ObjectiveTo systematically evaluate the relationship between the-2548G/A polymorphism in the leptin gene and antipsychotic-induced weight gain (AIWG).
MethodsLiterature for the relationship between the-2548G/A polymorphism in the leptin gene and AIWG was retrieved in electronic databases including PubMed, EMbase, CNKI and WanFang Data from establishment dates to June, 2013. Two reviewers independently screened studies according to the inclusion and exclusion criteria, extracted data and evaluated the methodological quality of the included studies. Then meta-analysis was performed using RevMan 5.2 software.
ResultsA total of 7 case-control studies were included, involving 404 AIWG cases and 508 controls (patients with no significant changes of weight after taking antipsychotic drugs). The results of meta-analysis showed that, regarding the total population, the-2548G/A polymorphism of the leptin gene was not associated with AIWG (OR=1.16, 95%CI 0.70 to 1.93, P=0.57). After stratification analysis, according to Chinese or non-Chinese origin, the results showed that significant association was found between the-2548G/A polymorphism of leptin gene and AIWG for Chinese (OR=2.15, 95%CI 1.41 to 3.26, P=0.000 4) but not for non-Chinese (OR=0.69, 95%CI 0.45 to 1.07, P=0.10).
ConclusionThe current evidence suggests that the-2548G/A polymorphism in the leptin gene is associated with increased risk of AIWG for Chinese. Due to limited quantity of the included studies, the aforementioned conclusion needs to be further validate by more high-quality and large-scale studies.
Objective
To discuss the correlation between the letpin level and the pathogenesis of avascular necrosis of the femoral head (ANFH) by measuring the leptin expression of the femoral head in patients with ANFH.
Methods
Between July 2009 and February 2011, 16 patients with ANFH (including 10 cases of steroid-induced ANFH and 6 cases of alcohol-induced ANFH, ANFH group) and 11 patients with proximal femur fracture (control group) were included in the experiment. There was no significant difference in age, weight, and body mass index between 2 groups (P gt; 0.05). The peripheral blood and bone marrow were extracted to measure the blood lipid level and the free fat (FF) content, respectively. ELISA was used to detect the levels of the leptin, soluble leptin receptor (sLR), osteoprotegerin (OPG), and soluble receptor activator of nuclear factor κB (sRANKL); the leptin biological activity and the activity of osteoclasts were calculated. The femoral head specimens were harvested to count leptin-positive cells by immunohistochemical staining.
Results
No significant difference in the blood lipid level was found between 2 groups (P gt; 0.05), but the FF content in ANFH group was significantly lower than that in control group (t=
—
14.230, P=0.000). The intramedullary leptin expression was found in both groups; however, the intramedullary leptin level in ANFH group decreased significantly when compared with the level in control group (t=4.425, P=0.002). There were significant differences in the levels of leptin, OPG, and sRANKL between 2 groups (P lt; 0.05). The leptin biological activity of ANFH group was significantly lower than that of control group (P lt; 0.05), but the activity of osteoclasts of ANFH group was significantly higher than that of control group (P lt; 0.05). There was a positive correlation between the leptin level and leptin biological activity (r=0.922 7, P=0.000 0), and a negative correlation between the leptin level and OPG content (r=
—
0.396 2, P=0.040 8), FF content (r=
—
0.806 1, P=0.000 0), while it had no correlation between the leptin level and sLR and sRANKL content (P gt; 0.05).
Conclusion
Intramedullary expression and bioactivity of the leptin decrease significantly in ANFH patients, which may play an important role in the pathogenesis of ANFH.
Objective
To assess the correlation between central sleep apnea (CSA) and serum leptin (LEP) levels in patients with chronic heart failure.
Methods
The level of serum LEP and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured by forward-looking method in patients with chronic heart failure who underwent polysomnography during hospitalization from December 2015 to April 2017 in Department of Cardiology and Respiratory Medicine, Renmin Hospital of Wuhan University. And its correlation with CSA was analyzed. Patients were divided into three groups according to the left ventricular ejection fraction (LVEF), and then according to the presence or absence of CSA into CSA group and without SDB group.
Results
Of the 71 patients with heart failure, 31 had LVEF≥45%, 19 were between 35% and 45% and 21 were≤35% ; 32 of whom were CSA and 39 had no SDB. The lEP concentrations in the LVEF subgroup of CSA groups were significantly lower than those in the control group without SDB, with significantly higher levels of NT-proBNP. Logistic regression showed that CSA was associated with logarithmic LEP (lnLEP) (OR=0.047, 0.030, 0.021, P<0.05). In severe heart failure (LVEF≤35%) group, high NT-proBNP was the risk of CSA (OR=5.942, P=0.045) and the incidence of CSA was as high as 71.4%, which was significantly higher than other groups. However, after adjustment for confounding factors such as age, sex and body mass index (BMI), the correlation no longer existed (OR=6.432, P=0.105). Moreover, CSA with severe cardiac insufficiency had lower LEP than those without SDB. After adjustment for confounding factors such as age, sex and BMI, CSA and lnLEP remained significantly correlated (OR=0.013, P=0.002). Meanwhile, linear correlation analysis also showed that NT-proBNP was negatively correlated with lnLEP (R=–0.751, P<0.001). After adjusting for age, sex, and BMI, this relationship still existed (R=–0.607, P=0.004).
Conclusion
Decreased levels of leptin and elevated NT-proBNP in patients with chronic heart failure may indicate the presence of CSA.
ObjectiveTo investigate the role of leptin receptor gene Gln223Arg polymorphism in pathogenesis of asthma.
MethodsOne hundred and eighty-five asthmatic outpatients and inpatients in the Qingdao Municipal Hospital between June 2009 and May 2012 were recruited in the study.Two hundred and seven healthy volunteers were recruited as control.Peripheral blood was sampled from all subjects for measuring serum leptin level by ELISA,and analyzing leptin receptor gene Gln223Arg genotypes by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) in white blood cells.
ResultsThere was significant difference in frequency distribution of leptin receptor gene Gln223Arg genotype between the asthma group and the health group (χ2=6.173,P=0.013,OR=1.697,95%CI 1.115-2.585).The GG genotype was associated with a 1.895-fold increased risk for asthma than the GA+AA genotype (χ2=7.283,P=0.007,OR=1.895,95%CI 1.187-3.024).The serum leptin level of the GG genotype group was significantly higher than that in the GA+AA genotype group[(2.56±1.47) ng/mL vs.(2.16±1.66) ng/mL].
ConclusionLeptin receptor gene Gln223Arg polymorphism is correlated with asthma, and the G allele might be the genetic factor that contributes to individual susceptibility for asthma by causing high serum leptin level.
ObjectiveTo investigate the effects of leptin on the oxidative damage in human retinal pigment epithelial (RPE) cells.
MethodsHuman RPE cells (ARPE-19) were cultured in vitro, and randomly divided into control group and insulin resistance group. RPE cells were treated with 0, 10, 100 ng/mL leptin for 24, 48, 72 hours respectively. Then the levels of reactive oxygen species (ROS) expression in RPE cells were detected by 2', 7'-dichlorofluorescin-diacetate (DCFH-DA), and the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) expression in RPE cells were observed by immunocytochemistry (ICC), and the levels of human 8-oxoguanine DNA glycosylase l (hOGG1) expression in lysate were measured by Western blot.
ResultsAfter 24, 48, 72 hours, the level of ROS (Control group:F=37.136, 37.178, 49.634; P < 0.05. Insulin resistance group:F=9.822, 28.881, 71.150;P < 0.05), 8-OHdG (Control group:F=88.643, 390.920, 1039.276;P < 0.05.Insulin resistance group:F=273.311, 299.155, 82.237;P < 0.05) and hOGGl (Control group:F=470.062, 1073.113, 295.456;P < 0.05. Insulin resistance group:F=240.032, 592.389, 527.760;P < 0.05) expression increased significantly with the increase of leptin concentration in control group and insulin resistance group. Under the same leptin concentration, the level of 8-OHdG has a trend that it was higher in the insulin resistance group than the control group. After 24 hours, the difference of hOGGl expression between control group and insulin resistance group was not significant (F=23.392, P > 0.05). After 72 hours, the level of hOGGl expression was significantly higher in the insulin resistance group than the control group (F=129.394, P < 0.05). The level of hOGGl expression was significantly higher at 48 hours than that at 24 hours and 72 hours (P < 0.05).
ConclusionLeptin could induce the oxidative damage of RPE cells in normal and insulin resistance status. With the increase of leptin concentration and time extended, the degree of oxidative damage and its repair were both increased. The degree of oxidative repair increased with the increase of leptin concentration, but decreased with time extended.
Objective To investigate the effect and mechanism of leptin (LEP) on the osteoblastic differentiation of hBMSCs in vitro. Methods Whole bone marrow culture method was appl ied to culture hMBSCs and hBMSCs at passage 3 were divided into groups A, B, C, D, E and F, and when cell attachment was evident, 400, 200, 100 and 50 ng/mL LEP, 100 ng/mLBMP and common nutrient medium were added into each group, respectively. ALP staining and mineral ized nodules staining were conducted at 7 and 21 days after culture, respectively. And inverted phase contrast microscope observation was performed. ALP activity and osteocalcin (OCN) level of hBMSCs in each group was detected at 7, 14 and 21 days after culture to select the best induced concentration of LEP on osteoblastic differentiation. For groups of B, E and F at 7 days after culture, RT-PCR was adopted to detect the expression of such osteogenesis-related genes as core-binding factor α 1 (Cbfα1), ALP, Col I and OCN mRNA. Results At 7 days after induced culture, the ALP staining result showed that the endochylema in groups A, B, C, D and E were stained blue and the endochylema in the group F was sl ightly positive. At 21 days after induced culture, the mineralized nodules staining showed that cells in groups A, B, C, D and E were stained positively and cells in group F were negative. At 7, 14 and 21 days after culture, ALP and OCN activities in group B were less than that of group E (P lt; 0.05), but significant higher than that of groups A, C, D and F (P lt; 0.05), the optimal concentration of LEP was 200 ng/mL. At 7 days after culture, group F witnessed no expression of Cbfα1, ALP, Col I and OCN mRNA, while groups B and E witnessed expressions of all those indexes, but the expressions in group B were less than those of group E. Conclusion LEP can stimulate osteoblastic differentiation of hBMSCs in vitro, and the possible mechanism is its role of promoting the expression of osteoblastic related genes.
Myocardial remodeling is a common pathological physiology change for a variety of heart diseases under stimulation such as stress or ischemia. The engine body will release a lot of cytokines to promote the change of myocardial structure and ultimately lead to heart failure. Myocardial remodeling includes myocardial cells remodeling and the extracellular matrix remodeling. In recent years, we find that the function of adipose tissue is not only about energy storage, buffering to protect, supporting and filling, but also has a powerful function of secretion. Adipose tissue can secrete various adipocytokines, such as leptin, adiponectin, visfatin, omentin, angiotensin Ⅱ, and so on. Current studies have shown that adipocytokines and myocardial remodeling are intimated. And this article will summarize the function of adipocytokines on myocardial remodeling.
Obesity is closely related to thyroid function. The concentration of thyroid stimulating hormone (TSH) in obese patients is higher than that in the general population, and TSH will decrease accordingly after weight loss. Leptin is a bridge linking obesity and thyroid hormones, which can affect the release of TSH. There are many kinds of weight-reducing drugs that target the thyroid gland. Among them, thyroid hormone receptor-specific agonists may be potential drugs for future obesity treatment, but further studies are still needed.
Objective To investigate the role of inflammatory factors like serumleptin, adiponectin,interleukin-6( IL-6) , and C-reactive protein ( CRP) in the systemic inflammatory response of smokinginduced COPD. Methods Thirty male Wistar rats were randomly divided into three groups, ie. a high-dose smoking group, a low-dose smoking group, and a control group. Serum leptin, adiponectin, IL-6, and CRP levels were measured by ABC-ELISA. Results The serum leptin and adiponectin levels in both smoking groups decreased significantly compared with the control group( P lt; 0. 05) , while the difference was not significant between the two smoking groups ( P gt; 0. 05) . The serum IL-6 and CRP levels in both smoking groups increased significantly compared with the control group( P lt; 0. 05) , which were higher in the highdosesmoking group than those in the low-dose smoking group( P lt;0. 05) . Conclusions Smoking increases the serum levels of IL-6 and CRP, but reduces the serum levels of leptin and adiponectin in rats. These results suggest that leptin, adiponectin, IL-6, and CRP may be involved in the systemic inflammatory response of smoking-induced COPD.
Objective To investigate the effect of leptin on fibroblast proliferation and collagen synthesis as to elucidate that fibroblasts play a role in leptin’s effect on wound healing. Methods Purified dermal fibroblasts were derived from sucking wistar rat skin and exposedto leptin at concentration of 0, 10, 50, 100, 200, and 400 ng/ml. The survived fibroblasts were assessed by the colorimetric thiazolyl blue (MTT) assay. Replication of fibroblast was quantified by the incorporation of 3H-thymidine. Collagen synthesis of fibroblast cell was measured by the incorporation of 3H-proline into collagenasesensitive protein. Results The absorption of fibroblast exposed to leptin at concentration of 200 and 400 ng/ml 0.082±0.013, 0.091±0.018 was higher than that of control group 0.063±0.010, P＜0.05. The incorporations of 3H-thymidine of fibroblast exposed to leptin at concentration of 200 and 400 ng/ml 379±101 cpm,326±33 cpm were significantly higher than those of control group 219±56 cpm, P＜0.05. The incorporations of 3H-proline of fibroblast exposed to leptin at concentration of 200 and 400 ng/ml 911±55 cpm, 1 072±259 cpm were significantly higher than that of control group 679±176 cpm, P＜0.05. Conclusion Leptin can promote rat cutaneous fibroblast proliferation and collagen synthesis in vitro. This suggests that cutaneous fibroblast plays a role in leptin’s promoting skin wound healing and it may be one of the main mechanisms by which leptin enhances skin wound healing.
