diabetes mellitus (DM). Materials and methods. 42 patients with MAFLD and type 2 diabetes took part in the study, and were examined and divided into groups. The first group included 22 patients with MAFLD and type 2 DM without bacterial overgrowth syndrome (BOS), the second group included 20 patients with MAFLD in combination with 2D DM and BOS. 15 practically healthy persons were included in the control group. During the physical examination of the patient, anthropometric indicators were measured, including height, body weight, body mass index (BMI) according to the Quetelet formula, waist circumference (WC) and hip circumference (HC) and the WC/HC ratio. The content of serum zonulin was determined by ELISA using test systems IDK Zonulin ELISA, KR5601 (Immunodiagnostic AG, Germany). An ELISA method was used to quantify serum leptin. Results. It was found that zonulin concentration in blood serum was significantly increased in patients of the first and second groups – 67.79±2.12 ng/ml and 80.36±3.44 ng/ml, respectively. In patients of the control group the zonulin amount was 12.34±1.41 ng/ml (p&lt;0.001). Quantitative research of the leptin level in blood serum revealed a significant increase in patients of the first and second groups – 25.09±0.35 ng/ml and 28.21±1.03 ng/ml, respectively. In patients of the control group the level of leptin was 4.69±0.37 ng/ml (p&lt;0.001). There was no significant difference in anthropometric parameters between the patients of the first and second groups (p&gt;0.05). When comparing statistical indicators of anthropometry of patients of the first and second groups with the control group, significant differences were found in body weight, BMI, WC, HC, CTC (p&lt;0.001), which indicates excess body weight and obesity in patients of the first and second groups. Conclusions. The results of the study present that in patients with MAFLD in combination with type 2 DM without BOS and BOS, increased intestinal permeability and hyperleptinemia were found, and a direct correlation of medium strength was established between the level of zonulin and body weight, BMI, a weak correlation between the level of zonulin and WC, HC, CTC was determined and mean strength correlation between zonulin and leptin levels was found.

Gender-specific Reference Range for Serum Leptin in Omani Population.

Leptin is a hormone that contributes to glucose homeostasis and food intake regulation via its action on the hypothalamus. Leptin level increases with obesity and overfeeding and decreases with energy deficiency. Serum leptin levels vary between different ethnic groups with no reports of its reference range in the Arabic population. We sought to determine gender-specific reference ranges for serum leptin in a cohort of the Arabic population and identify the cut-off value for different metabolic derangements. The study data were obtained from the records of 1198 subjects included in the Oman Family Study. The percentile method was used in the estimation reference range and the receiver operating characteristic to identify cut-off points for multiple metabolic derangements. The reference range of serum leptin was 0.5-90.6 ng/mL, and it was not correlated with the age of the subjects. Higher leptin was observed in females compared to males (p < 0.001), and the reference range for serum leptin in females was 4.9-96.3 ng/mL compared to 0.25-48.8 ng/mL in males. The optimum cut-off value for leptin ranged between 24.1-28.9 ng/mL for metabolic syndrome, obesity, central obesity, and type 2 diabetes. We identified gender-specific reference ranges for serum leptin in a large cohort of Arabs. The optimum cut-off value for serum leptin to determine metabolic derangement with the highest sensitivity and specificity was 24.1-28.9 ng/mL. Future studies are needed to study the relative risk of higher serum leptin using prospective studies.