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International Journal of Environmental... Apr 2017Few studies have assessed the association between leptin receptor (LEPR) gene polymorphism and the risk of cardiovascular disease (CVD). Of the few epidemiological... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Few studies have assessed the association between leptin receptor (LEPR) gene polymorphism and the risk of cardiovascular disease (CVD). Of the few epidemiological studies on this topic, the results are still controversial.
METHODS
PubMed and Embase were screened for studies from their inception to 9 October 2016. The pooled odds ratio (OR) with the corresponding confidence intervals (CI) were used to measure the effect size for studies that reported the association under allelic, homozygous, and dominant models. Pre-specified characteristics were conducted in the subgroup analysis. Heterogeneity between subgroups was evaluated by meta-regression analysis.
RESULTS
Seven eligible studies involving 44,133 participants were included in our meta-analysis. Borderline significant association was observed between the LEPR gene polymorphism (rs1137101, rs1137100, rs6700896, and rs8179183) and the increased risk of CVD with considerable heterogeneity under the allelic model, and the overall pooled OR (95% CI) was 1.10 (0.99, 1.22). The LEPR gene variant rs6700896, 109G allele, and 109GG genotype were significantly associated with the increased risk of CVD. Furthermore, stratified group analysis revealed that the association was more pronounced for stroke. Race-differences might also cause the considerable heterogeneity and non-significant association.
CONCLUSIONS
This is the first systematic review and meta-analysis to investigate the association between LEPR gene variants and CVD risk. Some LEPR gene variants were significantly associated with the increased risk of CVD. However, the present study is limited in its small number of included studies, considerable heterogeneity, and observational study design. Further research is still warranted to confirm the magnitude of the association.
Topics: Cardiovascular Diseases; Humans; Polymorphism, Genetic; Receptors, Leptin; Risk
PubMed: 28368354
DOI: 10.3390/ijerph14040375 -
PloS One 2011Three non-synonymous single nucleotide polymorphisms (Q223R, K109R and K656N) of the leptin receptor gene (LEPR) have been tested for association with obesity-related... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Three non-synonymous single nucleotide polymorphisms (Q223R, K109R and K656N) of the leptin receptor gene (LEPR) have been tested for association with obesity-related outcomes in multiple studies, showing inconclusive results. We performed a systematic review and meta-analysis on the association of the three LEPR variants with BMI. In addition, we analysed 15 SNPs within the LEPR gene in the CoLaus study, assessing the interaction of the variants with sex.
METHODOLOGY/PRINCIPAL FINDINGS
We searched electronic databases, including population-based studies that investigated the association between LEPR variants Q223R, K109R and K656N and obesity- related phenotypes in healthy, unrelated subjects. We furthermore performed meta-analyses of the genotype and allele frequencies in case-control studies. Results were stratified by SNP and by potential effect modifiers. CoLaus data were analysed by logistic and linear regressions and tested for interaction with sex. The meta-analysis of published data did not show an overall association between any of the tested LEPR variants and overweight. However, the choice of a BMI cut-off value to distinguish cases from controls was crucial to explain heterogeneity in Q223R. Differences in allele frequencies across ethnic groups are compatible with natural selection of derived alleles in Q223R and K109R and of the ancient allele in K656N in Asians. In CoLaus, the rs10128072, rs3790438 and rs3790437 variants showed interaction with sex for their association with overweight, waist circumference and fat mass in linear regressions.
CONCLUSIONS
Our systematic review and analysis of primary data from the CoLaus study did not show an overall association between LEPR SNPs and overweight. Most studies were underpowered to detect small effect sizes. A potential effect modification by sex, population stratification, as well as the role of natural selection should be addressed in future genetic association studies.
Topics: Animals; Cohort Studies; Gene Frequency; Genotype; Humans; Overweight; Polymorphism, Single Nucleotide; Receptors, Leptin
PubMed: 22028824
DOI: 10.1371/journal.pone.0026157 -
Journal of Clinical Medicine Jul 2023A well-balanced metabolism means a lower risk for metabolism-related neuropsychiatric disorders. Leptin is a secretory adipokine involved in the central control of... (Review)
Review
A well-balanced metabolism means a lower risk for metabolism-related neuropsychiatric disorders. Leptin is a secretory adipokine involved in the central control of appetite that appears to play a role in the etiology of feeding-related disorders. Additionally, the influence of exercise on feeding behaviors potentially modulates the circulation of metabolites that signal through the central nervous system. In this systematic review, we collected the recent clinical evidence on the effect of exercise on leptin concentrations in health individuals published from 2000 to 20 September 2022, according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA 2020 statement). Six hundred and thirty-eight papers were retrieved and forty-eight papers were included in the qualitative synthesis. Data supports that exercise positively influences appetite via enhancing peripheral and central leptin signaling (reuptake), especially during weight loss. Exercise modulation of leptin signaling through leptin receptors helps to stabilize increases in food intake during periods of negative energy balance, prior to a decrease in the body fat tissue content. At a high intensity, exercise appears to counteract leptin resistance.
PubMed: 37445524
DOI: 10.3390/jcm12134490 -
Journal of Clinical Medicine Dec 2021Obesity and being overweight have been described as potential causes of neurological disorders. Leptin, a peptide expressed in fat tissue, importantly participates in... (Review)
Review
BACKGROUND
Obesity and being overweight have been described as potential causes of neurological disorders. Leptin, a peptide expressed in fat tissue, importantly participates in energy homeostasis and storage and has recently been identified for its signaling receptors in neuronal circuits of the brain.
AIM
To elucidate whether the endogenous modulation of leptin can be a protection against neuropsychiatric disorders.
METHOD
A systematic review was performed in accordance with the PRISMA-P method, and reports of studies containing data of leptin concentrations in healthy individuals with or without obesity were retrieved from the PubMed database, using the combinations of Mesh terms for "Leptin" and "Metabolism".
RESULTS
Forty-seven randomized and non-randomized controlled trials, dating from 2000 to 2021, were included in the qualitative synthesis.
DISCUSSION AND CONCLUSIONS
Leptin secretion displays a stabilizing pattern that is more sensitive to a negative energy intake imbalance. Leptin levels influence body weight and fat mass as a pro-homeostasis factor. However, long-term exposure to elevated leptin levels may lead to mental/behavioral disorders related to the feeding and reward systems.
PubMed: 34884416
DOI: 10.3390/jcm10235714 -
Clinical and Experimental Rheumatology 2020Initial studies investigating peripheral levels of leptin and soluble leptin receptor (LepR) in systemic lupus erythematosus (SLE) patients have generated a number of... (Meta-Analysis)
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.
Topics: Female; Genetic Predisposition to Disease; Humans; Leptin; Lupus Erythematosus, Systemic; Male; Patients; Polymorphism, Genetic; Receptors, Leptin
PubMed: 32662402
DOI: No ID Found -
Bioscience Reports Jun 2019Some pilot studies already tried to investigate potential associations of leptin () and LEP receptor () variants with coronary artery disease (CAD). However, the... (Meta-Analysis)
Meta-Analysis
Some pilot studies already tried to investigate potential associations of leptin () and LEP receptor () variants with coronary artery disease (CAD). However, the results of these studies were not consistent. Thus, we performed the present meta-analysis to explore associations between variants and CAD in a larger pooled population. Systematic literature research of PubMed, Web of Science, Embase and CNKI was performed to identify eligible case-control studies on associations between variants and CAD. The initial search was conducted in September 2018 and the latest update was performed in December 2018. Q test and statistic were employed to assess between-study heterogeneities. If probability value(-value) of Q test was less than 0.1 or was greater than 50%, random-effect models (REMs) would be used to pool the data. Otherwise, fixed-effect models (FEMs) would be applied for synthetic analyses. A total of ten studies published between 2006 and 2018 were eligible for analyses (1989 cases and 2601 controls). Pooled analyses suggested that rs7799039 variant was significantly associated with CAD under over-dominant model (=0.0007, odds ratio (OR) = 1.36, 95% confidence interval (CI): 1.14-1.63, = 41%, FEM) in overall population, and this significant finding was further confirmed in East Asians in subsequent subgroup analyses. However, no positive findings were observed for rs1137100 and rs1137101 variants in overall and subgroup analyses. Our meta-analysis suggested that rs7799039 variant might affect individual susceptibility to CAD.
Topics: Coronary Artery Disease; Genetic Predisposition to Disease; Humans; Leptin; Polymorphism, Genetic; Receptors, Leptin
PubMed: 31113873
DOI: 10.1042/BSR20190466 -
Journal of Orthopaedic Surgery and... Oct 2020Adolescents with scoliosis consistently demonstrate lower body weight, lean muscle mass, and bone mineral density than healthy adolescent counterparts. Recent studies... (Meta-Analysis)
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.
Topics: Adolescent; Biomarkers; Disease Progression; Female; Ghrelin; Humans; Leptin; Male; Predictive Value of Tests; Receptors, Leptin; Scoliosis; Signal Transduction
PubMed: 33121521
DOI: 10.1186/s13018-020-01988-w -
Clinical and Experimental Immunology Sep 2014Numerous studies have suggested the importance of leptin against autoimmune diseases such as systemic lupus erythematosus (SLE), multiple sclerosis (MS) and psoriasis.... (Meta-Analysis)
Meta-Analysis Review
Numerous studies have suggested the importance of leptin against autoimmune diseases such as systemic lupus erythematosus (SLE), multiple sclerosis (MS) and psoriasis. To summarize our current understanding of the role of leptin in inflammatory responses and rheumatoid arthritis (RA), a systematic review was conducted to assess the discrepancy of leptin in RA and its effect on immunity according to different studies. Recently, emerging data have indicated that leptin is involved in the pathological function of RA, which is common in autoimmune disorders. This review discusses the possible consequences of leptin levels in RA. Blocking the key signal pathways of leptin and inhibiting the leptin activity-like leptin antagonist may be a promising way for potential therapeutic treatment of RA at risk of detrimental effects. However, leptin was increased in patients with RA and may also regulate joint damage. Thus, more understanding of the mechanism of leptin in RA would be advantageous in the future.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Leptin; Receptors, Leptin; Signal Transduction
PubMed: 24802245
DOI: 10.1111/cei.12372 -
Oncotarget Nov 2015The prevalence of global obesity is increasing. Obesity is associated with general cancer-related morbidity and mortality and is a known risk factor for development of... (Review)
Review
The prevalence of global obesity is increasing. Obesity is associated with general cancer-related morbidity and mortality and is a known risk factor for development of specific cancers. A recent large systematic review of 24 studies based on meta-analysis of 11,149 patients with prostate cancer showed a significant correlation between obesity and the risk of advanced prostate cancer. Further, a sustained reduction in BMI correlates with a decreased risk of developing aggressive disease. On the other hand, the correlation between consuming different products and prostate cancer occurrence/risk is limited.Here, we review the role of adipose tissue from an endocrine perspective and outline the effect of adipokines on cancer metabolism, with particular focus on leptin. Leptin exerts its physiological and pathological effects through modification of intracellular signalling, most notably activating the Janus kinase (JAK) 2/signal transducer and activator of transcription (STAT) 3 pathway and recently shown sphingolipid pathway. Both high levels of leptin in circulation and leptin receptor mutation are associated with prostate cancer risk in human patients; however, the in vivo mechanistic evidence is less conclusive.Given the complexity of metabolic cancer pathways, it is possible that leptin may have varying effects on prostate cancer at different stages of its development, a point that may be addressed by further epidemiological studies.
Topics: Adipose Tissue; Animals; Carcinogenesis; Genetic Predisposition to Disease; Humans; Janus Kinases; Leptin; Male; Obesity; Polymorphism, Genetic; Prostatic Neoplasms; Receptors, Leptin; STAT3 Transcription Factor; Signal Transduction
PubMed: 26376613
DOI: 10.18632/oncotarget.5574 -
Frontiers in Endocrinology 2023Leptin (LEP) acts as a proinflammatory cytokine and may play an important role in the pathophysiology of cystic fibrosis (CF). This review aimed to assess the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Leptin (LEP) acts as a proinflammatory cytokine and may play an important role in the pathophysiology of cystic fibrosis (CF). This review aimed to assess the quantitative difference in leptin status between CF patients and non-CF controls.
METHODS
In this study, the researchers conducted systematic searches of various databases, such as PubMed, Excerpta Medica Database, Google Scholar, Web of Science, and the China National Knowledge Infrastructure. The data collected from the above databases were assessed using the Stata 11.0 and R 4.1.3 software. The correlation coefficients and the Standardized Mean Differences (SMD) were employed to assess the effect size. A combination analysis was also carried out with the help of either a fixed-effects or random-effects model. In addition, the single-cell sequencing GSE193782 dataset was obtained to determine the mRNA expression levels of LEP and leptin receptor (LEPR) in the bronchoalveolar lavage fluid, to verify the different leptin expression between the CF patients and healthy controls.
RESULTS
A total of 919 CF patients and 397 controls from 14 articles were included in this study. CF patients and non-CF controls showed similar serum/plasma leptin levels. Gender, specimen testing, age, and study design were all taken into account for carrying out subgroup analyses. The results revealed no variations in serum/plasma leptin levels between the controls and CF patients in the various subgroups. Female CF patients exhibited higher leptin concentrations compared to male CF patients, and male healthy individuals showed lower leptin levels than female healthy participants. Aside from the fact that serum/plasma leptin appeared to be favorably linked to fat mass and BMI, the findings in this study also indicated that serum/plasma concentrations were not associated with Forced Expiratory Volume in the first second (FEV1). No statistically significant differences were observed in the leptin and leptin receptor mRNA expression levels between the healthy controls and CF patients. The leptin receptor and leptin expression levels in alveolar lavage fluid were low in various cells, without any distinctive distribution patterns.
CONCLUSIONS
The current meta-analysis indicated the absence of significant differences in leptin levels between CF patients and healthy individuals. Gender, fat mass, and BMI may all be correlated with leptin concentrations.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42022380118.
Topics: Humans; Male; Female; Leptin; Cystic Fibrosis; Receptors, Leptin; RNA, Messenger; China
PubMed: 36992806
DOI: 10.3389/fendo.2023.1126129