Abstract
Several studies reported the association between total plasma phytosterol concentrations and the parenteral nutrition-associated cholestasis (PNAC). To date, no data are available on phytosterol esterification in animals and in humans during parenteral nutrition (PN). We measured free and esterified sterols (cholesterol, campesterol, stigmasterol, and sitosterol) plasma concentrations during PN in 16 preterm infants (500–1249 g of birth weight; Preterm-PN), in 11 term infants (Term-PN) and in 12 adults (Adult-PN). Gas chromatography–mass spectrometry was used for measurements. Plasma concentrations of free cholesterol (Free-CHO), free phytosterols (Free-PHY) and esterified phytosterols (Ester-PHY) were not different among the three PN groups. Esterified cholesterol (Ester-CHO) was statistically lower in Preterm-PN than Adult-PN. Preterm-PN had significantly higher Free-CHO/Ester-CHO and Free-PHY/Ester-PHY ratios than Adult-PN (Free-CHO/Ester-CHO: 1.1 ± 0.7 vs. 0.6 ± 0.2; Free-PHY/Ester-PHY: 4.1 ± 2.6 vs. 1.3 ± 0.8; *P < 0.05). Free-CHO/Ester-CHO and Free-PHY/Ester-PHY ratios of Term-PN (Free-CHO/Ester-CHO: 1.1 ± 0.4; Free-PHY/Ester-PHY: 2.9 ± 1.7) were not different from either Preterm-PN or from Adult-PN. Plasma Free-CHO/Ester-CHO and Free-PHY/Ester-PHY were unchanged after 24 h on fat-free PN both in Preterm-PN and in Adult-PN. Free-PHY/Ester-PHY did not correlate with phytosterol intake in Preterm-PN. Free-PHY/Ester-PHY of Preterm-PN was positively correlated with the Free-CHO/Ester-CHO and negatively correlated with gestational age and birth weight. In conclusion, PHY were esterified to a lesser extent than CHO in all study groups; the esterification was markedly decreased in Preterm-PN compared to Adult-PN. The clinical consequences of these findings warrant further investigations.
Similar content being viewed by others
Abbreviations
- ACAT:
-
Acyl-CoA cholesterol acyltransferase
- Adult-PN:
-
Adults on PN
- CAMP:
-
Campesterol
- CHO:
-
Cholesterol
- Ester:
-
Esterified
- IV:
-
Intravenous
- LCAT:
-
Lecithin cholesterol acyltransferase
- LE:
-
Lipid emulsion
- NICU:
-
Neonatal intensive care unit
- PHY:
-
Phytosterols
- PN:
-
Parenteral nutrition
- PNAC:
-
Parenteral nutrition-associated cholestasis
- Preterm-PN:
-
Preterm infants on PN
- SITO:
-
Sitosterol
- SO:
-
Soybean oil
- STIGM:
-
Stigmasterol
- Term-PN:
-
Term infants on PN
- Δ:
-
Difference
References
Kaufman SS, Gondolesi GE, Fishbein TM (2003) Parenteral nutrition associated liver disease. Semin Neonatol 8:375–381
La Scala GC, Le Coultre C, Roche BG, Bugmann P, Belli DC (1993) The addition of lipids increases the total parenteral nutrition-associated cholestasis in the rat. Eur J Pediatr Surg 3:224–227
Clayton PT, Bowron A, Mills KA, Massoud A, Casteels M, Milla PJ (1993) Phytosterolemia in children with parenteral nutrition-associated cholestatic liver disease. Gastroenterology 105:1806–1813
Whitfield PD, Clayton PT, Muller DP (2000) Effect of intravenous lipid emulsions on hepatic cholesterol metabolism. J Pediatr Gastroenterol Nutr 30:538–546
Llop JM, Virgili N, Moreno-Villares JM, Garcia-Peris P, Serrano T, Forga M, Solanich J, Pita AM (2008) Phytosterolemia in parenteral nutrition patients: implications for liver disease development. Nutrition 24:1145–1152
Bindl L, Lutjohann D, Buderus S, Lentzev MJ, Bergmann K (2000) High plasma levels of phytosterols in patients on parenteral nutrition: a marker of liver dysfunction. J Pediatr Gastroenterol Nutr 31:313–316
Iyer KR, Spitz L, Clayton P (1998) BAPS prize lecture: new insight into mechanisms of parenteral nutrition-associated cholestasis: role of plant sterols. British Association of Paediatric Surgeons. J Pediatr Surg 33:1–6
Pianese P, Salvia G, Campanozzi A, D’Apolito O, Dello Russo A, Pettoello-Mantovani M, Corso G (2008) Sterol profiling in red blood cell membranes and plasma of newborns receiving total parenteral nutrition. J Pediatr Gastroenterol Nutr 47:645–651
Ellegard L, Sunesson A, Bosaeus I (2005) High serum phytosterol levels in short bowel patients on parenteral nutrition support. Clin Nutr 24:415–420
Lin DS, Steiner RD, Merkens LS, Pappu AS, Connor WE (2010) The effects of sterol structure upon sterol esterification. Atherosclerosis 208:155–160
Lembcke J, Ceglarek U, Fiedler GM, Baumann S, Leichtle A, Thiery J (2005) Rapid quantification of free and esterified phytosterols in human serum using APPI-LC-MS/MS. J Lipid Res 46:21–26
Tilvis RS, Miettinen TA (1986) Serum plant sterols and their relation to cholesterol absorption. Am J Clin Nutr 43:92–97
Savini S, D’Ascenzo R, Biagetti C, Serpentini G, Pompilio A, Bartoli A, Cogo PE, Carnielli VP (2013) The effect of 5 intravenous lipid emulsions on plasma phytosterols in preterm infants receiving parenteral nutrition: a randomized clinical trial. Am J Clin Nutr 98:312–318
Xu Z, Harvey KA, Pavlina T, Dutot G, Hise M, Zaloga GP, Siddiqui RA (2012) Steroidal compounds in commercial parenteral lipid emulsions. Nutrients 4:904–921
Forchielli ML, Bersani G, Tala S, Grossi G, Puggioli C, Masi M (2010) The spectrum of plant and animal sterols in different oil-derived intravenous emulsions. Lipids 45:63–71
Sperry WM (1935) Cholesterol esterase in blood. J Biol Chem 111:467–478
Glomset JA (1968) The plasma lecithins: cholesterol acyltransferase reaction. J Lipid Res 9:155–167
Sperry WM, Stoyanoff VA (1938) The enzymatic synthesis and hydrolysis of cholesterol esters in blood serum. J Biol Chem 126:77–89
Lee RG, Kelley KL, Sawyer JK, Farese RV, Parks JS, Rudel LL (2004) Plasma cholesteryl esters provided by lecithin:cholesterol acyltransferase and acyl-coenzyme a: cholesterol acyltransferase 2 have opposite atherosclerotic potential. Circ Res 95:998–1004
Piran U, Nishida T (1979) Utilization of various sterols by lecithin-cholesterol acyltransferase as acyl acceptors. Lipids 14:478–482
Macauley SK, Billheimer JT, Ritter KS (1986) Sterol substrate specificity of acyl coenzyme A: cholesterol acyltransferase from the corn earworm, Heliothis zea. J Lipid Res 27:64–71
Tavani DM, Nes WR, Billheimer JT (1982) The sterol substrate specificity of acyl CoA: cholesterol acyltransferase from rat liver. J Lipid Res 23:774–781
Lee RG, Shah R, Sawyer JK, Hamilton RL, Parks JS, Rudel LL (2005) ACAT2 contributes cholesteryl esters to newly secreted VLDL, whereas LCAT adds cholesteryl ester to LDL in mice. J Lipid Res 46:1205–1212
Folch J, Lees M, Sloane Stanley GH (1957) A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 226:497–509
Corso G, Rossi M, De BD, Rossi I, Parenti G, Dello RA (2002) Effects of sample storage on 7- and 8-dehydrocholesterol levels analysed on whole blood spots by gas chromatography-mass spectrometry-selected ion monitoring. J Chromatogr B Analyt Technol Biomed Life Sci 766:365–370
Bhattacharyya AK, Connor WE (1974) Beta-sitosterolemia and xanthomatosis. A newly described lipid storage disease in two sisters. J Clin Invest 53:1033–1043
Vahouny GV, Connor WE, Subramaniam S, Lin DS, Gallo LL (1983) Comparative lymphatic absorption of sitosterol, stigmasterol, and fucosterol and differential inhibition of cholesterol absorption. Am J Clin Nutr 37:805–809
Papadopoulos A, Hamosh M, Chowdhry P, Scanlon JW, Hamosh P (1988) Lecithin-cholesterol acyltransferase in newborn infants: low activity level in preterm infants. J Pediatr 113:896–898
Jain SK (1985) Prematurity and lecithin-cholesterol acyltransferase deficiency in newborn infants. Pediatr Res 19:58–60
Nghiem-Rao TH, Tunc I, Mavis AM, Cao Y, Polzin EM, Firary MF, Wang X, Simpson PM, Patel SB (2015) Kinetics of phytosterol metabolism in neonates receiving parenteral nutrition. Pediatr Res 78:181–189
Wang J, Sun F, Zhang DW, Ma Y, Xu F, Belani JD, Cohen JC, Hobbs HH, Xie XS (2006) Sterol transfer by ABCG5 and ABCG8: in vitro assay and reconstitution. J Biol Chem 281:27894–27904
Chan YM, Varady KA, Lin Y, Trautwein E, Mensink RP, Plat J, Jones PJ (2006) Plasma concentrations of plant sterols: physiology and relationship with coronary heart disease. Nutr Rev 64:385–402
Hukkinen M, Mutanen A, Nissinen M, Merras-Salmio L, Gylling H, Pakarinen MP (2016) Parenteral plant sterols accumulate in the liver reflecting their increased serum levels and portal inflammation in children with intestinal failure. J Parenter Enteral Nutr. [Epub ahead of print]
Karim C, El Kasmi ALA, Devereaux Michael W, Vue Padade M, Zhang Wujuan, Setchell Kenneth D R, Karpen Saul J, Sokol Ronald J (2013) Phytosterols promote liver injury and kupffer cell activation in parenteral nutrition-associated liver disease. Sci Transl Med 5:1–10
Clayton PT, Whitfield P, Iyer K (1998) The role of phytosterols in the pathogenesis of liver complications of pediatric parenteral nutrition. Nutrition 14:158–164
Vlaardingerbroek H, Ng K, Stoll B, Benight N, Chacko S, Kluijtmans LA, Kulik W, Squires EJ, Olutoye O, Schady D, Finegold ML, van Goudoever JB, Burrin DG (2014) New generation lipid emulsions prevent PNALD in chronic parenterally fed preterm pigs. J Lipid Res 55:466–477
Zaloga GP (2015) Phytosterols, Lipid Administration, and Liver Disease During Parenteral Nutrition. JPEN J Parenter Enteral Nutr 39:39S–60S
Carter BA, Taylor OA, Prendergast DR, Zimmerman TL, Von Furstenberg R, Moore DD, Karpen SJ (2007) Stigmasterol, a soy lipid-derived phytosterol, is an antagonist of the bile acid nuclear receptor FXR. Pediatr Res 62:301–306
Yuan Q, Bie J, Wang J, Ghosh SS, Ghosh S (2013) Cooperation between hepatic cholesteryl ester hydrolase and scavenger receptor BI for hydrolysis of HDL-CE. J Lipid Res 54:3078–3084
Acknowledgments
The authors are grateful to the infants’ parents, to the NICU staff and to the adults of the Department of Dietetics and Clinical Nutrition. There are no conflicts of interest to declare. There were 12 authors who contributed to the work. We report below the contribution of each author: VPC was responsible for the design of the study; SS, AC, DP, MS and AP contributed to data collection and analysis; RD, GV, CB, MT and AN contributed to subject recruitment and data collection; PEC was in charge of the statistical analysis. All authors read and approved the final manuscript.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Savini, S., Correani, A., Pupillo, D. et al. Phytosterol Esterification is Markedly Decreased in Preterm Infants Receiving Routine Parenteral Nutrition. Lipids 51, 1353–1361 (2016). https://doi.org/10.1007/s11745-016-4197-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11745-016-4197-y