富含sn-2 DHA脂质对大脑的益处及其酶法合成综述
金俊 , 金青哲 , 王兴国 , Casimir C. Akoh
工程（英文） ›› 2020, Vol. 6 ›› Issue (4) : 424 -431.
富含sn-2 DHA脂质对大脑的益处及其酶法合成综述
金俊 , 金青哲 , 王兴国 , Casimir C. Akoh
工程（英文） ›› 2020, Vol. 6 ›› Issue (4) : 424 -431.
富含sn-2 DHA脂质对大脑的益处及其酶法合成综述
High Sn-2 Docosahexaenoic Acid Lipids for Brain Benefits, and Their Enzymatic Syntheses: A Review
大脑中二十二碳六烯酸（DHA, Ω-3脂肪酸）的含量与中枢神经系统的正常发育和功能维持高度相关。甘油酯sn-2位上的DHA可以被肠黏膜更好地吸收，从而实现机体对DHA的高效利用。然而，如今人们在饮食中摄入较多的饱和脂肪或富含Ω-6脂肪酸的油脂，而摄入较少的DHA，从而导致了部分个体在行为和神经生理学方面的缺陷。为了全面了解DHA对大脑的有益功能，本文系统介绍了天然油脂甘油骨架上DHA的位置分布（sn-2和sn-1,3位）特征，并讨论了DHA补充和通过肠-脑轴传递信息的潜在功能机制。肠-脑轴包含的多条双向信息通道为DHA、肠道菌群和大脑健康的相互作用提供了新的研究思路。为了在日常饮食中摄入更多的sn-2 DHA，我们建议通过更为高效和经济的酯交换制造技术生产富含sn-2 DHA脂质，其中需要解决的关键技术包括强化酶的特异性和优化纯化工艺。这类饮食可满足对sn-2 Ω-3脂质有强烈需求的人群，特别是婴儿、儿童、孕妇和哺乳期妇女。
The normal development and maintenance of central neural functions are highly correlated with the amount of docosahexaenoic acid (DHA; Ω-3 fatty acid) accumulated in the brain. DHA incorporated at the sn-2 position of lipids is well absorbed by intestinal mucosa and utilized efficiently in vivo. However, modern consumers have a reduced direct intake of DHA and increased intake of saturated fats or Ω-6 fatty acid oils, resulting in behavioral and neurophysiological deficits. To provide an understanding of the integrated beneficial effects of DHA on the human brain, this review introduces the positional difference (sn-2 and sn-1,3 positions) of DHA on a glycerol skeleton in natural fats and oils, and further discusses the possible functional mechanism regarding DHA supplementation and the gut-brain axis. The multiple bidirectional routes in this axis offer a novel insight into the interaction between DHA supplementation, the gut microbiota, and brain health. To achieve high sn-2 DHA in diets, it is suggested that sn-2 DHA lipids be enzymatically produced in more efficient and economical ways by improving the specific activities of lipases and optimizing the purification procedures. These types of diets will benefit individuals with strong needs for sn-2 Ω-3 lipids such as infants, children, and pregnant and lactating women.
DHA 和 sn-2 DHA / 单甘酯 / 大脑 / 肠-脑轴 / 结构脂质
| [1] |
Gharami K, Das M, Das S. Essential role of docosahexaenoic acid towards development of a smarter brain. Neurochem Int 2015;89:51–62. |
| [2] |
Carlson SJ, Fallon EM, Kalish BT, Gura KM, Puder M. The role of the x-3 fatty acid DHA in the human life cycle. J Parenter Enteral Nutr 2013;37(1):15–22. |
| [3] |
Wu A, Noble EE, Tyagi E, Ying Z, Zhuang Y, Gomez-Pinilla F. Curcumin boosts DHA in the brain: implications for the prevention of anxiety disorders. Biochim Biophys Acta 2015;1852(5):951–61. |
| [4] |
Innis SM. Dietary omega 3 fatty acids and the developing brain. Brain Res 2008;1237:35–43. |
| [5] |
Joffre C, Nadjar A, Lebbadi M, Calon F, Laye S. n-3 LCPUFA improves cognition: the young, the old and the sick. Prostaglandins Leukot Essent Fatty Acids 2014;91(1–2):1–20. |
| [6] |
Rapoport SI, Igarashi M. Can the rat liver maintain normal brain DHA metabolism in the absence of dietary DHA?. Prostaglandins Leukot Essent Fatty Acids 2009;81(2–3):119–23. |
| [7] |
Strauss KA, Wardley B, Robinson D, Hendrickson C, Rider NL, Puffenberger EG, et al. Classical maple syrup urine disease and brain development: principles of management and formula design. Mol Genet Metab 2010;99(4):333–45. |
| [8] |
Simopoulos AP. Evolutionary aspects of diet: the omega-6/omega-3 ratio and the brain. Mol Neurobiol 2011;44(2):203–15. |
| [9] |
Valentine CJ, Morrow G, Fernandez S, Gulati P, Bartholomew D, Long D, et al. Docosahexaenoic acid and amino acid contents in pasteurized donor milk are low for preterm infants. J Pediatr 2010;157(6):906–10. |
| [10] |
Bradbury J. Docosahexaenoic acid (DHA): an ancient nutrient for the modern human brain. Nutrients 2011;3(5):529–54. |
| [11] |
Brenna JT, Carlson SE. Docosahexaenoic acid and human brain development: evidence that a dietary supply is needed for optimal development. J Hum Evol 2014;77:99–106. |
| [12] |
Carlier H, Bernard A, Caselli C. Digestion and absorption of polyunsaturated fatty acids. Reprod Nutr Dev 1991;31(5):475–500. |
| [13] |
Michalski MC, Genot C, Gayet C, Lopez C, Fine F, Joffre F, et al. Multiscale structures of lipids in foods as parameters affecting fatty acid bioavailability and lipid metabolism. Prog Lipid Res 2013;52(4):354–73. |
| [14] |
Oxley A, Jutfelt F, Sundell K, Olsen RE. Sn-2-Monoacylglycerol, not glycerol, is preferentially utilised for triacylglycerol and phosphatidylcholine biosynthesis in Atlantic salmon (Salmo salar L.) intestine. Comp Biochem Physiol B Biochem Mol Biol 2007;146(1):115–23. |
| [15] |
Ramírez M, Amate L, Gil A. Absorption and distribution of dietary fatty acids from different sources. Early Hum Dev 2001;65:S95–S101. |
| [16] |
Christensen MS, Høy CE, Becker CC, Redgrave TG. Intestinal absorption and lymphatic transport of eicosapentaenoic (EPA), docosahexaenoic (DHA), and decanoic acids: dependence on intramolecular triacylglycerol structure. Am J Clin Nutr 1995;61(1):56–61. |
| [17] |
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 (Tokyo) 2002;48(1):30–5. |
| [18] |
Valenzuela A, Valenzuela V, Sanhueza J, Nieto S. Effect of supplementation with docosahexaenoic acid ethyl ester and sn-2 docosahexaenyl monoacylglyceride on plasma and erythrocyte fatty acids in rats. Ann Nutr Metab 2005;49(1):49–53. |
| [19] |
Koletzko B, Cetin I, Brenna JT. Dietary fat intakes for pregnant and lactating women. Br J Nutr 2007;98(5):873–7. |
| [20] |
Zhang HJ, Zhao H, Zhang YW, Shen YB, Su H, Jin J, et al. Characterization of positional distribution of fatty acids and triacylglycerol molecular compositions of marine fish oils rich in omega-3 polyunsaturated fatty acids. BioMed Res Int 2018;2018:1–10. |
| [21] |
He YJ, Li JB, Kodali S, Chen BL, Guo Z. The near-ideal catalytic property of Candida antarctica lipase A to highly concentrate n-3 polyunsaturated fatty acids in monoacylglycerols via one-step ethanolysis of triacylglycerols. Bioresour Technol 2016;219:466–78. |
| [22] |
Zhang Y, Wang XS, Xie D, Zou S, Jin QZ, Wang XG. Synthesis and concentration of 2-monoacylglycerols rich in polyunsaturated fatty acids. Food Chem 2018;250:60–6. |
| [23] |
Watanabe Y, Sato S, Asada M, Arishima T, Iida Y, Imagi J, et al. Enzymatic analysis of positional fatty acid distributions in triacylglycerols by 1 (3)- selective transesterification with Candida antarctica lipase B: a collaborative study. J Oleo Sci 2015;64(11):1193–205. |
| [24] |
Zhang Y, Wang XS, Zou S, Xie D, Jin QZ, Wang XG. Synthesis of 2- docosahexaenoylglycerol by enzymatic ethanolysis. Bioresour Technol 2018;251:334–40. |
| [25] |
Nagachinta S, Akoh CC. Enrichment of palm olein with long chain polyunsaturated fatty acids by enzymatic acidolysis. Lebensm Wiss Technol 2012;46(1):29–35. |
| [26] |
Amate L, Ramírez M, Gil A. Positional analysis of triglycerides and phospholipids rich in long-chain polyunsaturated fatty acids. Lipids 1999;34 (8):865–71. |
| [27] |
Jiao G, Hui JPM, Burton IW, Thibault MH, Pelletier C, Boudreau J, et al. Characterization of shrimp oil from Pandalus borealis by high performance liquid chromatography and high resolution mass spectrometry. Mar Drugs 2015;13(6):3849–76. |
| [28] |
Qi C, Sun J, Xia Y, Yu RQ, Wei W, Xiang JY, et al. Fatty acid profile and the sn-2 position distribution in triacylglycerols of breast milk during different lactation stages. J Agric Food Chem 2018;66(12):3118–26. |
| [29] |
López-López A, López-Sabater MC, Campoy-Folgoso C, Rivero-Urgell M, Castellote-Bargalló AI. Fatty acid and sn-2 fatty acid composition in human milk from Granada (Spain) and in infant formulas. Eur J Clin Nutr 2002;56 (12):1242–54. |
| [30] |
Sun C, Wei W, Su H, Zou XQ, Wang XG. Evaluation of sn-2 fatty acid composition in commercial infant formulas on the Chinese market: a comparative study based on fat source and stage. Food Chem 2018;242:29–36. |
| [31] |
Nagachinta S, Akoh CC. Synthesis of structured lipid enriched with omega fatty acids and sn-2 palmitic acid by enzymatic esterification and its incorporation in powdered infant formula. J Agric Food Chem 2013;61(18):4455–63. |
| [32] |
Di Marzo V, Griinari M, Carta G, Murru E, Ligresti A, Cordeddu L, et al. Dietary krill oil increases docosahexaenoic acid and reduces 2-arachidonoylglycerol but not N-acylethanolamine levels in the brain of obese Zucker rats. Int Dairy J 2010;20(4):231–5. |
| [33] |
Al MDM, Houwelingen AC, Hornstra G. Relation between birth order and the maternal and neonatal docosahexaenoic acid status. Eur J Clin Nutr 1997;51 (8):548–53. |
| [34] |
Morse NL. Benefits of docosahexaenoic acid, folic acid, vitamin D and iodine on foetal and infant brain development and function following maternal supplementation during pregnancy and lactation. Nutrients 2012;4(7):799–840. |
| [35] |
Guesnet P, Alessandri JM. Docosahexaenoic acid (DHA) and the developing central nervous system (CNS)—Implications for dietary recommendations. Biochimie 2011;93(1):7–12. |
| [36] |
Christensen MM, Høy CE. Early dietary intervention with structured triacylglycerols containing docosahexaenoic acid. Effect on brain, liver, and adipose tissue lipids. Lipids 1997;32(2):185–91. |
| [37] |
Thies F, Pillon C, Moliere P, Lagarde M, Lecerf J. Preferential incorporation of sn- 2 lysoPC DHA over unesterified DHA in the young rat brain. Am J Physiol 1994;267:R1273–9. |
| [38] |
Makrides M. Is there a dietary requirement for DHA in pregnancy?. Prostaglandins Leukot Essent Fatty Acids 2009;81(2–3):171–4. |
| [39] |
Bailey MT, Cryan JF. The microbiome as a key regulator of brain, behavior and immunity: commentary on the 2017 named series. Brain Behav Immun 2017;66:18–22. |
| [40] |
Russo R, Cristiano C, Avagliano C, de Caro C, La Rana G, Raso GM, et al. Gutbrain axis: role of lipids in the regulation of inflammation, pain and CNS diseases. Curr Med Chem 2018;25(32):3930–52. |
| [41] |
Dinan TG, Stilling RM, Stanton C, Cryan JF. Collective unconscious: how gut microbes shape human behavior. J Psychiatr Res 2015;63:1–9. |
| [42] |
Moloney RD, Desbonnet L, Clarke G, Dinan TG, Cryan JF. The microbiome: stress, health and disease. Mamm Genome 2014;25(1–2):49–74. |
| [43] |
Oriach CS, Robertson RC, Stanton C, Cryan JF, Dinan TG. Food for thought: the role of nutrition in the microbiota-gut-brain axis. Clin Nutr Experimental 2016;6:25–38. |
| [44] |
Russo F, Chimienti G, Clemente C, Ferreri C, Orlando A, Riezzo G. A possible role for ghrelin, leptin, brain-derived neurotrophic factor and docosahexaenoic acid in reducing the quality of life of coeliac disease patients following a gluten-free diet. Eur J Nutr 2017;56(2):807–18. |
| [45] |
Pusceddu MM, El Aidy S, Crispie F, O’Sullivan O, Cotter P, Stanton C, et al. N-3 polyunsaturated fatty acids (PUFAs) reverse the impact of early-life stress on the gut microbiota. PLoS ONE 2015;10(10):e0139721. |
| [46] |
Robertson RC, Oriach CS, Murphy K, Moloney GM, Cryan JF, Dinan TG, et al. Omega-3 polyunsaturated fatty acids critically regulate behaviour and gut microbiota development in adolescence and adulthood. Brain Behav Immun 2017;59:21–37. |
| [47] |
Davis DJ, Hecht PM, Jasarevic E, Beversdorf DQ, Will MJ, Fritsche K, et al. Sexspecific effects of docosahexaenoic acid (DHA) on the microbiome and behavior of socially-isolated mice. Brain Behav Immun 2017;59:38–48. |
| [48] |
Zhang H, Li Y, Cui C, Sun T, Han J, Zhang D, et al. Modulation of gut microbiota by dietary supplementation with tuna oil and algae oil alleviates the effects of Dgalactose-induced ageing. Appl Microbiol Biotechnol 2018;102(6):2791–801. |
| [49] |
García-Ródenas CL, Bergonzelli GE, Nutten S, Schumann A, Cherbut C, Turini M, et al. Nutritional approach to restore impaired intestinal barrier function and growth after neonatal stress in rats. J Pediatr Gastroenterol Nutr 2006;43 (1):16–24. |
| [50] |
Rogers LK, Valentine CJ, Keim SA. DHA supplementation: current implications in pregnancy and childhood. Pharmacol Res 2013;70(1):13–9. |
| [51] |
Hamam F, Shahidi F. Synthesis of structured lipids via acidolysis of docosahexaenoic acid single cell oil (DHASCO) with capric acid. J Agric Food Chem 2004;52(10):2900–6. |
| [52] |
Iwasaki Y, Han JJ, Narita M, Rosu R, Yamane T. Enzymatic synthesis of structured lipids from single cell oil of high docosahexaenoic acid content. J Am Oil Chem Soc 1999;76(5):563–9. |
| [53] |
Hita E, Robles A, Camacho B, Ramírez A, Esteban L, Jiménez MJ, et al. Production of structured triacylglycerols (STAG) rich in docosahexaenoic acid (DHA) in position 2 by acidolysis of tuna oil catalyzed by lipases. Process Biochem 2007;42(3):415–22. |
| [54] |
Jennings BH, Akoh CC. Enzymatic modification of triacylglycerols of high eicosapentaenoic and docosahexaenoic acids content to produce structured lipids. J Am Oil Chem Soc 1999;76(10):1133–7. |
| [55] |
Pande G, Sabir JS, Baeshen NA, Akoh CC. Synthesis of infant formula fat analogs enriched with DHA from extra virgin olive oil and tripalmitin. J Am Oil Chem Soc 2013;90(9):1311–8. |
| [56] |
Negishi S, Arai Y, Arimoto S, Tsuchiya K, Takahashi I. Synthesis of 1,3- dicapryloyl-2-docosahexaenoylglycerol by a combination of nonselective and sn-1,3-selective lipase reactions. J Am Oil Chem Soc 2003;80(10):971–4. |
| [57] |
Willett SA, Akoh CC. Application of Taguchi method in the enzymatic modification of menhaden oil to incorporate capric acid. J Am Oil Chem Soc 2018;95(3):299–311. |
| [58] |
Álvarez CA, Akoh CC. Enzymatic synthesis of high sn-2 DHA and ARA modified oils for the formulation of infant formula fat analogues. J Am Oil Chem Soc 2016;93(3):383–95. |
| [59] |
Irimescu R, Furihata K, Hata K, Iwasaki Y, Yamane T. Two-step enzymatic synthesis of docosahexaenoic acid-rich symmetrically structured triacylglycerols via 2-monoacylglycerols. J Am Oil Chem Soc 2001;78 (7):743–8. |
| [60] |
del Mar Muñío M, Robles A, Esteban L, González PA, Molina E. Synthesis of structured lipids by two enzymatic steps: ethanolysis of fish oils and esterification of 2-monoacylglycerols. Process Biochem 2009;44(7):723–30. |
| [61] |
Rodríguez A, Esteban L, Martín L, Jiménez MJ, Hita E, Castillo B, et al. Synthesis of 2-monoacylglycerols and structured triacylglycerols rich in polyunsaturated fatty acids by enzyme catalyzed reactions. Enzyme Microb Technol 2012;51 (3):148–55. |
| [62] |
He YJ, Qiu CY, Guo Z, Huang J, Wang MZ, Chen BL. Production of new human milk fat substitutes by enzymatic acidolysis of microalgae oils from Nannochloropsis oculata and Isochrysis galbana. Bioresour Technol 2017;238:129–38. |
| [63] |
Gunstone FD. Modifying lipids for use in food. Cambridge: Woodhead Publishing; 2006. p. 336–68. |
| [64] |
Zhang Y. Preparation of purification of DHA and 2-DHA-MAG and their regulation of lipid metabolism in HepG2 cells [dissertation]. Wuxi: Jiangnan University; 2019. Chinese. |
| [65] |
He YJ, Li JB, Kodali S, Balle T, Chen B, Guo Z. Liquid lipases for enzymatic concentration of n-3 polyunsaturated fatty acids in monoacylglycerols via ethanolysis: catalytic specificity and parameterization. Bioresour Technol 2017;224:445–56. |
| [66] |
He YJ, Li JB, Kodali S, Chen BL, Guo Z. Rationale behind the near-ideal catalysis of Candida antarctica lipase A (CAL-A) for highly concentrating x-3 polyunsaturated fatty acids into monoacylglycerols. Food Chem 2017;219:230–9. |
| [67] |
Solaesa ÁG, Sanz MT, Falkeborg M, Beltrán S, Guo Z. Production and concentration of monoacylglycerols rich in omega-3 polyunsaturated fatty acids by enzymatic glycerolysis and molecular distillation. Food Chem 2016;190:960–7. |
| [68] |
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(10):693–6. |
| [69] |
Akanbi TO, Sinclair AJ, Barrow CJ. Pancreatic lipase selectively hydrolyses DPA over EPA and DHA due to location of double bonds in the fatty acid rather than regioselectivity. Food Chem 2014;160:61–6. |
| [70] |
Solaesa ÁG, Bucio SL, Sanz MT, Beltrán S, Rebolleda S. Characterization of triacylglycerol composition of fish oils by using chromatographic techniques. J Oleo Sci 2014;63(5):449–60. |
| [71] |
del Mar Muñío M, Esteban L, Robles A, Hita E, Jiménez MJ, González PA, et al. Synthesis of 2-monoacylglycerols rich in polyunsaturated fatty acids by ethanolysis of fish oil catalyzed by 1,3 specific lipases. Process Biochem 2008;43(10):1033–9. |
| [72] |
Shen Z, Wijesundera C. Evaluation of ethanolysis with immobilized Candida antarctica lipase for regiospecific analysis of triacylglycerols containing highly unsaturated fatty acids. J Am Oil Chem Soc 2006;83(11):923–7. |
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