| 1.Knockdown of Tlr4 in the arcuate nucleus improves obesity related metabolic disordersObjective: To investigate whether down-regulation of TLR4 expression in hypothalamic ARC by stereotaxic injection of TLR4 sh RNA lentiviral particles can improve the metabolic disorders in high-fat diet-induced obesity rat model.Methods: Five-week-old rats were fed with high-fat diet for 14 weeks to establish highfat diet-induced obesity rat model,and then were treated with TLR4 sh RNA lentiviral particles or scrambled sh RNA lentiviral particles by stereotaxic injection at 15 th week.Four weeks later,the glucose homeostasis was determined by intraperitoneal glucose tolerance test.The insulin sensitivity was determined by intraperitoneal insulin tolerance test.The intraperitoneal pyruvate tolerance test was used to determine the gluconeogenesis in obese rats.The sections of livers and adipose tissue were stained by regular hematoxylin-eosin methodology for evaluation of liver and adipose histology.The m RNA expression of Tlr4,Tnf,Npy and Pomc in hypothalamus and the m RNA expression of Ccl2,Tnf and several metabolism genes(Pklr,G6 pc,Fasn and Acaca)in liver were measured by real time PCR.Results: Our results demonstrated that down-regulation of TLR4 expression,which was accompanied by the decreased expression of TNF-?,NPY and increased expression of POMC,in the hypothalamic ARC significantly alleviated diet-induced weight gain and energy intake,and improved peripheral glucose homeostasis,insulin sensitivity and abnormal gluconeogenesis.Moreover,our results found that the high-fat diet-induced hepatic steatosis and adipocyte hypertrophy were also partially reversed after inhibition of TLR4 expression in the hypothalamic ARC,which was accompanied by the expression restoration of several glucose and lipid metabolism-related genes and inflammatory marker genes in the liver.Conclusions: we demonstrate that specific down-regulation of TLR4 expression in the hypothalamic ARC is sufficient to improve glucose and lipid homeostasis during the course of diet-induced obesity by inhibition of hypothalamic inflammation.Our findings confirm the previous opinions that the TLR4 signaling pathway in hypothalamus is an attractive target for treatment of obese conditions,and further suggest that ARC-restricted TLR4 knockdown is a potential strategy to combat metabolic disorders associated with obesity.2.Alteration of Connexin43 Expression in a Rat Model of ObesityRelated GlomerulopathyObjective: It is accepted that the alteration of connexin43(Cx43)expression in glomeruli is a common pathological response in several forms of kidney diseases.To date,however the change of the Cx43 expression in obesity-related glomerulopathy(ORG)has not been reported.In this study,the alteration of Cx43 expression in the glomeruli of rat with ORG was defined.Methods: Five-week-old rats were fed with high-fat diet for 18 weeks to establish ORG model.The histological change of glomeruli was determined by Periodic acid Schiff staining.The foot process effacement of podocyte was observed by transmission electron microscope.The markers for podocyte injury(nephrin,podocin and WT1)and Cx43 expression in glomeruli were measured by immunostaining,real time RT-PCR and Western-blotting.Results: The results demonstrated metabolic disorder,hyperinsulinemia,systemic inflammation and microalbuminuria in ORG rats.There are significant hypertrophy,glomerular expansion and inflammatory cells infiltration in the kidney of ORG rats compared to control group.The significant foot process effacement of the podocyte in the glomeruli,nephrin loss and density reduction were shown in the ORG rats,and the Cx43 expression was significant upregulated in glomeruli of ORG rats compared to control group.Conclusions: The results indicate the correlation of overexpressed Cx43 with the obesity related renal inflammation and suggest that Cx43 might be a potential target in the development of obesity related glomerulopathy.3.Effect of obesity and overweight on the hospital stays and total course of common pneumonia in childrenObjective: To study the effect of obesity and overweight on the hospital stays and total course of common pneumonia in children and the possible reasons.Methods: A total of 455 children with common pneumonia aged from 2 to 7 years were enrolled in this study,included 147 obese children,147 overweight children and 167 normal weight children.Then all the cases were divided into 2 groups based on age: 2 ~ 4 years group and 4~7 years group.The information of patients was collected from the medical records management system of our hospital,and include gender,age,weight,height,hospital stays,total course,peripheral blood cell counts(white blood cell,neutrophil,monocyte and lymphocyte),CRP,ESR,Ig G,Ig A,CD4+T,CD8+T and the history of recurrent pneumonia.Results: In 2 ~ 4 years group,the average length of the hospital stays of common pneumonia in obese and overweight children are longer than that in the normal weight children(P value were 0.037 and 0.009,respectively),the total course of common pneumonia in obese children are longer than that in the normal weight children(P=0.014);In 4 ~ 7 years group,the average length of the hospital stays and total course of common pneumonia in obese and overweight children are longer than that in the normal weight children(The hospital stays: P value were 0.037 and 0.009,respectively;The total course: P value were 0.037 and 0.009,respectively).In 2 ~ 4 years group,the peripheral blood cell counts(white blood cell,neutrophil,monocyte and lymphocyte),CRP,ESR,Ig G,Ig A,CD4+T,CD8+T,CD4+T/CD8+T and the history of recurrent pneumonia were no significant difference among obese,overweight and normal weight children.In 4 ~ 7 years group,the peripheral blood cell counts(white blood cell,neutrophil,monocyte and lymphocyte),ESR were no significant difference among obese,overweight and normal weight children,but the level of Ig G,CD4+T and CD4+T/CD8+T in obese and overweight children were lower than that in the normal weight children,especially in the obese children.Moreover,obese and overweight children are more likely to suffer from recurrent pneumonia.Conclusions: Obese and overweight children with common pneumonia aged from 2 to 7 years may need longer hospital stays and total course than normal weight children.Impaired immunity may be the main reason for the 4 ~ 7 years group,but in the 2 ~ 4 years old group,it may be attribute to some non-immune factors.4.Obesity increases the risk of renal involvement in children with Henoch-Sch?nlein purpuraObjective: The main aim of this study was to evaluate the relationship between obesity and renal involvement in children with Henoch-Sch?nlein purpura(HSP).Methods: A retrospective study of 141 pediatric patients with HSP was conducted in our hospital.The clinical data of all patients were collected from the electronic medical record management system from January 2010 to June 2014.The possible risk factors of renal involvement,especially obesity,were analyzed using univariate and multivariate analysis.Results: Renal involvement occurred in 45/141 of the patients.A univariate analysis showed that an age more than 7 years at onset,persistent purpura,obesity,time from symptoms onset to diagnosis more than14 days,and decreased C3 all increased the risk of renal involvement in HSP.The forward stepwise logistic regression analysis indicated obesity(OR 4.43,95%CI 1.896 to 10.358),age more than 7 years at onset(OR 2.81,95%CI 1.142 to 6.907)and persistent purpura(OR 2.57,95%CI 1.119 to 5.909)were independent risk factors for renal involvement.Conclusions: Our results show that obesity can increase the hazard of renal involvement in children with HSP,and reconfirm that older age at onset and persistent purpura are the independent risk factors for renal involvement. |
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