Retinol,RetinoicAcid,andRetinol-BindingProtein 4areDifferentiallyAssociatedwithCardiovascular Disease,Type2Diabetes,andObesity:An OverviewofHumanStudies

Abstract

VitaminAisafat-solubleessentialnutrientobtainedfromplant-andanimal-basedsourcesthathasrolesingrowth,vision,andmetabolism.Vitamin Acirculatesmainlyasretinolboundtoretinol-bindingprotein4(RBP4),andisdeliveredtotissuesandconvertedtoretinoicacid,whichisaligandfor severalnuclearreceptors.Inrecentyears,aspectsofvitaminAmetabolismhavebeenunderscrutinywithregardstothedevelopmentofmetabolic andlifestylediseasesincludingcardiovasculardisease(CVD),type2diabetesmellitus(T2DM),andoverweightandobesityinhumans.Studieshave mainlyfocusedonRBP4inthiscontext,whereasthemajorcirculatingform,retinol,andthemajorbioactiveform,retinoicacid,havebeenoverlooked inthisregarduntilrecently.AsoneofthemainrolesofRBP4istodeliverretinoltotissuesforbiologicalaction,theassociationsofretinolandretinoic acidwiththesediseasesmustalsobeconsidered.Inthisreview,wesummarizeanddiscussrecentandavailableevidencefromhumanstudieswith focusonretinol,retinoicacid,andRBP4andprovideanoverviewofthesecrucialcomponentsofvitaminAmetabolisminCVD,T2DM,andobesity. Insummary,retinolwasfoundtobebothinversely andpositivelyassociatedwithCVD whereastheassociationswithT2DMandobesitywere less clear. Although only a few studies have been published on retinoic acid, it was inversely associated with CVD. In contrast, serum RBP4 was mostly foundtobepositivelyassociatedwithCVD,T2DM,andobesity.Atpresent,itisdifficulttoascertainwhythereportedassociationsdifferdepending onthecompoundunderstudy,butthereisaclearimbalanceintheliteratureindisfavorofretinolandretinoicacid,whichneedstobeconsidered infuturehumanstudies