Research progress of leptin and lung cancer microenvironment / 重庆医学

Leptin is a cytokine hormone secreted by white and brown adipose tissue to participate in the processes of cell proliferation,differentiation,apoptosis,and cytokine secretion.The latest research confirms that leptin is closely correlated with the occurrence and development of lung cancer.Lepdin can regulate the microenvironment of lung cancer by regulating immune response and nerve endocrine.This article reviews the role and mechanism of leptin in the microenvironment of lung cancer,aiming to provide reference for basic re-search on lung cancer.

Youguiwan Reduces Airway Inflammation in COPD Rats with Syndrome of Kidney-Yang Deficiency by Inhibiting Leptin/JAK2/STAT3 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effect of Youguiwan on the leptin/Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway in the lung tissue of the rat model of chronic obstructive pulmonary disease （COPD） due to kidney-Yang deficiency. MethodForty rats were modeled for COPD with the syndrome of kidney-Yang deficiency by intratracheal instillation of lipopolysaccharide on day 1 and day 14 and continuous fumigation for 6 weeks， during which hydrocortisone was injected intramuscularly at an interval of 3 days. The modeled rats were randomized into model， high- （11.7 g·kg-1）， medium- （5.85 g·kg-1）， and low-dose （2.93 g·kg-1） Youguiwan， and aminophylline （0.054 g·kg-1） group. In addition， 8 SD rats were set as the blank group. After the completion of modeling， the rats in each group were administrated with the corresponding drug by gavage for 28 consecutive days. After the last administration， samples were collected. A lung function analyzer was used to evaluate the lung function of rats. Enzyme-linked immunosorbent assay was employed to measure the levels of interleukin-17A （IL-17A）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the bronchoalveolar lavage fluid （BALF）. Hematoxylin-eosin staining was employed to observe the pathological changes in the lung tissue， and Masson staining was employed to observe the deposition of blue collagen fibers around bronchi in the lung tissue and calculate the inflammation score. The immunofluorescence assay was employed to measure the protein content of collagen type Ⅰ （ColⅠ） and α-smooth muscle actin （α-SMA） in the bronchi. The protein and mRNA levels of leptin， IL-17A， JAK2， and STAT3 in the lung tissue were determined by Western blot and real-time fluorescence quantitative polymerase chain reaction， respectively. ResultCompared with the blank group， the model group showed decreased lung function （P<0.01）， elevated levels of IL-6， IL-17A， and TNF-α in the BALF （P<0.01）， and increased lung inflammation score， deposition of subcutaneous collagen fibers in the airway， and ColⅠ and α-SMA proteins （P<0.01）. Furthermore， the modeling up-regulated the proteins and mRNA levels of leptin， IL-17A， JAK2， and STAT3 in the lung tissue （P<0.01） and enhanced the phosphorylation of JAK2 and STAT3 （P<0.01）. Compared with the model group， high- and medium-dose Youguiwan improved the lung function， decreased the inflammation score， reduced collagen fiber deposition and ColⅠ and α-SMA proteins， lowered the levels of IL-6， IL-17A， and TNF-α in the BALF， down-regulated the mRNA and protein levels of leptin， JAK2， STAT3， and IL-17A， and weakened the phosphorylation of JAK2 and STAT3 （P<0.05， P<0.01）. The aminophylline group had higher IL-17A and TNF-α levels than the high-dose Youguiwan group， lower IL-17A level than the medium and low-dose Youguiwan groups， and lower TNF-α level than the low-dose Youguiwan group. Compared with the aminophylline group， the high- and medium-dose Youguiwan groups showed reduced deposition of collagen fibers and protein levels of ColⅠ and α-SMA around the bronchi in the lung tissue （P<0.05， P<0.01）， decreased inflammation score， and down-regulated protein and mRNA levels of leptin， JAK2， STAT3， and IL-17A in the lung tissue. ConclusionYouguiwan can prevent airway remodeling by inhibiting IL-17A to reduce inflammation and collagen deposition in COPD rats， which may be related to the inhibition of the leptin/JAK2/STAT3 signaling pathway.

Association between plasma leptin/adiponectin ratio and insulin resistance indexes in prepubertal children

ABSTRACT Objective: To assess the association between leptin/adiponectin ratio (LAR) and insulin resistance surrogates in prepubertal children. Subjects and methods: Study based on data from the Growth and Obesity Chilean Cohort Study (GOCS) involving 968 Chilean prepubertal children. Plasma insulin, leptin, and adiponectin were determined by immunoassays. Several common insulin resistance surrogates were calculated, including the homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride/HDL cholesterol index, triglyceride-glucose (TyG) index, and the TyG index corrected for body mass index (BMI; TyG-BMI) and waist circumference (WC; TyG-WC). Associations among variables were assessed using multiple linear and logistic regression analysis. Results: There was a significant direct association between plasma leptin and LAR with BMI z-score but no association between plasma adiponectin and adiposity. After adjustments for sex and age, LAR was significantly associated with all insulin resistance surrogates (which were categorized using the 75th percentile as the cutoff point), with the TyG-WC index emerging as the surrogate with the highest magnitude of association (odds ratio [OR] 2.44, 95% confidence interval [CI] 2.05-2.9). After additional adjustment for BMI z-score, only the association between LAR and TyG-WC remained significant (OR 1.64, 95% CI 1.27-2.12). Conclusion: Plasma leptin and LAR were strongly associated with several common insulin resistance surrogates in prepubertal children, most notably with the TyG-WC index. Associations between LAR and insulin resistance indexes were mainly driven by the effect of plasma leptin, which is also directly associated with increased adiposity.

Status de expressão do receptor de leptina e adiponectina no carcinoma colorretal: A cross-estudo prospectivo seccional / Correlation of leptin and adiponectin receptor expression with clinicopathological parameters in colorectal carcinoma - a cross-sectional prospective study

ABSTRACT Background: Colorectal carcinoma (CRC) is one of the common carcinomas with a rising incidence of metastasis due to its advanced stage of presentation. The existing biomarkers such as CEA (Carcinoembryonic antigen) etc., for prognosis, have low sensitivity and specificity. Hence a need for a newer definitive biomarker. Obesity is the leading cause of CRC. Leptin and adiponectin secreted by adipose tissue have been studied as potential biomarkers in the field of CRC. The present study helps to understand the association of leptin and adiponectin receptors with clinicopathological parameters. Objective: To correlate the various clinicopathological parameters with the tissue expression of leptin and adiponectin receptors in CRC. Methods: It is a cross-sectional prospective study conducted at a tertiary care hospital. Formalin fixed paraffin blocks of all radical resection CRC cases were collected and immunohistochemistry (IHC)was carried out on tumor tissue for leptin and adiponectin receptor. Tumor characteristics and clinical parameters were collected from the hospital medical records. Pearson's correlation coefficient test was used. Results: Immunohistochemistry was performed on 60 cases of CRC. Significant positive correlation of leptin was observed with size, lymph node metastasis, advanced stage, and grade of tumor (P<0.05). A significant correlation between adiponectin receptor and CRC was observed concerning age, stage, lymph node metastasis, distant metastasis and grade of tumor. Conclusion: Positive expression of leptin and negative expression of adiponectin receptors in CRC helps to predict the risk of metastasis.

RESUMO Contexto: O carcinoma colorretal (CCR) é um dos carcinomas comuns com incidência crescente de metástases devido ao seu estágio avançado de apresentação. Os biomarcadores existentes como CEA (antígeno carcinoembrionário) etc., para prognóstico, apresentam baixa sensibilidade e especificidade. Daí a necessidade de um biomarcador definitivo mais recente. A obesidade é a principal causa do CCR. A leptina e a adiponectina secretadas pelo tecido adiposo têm sido estudadas como potenciais biomarcadores na área do CCR. O presente estudo ajuda a compreender a associação dos receptores de leptina e adiponectina com parâmetros clinicopatológicos. Objetivo: Correlacionar os diversos parâmetros clinicopatológicos com a expressão tecidual dos receptores de leptina e adiponectina no CCR. Métodos: Trata-se de um estudo transversal, prospectivo, realizado em um hospital terciário. Blocos de parafina fixados em formalina de todos os casos de CCR de ressecção radical foram coletados e a imuno-histoquímica (IHQ) foi realizada no tecido tumoral para receptor de leptina e adiponectina. As características do tumor e os parâmetros clínicos foram coletados dos prontuários médicos do hospital. Foi utilizado o teste do coeficiente de correlação de Pearson. Resultados: A imunohistoquímica foi realizada em 60 casos de CCR. Correlação positiva significativa da leptina foi observada com tamanho e metástase linfonodal, estágio avançado e grau do tumor (P<0,01). Foi observada uma correlação significativa entre o receptor de adiponectina e o CCR em relação à idade, estágio, metástase linfonodal, metástase à distância e grau do tumor. Conclusão: A expressão positiva de leptina e a expressão negativa de receptores de adiponectina no CCR ajudam a prever o risco de metástase.

The effects of leptin and cannabinoid CB1 receptor agonist/antagonist in cerebral tissues of epileptic rats

SUMMARY OBJECTIVE: In this study, the effects of leptin, cannabinoid-1 (CB1) receptor agonist ACEA and antagonist AM251, and the interactions between leptin and CB1 receptor agonist/antagonist on oxidant and antioxidant enzymes in the cerebrum, cerebellum, and pedunculus cerebri tissue samples were investigated in the penicillin-induced epileptic model. METHODS: Male Wistar albino rats (n=56) were included in this study. In anesthetized animals, 500 IU penicillin-G potassium was injected into the cortex to induce epileptiform activity. Leptin (1 μg), ACEA (7.5 μg), AM251 (0.25 μg), and the combinations of the leptin+ACEA and leptin+AM251 were administered intracerebroventricularly (i.c.v.) after penicillin injections. Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) levels were measured in the cerebral tissue samples and plasma with the ELISA method. RESULTS: MDA levels increased, while SOD and GPx levels decreased after penicillin injection in the cerebrum and cerebellum. The efficacy of penicillin on SOD, MDA and GPx levels was further enhanced after leptin or AM251 injections. Whereas, ACEA decreased the MDA levels and increased GPx levels compared with the penicillin group. Administration of AM251+leptin did not change any oxidation parameter compared with the AM251. Furthermore, co-administration of ACEA and leptin significantly increased oxidative stress compared with the ACEA-treated group by increasing MDA and decreasing GPx levels. CONCLUSION: It was concluded that leptin reversed the effect of ACEA on oxidative stress. Co-administration of AM251 and leptin did not change oxidative stress compared with the AM251-treated group suggesting AM251 and leptin affect oxidative stress using the same pathways.

Research progress on the correlation between weight loss and ghrelin, leptin and hypoxic environment in patients with Parkinson's disease / 中华老年医学杂志

Weight loss is a prevalent non-motor symptom of Parkinson's disease(PD), often appearing several years before motor symptoms and continuing throughout the course of the disease.The cause of weight loss in PD may be linked to an imbalance in energy and neuroendocrine function.Ghrelin and leptin are thought to be significant factors in the weight loss experienced by those with PD.Obstructive sleep apnea hypopnea syndrome may independently increase the risk of PD and significantly impact the cognitive and motor functions, as well as other non-motor symptoms, of PD patients.Research has shown that a hypoxic environment can enhance the expression and aggregation of the pathogenic protein α-synuclein.This suggests that hypoxic stress and intermittent hypoxia may be contributing factors to the development of PD.This article examines the correlation between weight loss in patients with Parkinson's disease and the hormones ghrelin and leptin, as well as the impact of a hypoxic environment on these hormones.

Exploring the Central Mechanism of Acupoint Catgut Embedding Therapy in Treating Rats with Diet-Induced Obesity Based on Hypothalamic LepR-Mediated JAK2/STAT3 Pathway / 广州中医药大学学报

Objective To observe the effects of acupoint catgut embedding therapy on body mass,lipid metabolism,serum leptin and mRNA and protein expressions of hypothalamic leptin receptor(LepR)-mediated Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathway in rats with diet-induced obesity(DIO).Methods Forty male SD rats were randomly divided into 10 in normal group and 30 in modeling group.A high-fat diet was used to establish the DIO rat model.After successful modeling,the modeled rats were randomly divided into the model group,the acupoint catgut embedding group and the acupoint catgut embedding + AG490(JAK2/STAT3 pathway blocker)group,with 10 rats in each group.The acupoint catgut embedding group and the acupoint catgut embedding + AG490 group were embedded on day(s)1,8,15 and 22 after successful modeling,the acupoints were selected from the Zhongwan(RN12),Shuidao(ST28),Tianshu(ST25),Pishu(BL20),Weishu(BL21),Sanjiaoshu(BL22)with a total of 4 treatments,and the acupoint catgut embedding + AG490 group was injected intraperitoneally with 1 mg/kg of AG490 every day during the treatment period;the normal group and the model group were only grasped and fixed.Body mass was measured before and after treatment.Lipid metabolism indexes of triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),and serum leptin levels were measured after treatment,and the mRNA expressions of hypothalamus LepR,JAK2 and STAT3 were detected by real-time quantitative polymerase chain reaction(RT-PCR),and the protein expressions of hypothalamus LepR,JAK2 and STAT3 were detected by Western Blot.Results Before treatment,compared with the normal group,the body mass of the model group,the acupoint catgut embedding group,and the acupoint catgut embedding+AG490 group were all elevated(P＜0.01),and compared with the model group,there was no significant difference in the body mass between the acupoint catgut embedding group and the acupoint catgut embedding+AG490 group(P＞0.05).After treatment,compared with the normal group,body mass,leptin and TG,TC,LDL-C levels were increased,and mRNA and protein expression levels of LepR,JAK2,STAT3 were decreased in the model group(all P＜0.01);compared with the model group,body mass,leptin and TG,TC,LDL-C levels were decreased in the acupoint catgut embedding group,and mRNA and protein levels of LepR,JAK2,STAT3 were increased in the acupoint catgut embedding + AG490 group(all P＜0.01);compared with the acupoint catgut embedding + AG490 group,the body mass,leptin and TG,TC,LDL-C levels were decreased,and mRNA and protein levels of LepR,JAK2,STAT3 were increased in the acupoint catgut embedding group(P＜0.05 or P＜0.01).Conclusion Acupoint catgut embedding has a good effect on weight loss and lipid reduction in DIO rats,and its central mechanism may be related to the down-regulation of serum leptin level and activation of hypothalamic LepR-mediated JAK2/STAT3 pathway.

Expression of leptin and its receptor correlates with hypoxia-inducible factor-1α in infants with cyanotic congenital heart disease / 基础医学与临床

Objective To investigate the correlation between serum leptin level and body mass index(BMI)in in-fants with cyanosis congenital heart disease,and the relationship between leptin and Ob gene receptor(Ob-R)and hypoxia-inducible factor 1α(HIF-1α)in myocardium.Methods A total of 52 children under 6 months of age with congenital heart disease who underwent surgical treatment in the Department of Congenital Heart Surgery,Fuwai Hospital from January 2019 to October 2020 were included in this study.According to the arterial partial pressure of oxygen(PaO2)of 90 mmHg,they were divided into cyanotic group(n=30)and acyanotic group(n=22).Their height and weight were collected to calculate BMI.The serum leptin level was measured by ELISA.The ex-pressions of HIF-1α and Ob-R in myocardial tissue were detected by RT-PCR and Western blot.In animal mod-el,SD rats were divided into normoxia group and hypoxia intervention group,which were subjected to continuous hypoxia(10％ O2)for 4 weeks.The hypoxia intervention group received intraperitoneal injection of HIF-1α in-hibitor digoxin(2 mg/kg)daily from the 14 th to 21st day of hypoxia,respectively.The body weight of rats was recorded,and the expressions of HIF-1α and Ob-R were detected by RT-qPCR and Western blot.Results Com-pared with the acyanosis group,the cyanosis group had a significantly lower BMI(P<0.05)and a lower leptin/BMI ratio(leptin/BMI)(P<0.05).Spearman correlation analysis confirmed that serum leptin in the circulatory system was positively correlated with BMI(P<0.05).In the cyanosis group,the expression of Ob-R increased with the upregulation of HIF-1α,showing a positive correlation.In animal model,with the down-regulation of HIF-1α expression in digoxin injection,the Ob-R level was significantly lower than that in the control group(P<0.05),the trend of weight loss was significantly inhibited(P<0.05).The right ventricular hypertrophy in-dex was significantly lower than that in the control group(P<0.05).Conclusions HIF-1α regulates the expres-sion of Ob-R in myocardial tissue,and the mechanism of its association with leptin and Ob-R may help to find new therapeutic target for improving the prognosis of infants with congenital heart disease.

Role and mechanism of miR-155/leptin receptor/adenosine phosphate-dependent protein kinase axis in tuberculin-induced osteoclast formation / 中国组织工程研究

BACKGROUND:Abnormal activation of osteoclasts plays an important role in the bone destruction due to spinal tuberculosis.During the pathogenesis of osteoporosis,miR-155 knockdown activates adenosine phosphate-dependent protein kinase(AMPK)by increasing the expression of leptin receptors,thereby inhibiting osteoclast differentiation and bone resorption.However,the role of miR-155/leptin receptor(LEPR)/AMPK axis in the bone destruction due to spinal tuberculosis remains unclear. OBJECTIVE:To investigate the role and mechanism of miR-155/LEPR/AMPK axis in tuberculin-induced osteoclast formation. METHODS:RAW264.7 cells were cultured and treated with different concentrations of purified protein derivative(PPD)(1.0,2.5,5.0,10.0 IU/mL)and transfected with negative control(NC)sequence or miR-155 inhibitor,NC siRNA sequence or LEPR siRNA sequence.Tartrate resistant acid phosphatase staining was used to detect the number of osteoclasts.Fluorescence quantitative PCR was used to detect the expression of miR-155.Western blot was used to detect the expression of LEPR and p-AMPK.Double luciferase reporter gene was used to verify miR-155 targeting LEPR. RESULTS AND CONCLUSION:Compared with the control group,the number of osteoclasts and the expression level of miR-155 significantly increased,while the expression level of LEPR and p-AMPK significantly decreased in 2.5,5.0,and 10.0 IU/mL PPD groups(P＜0.05).Compared with NC+5.0 IU/mL PPD group,the number of osteoclasts and the expression level of miR-155 significantly decreased,while the expression level of LEPR and p-AMPK significantly increased in the miR-155 inhibitor+5.0 IU/mL PPD group(P＜0.05).Compared with the NC group,the fluorescence activity of LEPR wild-type double luciferase reporter gene was increased in the miR-155 inhibitor group,and decreased in the miR-155 mimic group(P＜0.05).Compared with si-NC+miR-155 inhibitor+5.0 IU/mL PPD group,the expression level of miR-155 had no significant change,the number of osteoclasts significantly increased,and the expression levels of LEPR and p-AMPL significantly decreased in si-LEPR+miR-155 inhibitor+5.0 IU/mL PPD group(P＜0.05).To conclude,tuberculin can induce osteoclast formation by increasing miR-155 expression and inhibiting downstream LEPR expression and AMPK activation.

Serum levels and gestational curve of adiponectin and leptin during adolescent pregnancy

SUMMARY OBJECTIVE: This study aimed to develop a curve of weekly serum levels of adiponectin and leptin among pregnant adolescents. In addition, pregestational body mass index and weight gain were assessed and correlated with the serum concentration of these molecules. METHODS: This was a prospective cohort study, including only pregnant adolescents with eutrophic pre-gestational body mass index who were weekly followed during the evolution of gestation. The serum concentrations of adipokines were determined using commercial ELISA kits and were correlated to pre-gestational body mass index and pregnancy weight gain. A total of 157 pregnant women participated in this study. RESULTS: Adiponectin levels showed a significant decrease among the trimesters (p=0.0004). However, we did not observe significant differences among its levels when compared weekly, neither of which was between adiponectin concentration and pre-gestational body mass index or weight gain (p=0.36 and p=0.10, respectively). In contrast, we detected a significant increase in weekly serum leptin levels (p<0.0001), positively correlated to both pre-gestational body mass index and weight gain (p=0.003 and p=0.0007, respectively). CONCLUSION: These adipokines present a different profile throughout adolescent pregnancy.

Association of serum leptin and the risk of acute exacerbation of chronic obstructive pulmonary disease / 中国医师杂志

Objective:To analyze the association between serum leptin and the risk of acute exacerbation of chronic obstructive pulmonary disease (COPD).Methods:The clinical data of 127 COPD patients admitted to the Ninth People′s Hospital of Suzhou from November 2019 to December 2021 were retrospectively analyzed. According to whether acute exacerbation occurred in COPD patients, they were divided into acute exacerbation group (35 cases) and stable group (92 cases). General data of all patients were collected, including gender, age, body mass index (BMI), education level, disease course, smoking history, hypertension, diabetes, pneumonia, asthma and treatment methods. The forced expiratory volume in the first second/forced vital capacity (FEV 1/FVC), partial pressure of carbon dioxide (PCO 2), arterial blood pH and laboratory indicators [serum leptin, tumor necrosis factor (TNF-α) and C-reactive protein (CRP) levels] were detected. Receiver operating characteristic (ROC) curve was used to analyze the value of serum leptin, TNF-α and CRP in predicting acute exacerbation in COPD patients, and non-conditional logistic stepwise regression was used to analyze the risk factors of acute exacerbation in COPD patients. Results:Compared with the stable group, the proportion of patients with BMI<18.5 kg/m 2, complicated with pneumonia and asthma was higher, and the levels of serum leptin, TNF-α and CRP were also higher in acute exacerbation group (all P<0.05); ROC analysis showed that leptin≥3.683 ng/ml, TNF-α≥95.746 pg/ml and CRP≥22.405 mg/L were the best cut-off values of acute exacerbation in COPD patients(all P<0.05). Logistic regression analysis showed that BMI<18.5 kg/m 2, combined pneumonia, combined asthma, leptin≥3.683 ng/ml, TNF-α≥95.746 pg/ml, CRP≥22.405 mg/L were the risk factors for acute exacerbation of COPD patients(all P<0.05). Conclusions:Serum leptin level is elevated in COPD patients, and elevated serum leptin can lead to increased risk of acute exacerbation of COPD. In addition, low BMI, combined pneumonia or asthma, abnormally elevated TNF-α and CRP may be risk factors for acute exacerbation of COPD patients.

Comparison of corneal biomechanics and levels of serum Leptin and extracellular superoxide dismutase in patients with non-proliferative diabetic retinopathy or proliferative diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore the differences of corneal biomechanical parameters, serum Leptin and extracellular superoxide dismutase(ecSOD)levels in patients with non-proliferative diabetic retinopathy(NPDR)or proliferative diabetic retinopathy(PDR).METHODS: This article is a prospective study. A total of 118 patients with type 2 diabetes mellitus(T2DM)and diabetic retinopathy(DR)who were admitted to our hospital from May 2020 to May 2022 were selected, and they were divided into NPDR group(n=57)and PDR group(n=61)according to the degree of lesion. Another 54 patients with T2DM but no retinopathy and 52 healthy individuals were set as NDR group and control group. Then the differences in the corneal biomechanics measured with [central corneal thickness(CCT), intraocular pressure(IOP), spherical equivalent(SE), the first applanation time(A1T), the first applanation length(A1L), deformation amplitude(DA)] and serum Leptin and ecSOD levels were analyzed, and multivariate Logistic regression analysis was conducted to analyze the high-risk factors affecting the occurrence of PDR.RESULTS: The CCT, IOP and A1T in PDR and NPDR groups were higher than those in control and NDR groups, and DA was lower than those in control and NDR groups(all P&#x0026;#x003C;0.05), and the CCT, IOP and A1T in the PDR group were higher than those in the NPDR group(all P&#x0026;#x003C;0.05). The levels of serum Leptin and ecSOD in PDR group, NPDR group and NDR group were higher than those in the control group(all P&#x0026;#x003C;0.05). The course of DM, CCT, IOP, A1T, and serum Leptin and ecSOD levels between NPDR group and PDR group were statistically significant(all P&#x0026;#x003C;0.05). Multivariate Logistic regression analysis denoted that DM course, CCT, IOP, A1T, Leptin, and ecSOD are risk factors that affect the occurrence of PDR, while DA is a protective factor that affects the occurrence of PDR(all P&#x0026;#x003C;0.05). CONCLUSION: CCT, IOP and levels of serum Leptin and ecSOD in PDR patients were significantly increased compared to those in the NPDR patients, while DA was significantly reduced. Furthermore, CCT, IOP, A1T and levels of serum Leptin and ecSOD were risk factors affecting the occurrence of PDR, while DA was a protective factor affecting the occurrence of the PDR.

Study on Role and Mechanism of Leptin and BDNF in DSS Induced Colitis in Mice / 胃肠病学

Background: Abnormal expression of leptin and brain⁃derived neurotrophic factor (BDNF) is an important link in the occurrence of ulcerative colitis (UC), but the mechanism of leptin and BDNF in UC is still unclear. Aims: To explore the effect and mechanism of leptin and BDNF in DSS induced colitis in mice. Methods: Thirty⁃six male 8⁃10 weeks healthy leptin⁃deficient ob mice and leptin⁃normal expressing wild type (WT) mice were selected and randomly divided into WT experimental group, ob experimental group, WT control group and ob control group. The mice in experimental groups were given 3% DSS solution for 7 days to induce colitis model, and the mice in control group were given distilled water. After modeling, disease activity index (DAI) score, colon length, behavior and visceral sensitivity were observed. The mRNA expressions of leptin and BDNF in colon and hippocampus were detected by real⁃time fluorescent quantitative PCR, and the protein expression of BDNF in colon was detected by Western blotting. Results: Compared with corresponding control groups, DAI score, visceral sensitivity in WT experimental group and ob experimental group were significantly increased (P< 0.05), mRNA and protein expressions of BDNF in colon were significantly increased (P<0.05). Compared with WT control group, anxiety and depression⁃like behavior were found in WT experimental group, mRNA expressions of leptin, BDNF in hippocampus were significantly decreased (P<0.05). Correlation analysis showed that anxiety was positively correlated with length of colon in WT experimental group (P<0.05), and negatively correlated with DAI score (P<0.05); depression, expression of BDNF mRNA in colon were negatively correlated with length of colon (P<0.05), and positively correlated with DAI score (P<0.05); leptin in hippocampus was positively correlated with anxiety (P<0.05), while was negatively correlated with depression (P<0.05); expression of BDNF mRNA in colon was negatively correlated visceral sensitivity (P<0.05). Conclusions: Colonic BDNF secretion is associated with leptin expression, and both may be involved in the DSS⁃induced colitis in mice by mediating anxiety, depression and visceral sensitivity.

Effect of prenatal exposure to passive smoking on leptin of neonatal cord blood and birth weight in a rural area of Yunnan Province / 环境与职业医学

Background Previous studies have shown that active smoking during pregnancy can reduce the level of neonatal cord blood leptin, and thereby affect birth weight. However, few studies have studied the association of passive smoking during pregnancy with leptin in neonatal cord blood and birth weight. Objective To explore the effects of passive smoking in varied pregnancy stages and entire pregnancy on neonatal cord blood leptin level and birth weight in a certain rural area of Yunnan, and potential mediating role of cord blood leptin. Methods Based on a prospective prenatal cohort study conducted in Xuanwei County, Yunnan Province, a total of 545 mother-infant pairs were included in this study from early pregnancy enrollment to delivery. The demographic information and reproductive history of the subjects were collected by questionnaire. The urine samples of pregnant women in the first, second, and third trimesters of pregnancy were collected during regular prenatal examinations. Umbilical cord blood samples were collected from newborns at birth. The concentration of urine cotinine (UC) was measured by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). According to the results of UC level during pregnancy, the study subjects were divided into three groups: negative group (<LOD), low exposure group (LOD-M), and high exposure group(>M). The level of leptin in cord blood was detected by ELISA. Multiple linear regression was used to analyze the effect of passive smoking on umbilical cord blood leptin in newborns during pregnancy. Path analysis was used to explore the relationship among passive smoking during pregnancy, neonatal cord blood leptin, and birth weight. Results The average exposure rate of passive smoking during pregnancy was 87.28%, and the exposure rate for entire pregnancy was 76.88%. The median concentration of leptin in neonatal cord blood was 4.17 μg·L−1. After adjusting for maternal age, ethnicity, educational level, pre-pregnancy body mass index (BMI), gestational weight gain, parity, annual household income, infant sex, and birth weight, we found that low level (b=−3.388, P=0.001) and high level (b=−2.738, P=0.006) of passive smoking in the first trimester of pregnancy had negative associations with leptin concentration of cord blood by multiple linear model. The path analysis results showed that passive smoking in the first trimester and pre-pregnancy BMI directly affected leptin levels, and the sizes of direct effects were −0.073 and −0.087 (both P<0.05) respectively. Passive smoking in late pregnancy, gestational weight gain, premature, newborn girls, parity, and pre-pregnancy BMI directly affected birth weight, and the sizes of direct effects were −0.063, 0.191, −0.301, −0.128, −0.121, and 0.167 (all P<0.05), respectively. No mediating role of leptin was found in the effect of passive smoking on neonatal birth weight. Conclusion Passive smoking exposure during pregnancy is common among rural women in Yunnan Province. Passive smoking in the first trimester may be key in decreasing the leptin level of neonatal cord blood. Passive smoking in third trimester may lead to a decrease in birth weight. No evidence shows that leptin mediates the relationship between passive smoking and birth weight.

The relationship between serum leptin, insulin-like growth factor-1, and insulin-like growth factor binding protein-3 levels and clinical parameters in primary fibromyalgia patients

SUMMARY OBJECTIVE: The aim of this study was to investigate the levels of leptin, growth hormone, insulin-like growth factor-1, and insulin-like growth factor binding protein-3 and their relations with clinical parameters in patients with primary fibromyalgia and healthy controls. METHODS: Our study was performed on 30 female patients with primary fibromyalgia and 30 healthy controls. The levels of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 were measured by a two-site immunoradiometric assay. The serum level of leptin was measured by the ELISA kit. RESULTS: The serum level of leptin was significantly higher, but the serum levels of insulin-like growth factor-1 were significantly lower in patients with fibromyalgia syndrome than healthy controls (p<0.001). The leptin level was positively correlated with the Visual Analog Scale, Fibromyalgia Impact Questionnaire score, Beck Depression Inventory score, tender point count, age, and duration of disease (p<0.001), but it was negatively correlated with insulin-like growth factor-1 (p<0.001). The insulin-like growth factor-1 level was negatively correlated with age, Visual Analog Scale, Fibromyalgia Impact Questionnaire and Beck Depression Inventory scores, duration of disease, and tender point count (p<0.001). CONCLUSION: Our results indicate that high levels of serum leptin and low levels of serum insulin-like growth factor-1 may play a role in the physiopathogenesis of fibromyalgia and may be related to some symptoms.

Leptin and interleukin-1β levels associated with osteoarthritis in Vietnamese patients: a cross-sectional analysis

Leptin and interleukin-1 beta (IL-1β) are two extensively studied biomarkers associated with metabolic syndrome (MetS) and osteoarthritis (OA). Previous studies have mostly focused on either MetS or OA alone, with no available data on Vietnamese patients. This study aimed to investigate the levels of leptin and IL-1β in this patient population and explore their association with clinical parameters of MetS and OA. The study included 164 patients with primary knee OA, who were classified into two categories based on the presence of MetS, and 78 healthy controls. The plasma leptin and IL-1β levels were quantified by ELISA and correlated with clinical parameters. Leptin levels were higher in patients with OA (11.50±10.04 ng/mL) than in healthy controls (0.54±0.37 ng/mL) and increased in patients with MetS compared to those without MetS. IL-1β levels were also significantly higher in OA patients (14.63±15.87 pg/mL) than in controls (7.79±5.11 pg/mL), but were not significantly different between the MetS and non-MetS groups. Leptin levels were positively correlated with body mass index, waist-to-hip ratio, visual analogue scale scores, HbA1c and insulin levels, and HOMA-IR index, whereas IL-1β levels were only correlated with insulin levels and HOMA-IR index. ROC curve analysis revealed that leptin and IL-1β levels could distinguish individuals with and without OA (AUC=0.96; 0.88, respectively), and individuals with and without MetS (AUC=0.82; 0.71, respectively). Our findings suggested that both leptin and IL-1β levels were associated with both MetS and OA and may play a critical role in the pathogenesis of MetS-related OA.

Leptin-mediated ERK Signaling Pathway Promotes the Transformation of Rat Alveolar Type II Epithelial Cells Induced by Yunnan Tin Mine Dust / 中国肺癌杂志

BACKGROUND@#Currently, a significant number of miners are involved in mining operations at the Gejiu tin mine in Yunnan. This occupational setting is associated with exposure to dust particles, heavy metals, polycyclic aromatic hydrocarbons, and radioactive radon, thereby significantly elevating the risk of lung cancer. This study aims to investigate the involvement of leptin-mediated extracellular regulated protein kinase (ERK) signaling pathway in the malignant transformation of rat alveolar type II epithelial cells induced by Yunnan tin mine dust.@*METHODS@#Immortalized rat alveolar cells type II (RLE-6TN) cells were infected with Yunnan tin mine dust at a concentration of 200 μg/mL for nine consecutive generations to establish the infected cell model, which was named R₂₀₀ cells. The cells were cultured normally, named as R cells. The expression of leptin receptor in both cell groups was detected using the Western blot method. The optimal concentration of leptin and mitogen-activated protein kinase kinase (MEK) inhibitor (U0126) on R₂₀₀ cells was determined using the MTT method. Starting from the 20th generation, the cells in the R group were co-cultured with leptin, while the cells in the R₂₀₀ group were co-cultured with the MEK inhibitor U0126. The morphological alterations of the cells in each group were visualized utilizing hematoxylin-eosin staining. Additionally, concanavalin A (ConA) was utilized to detect any morphological differences, and an anchorage-independent growth assay was conducted to assess the malignant transformation of the cells. The changes in the ERK signaling pathway in epithelial cells after the action of leptin were detected using the Western blot method.@*RESULTS@#Both the cells in the R group and R₂₀₀ group express leptin receptor OB-R. Compared to the R₂₀₀ group, the concentration of leptin at 100 ng/mL shows the most significant pro-proliferation effect. The proliferation of R₂₀₀ cells infected with the virus is inhibited by 30 μmol/L U0126, and a statistically significant divergence was seen when compared to the control group (P<0.05). Starting from the 25th generation, the cell morphology of the leptin-induced R₂₀₀ group (R₂₀₀L group) underwent changes, leading to malignant transformation observed at the 30th generation. The characteristics of malignant transformation became evident by the 40th generation in the R₂₀₀L group. In contrast, the other groups showed agglutination of P40 cells, and the speed of cell aggregation increased with an increase in ConA concentration. Notably, the R₂₀₀L group exhibited faster cell aggregation compared to the U0126-induced R₂₀₀ (R₂₀₀LU) group. Additionally, the cells in the R₂₀₀L group were capable of forming clones starting from P30, with a colony formation rate of 2.25‰±0.5‰. However, no clonal colonies were observed in the R₂₀₀LU group and R₂₀₀ group. The expression of phosphorylated extracellular signal-regulated kinase (pERK) was enhanced in cells of the R₂₀₀L group. However, when the cells in the R₂₀₀L group were treated with U0126, a blocking agent, the phosphorylation level of pERK decreased.@*CONCLUSIONS@#Leptin can promote the malignant transformation of lung epithelial cells infected by mine dust, and the ERK signaling pathway may be necessary for the transformation of alveolar type II epithelial cells induced by Yunnan tin mine dust.

Obesity and male reproductive health: An update / 中华内分泌代谢杂志

Obesity has become a growing epidemic that seriously affects the quality of human life. Obesity not only adds the burden to the body but may have negative impacts on various body systems and organs, such as the cardiovascular and metabolic systems. In recent years, some studies have shown that obesity also negatively affects the reproductive system and influences male reproductive health. Male reproductive health is not only related to the normalization of male reproductive function but also plays a role in the ability to conceive healthy offspring. This article summarizes research progress on the effects of obesity on male reproductive health, including endocrine hormone disruption, reproductive organ structural damage, increased oxidative stress, and reproductive cell epigenetic alterations, providing insights for a deeper understanding of the influence of obesity on male reproduction and potential treatments.

Brain glucose hypometabolism and hippocampal inflammation in Goto-Kakizaki rats

Brain glucose hypometabolism and neuroinflammation are early pathogenic manifestations in neurological disorders. Neuroinflammation may also disrupt leptin signaling, an adipokine that centrally regulates appetite and energy balance by acting on the hypothalamus and exerting neuroprotection in the hippocampus. The Goto-Kakizaki (GK) rat is a non-obese type 2 diabetes mellitus (T2DM) animal model used to investigate diabetes-associated molecular mechanisms without obesity jeopardizing effects. Wistar and GK rats received the maintenance adult rodent diet. Also, an additional control group of Wistar rats received a high-fat and high-sugar diet (HFHS) provided by free consumption of condensed milk. All diets and water were provided ad libitum for eight weeks. Brain glucose uptake was evaluated by 2-deoxy-2-[fluorine-18] fluoro-D-glucose under basal (saline administration) or stimulated (CL316,243, a selective β3-AR agonist) conditions. The animals were fasted for 10-12 h, anesthetized, and euthanized. The brain was quickly dissected, and the hippocampal area was sectioned and stored at -80°C in different tubes for protein and RNA analyses on the same animal. GK rats exhibited attenuated brain glucose uptake compared to Wistar animals and the HFHS group under basal conditions. Also, the hippocampus of GK rats displayed upregulated leptin receptor, IL-1β, and IL-6 gene expression and IL-1β and the subunit of the transcription factor NF-κB (p-p65) protein expression. No significant alterations were detected in the hippocampus of HFHS rats. Our data indicated that a genetic predisposition to T2DM has significant brain deteriorating features, including brain glucose hypometabolism, neuroinflammation, and leptin signaling disruption in the hippocampal area.

Correlación entre Leptina, indicadores antropométricos y parámetros metabólicos en paciente de 5-15 años con sobrepeso-obesidad

Introducción: la obesidad es un estado patológico caracterizado por una acumulación excesiva de tejido adiposo, la misma secreta adipocinas entre las cuales se encuentra la Leptina que está implicada en importantes funciones metabólicas como el control de apetito y peso corporal. Objetivos: se realizo este estudio de la correlación entre la concentración de Leptina sérica con indicadores antropométricos y parámetros bioquímicos en pacientes entre 5 a 15 años de edad, con sobrepeso u obesidad. Métodos: se efectuó e estudio observacional descriptivo de corte transversal, con 148 pacientes entre 5 y 15 años de edad, se realizaron exámenes bioquímicos para evaluar la concentración de Leptina, Glucosa, Insulina, perfil lipídico e indicadores antropométricos. IMC, %GC y RCE. Resultados Se determinó correlaciones positivas entre las concentraciones de Leptina sérica con el IMC (75,4; p< 0,000), el (% GC) Porcentaje de grasa corporal (70,7: p< 0,000) y el (RCE) Razón Cintura estatura (75,4; p< 0,000), encontramos que no existe correlación entre la concentración de Leptina y Colesterol Total, por otra parte encontramos correlación negativa inversa con la concentración de Colesterol HDL en el sexo masculino, mientras que los Triglicéridos presentaron una correlación estadísticamente significativa. Por otra parte, no encontramos correlación significativa entre la determinación de la Leptina y la glicemia, por el contrario, la insulina presento una correlación alta estadísticamente significativa (p<0,000). Conclusiones: este estudio muestra la existencia de correlación estadísticamente significativa entre la Leptina sérica con indicadores antropométricos y parámetros bioquímicos en pacientes entre 5 a 15 años de edad, que tienen sobrepeso u obesidad.

Introduction: Obesity is a pathological state characterized by an excessive accumulation of adipose tissue, which secretes adipokines where there is Leptin, that is involved in important metabolic functions such as appetite control and body weight. Objectives: a study was carried out on the correlation between the serum Leptin concentration with anthropometric indicators and biochemical parameters in patients between 5 and 15 years old, overweight and obesity. Methods: the cross-sectional descriptive observational study was carried out, with 148 patients between 5 and 15 years of age, biochemical tests were performed to evaluate the concentration of Leptin Glucose, insulin, lipid profile and anthropometric indicators BMI, % BF y WHR. Results: positive correlations were found between serum Leptin concentrations with BMI (75.4; p <0.000), the (% BF) Body fat percentage (70.7: p <0.000) and the (WHR) Waist Ratio height (75,4 p <0.000). A low correlation was observed between the Leptin concentration and Total Cholesterol, with the concentration of HDL Cholesterol an inverse correlation was found in male sex, while Triglycerides presented higher levels in the adolescent group, there was no statistically significant. Also, we did not find a significant between the determination of Leptin and glycemia, on the contrary, insulin presented a statistically significant higher correlation (p <0.000). Conclusion: this study shows the existence of a statistically significant correlation between serum Leptin with anthropometric indicators and biochemical parameters in patients between 5 and 15 years of age, who are overweight or obese.