Fatty acid composition of adipose tissue at term indicates deficiency of arachidonic and docosahexaenoic acid and excessive linoleic acid supply in preterm infants

K A Böckmann, A von Stumpff, W Bernhard, A Shunova, M Minarski, B Frische, S Warmann, E Schleicher, C F Poets, A R Franz, K A Böckmann, A von Stumpff, W Bernhard, A Shunova, M Minarski, B Frische, S Warmann, E Schleicher, C F Poets, A R Franz

Abstract

Background: Arachidonic (ARA) and docosahexaenoic acid (DHA) are constitutive to membrane phospholipids, and essential for brain and overall development. ARA/DHA pools in term infants (TI) are built during the third trimester, stored as adipose tissue triglycerides and predominantly distributed via plasma phosphatidylcholine (PC). In preterm infants (PTI), placental ARA/DHA supply is replaced by linoleic-acid (LA)-enriched nutrition. This study aimed to investigate the impact of PTI nutrition, compared to placental supply, on fatty acid composition in adipose tissue and blood.

Methods: Prospective observational study (4/2017-3/2019) in 12 PTI and 3 PTI with enterostomy (PTI/E) (gestational age (GA) < 32 weeks) with surgical intervention at term (± 6 weeks) and 14 TI (GA ≥ 34 weeks, surgical intervention < 2 weeks postnatally). PTI/E were analyzed descriptively only. PC and triglyceride fatty acids were analyzed with tandem mass spectrometry and gas chromatography, respectively. Results were compared between TI and PTI with Wilcoxon Test and shown as median [25th percentile-75th percentile] mol%.

Results: PTI had less ARA in adipose tissue TG (0.77[0.67-0.87]% vs. 1.04[0.95-1.14]%, p = 0.0003) and plasma PC (20.7[18.7-22.8]% vs. 28.3[22.7-33.5]%, p = 0.011) than TI. PTI also had less DHA in adipose tissue TG (0.6[0.4-0.8]% vs. 1.1[0.8-1.4]%, p = 0.006) and plasma PC (6.4[5.6-7.1]% vs. 8.4[7.8-13.1]%, p = 0.002). LA was increased in PTI's adipose tissue TG (10.0[8.8-12.3]% vs. 3.0[2.5-3.6]%, p < 0.0001) and plasma PC (48.4[44.6-49.6]% vs. 30.6[24.9-35.6]%, p = 0.0002). Similar differences were observed in erythrocyte PC.

Conclusion: In PTI, LA is increased and ARA/DHA decreased in adipose tissue, plasma and erythrocyte lipids as proxies for other tissues, likely caused by PTI nutrition. This may contribute to impaired PTI development.

Trial registration: ClinicalTrials.gov NCT03785990.

Keywords: Adipose tissue; Arachidonic acid; Docosahexaenoic acid; Polyunsaturated fatty acids; Preterm infants; Triglycerides.

Conflict of interest statement

The authors declare that they have no conflict of interest to disclose.

Figures

Fig. 1
Fig. 1
Arachidonic Acid (ARA) in adipose tissue, plasma and erythrocytes. Panels a–c show the proportion of ARA in mol% in adipose tissue triglycerides (TG), plasma phosphatidylcholine (PC) and erythrocyte PC, respectively, each in term infants (TI), preterm infants without gastrointestinal problems (PTI), and preterm infants with enterostomy (PTI/E). Panels d–f show the proportion of ARA in mol% to postnatal age in adipose tissue TG, plasma PC and erythrocytes PC in PTI and TI (PTI/E are not shown). All blood and adipose tissue samples were collected during clinically indicated surgery at term-equivalent age. filled diamond = term infants, filled circle = preterm infants
Fig. 2
Fig. 2
Docosahexaenoic Acid (DHA) in adipose tissue, plasma and erythrocytes. Panels a–c show the proportion of DHA in mol% in adipose tissue triglycerides (TG), plasma phosphatidylcholine (PC) and erythrocyte PC, respectively, each in term infants (TI), preterm infants without gastrointestinal problems (PTI), and preterm infants with enterostomy (PTI/E). Panels d–f show the proportion of DHA in mol% to postnatal age in adipose tissue TG, plasma PC and erythrocytes PC in PTI and TI (PTI/E are not shown). All blood and adipose tissue samples were collected during clinically indicated surgery at term-equivalent age. filled diamond = term infants, filled circle = preterm infants
Fig. 3
Fig. 3
Linoleic Acid (LA) in adipose tissue, plasma and erythrocytes. Panels a–c show the proportion of LA in mol% in adipose tissue triglycerides (TG), plasma phosphatidylcholine (PC) and erythrocyte PC, respectively, each in term infants (TI), preterm infants without gastrointestinal problems (PTI), and preterm infants with enterostomy (PTI/E). Panels d–f show the proportion of LA in mol% to postnatal age in adipose tissue TG, plasma PC and erythrocytes PC in PTI and TI (PTI/E are not shown). All blood and adipose tissue samples were collected during clinically indicated surgery at term-equivalent age. filled diamond = term infants, filled circle = preterm infants
Fig. 4
Fig. 4
Docosahexaenoic acid (DHA), arachidonic acid (ARA) and linoleic acid (LA) correlations of the different compartments: adipose tissue, plasma and erythrocytes. Panels a–i shows the correlations of DHA, ARA and LA in mol% in adipose tissue triglycerides (TG), plasma phosphatidylcholine (PC) and erythrocyte PC, respectively, in term infants (TI) and preterm infants without gastrointestinal problems (PTI). Preterm infants with enterostomy (PTI/E) are not shown. All blood and adipose tissue samples were collected during clinically indicated surgery at term-equivalent age. filled diamond = term infants, filled circle = preterm infants

References

    1. The AOCS Lipid Library (2017) Plasma lipoproteins—composition, structure and biochemistry. https://lipidlibraryaocsorg/
    1. Martin CR, Dasilva DA, Cluette-Brown JE, Dimonda C, Hamill A, Bhutta AQ, Coronel E, Wilschanski M, Stephens AJ, Driscoll DF, Bistrian BR, Ware JH, Zaman MM, Freedman SD. Decreased postnatal docosahexaenoic and arachidonic acid blood levels in premature infants are associated with neonatal morbidities. J Pediatr. 2011;159(5):743–749. doi: 10.1016/j.jpeds.2011.04.039.
    1. Lauritzen L, Hansen HS, Jorgensen MH, Michaelsen KF. The essentiality of long chain n-3 fatty acids in relation to development and function of the brain and retina. Prog Lipid Res. 2001;40(1–2):1–94. doi: 10.1016/S0163-7827(00)00017-5.
    1. Mitchell DC, Niu SL, Litman BJ. Enhancement of G protein-coupled signaling by DHA phospholipids. Lipids. 2003;38(4):437–443. doi: 10.1007/s11745-003-1081-1.
    1. Mitchell DC, Niu SL, Litman BJ. DHA-rich phospholipids optimize G-Protein-coupled signaling. J Pediatr. 2003;143(4 Suppl):S80–S86. doi: 10.1067/s0022-3476(03)00405-0.
    1. German OL, Monaco S, Agnolazza DL, Rotstein NP, Politi LE. Retinoid X receptor activation is essential for docosahexaenoic acid protection of retina photoreceptors. J Lipid Res. 2013;54(8):2236–2246. doi: 10.1194/jlr.M039040.
    1. SanGiovanni JP, Chew EY. The role of omega-3 long-chain polyunsaturated fatty acids in health and disease of the retina. Prog Retin Eye Res. 2005;24(1):87–138. doi: 10.1016/j.preteyeres.2004.06.002.
    1. Gawrisch K, Soubias O, Mihailescu M. Insights from biophysical studies on the role of polyunsaturated fatty acids for function of G-protein coupled membrane receptors. Prostaglandins Leukot Essent Fatty Acids. 2008;79(3–5):131–134. doi: 10.1016/j.plefa.2008.09.002.
    1. Bazan NG. Docosanoids and elovanoids from omega-3 fatty acids are pro-homeostatic modulators of inflammatory responses, cell damage and neuroprotection. Mol Aspects Med. 2018;64:18–33. doi: 10.1016/j.mam.2018.09.003.
    1. Jun B, Mukherjee PK, Asatryan A, Kautzmann MA, Heap J, Gordon WC, Bhattacharjee S, Yang R, Petasis NA, Bazan NG. Elovanoids are novel cell-specific lipid mediators necessary for neuroprotective signaling for photoreceptor cell integrity. Sci Rep. 2017;7(1):5279. doi: 10.1038/s41598-017-05433-7.
    1. Clandinin MT, Chappell JE, Heim T, Swyer PR, Chance GW. Fatty acid utilization in perinatal de novo synthesis of tissues. Early Hum Dev. 1981;5(4):355–366. doi: 10.1016/0378-3782(81)90016-5.
    1. Axelrod J. Receptor-mediated activation of phospholipase A2 and arachidonic acid release in signal transduction. Biochem Soc Trans. 1990;18(4):503–507. doi: 10.1042/bst0180503.
    1. Ordway RW, Singer JJ, Walsh JV., Jr Direct regulation of ion channels by fatty acids. Trends Neurosci. 1991;14(3):96–100. doi: 10.1016/0166-2236(91)90069-7.
    1. Innis SM, Adamkin DH, Hall RT, Kalhan SC, Lair C, Lim M, Stevens DC, Twist PF, Diersen-Schade DA, Harris CL, Merkel KL, Hansen JW. Docosahexaenoic acid and arachidonic acid enhance growth with no adverse effects in preterm infants fed formula. J Pediatr. 2002;140(5):547–554. doi: 10.1067/mpd.2002.123282.
    1. Piomelli D. Eicosanoids in synaptic transmission. Crit Rev Neurobiol. 1994;8(1–2):65–83.
    1. Rau GA, Vieten G, Haitsma JJ, Freihorst J, Poets C, Ure BM, Bernhard W. Surfactant in newborn compared with adolescent pigs: adaptation to neonatal respiration. Am J Respir Cell Mol Biol. 2004;30(5):694–701. doi: 10.1165/rcmb.2003-0351OC.
    1. Dombrowsky H, Clark GT, Rau GA, Bernhard W, Postle AD. Molecular species compositions of lung and pancreas phospholipids in the cftr(tm1HGU/tm1HGU) cystic fibrosis mouse. Pediatr Res. 2003;53(3):447–454. doi: 10.1203/01.pdr.0000049937.30305.8a.
    1. Bernhard W, Haagsman HP, Tschernig T, Poets CF, Postle AD, van Eijk ME, von der Hardt H. Conductive airway surfactant: surface-tension function, biochemical composition, and possible alveolar origin. Am J Respir Cell Mol Biol. 1997;17(1):41–50. doi: 10.1165/ajrcmb.17.1.2594.
    1. Bernhard W, Hoffmann S, Dombrowsky H, Rau GA, Kamlage A, Kappler M, Haitsma JJ, Freihorst J, von der Hardt H, Poets CF. Phosphatidylcholine molecular species in lung surfactant: composition in relation to respiratory rate and lung development. Am J Respir Cell Mol Biol. 2001;25(6):725–731. doi: 10.1165/ajrcmb.25.6.4616.
    1. Bernhard W, Maas C, Shunova A, Mathes M, Bockmann K, Bleeker C, Vek J, Poets CF, Schleicher E, Franz AR. Transport of long-chain polyunsaturated fatty acids in preterm infant plasma is dominated by phosphatidylcholine. Eur J Nutr. 2018;57(6):2105–2112. doi: 10.1007/s00394-017-1484-1.
    1. Svennerholm L. Distribution and fatty acid composition of phosphoglycerides in normal human brain. J Lipid Res. 1968;9(5):570–579. doi: 10.1016/S0022-2275(20)42702-6.
    1. Makrides M, Neumann MA, Byard RW, Simmer K, Gibson RA. Fatty acid composition of brain, retina, and erythrocytes in breast- and formula-fed infants. Am J Clin Nutr. 1994;60(2):189–194. doi: 10.1093/ajcn/60.2.189.
    1. Haggarty P. Fatty acid supply to the human fetus. Annu Rev Nutr. 2010;30:237–255. doi: 10.1146/annurev.nutr.012809.104742.
    1. Bernhard W, Raith M, Koch V, Kunze R, Maas C, Abele H, Poets CF, Franz AR. Plasma phospholipids indicate impaired fatty acid homeostasis in preterm infants. Eur J Nutr. 2014;53(7):1533–1547. doi: 10.1007/s00394-014-0658-3.
    1. Farquharson J, Cockburn F, Patrick WA, Jamieson EC, Logan RW. Effect of diet on infant subcutaneous tissue triglyceride fatty acids. Arch Dis Child. 1993;69(5):589–593. doi: 10.1136/adc.69.5.589.
    1. Bernhard W, Poets CF, Franz AR. Choline and choline-related nutrients in regular and preterm infant growth. Eur J Nutr. 2019;58(3):931–945. doi: 10.1007/s00394-018-1834-7.
    1. Pynn CJ, Henderson NG, Clark H, Koster G, Bernhard W, Postle AD. Specificity and rate of human and mouse liver and plasma phosphatidylcholine synthesis analyzed in vivo. J Lipid Res. 2011;52(2):399–407. doi: 10.1194/jlr.D011916.
    1. Maas C, Poets CF, Franz AR. Avoiding postnatal undernutrition of VLBW infants during neonatal intensive care: evidence and personal view in the absence of evidence. Arch Dis Child Fetal Neonatal Ed. 2015;100(1):F76–F81. doi: 10.1136/archdischild-2014-306195.
    1. Agostoni C, Buonocore G, Carnielli VP, De Curtis M, Darmaun D, Decsi T, Domellof M, Embleton ND, Fusch C, Genzel-Boroviczeny O, Goulet O, Kalhan SC, Kolacek S, Koletzko B, Lapillonne A, Mihatsch W, Moreno L, Neu J, Poindexter B, Puntis J, Putet G, Rigo J, Riskin A, Salle B, Sauer P, Shamir R, Szajewska H, Thureen P, Turck D, van Goudoever JB, Ziegler EE. Enteral nutrient supply for preterm infants: commentary from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition. J Pediatr Gastroenterol Nutr. 2010;50(1):85–91. doi: 10.1097/MPG.0b013e3181adaee0.
    1. Bligh EG, Dyer WJ. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959;37(8):911–917. doi: 10.1139/o59-099.
    1. Maas C, Franz AR, Shunova A, Mathes M, Bleeker C, Poets CF, Schleicher E, Bernhard W. Choline and polyunsaturated fatty acids in preterm infants’ maternal milk. 2017;56(4):1733–1742. doi: 10.1007/s00394-016-1220-2.
    1. Raith M, Schaal K, Koslowski R, Fehrenbach H, Poets CF, Schleicher E, Bernhard W. Effects of recombinant human keratinocyte growth factor on surfactant, plasma, and liver phospholipid homeostasis in hyperoxic neonatal rats. J Appl Physiol. 2012;112(8):1317–1328. doi: 10.1152/japplphysiol.00887.2011.
    1. Pynn CJ, Picardi MV, Nicholson T, Wistuba D, Poets CF, Schleicher E, Perez-Gil J, Bernhard W. Myristate is selectively incorporated into surfactant and decreases dipalmitoylphosphatidylcholine without functional impairment. Am J Physiol Regul Integr Comp Physiol. 2010;299(5):R1306–R1316. doi: 10.1152/ajpregu.00380.2010.
    1. Bernhard W, Raith M, Koch V, Maas C, Abele H, Poets CF, Franz AR. Developmental changes in polyunsaturated fetal plasma phospholipids and feto-maternal plasma phospholipid ratios and their association with bronchopulmonary dysplasia. Eur J Nutr. 2016;55(7):2265–2274. doi: 10.1007/s00394-015-1036-5.
    1. Lapillonne A, Jensen CL. Reevaluation of the DHA requirement for the premature infant. Prostaglandins Leukot Essent Fatty Acids. 2009;81(2–3):143–150. doi: 10.1016/j.plefa.2009.05.014.
    1. Innis SM. Essential fatty acid transfer and fetal development. Placenta. 2005;26:S70–S75. doi: 10.1016/j.placenta.2005.01.005.
    1. Liefaard G, Heineman E, Molenaar JC, Tibboel D. Prospective evaluation of the absorptive capacity of the bowel after major and minor resections in the neonate. J Pediatr Surg. 1995;30(3):388–391. doi: 10.1016/0022-3468(95)90038-1.
    1. Bernhard W, Bockmann K, Maas C, Mathes M, Hovelmann J, Shunova A, Hund V, Schleicher E, Poets CF, Franz AR. Combined choline and DHA supplementation: a randomized controlled trial. Eur J Nutr. 2019 doi: 10.1007/s00394-019-01940-7.
    1. Alshweki A, Munuzuri AP, Bana AM, de Castro MJ, Andrade F, Aldamiz-Echevarria L, de Pipaon MS, Fraga JM, Couce ML. Effects of different arachidonic acid supplementation on psychomotor development in very preterm infants; a randomized controlled trial. Nutr J. 2015;14:101. doi: 10.1186/s12937-015-0091-3.
    1. Delplanque B, Gibson R, Koletzko B, Lapillonne A, Strandvik B. Lipid quality in infant nutrition: current knowledge and future opportunities. J Pediatr Gastroenterol Nutr. 2015;61(1):8–17. doi: 10.1097/mpg.0000000000000818.
    1. Commission E (2016) Commission Delegated Regulation (EU) 2016/127 of 25 September 2015 supplementing Regulation (EU) No 609/2013 of the European Parliament and of the Council as regards the specific compositional and information requirements for infant formula and follow-on formula and as regards requirements on information relating to infant and young child feeding. Off J Eur Union:(L 25/21):21–29
    1. Koletzko B, Bergmann K, Brenna JT, Calder PC, Campoy C, Clandinin MT, Colombo J, Daly M, Decsi T, Demmelmair H, Domellof M, FidlerMis N, Gonzalez-Casanova I, van Goudoever JB, Hadjipanayis A, Hernell O, Lapillonne A, Mader S, Martin CR, Matthaus V, Ramakrishan U, Smuts CM, Strain SJJ, Tanjung C, Tounian P, Carlson SE. Should formula for infants provide arachidonic acid along with DHA? A position paper of the European Academy of Paediatrics and the Child Health Foundation. Am J Clin Nutr. 2020;111(1):10–16. doi: 10.1093/ajcn/nqz252.
    1. Christoph Bührer RE, Frank Jochum, Hermann Kalhoff, Antje Körner, Berthold Koletzko, Burkhard Lawrenz, Walter Mihatsch, Silvia Rudloff, Klaus-Peter Zimmer &, V.) EdDGfK-uJDe (2020) Sollen Säuglingsnahrungen sowohl Docosahexaensäure als auch Arachidonsäure enthalten? Monatsschrift Kinderheilkunde March 24
    1. Collins CT, Gibson RA, Makrides M, McPhee AJ, Sullivan TR, Davis PG, Thio M, Simmer K, Rajadurai VS. The N3RO trial: a randomised controlled trial of docosahexaenoic acid to reduce bronchopulmonary dysplasia in preterm infants < 29 weeks’ gestation. BMC Pediatr. 2016;16:72. doi: 10.1186/s12887-016-0611-0.

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться