Pro-Inflammatory wnt5a and Anti-Inflammatory sFRP5 Are Differentially Regulated by Nutritional Factors in Obese Human Subjects 英文参考文献.docVIP

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Pro-Inflammatory wnt5a and Anti-Inflammatory sFRP5 Are Differentially Regulated by Nutritional Factors in Obese Human Subjects 英文参考文献.doc

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Pro-Inflammatory wnt5a and Anti-Inflammatory sFRP5 Are Differentially Regulated by Nutritional Factors in Obese Human Subjects 英文参考文献

Pro-Inflammatorywnt5aandAnti-InflammatorysFRP5 AreDifferentiallyRegulatedbyNutritionalFactorsin ObeseHumanSubjects DominikM.Schulte1,NikeMu¨ller1,KatrinNeumann1,FrankOberha¨user2,MichaelFaust2 ,Heike Gu¨delho¨fer2,BurkhardBrandt3,WilhelmKrone2,MatthiasLaudes1* 1DepartmentIofInternalMedicine,UniversityofKiel,Kiel,Germany,2CenterofEndocrinology,DiabetesandPreventiveMedicine,UniversityofCologne(Germany), Ko¨ln,Germany,3InstituteforClinicalChemistry,UniversityofKiel,Kiel,Germany Abstract Background: Obesity is associated with macrophage infiltration of adipose tissue. These inflammatory cells affect adipocytes not only by classical cytokines but also by the secreted glycopeptide wnt5a. Healthy adipocytes are able to releasethewnt5ainhibitorsFRP5.Thisprotectiveeffect,however,wasfoundtobediminishedinobesity.Theaimofthe presentstudywastoexamine(1)whetherobesehumansubjectsexhibitincreasedserumconcentrationsofwnt5aand(2) whetherwnt5aand/orsFRP5serumconcentrationsinobesesubjectscanbeinfluencedbycaloricrestriction. Methodology: 23 obese human subjects (BMI 44.161.1kg/m2) and 12 age- and sex-matched lean controls (BMI 22.360.4kg/m2) were included in the study. Obese subjects were treated with a very low-calorie diet (approximately 800kcal/d) for 12 weeks. Body composition was assessed by impedance analysis, insulin sensitivity was estimated by HOMA-IRandtheleptin-to-adiponectinratioandwnt5aandsFRP5serumconcentrationsweremeasuredbyELISA.sFRP5 expressioninhumanadiposetissuebiopsieswasfurtherdeterminedonproteinlevelbyimmunohistology. PrincipalFindings:Pro-inflammatorywnt5awasnotmeasurableinanyserumsampleofleancontrolsubjects.Inpatients with obesity, however, wnt5a became significantly detectable consistent with low grade inflammation in such subjects. Caloric restriction resulted in a weight loss from 131.964.0 to 112.363.2kg in the obese patients group. This was accompaniedbyasignificantdecreaseofHOMA-IRandleptin-to-adiponectinratio,indicatingimprovedinsulinsensitivity. Intere