Abstract
Background
Excess vernix caseosa produced by the fetal skin appears as particles suspended in the amniotic fluid in late gestation, is swallowed by the fetus, and is found throughout the newborn gastrointestinal tract as the first organisms are arriving to colonize the gut. Lipid-rich vernix contains an unusually high 29% branched chain fatty acids (BCFA). BCFAs reduce the incidence of necrotizing enterocolitis in an animal model, and were recently found predominantly in the sn-2 position of human milk triacylglycerols. Nothing is known about the influence of vernix BCFA on proinflammatory markers in human enterocytes.
Methods
We investigated the effect of vernix-monoacylglycerides (MAGs) (enriched with 30% BCFA) on interleukin (IL)-8 and NF-κB production in a human intestinal epithelial cell line (Caco-2). Caco-2 cells were pretreated with vernix-MAG or vernix-free fatty acid (FFA) prior to lipopolysaccharide (LPS) activation.
Results
Both vernix-MAG and vernix-FFA increased cell BCFA and eliminated an LPS-induced 20% reduction in cell viability. In stimulated Caco-2 cells, vernix-MAG was more effective than vernix-FFA in suppressing IL-8 and NF-κB. Activated vernix-MAG-treated cells expressed less of the cell-surface Toll-like receptor4 (TLR-4) compared with controls.
Conclusion
This is the first study to show the reduction of proinflammatory markers in human cells mediated by BCFA-MAG.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Hoeger P, Schreiner V, Klaassen I, Enzmann C, Friedrichs K, Bleck O . Epidermal barrier lipids in human vernix caseosa: corresponding ceramide pattern in vernix and fetal skin. Br J Dermatol 2002;146:194–201.
Nicolaides N, Fu HC, Ansari M, Rice GR . The fatty acids of wax esters and sterol esters from vernix caseosa and from human skin surface lipid. Lipids 1972;7:506–17.
Rissmann R, Groenink HW, Weerheim AM, Hoath SB, Ponec M, Bouwstra JA . New insights into ultrastructure, lipid composition and organization of vernix caseosa. J Invest Dermatol 2006;126:1823–33.
Kaerkkaeinen J, Nikkari T, Ruponen S, Haahti E . Lipids of vernix caseosa. J Invest Dermatol 1965;44:333–8.
Nazzaro-Porro M, Passi S, Boniforti L, Belsito F . Effects of aging on fatty acids in skin surface lipids. J Invest Dermatol 1979;73:112–7.
Ran-Ressler RR, Khailova L, Arganbright KM et al. Branched chain fatty acids reduce the incidence of necrotizing enterocolitis and alter gastrointestinal microbial ecology in a neonatal rat model. PLoS ONE 2011;6:e29032.
Chen W, Esselman WJ, Jump DB, Busik JV . Anti-inflammatory effect of docosahexaenoic acid on cytokine-induced adhesion molecule expression in human retinal vascular endothelial cells. Invest Ophthalmol Vis Sci 2005;46:4342–7.
Marion-Letellier R, Butler M, Déchelotte P, Playford RJ, Ghosh S . Comparison of cytokine modulation by natural peroxisome proliferator–activated receptor γ ligands with synthetic ligands in intestinal-like Caco-2 cells and human dendritic cells—potential for dietary modulation of peroxisome proliferator–activated receptor γ in intestinal inflammation. Am J Clin Nutr 2008;87:939–48.
De Caterina R, Cybulsky MI, Clinton SK, Gimbrone MA, Libby P . The omega-3 fatty acid docosahexaenoate reduces cytokine-induced expression of proatherogenic and proinflammatory proteins in human endothelial cells. Arterioscler Thromb 1994;14:1829–36.
Morin C, Hiram R, Rousseau E, Blier PU, Fortin S . Docosapentaenoic acid monoacylglyceride reduces inflammation and vascular remodeling in experimental pulmonary hypertension. Am J Physiol Heart Circ Physiol 2014;307:H574–86.
Morin C, Blier PU, Fortin S . MAG-EPA reduces severity of DSS-induced colitis in rats. Am J Physiol Gastrointest Liver Physiol 2016;310:G808–G21.
Banno F, Doisaki S, Shimizu N, Fujimoto K . Lymphatic absorption of docosahexaenoic acid given as monoglyceride, diglyceride, triglyceride, and ethyl ester in rats. J Nutr Sci Vitaminol 2002;48:30–5.
Yan Y, Wang Z, Wang X et al. Branched chain fatty acids positional distribution in human milk fat and common human food fats and uptake in human intestinal cells. J Funct Foods 2017;29:172–7.
Yan Y, Wang Z, Greenwald J et al. BCFA suppresses LPS induced IL-8 mRNA expression in human intestinal epithelial cells. Prostaglandins Leukot Essent Fatty Acids 2017;116:27–31.
Bligh EG, Dyer WJ . A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959;37:911–7.
Luddy FE, Barford RA, Herb SF, Magidman P, Riemenschneider RW . Pancreatic lipase hydrolysis of triglycerides by a semimicro technique. J Am Oil Chem Soc 1964;41:693–6.
Garcés R, Mancha M . One-step lipid extraction and fatty acid methyl esters preparation from fresh plant tissues. Anal Biochem 1993;211:139–43.
Van Pelt CK, Brenna JT . Acetonitrile chemical ionization tandem mass spectrometry to locate double bonds in polyunsaturated fatty acid methyl esters. Anal Chem 1999;71:1981–9.
Lawrence P, Brenna JT . Acetonitrile covalent adduct chemical ionization mass spectrometry for double bond localization in non-methylene-interrupted polyene fatty acid methyl esters. Anal Chem 2006;78:1312–7.
Hamosh M, Scow RO . Lingual lipase and its role in the digestion of dietary lipid. J Clin Invest 1973;52:88–95.
Hamosh M, Sivasubramanian K, Salzman-Mann C, Hamosh P . Fat digestion in the stomach of premature infants: I. Characteristics of lipase activity. J Pediatr. 1978;93:674–9.
Hamosh M, Scanlon JW, Ganot D, Likel M, Scanlon KB, Hamosh P . Fat digestion in the newborn: characterization of lipase in gastric aspirates of premature and term infants. J Clin Invest 1981;67:838.
Innis SM, Dyer RA, Lien EL . Formula containing randomized fats with palmitic acid (16: 0) in the 2-position increases 16: 0 in the 2-position of plasma and chylomicron triglycerides in formula-fed piglets to levels approaching those of piglets fed sow's milk. J Nutr 1997;127:1362–70.
Small DM . The effects of glyceride structure on absorption and metabolism. Annu Rev Nutr 1991;11:413–34.
Kiechle FL, Zhang X . Apoptosis: biochemical aspects and clinical implications. Clin Chim Acta 2002;326:27–45.
Nishijima K, Shukunami K-i, Yoshinari H et al. Interactions among pulmonary surfactant, vernix caseosa, and intestinal enterocytes: intra-amniotic administration of fluorescently liposomes to pregnant rabbits. Am J Physiol Lung Cell Mol Physiol 2012;303:L208–L14.
Fortin S Compositions comprising polyunsaturated fatty acid monoglycerides or derivatives thereof and uses thereof. Google Patents 2012 Patent number 8,222,295 B2.
Morin C, Fortin S, Cantin AM, Rousseau É . Docosahexaenoic acid derivative prevents inflammation and hyperreactivity in lung: implication of PKC-Potentiated inhibitory protein for heterotrimeric myosin light chain phosphatase of 17 kD in asthma. Am J Respir Cell Mol Biol 2011;45:366–75.
Calder PC Fatty acids and gene expression related to inflammation. In: Labadarious D, Pichard C, eds. Clinical Nutrition: Early Intervention. Karger Publishers: Basel, Switzerland, 2002: 19–40.
Lawrence T . The nuclear factor NF-κB pathway in inflammation. Cold Spring Harb Perspect Biol 2009;1:a001651.
Chow JC, Young DW, Golenbock DT, Christ WJ, Gusovsky F . Toll-like receptor-4 mediates lipopolysaccharide-induced signal transduction. J Biol Chem 1999;274:10689–92.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Additional information
STATEMENT OF FINANCIAL SUPPORT
This work was supported by grants from the Chinese Scholarship Council (to Y.Y.).
Rights and permissions
About this article
Cite this article
Yan, Y., Wang, Z., Wang, D. et al. BCFA-enriched vernix-monoacylglycerol reduces LPS-induced inflammatory markers in human enterocytes in vitro. Pediatr Res 83, 874–879 (2018). https://doi.org/10.1038/pr.2017.297
Received:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/pr.2017.297
This article is cited by
-
Sea Lions Develop Human-like Vernix Caseosa Delivering Branched Fats and Squalene to the GI Tract
Scientific Reports (2018)