CellMetabolismPerspectiveEpigeneticMechanismsofTransmissionofMetabolicDiseaseacrossGenerationsVicenciaMichelineSales,1AnneC.Ferguson-Smith,2andMary-ElizabethPatti1,*1IntegrativePhysiologyandMetabolism,ResearchDivision,JoslinDiabetesCenterandHarvardMedicalSchool,OneJoslinPlace,SixthFloor,Boston,MA02215,USA2DepartmentofGenetics,UniversityofCambridge,DowningStreet,CambridgeCB23EH,UK*Correspondence:mary.elizabeth.patti@joslin.harvard.eduhttp://dx.doi.org/10.1016/j.cmet.2017.02.016Bothhumanandanimalstudiesindicatethatenvironmentalexposuresexperiencedduringearlylifecanrobustlyinfluenceriskforadultdisease.Moreover,environmentalexposuresexperiencedbyparentsduringeitherintrauterineorpostnatallifecanalsoinfluencethehealthoftheiroffspring,thusinitiatingacycleofdis-easeriskacrossgenerations.InthisPerspective,wefocusonepigeneticmechanismsingermcells,includingDNAmethylation,histonemodification,andnon-codingRNAs,whichcollectivelymayprovideanon-geneticmolecularlegacyofpriorenvironmentalexposuresandinfluencetranscriptionalregulation,developmentaltrajectories,andadultdiseaseriskinoffspring.IntroductionMetabolicdiseasearisesattheconfluenceofgeneticsandenvi-ronmentalfactors,suchasnutrition,exercise,chemicalexpo-sure,behavior,andthemicrobiome(BaccarelliandBollati,2009;Barre`sandZierath,2016;Gallou-KabaniandJunien,2005;McGowanetal.,2009;MiskaandFerguson-Smith,2016;Skinneretal.,2010;Songetal.,2013).Interestingly,studiesinbothhumansandanimalmodelsindicatethatenviron-mentalexposuresexperiencedbyparentsduringeitherintra-uterineorpostnatallifecanalsoinfluencethehealthoftheiroffspring,thusinitiatingacycleofdiseaseriskacrossgenera-tions.Inthisreview,webrieflydiscusspotentialepigeneticmechanismsthatmaycontributetoenvironmentallyinducedmetabolicdiseaseafterdirectexposureandinsubsequentgen-erations,withaparticularfocusonpaternallineageeffectsmedi-atedbygermcells.EvidenceforNon-geneticImpactonMetabolicDiseaseRiskinSubsequentGenerationsMetabolicdisease,includingobesityandtype2diabetes(T2D),arises...
