Propionyl-L-carnitine Corrects Metabolic and Cardiovascular Alterations in Diet-Induced Obese Mice and Improves Liver Respiratory Chain Activity 英文参考文献.docVIP

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Propionyl-L-carnitine Corrects Metabolic and Cardiovascular Alterations in Diet-Induced Obese Mice and Improves Liver Respiratory Chain Activity 英文参考文献.doc

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Propionyl-L-carnitine Corrects Metabolic and Cardiovascular Alterations in Diet-Induced Obese Mice and Improves Liver Respiratory Chain Activity 英文参考文献

Propionyl-L-carnitineCorrectsMetabolicand CardiovascularAlterationsinDiet-InducedObeseMice andImprovesLiverRespiratoryChainActivity CarmenMingorance1,LucieDuluc2,3,MatthieuChalopin2,3,GillesSimard2,3,4,Pierre-HenriDucluzeau2,3 , MariaDoloresHerrera1,MariaAlvarezdeSotomayor1,RamarosonAndriantsitohaina2,3* 1DepartmentofPharmacology,SchoolofPharmacy,UniversityofSevilla,Sevilla,Spain,2LUNAMUniversite′,Anger,France,3INSERMU1063,Angers,France,4Universite′ d’Angers,CHUAngers,DepartmentofBiochemistry,Angers,France Abstract Aims:Obesityisaprimarycontributortoacquiredinsulinresistanceleadingtothedevelopmentoftype2diabetesand cardiovascularalterations.Thecarnitinederivate,propionyl-L-carnitine(PLC),playsakeyroleinenergycontrol.Ouraimwas toevaluatemetabolicandcardiovasculareffectsofPLCindiet-inducedobesemice. Methods: C57BL/6 mice were fed a high-fat diet for 9 weeks and then divided into two groups, receiving either free- (vehicle-HF)orPLC-supplementedwater(200mg/kg/day)during4additionalweeks.Standarddiet-fedanimalswereused as lean controls (vehicle-ST). Body weight and food intake were monitored. Glucose and insulin tolerance tests were assessed,aswellastheHOMAIR,theserumlipidprofile,thehepaticandmuscularmitochondrialactivityandthetissuenitric oxide(NO)liberation.Systolicbloodpressure,cardiacandendothelialfunctionswerealsoevaluated. Results:Vehicle-HFdisplayedagreaterincreaseofbodyweightcomparedtovehicle-STthatwascompletelyreversedby PLC treatment without affecting food intake. PLC improved the insulin-resistant state and reversed the increased total cholesterol but not the increase in free fatty acid, triglyceride and HDL/LDL ratio induced by high-fat diet. Vehicle-HF exhibitedareducedcardiacoutput/bodyweightratio,endothelialdysfunctionandtissuedecreaseofNOproduction,allof thembeingimprovedbyPLCtreatment.Finally,thedecreaseofhepaticmitochondrialactivitybyhigh-fatdietwasreversed byPLC. Conclusions:OraladministrationofPLCimprovestheinsulin-resistantstatedevelopedbyobeseanimals