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Association between maternal obesity, essential fatty acids and biomarkers of fetal liver function

Published:January 16, 2023DOI:https://doi.org/10.1016/j.plefa.2023.102541

      Highlights

      • Maternal obesity affects the composition of fatty acids in maternal erythrocytes and placenta, which could impact on their bioavailability for maternal-fetal transfer.
      • The composition of fetal VLDL lipoproteins from newborns of women with obesity is characterized by lower levels of stearic acid, suggesting modifications on fetal fatty acid metabolism.
      • Maternal erythrocytes content of linoleic acid and alpha-linolenic acid are correlated with gamma-glutamyl (GGT) transferase activity in umbilical cord blood, indicating its relationship with fetal liver function.

      Abstract

      Maternal obesity and the imbalance in linoleic acid (C18:2 n-6, LA) and alpha-linolenic acid (C18:3 n-3, ALA) levels are related with hepatic disturbances in the offspring. However, whether these alterations are present during fetal life is not well understood. Obese and normal weight pregnant women were recruited to determine fatty acids (FAs) consumption, FAs profile (in maternal erythrocytes, placenta and neonatal very low-density lipoproteins VLDL) and biomarkers of fetal liver function, such as gamma-glutamyl transferase (GGT), alpha-fetoprotein (AFP) and albumin, in umbilical cord blood. Stearic acid (C18:0, ST) was lower, and total n-3 FAs tended to be lower in umbilical cord VLDLs of obese women compared to controls. Independently of maternal obesity, GGT levels in umbilical cord blood was positively correlated with the LA content and negatively correlated with the ALA content in maternal erythrocytes. We conclude that maternal obesity and its imbalance of LA and ALA are associated with changes in biomarkers of fetal liver function.

      Keywords

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      References

        • Catalano P.M.
        Management of obesity in pregnancy.
        Obstet. Gynecol. 2007; 109: 419-433
        • Santos Ferreira D.L.
        • Williams D.M.
        • Kangas A.J.
        • Soininen P.
        • Ala-Korpela M.
        • Smith G.D.
        • Jarvelin M.-.R.
        • Lawlor D.A.
        Association of pre-pregnancy body mass index with offspring metabolic profile: analyses of 3 European prospective birth cohorts.
        PLoS Med. 2017; 14e1002376
        • Catalano P.M.
        • Shankar K.
        Obesity and pregnancy: mechanisms of short term and long term adverse consequences for mother and child.
        BMJ. 2017; 356: 1-21
        • Cetin I.
        • Parisi F.
        • Berti C.
        • Mando C.
        • Desoye G.
        Placental fatty acid transport in maternal obesity.
        J. Dev. Orig. Health Dis. 2012; 3: 409-414
        • Lynch C.
        • Chan C.S.
        • Drake A.J.
        Early life programming and the risk of non-alcoholic fatty liver disease.
        J. Dev. Orig. Health Dis. 2017; 8: 263-272
        • Santos Ferreira D.L.
        • Williams D.M.
        • Kangas A.J.
        • Soininen P.
        • Ala-Korpela M.
        • Smith G.D.
        • Jarvelin M.R.
        • Lawlor D.A.
        Association of pre-pregnancy body mass index with offspring metabolic profile: analyses of 3 European prospective birth cohorts.
        PLoS Med. 2017; 14e1002376
        • Wahab R.J.
        • Jaddoe V.W.V.
        • Mezzoiuso A.G.
        • Gaillard R.
        Maternal polyunsaturated fatty acid concentrations during pregnancy and childhood liver fat accumulation.
        Clin. Nutr. 2022; 41: 847-854
        • Simopoulos A.P.
        Evolutionary aspects of diet: the omega-6/omega-3 ratio and the brain.
        Mol. Neurobiol. 2011; 44: 203-215
        • Chamorro R.
        • Bascunan K.A.
        • Barrera C.
        • Sandoval J.
        • Puigrredon C.
        • Valenzuela R.
        Reduced n-3 and n-6 PUFA (DHA and AA) concentrations in breast milk and erythrocytes phospholipids during pregnancy and lactation in women with obesity.
        Int. J. Environ. Res. Public Health. 2022; : 19
        • Shrestha N.
        • Cuffe J.S.M.
        • Holland O.J.
        • Perkins A.V.
        • McAinch A.J.
        • Hryciw D.H.
        Linoleic acid increases prostaglandin E2 release and reduces mitochondrial respiration and cell viability in human trophoblast-like cells.
        Cell. Physiol. Biochem. 2019; 52: 94-108
        • Fornes R.
        • Manti M.
        • Qi X.
        • Vorontsov E.
        • Sihlbom C.
        • Nystrom J.
        • Jerlhag E.
        • Maliqueo M.
        • Hirschberg A.L.
        • Carlstrom M.
        • Benrick A.
        • Stener-Victorin E.
        Mice exposed to maternal androgen excess and diet-induced obesity have altered phosphorylation of catechol-O-methyltransferase in the placenta and fetal liver.
        Int. J. Obes. (Lond). 2019;
        • Bader D.
        • Riskin A.
        • Vafsi O.
        • Tamir A.
        • Peskin B.
        • Israel N.
        • Merksamer R.
        • Dar H.
        • David M.
        Alpha-fetoprotein in the early neonatal period–a large study and review of the literature.
        Clin. Chim. Acta. 2004; 349: 15-23
        • Pekor C.
        • Gerlach J.C.
        • Nettleship I.
        • Schmelzer E.
        Induction of hepatic and endothelial differentiation by perfusion in a three-dimensional cell culture model of human fetal liver.
        Tissue Eng. Part C Methods. 2015; 21: 705-715
        • Mirlesse V.
        • Jacquemard F.
        • Daffos F.
        • Forestier F.
        Fetal gammaglutamyl transferase activity: clinical implication in fetal medicine.
        Biol. Neonate. 1996; 70: 193-198
        • Tiwari S.
        • Siddiqi S.A.
        Intracellular trafficking and secretion of VLDL.
        Arterioscler. Thromb. Vasc. Biol. 2012; 32: 1079-1086
        • Yee J.K.
        • Mao C.S.
        • Ross M.G.
        • Lee W.N.
        • Desai M.
        • Toda A.
        • Kjos S.L.
        • Hicks R.A.
        • Patterson M.E.
        High oleic/stearic fatty-acid desaturation index in cord plasma from infants of mothers with gestational diabetes.
        J. Perinatol. 2014; 34: 357-363
        • Mena Nannig P.
        • Cubillos Celis M.P.
        • Toro Jara C.
        • Zuniga Vergara C.
        Intrauterine growth and biochemical levels in cord blood samples in infants less than 31 weeks gestation.
        Rev. Chil. Pediatr. 2016; 87: 250-254
        • Barrera C.
        • Valenzuela R.
        • Chamorro R.
        • Bascunan K.
        • Sandoval J.
        • Sabag N.
        • Valenzuela F.
        • Valencia M.P.
        • Puigrredon C.
        • Valenzuela A.
        The impact of maternal diet during pregnancy and lactation on the fatty acid composition of erythrocytes and breast milk of chilean women.
        Nutrients. 2018; 10
        • Maliqueo M.
        • Lara H.E.
        • Sanchez F.
        • Echiburu B.
        • Crisosto N.
        • Sir-Petermann T.
        Placental steroidogenesis in pregnant women with polycystic ovary syndrome.
        Eur. J. Obstet. Gynecol. Reprod. Biol. 2013; 166: 151-155
        • Fowden A.L.
        • Sferruzzi-Perri A.N.
        • Coan P.M.
        • Constancia M.
        • Burton G.J.
        Placental efficiency and adaptation: endocrine regulation.
        J. Physiol. 2009; 587: 3459-3472
        • Bligh E.G.
        • Dyer W.J.
        A rapid method of total lipid extraction and purification.
        Can. J. Biochem. Physiol. 1959; 37: 911-917
        • Sreckovic I.
        • Birner-Gruenberger R.
        • Obrist B.
        • Stojakovic T.
        • Scharnagl H.
        • Holzer M.
        • Scholler M.
        • Philipose S.
        • Marsche G.
        • Lang U.
        • Desoye G.
        • Wadsack C.
        Distinct composition of human fetal HDL attenuates its anti-oxidative capacity.
        Biochim. Biophys. Acta. 2013; 1831: 737-746
        • Morrison W.R.
        • Smith L.M.
        Preparation of fatty acid methyl esters and dimethylacetals from lipids with boron fluoride–methanol.
        J. Lipid Res. 1964; 5: 600-608
        • Brass E.
        • Hanson E.
        • O'Tierney-Ginn P.F.
        Placental oleic acid uptake is lower in male offspring of obese women.
        Placenta. 2013; 34: 503-509
        • Rasool A.
        • Mahmoud T.
        • Mathyk B.
        • Kaneko-Tarui T.
        • Roncari D.
        • White K.O.
        • O'Tierney-Ginn P.
        Obesity downregulates lipid metabolism genes in first trimester placenta.
        Sci. Rep. 2022; 12: 19368
        • Calder P.C.
        Omega-3 fatty acids and inflammatory processes: from molecules to man.
        Biochem. Soc. Trans. 2017; 45: 1105-1115
        • Grant W.F.
        • Gillingham M.B.
        • Batra A.K.
        • Fewkes N.M.
        • Comstock S.M.
        • Takahashi D.
        • Braun T.P.
        • Grove K.L.
        • Friedman J.E.
        • Marks D.L.
        Maternal high fat diet is associated with decreased plasma n–3 fatty acids and fetal hepatic apoptosis in nonhuman primates.
        PLoS ONE. 2011; 6: e17261
        • Vidakovic A.J.
        • Gishti O.
        • Voortman T.
        • Felix J.F.
        • Williams M.A.
        • Hofman A.
        • Demmelmair H.
        • Koletzko B.
        • Tiemeier H.
        • Jaddoe V.W.
        • Gaillard R.
        Maternal plasma PUFA concentrations during pregnancy and childhood adiposity: the Generation R Study.
        Am. J. Clin. Nutr. 2016; 103: 1017-1025
        • Voortman T.
        • Tielemans M.J.
        • Stroobant W.
        • Schoufour J.D.
        • Kiefte-de Jong J.C.
        • Steenweg-de Graaff J.
        • van den Hooven E.H.
        • Tiemeier H.
        • Jaddoe V.W.V.
        • Franco O.H.
        Plasma fatty acid patterns during pregnancy and child's growth, body composition, and cardiometabolic health: the Generation R Study.
        Clin. Nutr. 2018; 37: 984-992
        • Rioux V.
        • Catheline D.
        • Bouriel M.
        • Legrand P.
        Dietary myristic acid at physiologically relevant levels increases the tissue content of C20:5 n-3 and C20:3 n-6 in the rat.
        Reprod. Nutr. Dev. 2005; 45: 599-612
        • Martinez L.
        • Torres S.
        • Baulies A.
        • Alarcon-Vila C.
        • Elena M.
        • Fabrias G.
        • Casas J.
        • Caballeria J.
        • Fernandez-Checa J.C.
        • Garcia-Ruiz C.
        Myristic acid potentiates palmitic acid-induced lipotoxicity and steatohepatitis associated with lipodystrophy by sustaning de novo ceramide synthesis.
        Oncotarget. 2015; 6: 41479-41496
        • Ailhaud G.
        • Massiera F.
        • Weill P.
        • Legrand P.
        • Alessandri J.M.
        • Guesnet P.
        Temporal changes in dietary fats: role of n-6 polyunsaturated fatty acids in excessive adipose tissue development and relationship to obesity.
        Prog. Lipid Res. 2006; 45: 203-236
        • Sioen I.
        • van Lieshout L.
        • Eilander A.
        • Fleith M.
        • Lohner S.
        • Szommer A.
        • Petisca C.
        • Eussen S.
        • Forsyth S.
        • Calder P.C.
        • Campoy C.
        • Mensink R.P.
        Systematic review on N-3 and N-6 polyunsaturated fatty acid intake in European countries in light of the current recommendations - focus on specific population groups.
        Ann. Nutr. Metab. 2017; 70: 39-50
        • Harris W.S.
        • Mozaffarian D.
        • Rimm E.
        • Kris-Etherton P.
        • Rudel L.L.
        • Appel L.J.
        • Engler M.M.
        • Engler M.B.
        • Sacks F.
        Omega-6 fatty acids and risk for cardiovascular disease: a science advisory from the American Heart Association Nutrition Subcommittee of the Council on Nutrition, Physical Activity, and Metabolism.
        Council on Cardiovascular Nursing; and Council on Epidemiology and Prevention, Circulation. 2009; 119: 902-907
        • Shiozawa M.
        • Hiraoka Y.
        • Yasuda K.
        • Imamura T.
        • Sakamuro D.
        • Taniguchi N.
        • Yamazoe M.
        • Yoshikawa H.
        Synthesis of human gamma-glutamyl transpeptidase (GGT) during the fetal development of liver.
        Gene. 1990; 87: 299-303
        • Gruccio
        Biochemical profiling study in umbilical cord blood as predictors of neonatal damage.
        Int. J. Clin. Pediatr. 2014;
        • Bedogni G.
        • Bellentani S.
        • Miglioli L.
        • Masutti F.
        • Passalacqua M.
        • Castiglione A.
        • Tiribelli C.
        The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population.
        BMC Gastroenterol. 2006; 6: 33
        • Lee D.S.
        • Evans J.C.
        • Robins S.J.
        • Wilson P.W.
        • Albano I.
        • Fox C.S.
        • Wang T.J.
        • Benjamin E.J.
        • D'Agostino R.B.
        • Vasan R.S.
        Gamma glutamyl transferase and metabolic syndrome, cardiovascular disease, and mortality risk: the Framingham Heart Study.
        Arterioscler. Thromb. Vasc. Biol. 2007; 27: 127-133
        • Paquette M.
        • Gauthier D.
        • Chamberland A.
        • Prat A.
        • Rolfe E.D.
        • Rasmussen J.J.
        • Kaduka L.
        • Seidah N.G.
        • Bernard S.
        • Christensen D.L.
        • Baass A.
        Circulating PCSK9 is associated with liver biomarkers and hepatic steatosis.
        Clin. Biochem. 2020; 77: 20-25
        • Marchix J.
        • Catheline D.
        • Duby C.
        • Monthean-Boulier N.
        • Boissel F.
        • Pedrono F.
        • Boudry G.
        • Legrand P.
        Interactive effects of maternal and weaning high linoleic acid intake on hepatic lipid metabolism, oxylipins profile and hepatic steatosis in offspring.
        J. Nutr. Biochem. 2020; 75108241