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Nutrizione ed epigenetica - Prof.ssa Franca Saccucci

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Nutrizione ed epigenetica - Prof.ssa Franca Saccucci

  1. 1.  Nutrizione ed epigenetica Prof.ssa Franca Saccucci Dipartimento Scienze Cliniche Specialistiche ed Odontostomatologiche
  2. 2. Il nostro fenotipo (quello che siamo fisicamente e nelle nostre capacità, funzioni e comportamenti) anche se deriva principalmente dal nostro “programma” genetico è determinato anche dall’epigenetica L’epigenetica è lo studio dei fattori che determinano cambiamenti stabili ed ereditabili, ma reversibili, nell’espressione dei geni senza cambiamenti nella sequenza originale del DNA
  3. 3. <ul><li>I principali meccanismi epigenetici che regolano l’espressione sono: </li></ul><ul><li>metilazione del DNA </li></ul><ul><li>modificazione degli istoni </li></ul><ul><li>rimodellamento della cromatina </li></ul>Sono tutti necessari per un corretto sviluppo e differenziamento, se mal controllati sono coinvolti in severe patologie umane
  4. 4. <ul><li>Sindrome di Rett </li></ul><ul><li>Sindrome di Rubinstein-Taybi </li></ul><ul><li>Angelman/Prader-Willi </li></ul><ul><li>Sindrome di Silver-Russell </li></ul>Delezione, disomia uniparentale paterna, difetto di imprinting Perdita della acetil-transferasi istonica Aberrante metilazione DNA (MECP2) Nel 30% dei casi ipometilazione gene H19
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  6. 6. Demetilazione passiva
  7. 7. Le differenze fra gemelli MZ possono essere il risultato di scelte personali
  8. 8. <ul><li>Incremento di differenza di metilazione </li></ul><ul><li>Verde: area di ipermetilazione </li></ul><ul><li>Rosso: area di ipometilazione </li></ul><ul><li>Giallo: area di egual metilazione </li></ul>
  9. 9. <ul><li>Ambiente interno: </li></ul><ul><ul><li>ormoni </li></ul></ul><ul><ul><li>metabolismo </li></ul></ul><ul><ul><li>sesso </li></ul></ul><ul><ul><li>età </li></ul></ul><ul><li>Ambiente esterno: </li></ul><ul><ul><li>temperatura </li></ul></ul><ul><ul><li>dieta </li></ul></ul><ul><ul><li>farmaci </li></ul></ul><ul><ul><li>Sostanze chimiche (inquinamento) </li></ul></ul>
  10. 10. L’epigenetica della nutrizione studia come l'alimentazione o particolari alimenti regolano l'espressione genica
  11. 11. Le api operaie o regine hanno genotipo identico ma fenotipo diverso
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  13. 13. Geneticamente identici, stessa età e stesso sesso Durante la gravidanza le due madri sono state trattate con diete diverse Normale dieta per topi Dieta supplementata con colina, acido folico, betaina, vitamina B12 Wolff at al. 1998 Waterland et al. 2003
  14. 14. Durante la gravidanza le due madri sono state trattate entrambe con Bisfenolo A (BPA) ma con diete diverse Normale dieta per topi Dieta supplementata acido folico e ginesteina 2000, Randy Jirtle e Robert Waterland
  15. 15. HMT DNMT HISTONE METHYLATION DNA METHYLATION BHMT SHMT MTRR CBS MTHFR COMT
  16. 16. NUTRIENTI AZIONE Vitamine B Folati Vitamina B-12 Vitamina B-6 Vitamina B-2 Accettori e donatori di metili nel metabolismo 1-C Cofattore per MS Cofattore per SHMT, CBS Cofattore per MTHFR Nutrienti della dieta donatori di metili Metionina Coline Betaina Serina Precursore di SAM Rimetilazione omocisteina da parte di BHMT Rimetilazione omocisteina da parte di BHMT Donatore di metili al tetraidrofolato da parte di SHMT Micronutrienti Acido retinoico Zinco Selenio Incremento di attività di GNMT Cofattori per MAT Incremento del pathway transolfurazione Composti bioattivi del cibo Genisteina del te Polifenoli Inibizione delle metiltransferasi del DNA Inibizione delle metiltransferasi del DNA
  17. 17. ORIGINE VEGETALE COMPONENTI DELLA DIETA modulatori di HDAC Allium sativum L. Fermentazione fibre della dieta Famiglia delle brassinacee Broccoli Rafano Diallil disolfito(DADS) S -allilmercaptocisteina Allil mercaptano Butirrato Sulforafano 6-metilsulfiniexil-isotiocianato modulatori di SIRT vitis vinifera (uve rosse, vino) Rhus toxicodendron (leaves) Rhus verniciflua (stems) Mela, tè, cipolla, noci, frutti di bosco, Mirtilli Peperone rosso, sedano, prezzemolo Resveratrolo Fisertina Buteina Quercetino Piceatannolo Luteolina modulatori di HAT Curcuma Longa Garcina indica (frutta) Camelia sinensis (te nero e verde) Curcumina Garcinolo Teofilina
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  24. 24. 74 campioni 227 regioni mostrano una alta variabilità interindividuale e circa la metà stabili dopo gli 11 anni 4 di queste regioni variavano insieme all’indice di massa corporea ed erano localizzate vicino o nei geni precedentemente implicati nella regolazione della massa corporea o diabete
  25. 25.
  26. 26. Durante la vita i nutrienti possono modificare i processi fisiologici e patologici attraverso meccanismi epigenetici che sono critici per l’espressione dei geni La modulazione di questi processi attraverso la dieta o specifici nutrienti può prevenire la patologia e mantenere la salute Tuttavia è difficile delineare i precisi effetti dei nutrienti o delle componenti bioattive del cibo su ciascuna modifica epigenetica e la loro associazione con processi fisiologici perché essi interagiscono con i geni, con altri nutrienti e altri fattori ambientali Inoltre ogni fenomeno epigenetico interagisce con altri fenomeni epigenetici, aggiungendo complessità al sistema
  27. 27. La comprensione del ruolo dei nutrienti o delle componenti bioattive del cibo nell’alterazione dei patterns epigenetici ci potrebbe fornire una via per il mantenimento della salute attraverso la modulazione della dieta che è più fisiologica di qualsiasi farmacoterapia.

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