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Abstract Objectives The authors determined the level of Expression of Leptin (LEP) in Polycystic Ovary Syndrome (PCOS) patients with or without obesity and in GCs treated with insulin. Methods LEP expression was first assessed in ovary cortex specimens collected from women with PCOS with or without obesity as well as from healthy controls. Ovarian Granulosa Cells (OGCs) induced by insulin extracted from a mouse model were used in further functional research. Results Real-time PCR and western blotting indicated that LEP expression was upregulated in GCs induced by insulin, in comparison with that in GCs not induced by insulin. Furthermore, the knockdown of LEP resulted in a reduction in growth and multiplication and an increase in apoptosis and inflammation in GCs induced by insulin. Next, the authors evaluated the effect of LEP on three key pathways of inflammation (MAPK, NF-kB, and JAK1/STAT3); results showed that the JAK1/STAT3 pathway was induced by LEP knockdown, as evidenced by the upregulation of phosphor-JAK1, phosphor-STAT3, and nuclear STAT3 expression. Administration of curcumin, a specific inhibitor of STAT3, counteracted the effect of LEP knockdown on cell inflammation and apoptosis. Conclusion The present data suggest that upregulation of LEP expression in the PCOS granulosa cell model is essential for reducing apoptosis and inflammation by modulating the JAK1/STAT3 pathway axis.
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Objective To investigate the effect of obesity on the expression of inflammatory factors, and to explore the molecular mechanism of inflammatory factors in the adipose tissue. Methods Twenty Lep
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Objective: To study the preliminary pharmacodynamics effect of Shuiludihuang Capsule on rats with type 2 diabetic nephopathy induced by high-fat and sugar diet combined low dose streptozotocin (STZ), and to investigate its mechanism. Methods: Type 2 diabetic nephropathy animal model was established by feeding with high fat and sugar diet combined with low dose of STZ. The FBS, TC, TG, UMA, kidney weight, the hypertrophy index, etc were measured to study its effects of reducing blood glucose and protecting kidney, and its pharmacodynamic effects were expounded by kidney pathological section. The expressions of Angptl4, Desmin and NF-κB in kidney tissues were tested by immunohistochemistry, The expressions of Angptl4 and Desmin in kidney tissues were tested by western blotting, and APN, LEP and Urine Angptl4 were tested by ELISA to probe into its mechanism tentatively. Results: Compared with the model control group, kidney weight, the hypertrophy index, FBG, TC, TG, LEP and the expressions of Angptl4, Desmin and NF-κB in rats of each group (9, 6 mg/kg) were significantly decreased, and body mass, the serum APN level were significantly increased, with significant difference (P < 0.05, P < 0.01). Conclusion: Shuiludihuang capsule can regulate glucose and fat metabolism, reduce inflammation, reduce Angptl4, Desmin and NF-κB expression levels in renal tissue, improve renal podocyte injury, reduce urinary protein, and delay renal fibrosis and sclerosis. Its mechanism may be related to Angptl4, Desmin and NF-κB pathways.
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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.
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Leptin is involved in the regulation of food intake and energy expenditure, and therefore, is central to adipositysensing pathway. We examined the relationship of the leptin G-2548A polymorphism with obesity and obesityrelated anthropometric and metabolic parameters in a total of 394 (239 obese and 155 non-obese) subjects between 5 and 45 years of age. Body weight, height, waist circumference (WC), hip circumference (HC) and blood pressure (BP) were measured. Body mass index (BMI) and waist-to-hip ratio (WHR) were calculated. Levels of fasting blood glucose (FBG), insulin, leptin and leptin receptor were determined, and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The LEP G-2548A polymorphism showed association with obesity in children and adolescents ( 18 years of age) but not in adults. However, analysis by gender stratification revealed association with obesity in girls only. In addition, G-2548A polymorphism showed association with BMI, WC, HC, fasting blood glucose and serum leptin levels. This suggests that G-2548A polymorphism may influence the susceptibility to metabolic disturbances and obesity at an early life. Further investigation with a larger sample size is required to validate the effect of LEP G-2548A polymorphism in obese Pakistani girls.
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Objective To assess the effect of Lep d2 from Lepidoglyphus destructor as a vaccine for specific immunothera?py on murine model of asthma. Methods Thirty BALB/c mice(SPF)were randomly categorized into a PBS group,an asthma group,and a Lep d2 SIT group. The mice in the asthma group and Lep d2 SIT group were sensitized by intraperitoneal injection with extracts of dust mites on Days 0,7th,and 14th,while those in the PBS group were injected with PBS. From the 21st day, the asthma group and Lep d2 SIT group exposed to the extracts of dust mites were stimulated by aerosol inhalation for 7 succes?sive days. During the period of the 25th-27th Day,the mice in Lep d2 SIT group were injected intraperitoneally with Lep d2 al?lergen for SIT 30 min before nasal inhalation,whereas the PBS group and asthma group were treated with only PBS. Twenty?four hours after the final inhalation,all the mice were sacrificed,the bronchoalveolar lavage fluids(BALFs)were collected. The lev?els of IFN?γ,IL?5 and IL?13 in the BALF and the supernatant of splenocyte culture solution(SSCS)as well as the levels of spe?cific IgE(sIgE)and sIgG2a in the sera were detected by ELISA. The lung tissues of the mice in the above 3 groups were stained by haematoxylin and eosin(H&E)and observed by a microscope. Results The symptoms of acute asthma attack were observed in the mice of the asthma group and Lep d2 group,but not in the PBS group. The allergic inflammation changes in lung in the Lep d2 SIT group were significantly alleviated compared with those in the asthma group. The concentrations of IFN?γin BALFs and SSCS of the mice in the Lep d2 SIT group were significantly higher than those in the asthma group(both P<0.01),while the levels of IL?5 and IL?13 in the former group were significantly lower than those in the latter group(all P<0.01). Mean?while,the level of sIgE of mice in the Lep d2 SIT group was significantly lower than those in the asthma group(P<0.01),while the level of sIgG2a of mice in the former group was higher than those in the latter group(P<0.01). Conclusion Lep d2 allergen as a vaccine can alleviate the allergic symptoms in the lung of mice effectively after allergen specific immunotherapy.
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BACKGROUND: Lupus erythematosus panniculitis (LEP), (or lupus erythematosus profundus), is an unusual variant of lupus erythematosus which primarily affects subcutaneous fat. LEP may occur with or without other manifestations of cutaneous or systemic lupus erythematosus. Only a few studies on the clinical and histopathologic manifestation of LEP have been conducted in Korea. OBJECTIVE: The purpose of this study was to investigate clinical, laboratory, and histopathologic features of LEP in Korean patients. METHOD: A total of 30 patients confirmed as having LEP at the Chungbuk National University Hospital between 1 July 1994 and 31 June 2004 were included in this study. The medical records and histopathologic findings were reviewed. RESULTS AND CONCLUSION: 1. LEP occurred predominantly in females, with the female to male ratio being 4: 1. The mean age at diagnosis was 38.5 years. 2. The most common clinical features were nodules or plaques, and 60% of the patients had pain or tenderness. Skin lesions affected the proximal arm area, face, trunk, scalp, and buttocks. In 26% of cases, LEP was associated with discoid lupus erythematosus (DLE), and 13% had evidence of mild systemic lupus erythematosus (SLE). The antinuclear antibody (ANA) was positive in 30% of cases. 3. The main histopathologic characteristics of LEP were predominant lymphocytic lobular panniculitis, hyaline necrosis, mucin deposit, and lymphoid aggregates. 4. Treatments included antimalarial drugs, systemic corticosteroids, intralesional corticosteroids, or topical potent corticosteroids under occlusion. They produced some improvement in most cases, however LEP exhibited a chronic nature with a high relapse rate.