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 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.
Objective To study the leptin-mediated intracellular signal pathways and their effects on wound healing.Methods The literature was reviewed extensively, concerning the physical and chemical characters of leptin, the mechanism of its receptor action, the receptor-related intracellular signal pathways and their roles on wound healing. Results Leptin was a protein hormone expressed by ob gene with relative molecular mass 16×103, it could activate the main singal pathways such as Janus kinase/signal transducer and activator of transcription, mitogenactivated protein kinases and phosphoinositide-3-kinase pathways through binding with its specific receptor, to participate in the modulation of multiple functions including energy metabolism, weight balance and wound healing. Leptin receptors were widely distributed in various tissues, which suggest the multiple functions of leptin. Local leptin expression was increased after skin injured, and it could stimulate keratinocytes proliferation, epithelialization, fibroblast proliferation and collagen synthesis, resulting in accelarated wound repair. Leptin expression was significantly increased after mucosal injury or bacteria infections, leading to accelarated mucosal repair through modulation of mucosal glandular secretion, improvment of mucosal blood flow, and synergistic action with endothelin-1.Conclusion Leptin can promote wound healing through activating its receptor-related intracellular signal pathways.
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 relatingship between leptin receptor gene Gln223Arg polymorphism and obstructive sleep apnea hyponea syndrome (OSAHS) in Han population in Southwest China. Methods Two hundred and fifteen cases of subjects (including 116 cases in OSAHS group and 99 cases in control group) were selected in Han population in Southwest China. Polymerase chain reaction (PCR) was used to analyse Gln223Arg leptin receptor gene polymorphism. The levels of serum LEP and TI were determined by double antibody sandwich enzyme-linked immunosorbent assay (ELISA). Simultaneous determination of body mass index (BMI) and neck circumference (NC) and waist circumference (WC) were conducted. Results In the OSAHS group, the leptin receptor gene polymorphism Gln223Arg GG, AA and GA genotype frequency was 0.854, 0.017 and 0.129, respectively. G allele and A allele frequency frequency was 0.918 and 0.082, respectively. In the control group, leptin receptor gene polymorphisms Gln223Arg GG, AA and GA genotype frequency was 0.840, 0.020 and 0.14,respectively. G allele and A allele frequency was 0.90 and 0.10, respectively. Genotype frequencies of the two groups were not statistically significant (χ2=0.784, P>0.05). There were differences in BMI, WC and NC between the OSAHS patients with GG and the OSAHS patients with (GA+AA) genotype (P<0.05), but no difference was found in LEP and TI levels (allP>0.05). In control, mild, moderate and severe OSAHS group, the levels of serum LEP and TI were increased gradually, and the difference was statistically significant (allP<0.05). Conclusions Gln223Arg leptin receptor genotype polymorphisms may be involved in obesity, but they have no relationship with the incidence of OSAHS in Han population in Southwest China. In OSAHS patients, Gln223Arg polymorphism has no relationship with LEP or TI. Patients with OSAHS have hyperleptinemia and hyperinsulinemia.
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 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.
ObjectiveTo explore the levels of serum leptin,TNF-α,IL-8 and hypersensitivity C-reactive protein (hs-CRP) in stable COPD patients with different body mass index (BMI). Methods30 healthy controls with BMI 18.5 to 23.9 kg/m2 and 105 patients with stable COPD were recruited in the study. The serum levels of leptin,TNF-α,and IL-8 were determined by radioimmunoassay and hs-CRP level was determined by versatile biochemical automatic analyzer. The COPD patients were divided into a low BMI group (BMI<18.5 kg/m2,n=32),a normal BMI group (BMI 18.5-23.9 kg/m2,n=48),and a high BMI group (BMI≥23.9 kg/m2,n=25). ResultsSerum leptin level in the COPD patients was significantly reduced compared with the control subjects (P<0.05). Serum leptin levels were reduced in the low BMI and the high BMI groups compare with the normal BMI group [(7.89±3.16)ng/L and (10.52±5.98)ng/L vs. (13.04±5.73) ng/L,P<0.01 or P<0.05]. Leptin level in the low BMI group was lower than that in the high BMI group (P<0.05). Serum TNF-α levels were significantly increased in the low BMI group compared with the normal BMI and high BMI groups [(229.39±89.57)μg/L vs. (180.06±74.24) μg/L and (189.46±82.41) μg/L,P<0.01]. Serum TNF-α level in the COPD patients was significantly increased compared with the control subjects [(192.37±83.65) μg/L vs. (178.59±60.38) μg/L,P<0.05]. The IL-8 levels were not significant different among three BMI groups with COPD. The hs-CRP level in the high BMI group was higher than that in the low BMI and normal BMI groups (P<0.05). ConclusionLeptin and TNF-α may be involved in weight-loss of COPD malnutritional patients.
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 explore the relationship between the -2548 G/A functional polymorphism in the 5′ promoter region of the leptin gene and gallstones. Methods The -2548 G/A polymorphisms of leptin gene were determined by polymerase chain reactionrestriction fragment length polymorphism technology (PCRRFLP) in 118 patients with cholesterol gallstones and 53 normal control subjects. Then the allele and genotype distribution were studied. Results The distribution of leptin2458 G/A in two groups was statistically significantly different: the genotype frequency of AA+GA of patients in gallstone group was higher than that in control group (χ2=4.251, P=0.039). AA+AG genotype had 2.813 times greater risk for gallstone disease compared with GG genotype (OR=2.813, 95% CI=1.020-7.757). Allele frequency distribution in the two groups was different: the allele frequency of A of patients in gallstone group was higher than that in control group (χ2=5.791, P=0.016). The risk of gallstone disease in the A alleles carriers was 1.777 times as higher as the carriers of G alleles (OR=1.777, 95% CI=1.110-2.844). ConclusionThe -2548 G/A polymorphism in the 5′ promoter region of leptin gene is significantly correlated with the gallstones. The A alleles of leptin may be a genetic factor which contributes to individual susceptibility for gallstone, while the G alleles of leptin may be a genetic factor that prevents people from gallstone.