Sugarleadstoearlydeath,butnotduetoobesity

StudywiththeparticipationofthePMIClusterofExcellencepointsoutthatthereducedlifeexpectancyduetosugarconsumptioncouldhaveothercausesthanpreviouslyassumed

Weallknowthatconsumingtoomuchsugarisunhealthy.Itincreasesourriskofdevelopingmetabolicdisorders,suchasobesityanddiabetes,andcanshortenourlifeexpectancybyseveralyears.Itiswidelybelievedthatthisreductioninlifespaniscausedbymetabolicdefects.However,thisassumptioncouldbewrong,asshownbyanewstudypublishedyesterdayinthejournalCellMetabolismbyresearchersfromtheImperialCollegeLondonincollaborationwithresearchersfromKielUniversityandtheUniversityMedicalCenterSchleswig-Holstein(UKSH),CampusKiel.Theresultssuggestthatinsteadtheaccumulationofanaturalwasteproduct,uricacid,mayberelatedtosugar-relatedshortenedlifeexpectancy.

Sugarconsumptionincreasesuricacidlevels

TheLondonteamhasinvestigatedtheinfluenceofsugaryfoodonthelifespanoffruitflies.Justlikehumans,fliesfedahigh-sugardietshowmanyhallmarksofmetabolicdiseaseforinstance,theybecomefatandinsulinresistant,saysDr.HelenaCochemoftheImperialCollegeLondon,principalinvestigatorofthestudy.Obesityanddiabetesareknowntoincreasemortalityinhumans,andsopeoplealwaysassumedthatthiswashowexcesssugarisdamagingforsurvivalinflies.However,likesalt,sugaralsocausesdehydration.Therefore,theresearchersgavethefruitfliesadditionalwater.Surprisinglytheyfoundthatfliesfedahigh-sugardietdidnotshowareducedlifespan,simplybyprovidingthemwithanextrasourceofwatertodrink.Unexpectedly,thesefliesstillexhibitedthetypicalmetabolicdefectsassociatedwithhighdietarysugar.

Basedonthiswatereffect,theteamdecidedtofocusontheflyrenalsystem.Theyshowedthatexcessdietarysugarcausedthefliestoaccumulateamoleculecalleduricacid.Uricacidisanend-productfromthebreakdownofpurines,whichareimportantbuildingblocksinourDNA.Buturicacidisalsopronetocrystallise,givingrisetokidneystonesinthefly.Researcherscouldpreventthesestones,eitherbydilutingtheirformationwithdrinkingwaterorbyblockingtheproductionofuricacidwithadrug.Inturn,thisprotectedagainsttheshortenedsurvivalassociatedwithasugar-richdiet.Althoughthesugar-fedfruitflieslivelongerifwegivethemmorewater,theyarestilluhealthy.Butourstudysuggeststhatdisruptionofthepurinepathwayisthelimitingfactorforsurvivalinhigh-sugar-fedflies.Thismeansthatearlydeathbysugarisnotnecessarilyadirectconsequenceofobesityitself,saidCochem.

Increaseduricacidlevelsthroughsugarinhumans

Asimilarmechanismcouldalsoworkinhumans,asresearchersoftheClusterofExcellencePrecisionMedicineinChronicInflammation(PMI)haveshown.AteamledbyProfessorChristophKaleta,ProfessorAndreFranke,ProfessorMatthiasLaudesandProfessorWolfgangLieb-allfromKielUniversity-hasinvestigatedtheinfluenceofsugar-richnutritioninhealthyhumans.Strikingly,justlikeflies,wefoundthatdietarysugarintakeinhumanswasassociatedwithworsekidneyfunctionandhigherpurinelevelsintheblood,saysProf.ChristophKaletafromtheInstituteforExperimentalMedicineatKielUniversity.

Accumulationofuricacidisaknowndirectcauseofkidneystonesinhumans,aswellasgout,aformofinflammatoryarthritis.Uricacidlevelsalsotendtoincreasewithage,andcanpredicttheonsetofmetabolicdiseasessuchasdiabetes.Itwillbeinterestingtoinvestigatehowtheaccumulationofuricacidduetoincreasedsugarconsumptionisrelatedtometabolicdiseasessuchasdiabetesandwhetheritmightevenhaveadirecteffectonlifeexpectancyinhumans,"saidKaleta."Inthefuture,wemightalsobeabletofindnewtherapeutictargetsandstrategiesthatpromotehealthyageing,"predictsKaleta.

Contact:

Prof.ChristophKaleta
InstituteforExperimentalMedicine,KielUniversity
0049431500-30340
c.kaleta@iem.uni-kiel.de

a pile of sugar
©Pixabay

Toomuchsugarcanshortenlifeexpectancybyseveralyears.However,atleastinfruitflies,thecauseforthisisnot,aspreviouslyassumed,obesityanddiabetesresultingfromsugarconsumption.

Fruitfly Drosophila
©C.Urban,UniKiel.

Fruitfliesthathadbeenfedasugarydietdiedearlierthanconspecificswithotherfood.Theeffectcouldbepreventedbyanadditionalwatersource.

Professor Christoph Kaleta from Kiel University
©T.BÃschen,UniKiel.

ProfessorChristophKaleta,memberoftheClusterofExcellence"PrecisionMedicineinChronicInflammation"(PMI)andheadoftheMedicalSystemsBiologygroupattheInstituteforExperimentalMedicine,CAU.

Originalpublication:

EsthervanDam*,LucieA.G.vanLeeuwen*,ElianodosSantos*,JoelJames*,LenaBest*,,WolfgangLieb,MatthiasLaudes,AndreFranke,ChristophKaleta,andHelenaM.Cochem,Sugar-InducedObesityandInsulinResistanceAreUncoupledfromShortenedSurvival
inDrosophila,CellMetabolism(2020).https://doi.org/10.1016/j.cmet.2020.02.016
*Theseauthorscontributedequally.

AbouttheClusterofExcellencePMI

TheClusterofExcellence"PrecisionMedicineinChronicInflammation"(PMI)isbeingfundedfrom2019to2025throughtheGermanExcellenceStrategy(ExStra).Itsucceedsthe"InflammationatInterfacesCluster,whichwasalreadyfundedintwoperiodsoftheExcellenceInitiative(2007-2018).Around300membersfromeightinstitutionsatfourlocationsareinvolved:Kiel(KielUniversity,UniversityMedicalCenterSchleswig-Holstein(UKSH),MuthesiusUniversityofFineArtsandDesign,KielInstitutefortheWorldEconomy(IfW),LeibnizInstituteforScienceandMathematicsEducation(IPN)),Lbeck(UniversityofLbeck,UniversityMedicalCenterSchleswig-Holstein(UKSH)),Pln(MaxPlanckInstituteforEvolutionaryBiology)andBorstel(ResearchCenterBorstel-LeibnizLungCenter).

Thegoalistotranslateinterdisciplinaryresearchfindingsonchronicinflammatorydiseasesofbarrierorganstohealthcaremoreintensively,aswellastofulfilpreviouslyunsatisfiedneedsofthepatients.Threepointsareimportantinthecontextofsuccessfultreatment,andarethereforeattheheartofPMIresearch:theearlydetectionofchronicinflammatorydiseases,thepredictionofdiseaseprogressionandcomplications,andthepredictionofindividualresponsestotreatment.

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