Note: for non-commercil purposes only PLACENTAL TRANSFER OF FATTY ACIDS AND FETAL IMPLICATIONS Dr. Elvir Lrqué elvird@um.es Deprtment of Physiology Unversity of Murci (Spin)
FETAL PROGRAMMING BRAIN 6% FAT (dry mtter) ~ 4% LONG CHAIN POLYUNSATURATED FATTY ACIDS (LC-PUFA): - 15% DOCOSAHEΧAENOIC ACID (DHA, 22:6 n-3): Neuronl development - 1% ARACHIDONIC ACID (AA, 2:4 n-6) : Infntile Growth
EFA: LC-PUFA: Polyunsturted FA Synthesis 18:2ω-6 linoleic 18:3ω-6 γ-linolenic 2:4ω-6 rchidonic 6-desturse elongse & 5 desturse & elongse PROSTA- GLANDINS 18:3ω-3 α-linolenic 2:5ω-3 eicospentenoic MEMBRANES 22:6ω-3 docoshexenoic EFA nd LC-PUFA PROVIDED BY PLACENTAL TRANSFER
Ftty Acid Plcentl Uptke Mternl circultion FFA TG TG TG FFA PL memrne Lipse LPL FABPpm FATP, FAT Lipse EL Lipoprotein R? Trofolst cytosol FFA LPL, Lipoprotein lipse EL, Endothelil lipse FFA Fcilitted Trnsport FFA Psive Diffusion PLA2 Lipses AGL
Ftty Acid Plcentl Trnsfer Plcentl trnsfer of ftty cids is complex process tht includes their inding to memrne nd cytosolic protein crriers p-fabppm (plcentl plsm ftty cid inding protein) not sequenced??.
BIOMAGNIFICATION OF LC-PUFA Ftty-Acid Percentges of Mternl nd Cord Plsm Phospholipids [medin (IQR)] m te rn l c o rd S A T 4 7.1 (2.5 ) 4 9.9 (1.7 ) M U F A 1 4.9 (2.7 ) 1 3.4 (2.2 ) 1 8 :2 n -6 (LA) 2 1. (3.4 ) 7.4 (1.4 ) (ALA) 1 8 :3 n -3.2 (.1 ). (. 3 ) 2 :4 n -6 7.7 (1.9 ) 1 6.1 (2.5 ) (AA) 2 2 :6 n -3 (DHA) 2.9 (1. ) 4.8 (1.7 ) Koletzko et l. Eur J Peditr 1998
Stle Isotope Study on FA Plcentl Trnsfer Aim PERILIP PROJECT (FP6 EU) In vivo evlution of the plcentl trnsfer of ftty cids leled with stle isotopes in humns Mteril y methods Single orl dose of stle isotope trcer in sugr cue: - C-PA (Plmitic cid: sturted FA):.5 mg/kg - C-OA (Oleic cid: monounsturted FA):.5 mg/kg - C-LA (Linoleic cid: essentil FA):.5 mg/kg - C-DHA (Docoshexenoic cid, LC-PUFA):.1 mg/kg Study 4 hours efore cesren section (n=4) Study 12 hours efore cesren section (n=11)
C-APE (%) 1,,8,6,4,2 DHA LA OA PA 4h FA Trcer Study Appernce of C-FA enrichment in mternl plsm Mternl Plsm TG C-APE (%) 1,,8,6,4,2 Mternl Plsm FFA, -4-3 -2-1 1 time (h), -4-3 -2-1 1 time (h) C-APE (%),4,3,2,1 Mternl Plsm PL No enrichment in Mternl Cholesterol Esters N=4, -4-3 -2-1 1 time (h) (Lrqué et l. J. Lipid Res., 23)
Distriution of trcer etween plcent nd plsm (M ± SEM) (%) Rtio plcent/plsm 3 25 2 15 1 5 4h FA Trcer Study c c C-PA C-OA C-LA C-DHA (Lrqué et l. J. Lipid Res., 23) (%) Rtio ftty cid concentrtion in plcent (µmol/g) * APE-plcent = X 1 Plcent/plsm ftty cid concentrtion in plsm (µmol/ml) * APE-plsm
Design of 12h FA trcer Study Sujects: 11 pregnnt women, elective cesrin section weight: 78 ± 8 kg height: 161± 6 cm ge: 33 ± 4 yers gesttion: 39.8 ± 1 wk Trcer dministrtion (12h efore cesren section) Orl ppliction of stle isotope trcer in sugr cue: plmitic cid ( C-PA):.5 mg/kg oleic cid ( C-OA):.5 mg/kg linoleic cid ( C-LA):.5 mg/kg docoshexenoic cid ( C-DHA):.1 mg/kg - Mternl lood: h, 9h, 1,11h, 12h (c-section), h - Plcent collection nd venous cord lood C-enrichment of FA y gs chromtogrphy comustion isotope rtio mss spectrometry (GC-C-IRMS)
C-FA CONCENTRATION IN MATERNAL PLASMA SATURATED FA MONOUNSATURATED FA 12h FA trcer study C-PA (µmol/l) 16 14 12 1 C-LA (µmol/l) 8 6 4 2 14 12 1 8 6 4 2 sl 9 1 11 (h) ESSENTIAL FA sl 9 1 11 (h) 12 12 c c C-OA (µmol/l) C-DHA (µmol/l) 14 12 1 8 6 4 2 1,8,6,4,2 sl 9 1 (h) sl 9 1 11 (h) 11 LC-PUFA 12 12 TG PL FFA CE P <.5
C-FA Concentrtion in Plcent C-FA enrichment in plcentl TG nd NEFA tended to e high 12h FA trcer study Phospholipids constituted out 8-9% of FA in plcent C-FA (µmol/l) 16 14 12 1 8 6 4 2 c C-PA c c C-OA C-LA C-DHA PL NEFA TG EC 12h Men ± SD, P <.5
12h FA trcer study Distriution plcent/mternl plsm (M ± SEM) (Gil-Sánchez, Lrqué et l. Am. J. Clin. Nutr., 21) (%) Rtio plcent/ mternl plsm 5 4 3 2 1 Plcent C-PA C-OA C-LA C-DHA (%) Rtio plcent/ mternl plsm 5 45 4 35 3 25 2 15 1 5 Comprison 4h vs 12h * 4h * 12h α=4,17 (DHA) α=6,71( LA) α=4,75 (PA) α=4,18 (OA) Different letters: P<,5 α = slope * P<,5
Distriution Cord/Mternl Plsm 12h 12h FA trcer study (%) Rtio cord/plsm AUC 2 1,5 1,5 C-PA C-OA C-LA C-DHA (%) Rtio FA concentrtion in cord (µmol/g) * APE-cord plsm = X 1 Cord/plsm AUC FA concentrtion in plsm (µmol/ml) * APE-mt. plsm Men ± SD, P <.5
PROYECTO NUHEAL: Plcentl PL Supplementtion of 6 Spnish pregnnt women from wk 2 to delivery Control 4µg MTHF.5mgDHA DHA+MTHF 7 6 5 DHA 23 22 AA %-wt/wt 4 3 2 1 21 2 5 No significnt chnges in plcentl mrna expression of FATP-1, FATP-4, FATP-6, FAT, FABPpm, H-FABP, B-FABP, A-FABP mong the groups
NUHEAL: Correltions plcentl crriers-plcentl PL (Lrqué et l. Am J Clin Nutr. 26) FATP-1 (AU) 25 2 15 1 5 R = +.364; P =.1 R = +.387; P =.7 2 4 6 8 1 FATP-4 (AU) 1 9 8 7 6 5 4 3 2 1 2 4 6 8 1 DHA (%) DHA (%) DHA (%) IN MATERNAL PLASMA PL CORRELATES WITH PLACENTAL PROTEINS FATP-1 (r=.32, p=.1) AND FATP-4 (r=.23, p=.12)
NUHEAL: Correltions plcentl FA crriers-cord Plsm PL (Lrqué et l. Am J Clin Nutr. 26) FATP-4 plcent (AU) 1 9 8 7 6 5 4 3 2 1 5 1 15 2 DHA(%) cord lood PL r = +.2; P =.32*
GESTATIONAL DIABETES MELLITUS Norml plsm LC-PUFA in women with gesttionl dietes mellitus, ut low erytrocyte PL LC-PUFA in their ies (Wijendrn et l. 2) Delyed rin mturity in these neworns compred to controls? Pregesttionl or gesttionl dietes mellitus ws found to dversely ffect ttention spn nd motor functions of offspring t school ge (Ornoy et l. 21)
PREELIMINARY RESULTS (mg/dl) 1 9 8 7 6 5 4 3 2 1 GLUCOSE * (%l) 12 1 8 6 4 2 Mternl LC-PUFA n-3 Cord * Control (n=22) Gesttionl Dietes (n=26) Mternl Plcent Cord
PREELIMINARY RESULTS VENOUS CORD BLOOD (%) 45 4 35 3 25 2 15 * * SATURATED (SFA) EFA, LC-PUFA n-3 1 5 SFA MUFA PUFA 3 25 * Control (n=22) Gesttionl dietes (n=26) (%) 2 15 1 5 * * DHA P =.62 EFA LC-PUFA LC-PUFA n-3 DHA PLACENTAL TRANSFER OF LABELED FA IN GESTATIONAL DIABETES ON GOING
NEURONAL DEVELOPMENT IN BABIES FROM GESTATIONAL DIABETES MOTHERS DURING THE 1º YEAR OF LIFE Byleys test (6 months nd 12 months) Sleep/wke cycles y ctigrphy methods Evlution of circdin rhythms of temperture using temperture sensors.
EVOLUTION OF CHRONOBIOLOGICAL RHYTHMS Temperture sensor 36, Onds medis de tempertur de l piel 35,5 35, 34,5 34, 33,5 15 dís 3 dís 9 dís 33, 32,5 32, 9: 1:2 11:4 : 14:2 15:4 17: 18:2 19:4 21: 22:2 23:4 1: 2:2 3:4 5: 6:2 7:4 Tempertur (ºC) Hor del dí (hh:mm) Actimeter
EVOLUTION OF CORE BODY TEMPERATURE PREELIMINAR RESULTS MEAN OF TEMPERATURE AMPLITUD OF TEMPERATURE Temperture ºC 35,5 35, 34,5 34, 33,5 33, 32,5 Mesor 1 2 2 Temperture ºC 2,5 2, 1,5 1,,5 M5-L1 Vlues 1 1 2 32, 15 dys 3 dys 3 months 12 yers 2 yers Age, 15 dys 3 dys 3 months 12 yers 2 yers Age Different letters indicte significnt differences y repeted mesures ANOVA (for 15 dys, 3 dys nd 3 months comprisons). Different numers indicte significnt differences when compring ies (3 months) with child nd dult groups. Sri et l. 29. Act Physiologic, 195 (667):11
Thnk you for your kind ttention!!!! Finncil support y Alexnder von Humoldt Foundtion, HERO S.L. nd y the Commission of the Europen Communities, within the FP 6 (PERILIP PROJECT nd NUHEAL PROJECT). This presenttion does not necessrily reflect the views of the Commission nd in no wy nticiptes its future policy in this re. Elvir Lrqué is recipient of the ESPGHAN Awrd for Young Investigtors. Budpest. 29.
THANK YOU! University of ofmurci (SPAIN) An An Pgán Mrí Mrí Ster J.A. J.A. Mdrid Slvdor Zmor Gynecology Service Arrixc Hospitl Murci (SPAIN) Alfonso Gil-Sánchez Mrí Teres Priteo José Eliseo Blnco Jun José Prrill Peditric Service Arrixc Hospitl Murci ((Spin) Mtilde Zornoz Silvi Fuentes Vicente Bosch Mnuel Sánchez-Solís LMU Munich (GERMANY) Berthold Koletzko Hns Demmelmir Finne Hneut All Allstff