Hostname: page-component-cd9895bd7-gxg78 Total loading time: 0 Render date: 2024-12-27T10:29:33.820Z Has data issue: false hasContentIssue false
  • English
  • Français

Linoleic and α-linolenic acid as precursor and inhibitor for the synthesis of long-chain polyunsaturated fatty acids in liver and brain of growing pigs

Published online by Cambridge University Press:  07 September 2011

W. Smink ,
W. J. J. Gerrits ,
M. Gloaguen ,
A. Ruiter  and
J. van Baal
W. Smink
Affiliation:
Department of Animal Sciences, Animal Nutrition Group, Wageningen University, PO Box 338, 6700 AH, Marijkeweg 40, 6709 PG Wageningen, The Netherlands
W. J. J. Gerrits
Affiliation:
Department of Animal Sciences, Animal Nutrition Group, Wageningen University, PO Box 338, 6700 AH, Marijkeweg 40, 6709 PG Wageningen, The Netherlands
M. Gloaguen
Affiliation:
Department of Animal Sciences, Animal Nutrition Group, Wageningen University, PO Box 338, 6700 AH, Marijkeweg 40, 6709 PG Wageningen, The Netherlands
A. Ruiter
Affiliation:
Department of Animal Sciences, Animal Nutrition Group, Wageningen University, PO Box 338, 6700 AH, Marijkeweg 40, 6709 PG Wageningen, The Netherlands
J. van Baal*
Affiliation:
Department of Animal Sciences, Animal Nutrition Group, Wageningen University, PO Box 338, 6700 AH, Marijkeweg 40, 6709 PG Wageningen, The Netherlands
*
†E-mail: jurgen.vanbaal@wur.nl
Get access

Abstract

Studies suggested that in human adults, linoleic acid (LA) inhibits the biosynthesis of n-3 long-chain polyunsaturated fatty acids (LC-PUFA), but their effects in growing subjects are largely unknown. We used growing pigs as a model to investigate whether high LA intake affects the conversion of n-3 LC-PUFA by determining fatty acid composition and mRNA levels of Δ5- and Δ6 desaturase and elongase 2 and -5 in liver and brain. In a 2 × 2 factorial arrangement, 32 gilts from eight litters were assigned to one of the four dietary treatments, varying in LA and α-linolenic acid (ALA) intakes. Low ALA and LA intakes were 0.15 and 1.31, and high ALA and LA intakes were 1.48 and 2.65 g/kg BW0.75 per day, respectively. LA intake increased arachidonic acid (ARA) in liver. ALA intake increased eicosapentaenoic acid (EPA) concentrations, but decreased docosahexaenoic acid (DHA) (all P < 0.01) in liver. Competition between the n-3 and n-6 LC-PUFA biosynthetic pathways was evidenced by reductions of ARA (>40%) at high ALA intakes. Concentration of EPA (>35%) and DHA (>20%) was decreased by high LA intake (all P < 0.001). Liver mRNA levels of Δ5- and Δ6 desaturase were increased by LA, and that of elongase 2 by both ALA and LA intakes. In contrast, brain DHA was virtually unaffected by dietary LA and ALA. Generally, dietary LA inhibited the biosynthesis of n-3 LC-PUFA in liver. ALA strongly affects the conversion of both hepatic n-3 and n-6 LC-PUFA. DHA levels in brain were irresponsive to these diets. Apart from Δ6 desaturase, elongase 2 may be a rate-limiting enzyme in the formation of DHA.

Keywords

linoleic acidlinolenic acidliverbrainenzymes
Type
Full Paper
Information
animal , Volume 6 , Issue 2 , 03 January 2012 , pp. 262 - 270
Copyright
Copyright © The Animal Consortium 2011

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Arbuckle, LD, Innis, SM 2003. Docosahexaenoic acid in developing brain and retina of piglets fed high or low alpha-linolenate formula with and without fish oil. Lipids 27, 89–93.Google Scholar
Arbuckle, LD, Rioux, FM, Mackinnon, MJ, Hrboticky, N, Innis, SM 1991. Response of (n-3) and (n-6) fatty acids in piglet brain, liver and plasma to increasing, but low, fish oil supplementation of formula. Journal of Nutrition 121, 1536–1547.Google Scholar
Bazan, NG 2003. Synaptic lipid signaling: significance of polyunsaturated fatty acids and platelet-activating factor. Journal of Lipid Research 44, 222–233.CrossRefGoogle ScholarPubMed
Bézard, J, Blond, JP, Bernard, A, Clouet, P 1994. The metabolism and availability of essential fatty acids in animal and human tissues. Reproduction Nutrition Development 34, 539–568.CrossRefGoogle Scholar
Blank, C, Neumann, MA, Makrides, M, Gibson, RA 2002. Optimizing DHA levels in piglets by lowering the linoleic acid to α-linolenic acid ratio. Journal of Lipid Research 43, 1537–1543.Google Scholar
Bourre, JM, Dumont, O, Pascal, G, Durand, G 1993. Dietary α-linolenic acid at 1.3 g/kg maintains maximal docosahexaenoic acid concentration in brain, heart and liver of adult rats. Journal of Nutrition 123, 1313–1319.Google Scholar
Burdge, GC, Calder, PC 2005. α-Linolenic acid metabolism in adult humans: the effects of gender and age on conversion to longer-chain polyunsaturated fatty acids. European Journal of Lipid Science and Technology 107, 426–439.Google Scholar
Calder, PC 2009. The relationship between the fatty acid composition of immune cells and their function. Prostaglandins, Leukotrienes and Essential Fatty Acids 79, 101–108.CrossRefGoogle Scholar
Calder, PC, Yaqoob, P 2009. Omega-3 polyunsaturated fatty acids and human health outcomes. Biofactors 35, 266–272.CrossRefGoogle ScholarPubMed
Chaloupková, H, Illmann, G, Neuhauserová, K, Tománek, M, Valis, L 2007. Preweaning housing effects on behavior and physiological measures in pigs during the suckling and fattening periods. Journal of Animal Science 85, 1741–1749.CrossRefGoogle ScholarPubMed
Cheon, SH, Huh, MH, Lee, YB, Park, JS, Sohn, HS, Chung, CH 2000. Effect of dietary linoleate/alpha-linolenate balance on the brain lipid composition, reproductive outcome and behavior of rats during their prenatal and postnatal development. Bioscience, Biotechnology and Biochemistry 64, 2290–2297.Google Scholar
Cole, GM, Frautschy, SA 2006. Docosahexaenoic acid protects from amyloid and dendritic pathology in an Alzheimer's disease mouse model. Nutrition and Health 18, 249–259.CrossRefGoogle Scholar
CVB Table Pigs 2007. Chemical composition and nutritional value of feedstuffs and feeding standards. CVB series no 36, The Hague, The Netherlands.Google Scholar
D'Andrea, S, Guillou, H, Jan, S, Catheline, D, Thibault, JN, Bouriel, M, Rioux, V, Legrand, P 2002. The same rat delta 6-desaturase not only acts on 18- but also on 24-carbon fatty acids in very-long-chain polyunsaturated fatty acid biosynthesis. Biochemical Journal 364, 49–55.Google Scholar
De Jong, IC, Ekkel, ED, van de Burgwal, JA, Lambooij, E, Korte, SM, Ruis, MA, Koolhaas, JM, Blokhuis, HJ 1998. Effects of strawbedding on physiological responses to stressors and behavior in growing pigs. Physiological Behaviour 64, 303–310.CrossRefGoogle ScholarPubMed
DeLany, JP, Windhauser, MM, Champagne, CM, Bray, GA 2000. Differential oxidation of individual dietary fatty acids in humans. American Journal of Clinical Nutrition 72, 905–911.CrossRefGoogle ScholarPubMed
De la Presa-Owens, S, Innis, SH, Rioux, FM 1998. Addition of triglycerides with arachidonic acid or docosahexaenoic acid to infant formula has tissue- and lipid class-specific effects on fatty acids and hepatic desaturase activities in formula fed piglets. Journal of Nutrition 128, 1376–1384.Google Scholar
DeMar, JC Jr, Ma, K, Chang, L, Bell, JM, Rapoport, SI 2005. α-Linolenic acid does not contribute appreciably to docosahexaenoic acid within brain phospholipids of adult rats fed a diet enriched in docosahexaenoic acid. Journal of Neurochemistry 94, 1063–1076.Google Scholar
Dobbing, J, Sands, J 1979. Comparative aspects of the brain growth spurt. Early Human Development 311, 79–83.Google Scholar
Duhaime, AC 2006. Large animal models of traumatic injury to the immature brain. Developmental Neuroscience 28, 380–387.Google Scholar
Goyens, PLL, Spilker, ME, Zock, PL, Katan, MB, Mensink, RP 2006. Conversion of α-linolenic acid in humans is influenced by the absolute amounts of α-linolenic acid and linoleic in the diet and not by their ratio. American Journal of Clinical Nutrition 84, 44–53.CrossRefGoogle Scholar
Hrboticky, N, MacKinnon, MJ, Innis, SM 1990. Effect of a vegetable oil formula rich in linoleic acid on tissue fatty acid accretion in the brain, liver, plasma, and erythrocytes of infant piglets. American Journal of Clinical Nutrition 51, 173–182.Google Scholar
Igarashi, M, Ma, K, Chang, L, Bell, JM, Rapoport, SI 2007a. Dietary n-3 PUFA deprivation for 15 weeks upregulates elongase and desaturase expression in rat liver but not brain. Journal of Lipid Research 48, 2463–2470.Google Scholar
Igarashi, M, DeMar, JC, Ma, K, Chang, L, Bell, JM, Rapoport, SL 2007b. Docosahexaenoic acid synthesis from α-linolenic acid by rat brain is unaffected by dietary n-3 deprivation. Journal of Lipid Research 48, 1150–1158.Google ScholarPubMed
Innis, SM 1993. The colostrum deprived piglet as a model for study of infant lipid nutrition. Journal of Nutrition 123, 386–390.Google Scholar
Innis, SM 2007. Dietary (n-3) fatty acids and brain development. Journal of Nutrition 137, 855–859.Google Scholar
Innis, SM, Dyer, RA 2002. Brain astrocyte synthesis of docosahexaenoic acid from n-3 fatty acids is limited at the elongation of docosapentaenoic acid. Journal of Lipid Research 43, 1529–1536.CrossRefGoogle ScholarPubMed
Jan, S, Guillou, H, D'Andrea, S, Daval, S, Bouriel, M, Rioux, V, Legrand, P 2004. Myristic acid increases Δ6-desaturase activity in cultured rat hepatocytes. Reproduction Nutrition Development 44, 131–140.Google Scholar
Mantzioris, E, James, MJ, Gibson, RA, Cleland, LG 1995. Differences exist in the relationships between dietary linoleic and α-linolenic acids and their respective long-chain metabolites. American Journal of Clinical Nutrition 61, 320–324.CrossRefGoogle ScholarPubMed
McCann, J, Ames, BN 2005. Is docosahexaenoic acid, an n-3 long-chain polyunsaturated fatty acid, required for development of normal brain function? An overview of evidence from cognitive and behavioral tests in humans and animals. American Journal of Clinical Nutrition 82, 281–295.CrossRefGoogle ScholarPubMed
Morais, S, Monroig, O, Zheng, X, Leaver, MJ, Tocher, DR 2009. Highly unsaturated fatty acid synthesis in Atlantic salmon: characterization of ELOVL5- and ELOVL2-like elongases. Marine Biotechnology (New York) 11, 627–639.Google Scholar
Moughan, PJ, Cranwell, PD, Darragh, AJ, Rowan, AM 1991. The domestic pig as a model for studying digestion in humans. In Digestive Physiology in Pigs – Proceedings of the Vth International Symposium on Digestive Physiology in Pigs, 24–26 April 1991 (ed. Huisman J, Den Hartog LA and Verstegen MWA), EAAP Publications no. 80, pp. 389–396. Pudoc, Wageningen, The Netherlands.Google Scholar
National Research Council 1998. Nutrients requirements of swine, 10th edition. National Academy Press, Washington, DC, USA.Google Scholar
Ng, KF, Innis, SM 2003. Behavioral responses are altered in piglets with decreased frontal cortex docosahexaenoic acid. Journal of Nutrition 133, 3222–3227.Google Scholar
Odutuga, AA 1981. Reversal of brain essential fatty acid deficiency in the rat by dietary linoleate, linolenate and arachidonate. International Journal of Biochemistry 13, 1035–1038.Google Scholar
Pond, WG, Boleman, SL, Fiorotto, ML, Ho, H, Knabe, DA, Merssmann, HJ, Savell, JW, Su, DR 2000. Perinatal ontogeny of brain growth in the domestic pig. Proceedings of the Society for Experimental Biology and Medicine 223, 102–108.Google ScholarPubMed
Portolesi, R, Powell, BC, Gibson, RA 2007. Competition between 24:5n-3 and ALA for Δ6 desaturase may limit the accumulation of DHA in HepG2 cell membranes. Journal of Lipid Research 48, 1592–1598.CrossRefGoogle Scholar
Portolesi, R, Powell, BC, Gibson, RA 2008. Δ6 desaturase mRNA abundance in HepG2 cells is suppressed by unsaturated fatty acids. Lipids 43, 91–95.Google Scholar
Rioux, V, Cathelina, D, Beauchamp, E, Le Bloc'h, J, Pedrono, F, Legrand, P 2008. Substitution of dietary oleic acid for myristic acid increases the tissue storage of α-linolenic acid and the concentration of docosahexaenoic acid in the brain, red blood cells and plasma in the rat. Animal 2, 636–644.CrossRefGoogle ScholarPubMed
Rodriguez, A, Sarda, P, Nessmann, C, Boulot, P, Leger, CL, Descomps, B 1998. Δ6- and Δ5-desaturase activities in the human fetal liver: kinetic aspects. Journal of Lipid Research 39, 1825–1832.CrossRefGoogle ScholarPubMed
Romans, JR, Wulf, DM, Johnson, RC, Libal, GW, Costello, WJ 1995. Effects of ground flaxseed in swine diets on pig performance and on physical and sensory characteristics and omega-3 fatty acid content of pork: II duration of 15% dietary flaxseed. Journal of Animal Science 73, 1987–1999.CrossRefGoogle ScholarPubMed
Russo, GL 2009. Dietary n-6 and n-3 polyunsaturated fatty acids: from biochemistry to clinical implications in cardiovascular prevention. Biochemical Pharmacology 77, 937–946.Google Scholar
Sang, N, Chen, C 2006. Lipid signalling and synaptic plasticity. Neuroscientist 12, 425–434.CrossRefGoogle ScholarPubMed
Schellingerhout, AB 2002. Essential-fatty acid supply of weaning piglets. PhD, Utrecht University.Google Scholar
Smink, W, Gerrits, WJJ, Hovenier, R, Geelen, MJ, Lobee, HW, Verstegen, MW, Beynen, AC 2008. Fatty acid digestion and deposition in broiler chickens fed diets containing either native or randomized palm oil. Poultry Science 87, 506–513.Google Scholar
Sprecher, H 2000. Metabolism of highly unsaturated n-3 and n-6 fatty acids. Biochimica et Biophysica Acta 1486, 219–231.Google Scholar
Sprecher, H 2002. The roles of anabolic and catabolic reactions in the synthesis and recycling of polyunsaturated fatty acids. Prostaglandins Leukotrienes and Essential Fatty Acids 67, 79–83.Google Scholar
Theil, PK, Lauridsen, C 2007. Interactions between dietary fatty acids and hepatic gene expression in livers of pigs during the weaning period. Livestock Science 108, 26–29.Google Scholar