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In Vitro Evidence of Anti-Inflammatory and Anti-Obesity Effects of Medium-Chain Fatty Acid-Diacylglycerols

  • Yu, Seungmin (Department of Food Science and Biotechnology, Graduate School of Biotechnology, Kyung Hee University) ;
  • Choi, Jong Hun (R&D Center, Nongshim) ;
  • Kim, Hun Jung (R&D Center, Nongshim) ;
  • Park, Soo Hyun (R&D Center, Nongshim) ;
  • Go, Gwang-woong (Department of Foods and Nutrition, Kookmin University) ;
  • Kim, Wooki (Department of Food Science and Biotechnology, Graduate School of Biotechnology, Kyung Hee University)
  • Received : 2017.03.31
  • Accepted : 2017.07.28
  • Published : 2017.09.28

Abstract

Dietary approaches using structured lipids, including medium-chain fatty acids and diacylglycerols, have been adopted for the prevention of obesity-induced chronic inflammation. In an extension to previous studies, medium-chain fatty acid-diacylglycerol enriched dietary oil (MCDG) was prepared by interesterification of canola oil and medium-chain fatty acid-triacylglycerols. The consequent MCDG product was applied to RAW264.7 macrophages followed by the assessment of multiple inflammatory responses. Compared with conventionally used canola and olive oil controls, MCDG suppressed macrophage phagocytosis, as assessed by the uptake of microsphere beads. Furthermore, the production of IL-6 and $TNF-{\alpha}$, transcription of COX-2 and iNOS, and expression of CD80 on cell surfaces were downregulated by MCDG in LPS-stimulated macrophages. Subsequently, differentiated 3T3-L1 adipocytes were evaluated for proinflammatory cytokine production and lipid accumulation. IL-6 production was marginally affected and lipid accumulation was inhibited by MCDG. Taken together, these results suggest that MCDG has potential as an alternative oil for cooking in order to prevent obesity-induced inflammation.

Keywords

References

  1. Berry EM, Eisenberg S, Haratz D, Friedlander Y, Norman Y, Kaufmann NA, et al. 1991. Effects of diets rich in monounsaturated fatty acids on plasma lipoproteins - the Jerusalem nutrition study: high MUFAs vs high PUFAs. Am. J. Clin. Nutr. 53: 899-907. https://doi.org/10.1093/ajcn/53.4.899
  2. West DB, Delany JP, Camet PM, Blohm F, Truett AA, Scimeca J. 1998. Effects of conjugated linoleic acid on body fat and energy metabolism in the mouse. Am. J. Physiol. 275: R667-R672.
  3. Plat J, Mensink RP. 2005. Food components and immune function. Curr. Opin. Lipidol. 16: 31-37. https://doi.org/10.1097/00041433-200502000-00007
  4. Hoshimoto A, Suzuki Y, Katsuno T, Nakajima H, Saito Y. 2002. Caprylic acid and medium-chain triglycerides inhibit IL-8 gene transcription in Caco-2 cells: comparison with the potent histone deacetylase inhibitor trichostatin A. Br. J. Pharmacol. 136: 280-286. https://doi.org/10.1038/sj.bjp.0704719
  5. Bach AC, Ingenbleek Y, Frey A. 1996. The usefulness of dietary medium-chain triglycerides in body weight control: fact or fancy? J. Lipid Res. 37: 708-726.
  6. Ikeda Y, Okamura-Ikeda K, Tanaka K. 1985. Purification and characterization of short-chain, medium-chain, and long-chain acyl-CoA dehydrogenases from rat liver mitochondria. Isolation of the holo- and apoenzymes and conversion of the apoenzyme to the holoenzyme. J. Biol. Chem. 260: 1311-1325.
  7. Shinohara H, Shimada H, Noguchi O, Kubota F, Aoyama T. 2002. Effect of medium-chain fatty acids-containing dietary oil on hepatic fatty acid oxidation enzyme activity in rats. J. Oleo Sci. 51: 621-626. https://doi.org/10.5650/jos.51.621
  8. Seaton TB, Welle SL, Warenko MK, Campbell RG. 1986. Thermic effect of medium-chain triglycerides in man. Am. J. Clin. Nutr. 44: 630-634. https://doi.org/10.1093/ajcn/44.5.630
  9. Marten B, Pfeuffer M, Schrezenmeir J. 2006. Medium-chain triglycerides. Int. Dairy J. 16: 1374-1382. https://doi.org/10.1016/j.idairyj.2006.06.015
  10. Bierbach H. 1983. Triacylglycerol biosynthesis in human small intestinal mucosa. Acyl-CoA: monoglyceride acyltransferase. Digestion 28: 138-147. https://doi.org/10.1159/000198977
  11. Meng X, Zou D, Shi Z, Duan Z, Mao Z. 2004. Dietary diacylglycerol prevents high-fat diet-induced lipid accumulation in rat liver and abdominal adipose tissue. Lipids 39: 37-41. https://doi.org/10.1007/s11745-004-1199-1
  12. Cao J, Lockwood J, Burn P, Shi Y. 2003. Cloning and functional characterization of a mouse intestinal acyl-CoA: monoacylglycerol acyltransferase, MGAT2. J. Biol. Chem. 278: 13860-13866. https://doi.org/10.1074/jbc.M300139200
  13. Owen MR, Corstorphine CC, Zammit VA. 1997. Overt and latent activities of diacylglycerol acytransferase in rat liver microsomes: possible roles in very-low-density lipoprotein triacylglycerol secretion. Biochem. J. 323: 17-21. https://doi.org/10.1042/bj3230017
  14. Coppack SW. 2001. Pro-inflammatory cytokines and adipose tissue. Proc. Nutr. Soc. 60: 349-356. https://doi.org/10.1079/PNS2001110
  15. Chawla A, Nguyen KD, Goh YPS. 2011. Macrophage-mediated inflammation in metabolic disease. Nat. Rev. Immunol. 11: 738-749. https://doi.org/10.1038/nri3071
  16. Kim B, Lee JH, Seo MJ, Eom SH, Kim W. 2016. Linarin down-regulates phagocytosis, pro-inflammatory cytokine production, and activation marker expression in RAW264.7 macrophages. Food Sci. Biotechnol. 25: 1437-1442. https://doi.org/10.1007/s10068-016-0223-3
  17. Castoldi A, Naffah De Souza C, Camara NO, Moraes-Vieira PM. 2016. The macrophage switch in obesity development. Front. Immunol. 6: 1-11.
  18. Ntambi MJ, Kim Y-C. 2000. Symposium: adipocyte function, differentiation and metabolism regulation of leptin production in humans. J. Nutr. 130: 3127-3131. https://doi.org/10.1093/jn/130.12.3127S
  19. Tateya S, Kim F, Tamori Y. 2013. Recent advances in obesity-induced inflammation and insulin resistance. Front. Endocrinol. (Lausanne) 4: 1-14.
  20. Martinez FO, Gordon S. 2014. The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep. 6: 13.
  21. Huge-Jensen B, Galluzzo DR, Jensen RG. 1988. Studies on free and immobilized lipases from Mucor miehei. J. Am. Oil Chem. Soc. 65: 905-910. https://doi.org/10.1007/BF02544508
  22. Da Violante G, Zerrouk N, Richard I, Provot G, Chaumeil JC, Arnaud P, et al. 2002. Evaluation of the cytotoxicity effect of dimethyl sulfoxide (DMSO) on Caco2/TC7 colon tumor cell cultures. Biol. Pharm. Bull. 25: 1600-1603. https://doi.org/10.1248/bpb.25.1600
  23. Sokolovska A, Becker CE, Ip WKE, Rathinam VAK, Brudner M, Paquette N, et al. 2013. Activation of caspase-1 by the NLRP3 inflammasome regulates the NADPH oxidase NOX2 to control phagosome function. Nat. Immunol. 14: 543-553.
  24. Hull TD, Bolisetty S, DeAlmeida AC, Litovsky SH, Prabhu SD, Agarwal A, et al. 2013. Heme oxygenase-1 expression protects the heart from acute injury caused by inducible Cre recombinase. Lab. Invest. 93: 868-879. https://doi.org/10.1038/labinvest.2013.74
  25. Vitali R, Palone F, Pierdomenico M, Negroni A, Cucchiara S, Aloi M, et al. 2015. Dipotassium glycyrrhizate via HMGB1 or AMPK signaling suppresses oxidative stress during intestinal inflammation. Biochem. Pharmacol. 97: 292-299. https://doi.org/10.1016/j.bcp.2015.07.039
  26. Vendramini-Costa DB, Spindola HM, De Mello GC, Antunes E, Pilli RA, De Carvalho JE. 2015. Anti-inflammatory and antinociceptive effects of racemic goniothalamin, a styryl lactone. Life Sci. 139: 83-90. https://doi.org/10.1016/j.lfs.2015.08.010
  27. Mosmann T. 1983. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 65: 55-63. https://doi.org/10.1016/0022-1759(83)90303-4
  28. Gordon S. 1998. The role of the macrophage in immune regulation. Res. Immunol. 149: 685-688. https://doi.org/10.1016/S0923-2494(99)80039-X
  29. Klippel N, Bilitewski U. 2007. Phagocytosis assay based on living Candida albicans for the detection of effects of chemicals on macrophage function. Anal. Lett. 40: 1400-1411. https://doi.org/10.1080/00032710701327047
  30. Araki N, Johnson MT, Swanson JA. 1996. A role for phosphoinositide 3-kinase in the completion of macropinocytosis and phagocytosis by macrophages. J. Cell Biol. 135: 1249-1260. https://doi.org/10.1083/jcb.135.5.1249
  31. Morrissette N, Gold E, Aderem A. 1999. The macrophage - a cell for all seasons. Trends Cell Biol. 9: 199-201. https://doi.org/10.1016/S0962-8924(99)01540-8
  32. Aderem A, Underhill DM. 1999. Mechanisms of phagocytosis in macrophages. Annu. Rev. Immunol. 17: 593-623. https://doi.org/10.1146/annurev.immunol.17.1.593
  33. Calder PC. 2008. The relationship between the fatty acid composition of immune cells and their function. Prostaglandins Leukot. Essent. Fatty Acids 79: 101-108. https://doi.org/10.1016/j.plefa.2008.09.016
  34. Calder PC, Bond JA, Harvey DJ, Gordon S, Newsholme EA. 1990. Uptake and incorporation of saturated and unsaturated fatty acids into macrophage lipids and their effect upon macrophage adhesion and phagocytosis. Biochem. J. 269: 807-814. https://doi.org/10.1042/bj2690807
  35. Schobitz B, de Kloet ER, Holsboer F. 1994. Gene expression and function of interleukin I, interleukin 6 and tumor necrosis factor in the brain. Prog. Neurobiol. 44: 397-432. https://doi.org/10.1016/0301-0082(94)90034-5
  36. Akira S, Hirano T, Taga T, Kishimoto T. 1990. Biology of multifunctional cytokines: IL 6 and related molecules (IL 1 and TNF). FASEB J. 4: 2860-2867. https://doi.org/10.1096/fasebj.4.11.2199284
  37. Azuma Y, Kaji K, Katogi R, Takeshita S, Kudo A. 2000. Tumor necrosis factor-alpha induces differentiation of and bone resorption by osteoclasts. J. Biol. Chem. 275: 4858-4864. https://doi.org/10.1074/jbc.275.7.4858
  38. Temple SEL, Pham K, Glendenning P, Phillips M, Waterer GW. 2008. Endotoxin induced TNF and IL-10 mRNA production is higher in male than female donors: correlation with elevated expression of TLR4. Cell. Immunol. 251: 69-71. https://doi.org/10.1016/j.cellimm.2008.04.013
  39. Balkwill F. 2006. TNF-$\alpha$ in promotion and progression of cancer. Cancer Metastasis Rev. 25: 409-416. https://doi.org/10.1007/s10555-006-9005-3
  40. Bertevello PL, De Nardi L, Torrinhas RS, Logullo AF, Waitzberg DL. 2012. Partial replacement of TEX>${\omega}$-6 fatty acids with medium-chain triglycerides, but not olive oil, improves colon cytokine response and damage in experimental colitis. JPEN J. Parenter. Enter. Nutr. 36: 442-448. https://doi.org/10.1177/0148607111421788
  41. Kono H, Enomoto N, Connor HD, Wheeler MD, Bradford BU, Rivera CA, et al. 2000. Medium-chain triglycerides inhibit free radical formation and TNF-alpha production in rats given enteral ethanol. Am. J. Physiol. Gastrointest. Liver Physiol. 278: G467-G476. https://doi.org/10.1152/ajpgi.2000.278.3.G467
  42. Kono H, Fujii H, O giku M , T suchiya M, I shii K , Hara M . 2010. Enteral diets enriched with medium-chain triglycerides and N-3 fatty acids prevent chemically induced experimental colitis in rats. Transl. Res. 156: 282-291. https://doi.org/10.1016/j.trsl.2010.07.012
  43. Malapaka RRV, Khoo S, Zhang J, Choi JH, Zhou XE, Xu Y, et al. 2012. Identification and mechanism of 10-carbon fatty acid as modulating ligand of peroxisome proliferator-activated receptors. J. Biol. Chem. 287: 183-195. https://doi.org/10.1074/jbc.M111.294785
  44. Kono H, Fujii H, Asakawa M, Maki A, Amemiya H, Hirai Y, et al. 2004. Medium-chain triglycerides enhance secretory IgA expression in rat intestine after administration of endotoxin. Am. J. Physiol. Gastrointest. Liver Physiol. 286: G1081-G1089. https://doi.org/10.1152/ajpgi.00457.2003
  45. Wang J, Wu X, Simonavicius N, Tian H, Ling L. 2006. Medium-chain fatty acids as ligands for orphan G proteincoupled receptor GPR84. J. Biol. Chem. 281: 34457-34464. https://doi.org/10.1074/jbc.M608019200
  46. Kim SF. 2005. Inducible nitric oxide synthase binds, snitrosylates, and activates cyclooxygenase-2. Science 310: 1966-1970. https://doi.org/10.1126/science.1119407
  47. Salvemini D, Seibert K, Masferrer JL, Misko TP, Currie MG, Needleman P. 1994. Endogenous nitric oxide enhances prostaglandin production in a model of renal inflammation. J. Clin. Invest. 93: 1940-1947. https://doi.org/10.1172/JCI117185
  48. Blanchette J, Jaramillo M, Olivier M. 2003. Signalling events involved in interferon-gamma-inducible macrophage nitric oxide generation. Immunology 108: 513-522. https://doi.org/10.1046/j.1365-2567.2003.01620.x
  49. Suh N, H onda T , Finlay H J, B archowsky A, W illiams C, Benoit NE, et al. 1998. Novel triterpenoids suppress inducible nitric oxide synthase (iNOS) and inducible cyclooxygenase (COX-2) in mouse macrophages. Cancer Res. 58: 717-723.
  50. Wu W H, L in BY, K uo Y H, H uang C . 2009. Triglycerides constituted of short and medium chain fatty acids and dicarboxylic acids in Momordica charantia, as well as capric acid, inhibit PGE2 production in RAW264.7 macrophages. Food Chem. 117: 306-311. https://doi.org/10.1016/j.foodchem.2009.04.004
  51. Nanji AA, Jokelainen K, Tipoe GL, Rahemtulla A, Dannenberg AJ. 2001. Dietary saturated fatty acids reverse inflammatory and fibrotic changes in rat liver despite continued ethanol administration. J. Pharmacol. Exp. Ther. 299: 638-644.
  52. Papamandjaris AA, Macdougall DE, Jones PJH. 1998. Medium chain fatty acid metabolism and energy expenditure: obesity treatment implications. Life Sci. 62: 1203-1215. https://doi.org/10.1016/S0024-3205(97)01143-0
  53. Stafford P, Abdelwahab MG, Kim DY, Preul MC, Rho JM, Scheck AC. 2010. The ketogenic diet reverses gene expression patterns and reduces reactive oxygen species levels when used as an adjuvant therapy for glioma. Nutr. Metab. (Lond.) 7: 74. https://doi.org/10.1186/1743-7075-7-74
  54. Eckhardt A, Harorli T, Limtanyakul J, Hiller KA, Bosl C, Bolay C, et al. 2009. Inhibition of cytokine and surface antigen expression in LPS-stimulated murine macrophages by triethylene glycol dimethacrylate. Biomaterials 30: 1665-1674. https://doi.org/10.1016/j.biomaterials.2008.09.024
  55. Janeway CA Jr, Medzhitov R. 2002. Innate immune recognition. Annu. Rev. Immunol. 20: 197-216. https://doi.org/10.1146/annurev.immunol.20.083001.084359
  56. van Kasteren SI, Overkleeft H, Ovaa H, Neefjes J. 2014. Chemical biology of antigen presentation by MHC molecules. Curr. Opin. Immunol. 26: 21-31. https://doi.org/10.1016/j.coi.2013.10.005
  57. Germain RN, Jenkins MK. 2004. In vivo antigen presentation. Curr. Opin. Immunol. 16: 120-125. https://doi.org/10.1016/j.coi.2003.11.001
  58. Kuchroo VK, Prabhu Das M, Brown JA, Ranger AM, Zamvil SS, Sobel RA, et al. 1995. B7-1 and B7-2 costimulatory molecules activate differentially the Th1/Th2 developmental pathways: application to autoimmune disease therapy. Cell 80: 707-718. https://doi.org/10.1016/0092-8674(95)90349-6
  59. Sansom DM, Manzotti CN, Zheng Y. 2003. What's the difference between CD80 and CD86? Trends Immunol. 24: 313-318. https://doi.org/10.1016/S1471-4906(03)00111-X
  60. Fujii S, Liu K, Smith C, Bonito AJ, Steinman RM. 2004. The linkage of innate to adaptive immunity via maturing dendritic cells in vivo requires CD40 ligation in addition to antigen presentation and CD80/86 costimulation. J. Exp. Med. 199: 1607-1618. https://doi.org/10.1084/jem.20040317
  61. Manzoni Jacintho T, Gotho H, Gidlund M, Garcia Marques C, Torrinhas R, Mirtes Sales M, et al. 2009. Anti-inflammatory effect of parenteral fish oil lipid emulsion on human activated mononuclear leukocytes. Nutr. Hosp. 24: 288-296.
  62. Havel PJ. 2002. Control of energy homeostasis and insulin action by adipocyte hormones: leptin, acylation stimulating protein, and adiponectin. Curr. Opin. Lipidol. 13: 51-59. https://doi.org/10.1097/00041433-200202000-00008
  63. Fu Y, Luo N, Klein RL, Garvey WT. 2005. Adiponectin promotes adipocyte differentiation, insulin sensitivity, and lipid accumulation. J. Lipid Res. 46: 1369-1379. https://doi.org/10.1194/jlr.M400373-JLR200
  64. Kahn B, Flier J. 2000. Obesity and insulin resistance. J. Clin. Invest. 106: 473-481. https://doi.org/10.1172/JCI10842
  65. Ramirez-Zacarias JL, Castro-Munozledo F, Kuri-Harcuch W. 1992. Quantitation of adipose conversion and triglycerides by staining intracytoplasmic lipids with oil red O. Histochemistry 97: 493-497. https://doi.org/10.1007/BF00316069
  66. Murase T, Mizuno T, Omachi T, Onizawa K, Komine Y, Kondo H, et al. 2001. Dietary diacylglycerol suppresses high fat and high sucrose diet-induced body fat accumulation in C57BL/6J mice. J. Lipid Res. 42: 372-378.
  67. Han J, Hamilton JA, Kirkland JL, Corkey BE, Guo W. 2003. Medium-chain oil reduces fat mass and down-regulates expression of adipogenic genes in rats. Obes. Res. 11: 734-744. https://doi.org/10.1038/oby.2003.103
  68. Fried SK, Bunkin DA, Greenberg AS. 1998. Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid. J. Clin. Endocrinol. Metab. 83: 30-33.
  69. Gustafson B, Smith U. 2006. Cytokines promote Wnt signaling and inflammation and impair the normal differentiation and lipid accumulation in 3T3-L1 preadipocytes. J. Biol. Chem. 281: 9507-9516. https://doi.org/10.1074/jbc.M512077200
  70. Sopasakis VR, Sandqvist M, Gustafson B, Hammarstedt A, Schmelz M, Yang X, et al. 2004. High local concentrations and effects on differentiation implicate interleukin-6 as a paracrine regulator. Obes. Res. 12: 454-460. https://doi.org/10.1038/oby.2004.51
  71. Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, et al. 2003. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J. Clin. Invest. 112: 1821-1830. https://doi.org/10.1172/JCI200319451

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