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.

Polimorfismos G2548A del gen de leptina y GLN223ARG del gen del receptor de leptina en pre-puberes con riesgo cardiometabólico / Polymorphism G2548A in leptin and GLN223ARG in the leptin receptor gene in prepubertal children with cardiometabolic risk

La obesidad resulta de los efectos combinados de los genes, el ambiente y el estilo de vida. La leptina (LEP) y el receptor de leptina (LEPR) son genes que han sido evaluados en la búsqueda de variantes que podrían estar relacionadas con la obesidad y sus complicaciones cardiometabólicas. Objetivo: Evaluar la posible asociación entre los polimorfismos G2548A del gen LEP y Gln223Arg del gen LEPR con el desarrollo de obesidad y resistencia a la insulina (RI) en niños y adolescentes pre-púberes. Métodos: Se estudiaron 314 niños de 2-11 años, clasificados según los parámetros antropométricos y bioquímicos en: a) sobrepeso/obesos sin RI (n=133), b) sobrepeso/obesos con RI (n=75) y c) controles sanos (n=70). La genotipificación fue realizada por reacción en cadena de la polimerasapolimorfismos de longitud de fragmentos de restricción (PCR-RFLP); se estudiaron las asociaciones entre genotipo y riesgo, y se compararon los promedios de las medidas antropométricas y bioquímicas. Resultados: La frecuencia genotípica para el polimorfismo G2548A del gen LEP fue 51% G/A, 33% G/G y 16% A/A; para el polimorfismo Gln223Arg del gen LEPR fue Gln/Arg 49%, Gln/Gln 31% y Arg/Arg 20%. Se encontró diferencia significativa en la distribución de los diferentes genotipos del gen de LEPR en los niños con sobrepeso/obesidad y RI con respecto al grupo control (OR= 2,6; IC 95%=1,17-5,75; p < 0.05). Conclusión: Se observó una asociación entre la presencia del genotipo Gln/Gln del gen LEPR con la RI (factor de riesgo cardiometabólico), presentando los niños con sobrepeso/obesidad y RI 2,6 veces más riesgo a presentar RI.

Obesity is a result of the combined effects of genes, environment and lifestyle. The Leptin (LEP) and leptin receptor (LEPR) are genes that have been extensively evaluated in search for variants that may be associated with obesity and cardiometabolic complications. Objective: To evaluate the possible association between polymorphisms G2548A of the LEP gene and Gln223Arg of the LEPR gene with the development of obesity and insulin resistance (IR) in prepubertal children and adolescents. Methods: We studied 314 children 2-11 years, grouped by anthropometric and biochemical parameters: a) overweight /obese without IR (n = 133), b) overweight /obese with IR (n = 75) and c) healthy controls (n = 70). Genotyping was performed by Polymerase Chain Reaction-Restriction Fragment Length Polymorphisms (PCR-RFLP) method. Genotype-risk associations were studied. We then compared the average values for anthropometric and biochemical parameters. Results: The genotypic frequency for polymorphism G2548A of LEP gene was 51% for the G/A genotype, 33% G/G and 16% A/A genotype; for polymorphism Gln223Arg of LEPR gene was of Gln/Arg 49%, Gln/Gln 31% and Arg/Arg 20%. Significant difference was found in the distribution of different genotypes of the LEPR gene in children with overweight/obesity with IR compared to the control group (OR = 2.6; 95% CI = 1.17 to 5.75; p < 0.05). Conclusion: We observed an association between the presence of Gln/Gln genotype of the LEPR gene with insulin resistance (cardiometabolic risk factor) children, rendering these children with overweight/obese with IR 2,6 times more likely to be with insulin.

Genetics of obesity: an overview of current approaches and advancement.

Elucidation of obesity susceptibility genes through genome wide approaches as well as candidate gene approaches provides great promise in ultimately determining the genetic underpinnings of obesity. The complex nature of human obesity stems from the multiple interaction of several genes that control the physiology of food intake, energy expenditure, development of the body, and behavioural patterns towards food intake, and the environment. According to twin, adoptees and family studies, genetic factors account for 40-70% of the variability observed in human adiposity. Twin studies supported that the heritability of adiposity is higher than other quantitative traits. The heritability of obesity traits has been further evidenced by identification of quantitative trait loci (QTL) and genes through methods such as genome-wide scans (studies conducted on unrelated obese individuals), linkage analyses (conducted in families), and association studies (investigating the correlation between obesity and polymorphisms). The number of contributing genes, however, is still unknown. Although research on the genetic basis of obesity has advanced, the mechanisms underlying the condition are still complex due to its heterogeneity even within families.

Meta-analysis on the relationship between leptin receptor Gln223Arg and Prol019Pro gene polymorphism and obesity in the Chinese population / 中华流行病学杂志

Objective To evaluate the associations between polymorphisms of LEPR Gln223Arg,LEPR Pro 1019Pro and the risk on obesity.Methods A computerized search on literature was carried out in Wanfang,CNKI,VIP databases and CBM,PubMed,EMBASE databases to collect articles published between 1979 and 2010 concerning the associations between polymorphisms of LEPR Gln223Arg and/or LEPR Pro 1019Pro and risk of obesity in the Chinese population.Odds ratios (ORs) were used to assess the strength of the association,and 95％ confidence intervals (CIs) to present the precision of the estimates.Meta-analysis was performed using the STATA statistical software.Results Fifteen literature were collected for Meta-analysis by the uniform inclusion and exclusion criteria.There were 1096 obese patients and 949 controls for polymorphisms of LEPR Gln223Arg in 9 papers,together with 961 obese patients and 818 controls for polymorphisms of LEPR Prol019Pro in 8 papers.Overall,there were significant associations between decreased risk of obesity and LEPR Gln223Arg polymorphisms (-668 A→G) (G versus A,OR=0.66,95％CI:0.49-0.89; AG and GG versus AA,OR=0.50,95％CI:0.32-0.77; respectively).There were significant associations between increased risk of obesity and LEPR Prol019Pro polymorphisms (-3057 G→A) (A versus G,OR=1.61,95％CI:1.15-2.26; AG and AA versus GG,OR=1.50,95％CI:1.08-2.08; respectively).Conclusion Variant alleles at both LEPR-668 and LEPR-3057 were associated with obesity in the Chinese Han-dominated population.

Association of polymorphisms in leptin receptor gene with obesity and type 2 diabetes in the local population of Coimbatore.

BACKGROUND: Candidate gene association studies are very relevant to the area of clinical pharmacology. As information on candidate genes and candidate single nucleotide polymorphisms increases, a number of such candidates can be studied in a population to explore their association with their susceptible disease. One such attractive and popular Single Nucleotide Polymorphism (SNP) candidate for obesity is the gene coding for leptin receptor. The leptin receptor gene (LEPR) polymorphism plays an important role in obesity and type 2 diabetes. But the role of this polymorphism is not yet studied in Indian population. Hence, the study focused to explore the association of leptin receptor polymorphisms (K109R, Q223R and K656N) with obesity and type 2 diabetes in both diabetic and non-diabetic subjects recruited from the local population of Coimbatore. MATERIALS AND METHODS: Genotypic analysis for the three polymorphisms has been made for 300 subjects (150 diabetic and 150 non-diabetic) with the age range of 40–60 years using conventional Polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) techniques in a case–control fashion. Allele frequencies were estimated based on the gene count method. Correlation was made with phenotypic variables including body mass index (BMI), waist-to-hip ratio (WHR), insulin and leptin levels for those polymorphisms. RESULTS AND CONCLUSION: Among the polymorphisms tested in this study, significant association with BMI (P < 0.05), WHR (P < 0.05) leptin (P < 0.001) and insulin (P < 0.0001) was observed for the SNP Q223R, whereas in the case of the other two polymorphisms the association was not statistically significant. The significance value was calculated based on the χ2 test. The controls are also found to have a higher frequency of homozygous mutants for Q223R and are significantly associated with obesity. These findings support the hypothesis that Q223R polymorphism is associated with obesity. It can be speculated that the controls showing the same allele may develop Type 2 diabetes at a later stage and Q223R can act as a strong marker.

Genetic polymorphisms at the leptin receptor gene in three beef cattle breeds

The genetic diversity of a single nucleotide polymorphism (SNP) at the exon 20 (T945M) of the leptin receptor gene (LEPR) and of three short tandem repeats (STRs BM7225, BMS694, and BMS2145) linked to LEPR was investigated in three beef cattle herds (Brangus Ibagé, Charolais, and Aberdeen Angus). A cheap and effective new method to analyze the T945M polymorphism in cattle populations was developed and the possible role of these polymorphisms in reproduction and weight gain of postpartum cows was evaluated. High levels of genetic diversity were observed with the average heterozygosity of STRs ranging from 0.71 to 0.81. No significant association was detected between LEPR markers and reproductive parameters or daily weight gain. These negative results suggest that the LEPR gene polymorphisms, at least those herein described, do not influence postpartum cows production.

Effects of Inonotus Obliqua Extract on Blood Glucose Levels in Genetically Diabetic Mice

This study investigated the therapeutic effects of Inonotus obliqua extract on blood glucose, insulin, and other biochemical parameters in genetically diabetic mice (C57BL/KsJ-m+/+Lepr(db)). The mice were divided into four groups - control, Chaga 1 (dose of 0.09 mg/kg of body weight), Chaga 5 (5 times of Chaga 1), and Chaga 10 (10 times of Chaga 1)- according to supplemented dose. Inonotus obliqua extract was orally administered to the animals for 6 weeks. The body and organ (liver and kidney) weights were not different among groups. Fasting blood glucose level was significantly lower in the Chaga 5 group compared with the control (p < 0.05). Hemoglobin A1c content was significantly lower in the Chaga 5 group compared with either the control and Chaga 1 group (p < 0.05). There was no significant difference in serum insulin level among groups. The glucose-6-phosphatase activity in liver was significantly the lowest in Chaga 10 group and was significantly lower in Chaga 5 group as compared with those of control and Chaga 1 groups. Therefore, the results of this study demonstrate that Inonotus obliqua extract alleviates many of the symptoms of diabetes in genetically obese mice and may offer a possibility as a therapeutic supplement for the normalization of blood glucose levels in human with hyperglycemia and have beneficial effects in patients with noninsulin-dependent diabetes mellitus.