Dietary Combination of Fish Oil and Hemoglobin Hydrolysates Alters Serum and Liver Lipid Contents in Rat

Kenji Fukunaga, Noriko Yukawa, Ryota Hosomi, Toshimasa Nishiyama, Munehiro Yoshida

Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita, Japan.
Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita, Japan;.
Department of Public Health, Kansai Medical University, Hirakata, Japan..
Division of Food Science and Nutrition, Tottori College, Kurayoshi, Japan.

DOI: 10.4236/fns.2013.49A1014                

Abstract

Fish oil has been shown to have anti-inflammatory and anti-cancer effects, and to reduce serum triacylglycerol (TAG) levels by stimulating lipid oxidation and inhibiting lipogenesis in the liver. A small number of studies have demonstrated the synergistic effect of fish oil and other bioactive components. This study examined the effect of fish oil in combination with porcine hemoglobin (Hb) hydrolysates on serum and liver lipid contents in rats. Male Wistar rats were divided into four groups; one group was fed a casein and soybean oil-based semi-purified basal diet and other three groups were fed the basal diet supplemented with 2% fish oil, 0.175% Hb hydrolysates, and 2% fish oil plus 0.175% Hb hydrolysates, respectively, for 4 weeks. The fish oil diet decreased serum and liver TAG contents but did not change serum and liver cholesterol levels. The dietary combination of fish oil and Hb hydrolysates decreased serum and liver TAG and cholesterol contents owing to the additive effect of both compounds, and this diet reduced the serum non-high-density lipoprotein cholesterol content as a result of a synergistic effect. This hypolipidemic effect was in part caused by enhanced excretion of fecal fatty acids, neutral steroids, and acidic steroids. The results of this study suggest that the combined intake of fish oil and Hb hydrolysates may play beneficial roles in the prevention of cardiovascular disease as compared with fish oil alone.

Keywords

Fish Oil; n-3 Polyunsaturated Fatty Acid; Hemoglobin Hydrolysates; Lipid Metabolism

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	K. He, Y. Song, M. L. Daviglus, K. Liu, L. Van Horn, A. R. Dyer and P. Greenland, “Accumulated Evidence on Fish Consumption and Coronary Heart Disease Mortality: A Meta-Analysis of Cohort Studies,” Circulation, Vol. 109, No. 22, 2004, pp. 2705-2711. doi:10.1161/01.CIR.0000132503.19410.6B
[2]	J. Dyerberg, H. O. Bang, E. Stoffersen, S. Moncada and J. R. Vane, “Eicosapentaenoic Acid and Prevention of Thrombosis and Atherosclerosis?” Lancet, Vol. 2, No. 8081, 1978, pp. 117-119. doi:10.1016/S0140-6736(78)91505-2
[3]	F. B. Hu, L. Bronner, W. C. Willett, M. J. Stampfer, K. M. Rexrode, C. M. Albert, D. Hunter and J. E. Manson, “Fish and Omega-3 Fatty Acid Intake and Risk of Coronary Heart Disease in Women,” The Journal of the American Medical Association, Vol. 287, No. 14, 2002, pp. 1815-1821. doi:10.1001/jama.287.14.1815
[4]	R. K. Berge, L. Madsen, H. Vaagenes, K. J. Tronstad, M. Gottlicher and A. C. Rustan, “In Contrast with Docosahexaenoic Acid, Eicosapentaenoic Acid and Hypolipidaemic Derivatives Decrease Hepatic Synthesis and Secretion of Triacylglycerol by Decreased Diacylglycerol Acyltransferase Activity and Stimulation of Fatty Acid Oxidation,” Biochemical Journal, Vol. 343, No. 1, 1999, pp. 191-197.
[5]	Y. Adkins and D. S. Kelley, “Mechanisms Underlying the Cardioprotective Effects of Omega-3 Polyunsaturated Fatty Acids,” The Journal of Nutritional Biochemistry, Vol. 21, No. 9, 2010, pp. 781-792. doi:10.1016/j.jnutbio.2009.12.004
[6]	E. M. Balk, A. H. Lichtenstein, M. Chung, B. Kupelnick, P. Chew and J. Lau, “Effects of Omega-3 Fatty Acids on Serum Markers of Cardiovascular Disease Risk: A Systematic Review,” Atherosclerosis, Vol. 189, No. 1, 2006, pp. 19-30. doi:10.1016/j.atherosclerosis.2006.02.012
[7]	Z. S. Saify, F. Ahmed, S. Akhtar, S. Siddiqui, M. Arif, S. A. Hussain and N. Mushtaq, “Biochemical Studies on Marine Fish Oil Part-I: Effects of Fish Oil and Lipid Lowering Drugs on HDL/LDL Cholesterol Levels,” Pakistan Journal of Pharmaceutical Sciences, Vol. 16, No. 2, 2003, pp. 1-8.
[8]	V. Nambi and C. M. Ballantyne, “Combination Therapy with Statins and Omega-3 Fatty Acids,” American Journal of Cardiology, Vol. 98, No. 4A, 2006, pp. 34i-38i. doi:10.1016/j.amjcard.2005.12.025
[9]	T. Ide, D. D. Hong, P. Ranasinghe, Y. Takahashi, M. Kushiro and M. Sugano, “Interaction of Dietary Fat Types and Sesamin on Hepatic Fatty Acid Oxidation in Rats,” Biochimica et Biophysica Acta, Vol. 1682, No. 1-3, 2004, pp. 80-91. doi:10.1016/j.bbalip.2004.02.001
[10]	T. Yanagita, Y. M. Wang, K. Nagao, Y. Ujino and N. Inoue, “Conjugated Linoleic Acid-Induced Fatty Liver Can Be Attenuated by Combination with Docosahexaenoic Acid in C57BL/6N Mice,” Journal of Agricultural and Food Chemistry, Vol. 53, No. 24, 2005, pp. 96299633. doi:10.1021/jf052203i
[11]	H. Maeda, M. Hosokawa, T. Sashima and K. Miyashita, “Dietary Combination of Fucoxanthin and Fish Oil Attenuates the Weight Gain of White Adipose Tissue and Decreases Blood Glucose in Obese/Diabetic KK-Ay Mice,” Journal of Agricultural and Food Chemistry, Vol. 55, No. 19, 2007, pp. 7701-7706. doi:10.1021/jf071569n
[12]	N. Mikami, M. Hosokawa and K. Miyashita, “Dietary Combination of Fish Oil and Taurine Decreases Fat Accumulation and Ameliorates Blood Glucose Levels in Type 2 Diabetic/Obese KK-A(y) Mice,” Journal of Food Science, Vol. 77, No. 6, 2012, pp. H114-H120. doi:10.1111/j.1750-3841.2012.02687.x
[13]	R. Hosomi, K. Fukunaga, H. Arai, S. Kanda, T. Nishiyama and M. Yoshida, “Effect of Combination of Dietary Fish Protein and Fish Oil on Lipid Metabolism in Rats,” Journal of Food Science and Technology, Vol. 50, No. 2, 2013, pp. 266-274. doi:10.1007/s13197-011-0343-y
[14]	C. Brandsch, A. Shukla, F. Hirche, G. I. Stangl and K. Eder, “Effect of Proteins from Beef, Pork, and Turkey Meat on Plasma and Liver Lipids of Rats Compared with Casein and Soy Protein,” Nutrition, Vol. 22, No. 11-12, 2006, pp. 1162-1170. doi:10.1016/j.nut.2006.06.009
[15]	R. Hosomi, K. Fukunaga, H. Arai, S. Kanda, T. Nishiyama and M. Yoshida, “Fish Protein Decreases Serum Cholesterol in Rats by Inhibition of Cholesterol and Bile Acid Absorption,” Journal of Food Science, Vol. 76, No. 4, 2011, pp. H116-H121. doi:10.1111/j.1750-3841.2011.02130.x
[16]	K. Kagawa, H. Matsutaka, C. Fukuhama, Y. Watanabe and H. Fujino, “Globin Digest, Acidic Protease Hydrolysate, Inhibits Dietary Hypertriglyceridemia and ValVal-Tyr-Pro, One of Its Constituents, Possesses Most Superior Effect,” Life Sciences, Vol. 58, No. 20, 1996, pp. 1745-1755. doi:10.1016/0024-3205(96)00156-7
[17]	A. F. Prevot and F. X. Mordret, “Utilisation des Colonnes Capillaries de Verre Pour l’Analyse des Corps Gras par Chromotographie en Phase Gazeuse,” Revue Francaise des Corps Gras, Vol. 23, 1976, pp. 409-423.
[18]	J. A. White, R. J. Hart and J. C. Fry, “An Evaluation of the Waters Pico-Tag System for the Amino-Acid Analysis of Food Materials,” The Journal of Automatic Chemistry, Vol. 8, No. 4, 1986, pp. 170-177. doi:10.1155/S1463924686000330
[19]	P. G. Reeves, F. H. Nielsen and G. C. Fahey, “AIN-93 Purified Diets for Laboratory Rodents: Final Report of the American Institute of Nutrition Ad Hoc Writing Committee on the Reformulation of the AIN-76A Rodent Diet,” The Journal of Nutrition, Vol. 123, No. 11, 1993, pp. 1939-1951.
[20]	E. Bligh, and W. J. Dyer, “A Rapid Method of Total Lipid Extraction and Purification,” Canadian Journal of Biochemistry and Physiology, Vol. 37, No. 8, 1959, pp. 911-917.
[21]	G. Rouser, S. Fkeischer and A. Yamamoto, “Two Dimensional then Layer Chromatographic Separation of Polar Lipids and Determination of Phospholipids by Phosphorus Analysis of Spots,” Lipids, Vol. 5, No. 5, 1970, pp. 494-496.
[22]	J. H. Van de Kamer, H. Ten Bokkel Huinink and H. A. Weyers, “Rapid Method for the Determination of Fat in Feces,” The Journal of Biological Chemistry, Vol. 177, No. 1, 1949, pp. 347-355.
[23]	A. Bruusgaard, H. Sorensen, C. C. Gilhuus-Moe and B. A. Skalhegg, “Bile Acid Determination with Different Preparations of 3Alpha-Hydroxysteroid Dehydrogenase,” Clinica Chimica Acta, Vol. 77, No. 3, 1977, pp. 387-389. doi:10.1016/0009-8981(77)90245-5
[24]	H. Wergedahl, O. A. Gudbrandsen, T. H. Rost and R. K. Berge, “Combination of Fish Oil and Fish Protein Hydrolysate Reduces the Plasma Cholesterol Level with a Concurrent Increase in Hepatic Cholesterol Level in High-Fat-Fed Wistar Rats,” Nutrition, Vol. 25, No. 1, 2009, pp. 98-104. doi:10.1016/j.nut.2008.07.005
[25]	National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III), “Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report,” Circulation, Vol. 106, No. 25, 2002, pp. 3143-3421.
[26]	J.S. Rana, S. M. Boekholdt, J. J. Kastelein and P. K. Shah, “The Role of Non-HDL Cholesterol in Risk Stratification for Coronary Artery Disease,” Current Atherosclerosis Reports, Vol. 14, No. 2, 2012, pp. 130-134. doi:10.1007/s11883-011-0224-x
[27]	S. M. Boekholdt, B. J. Arsenault, S. Mora, T. R. Pedersen, J. C. LaRosa, P. J. Nestel, R. J. Simes, P. Durrington, G. A. Hitman, K. M. Welch, D. A. DeMicco, A. H. Zwinderman, M. B. Clearfield, J. R. Downs, A. M. Tonkin, H. M. Colhoun, A. M. Gotto Jr., P. M. Ridker and J. J. Kastelein, “Association of LDL Cholesterol, Non-HDL Cholesterol, and Apolipoprotein B Levels with Risk of Cardiovascular Events among Patients Treated with Statins: A Meta-Analysis,” The Journal of the American Medical Association, Vol. 307, No. 12, 2012, pp. 13021309. doi:10.1001/jama.2012.366
[28]	A. D. Sniderman, K. Williams, J. H. Contois, H. M. Monroe, M. J. McQueen, J. de Graaf and C. D. Furberg, “A Meta-Analysis of Low-Density Lipoprotein Cholesterol, Non-High-Density Lipoprotein Cholesterol, and Apolipoprotein B as Markers of Cardiovascular Risk,” Circulation: Cardiovascular Quality and Outcomes, Vol. 4, No. 3, 2011, pp. 337-345. doi:10.1161/CIRCOUTCOMES.110.959247
[29]	Y. Nagata, N. Ishiwaki and M. Sugano, “Studies on the Mechanism of Antihypercholesterolemic Action of Soy Protein and Soy Protein-Type Amino Acid Mixtures in Relation to the Casein Counterparts in Rats,” The Journal of Nutrition, Vol. 112, No. 8, 1982, pp. 1614-1625.
[30]	H. Oudart, R. Groscolas, C. Calgari, M. Nibbelink, C. Leray, Y. Le Maho and A Malan, “Brown Fat Thermogenesis in Rats Fed High-Fat Diets Enriched with n-3 Polyunsaturated Fatty Acids,” International Journal of Obesity, Vol. 21, No. 11, 1997, pp. 955-962.
[31]	B. Ren, A. P. Thelen, J. M. Peters, F. J. Gonzalez and D. B. Jump, “Polyunsaturated Fatty Acid Suppression of Hepatic Fatty Acid Synthase and S14 Gene Expression Does Not Require Peroxisome Proliferator-Activated Receptor Alpha,” The Journal of Biological Chemistry, Vol. 272, No. 43, 1997, pp. 26827-26832. doi:10.1074/jbc.272.43.26827
[32]	Y. Nagata, K. Tanaka and M. Sugano, “Serum and Liver Cholesterol Levels of Rats and Mice Fed Soy-Bean Protein or Casein,” Journal of Nutritional Science and Vitaminology, Vol. 27, No. 6, 1981, pp. 583-593. doi:10.3177/jnsv.27.583
[33]	B. Goodwin, S. A. Jones, R. R. Price, M. A. Watson, D. D. McKee, L. B. Moore, C. Galardi, J. G. Wilson, M. C. Lewis, M. E. Roth, P. R. Maloney, T. M. Willson and S. A. Kliewer, “A Regulatory Cascade of the Nuclear Receptors FXR, SHP-1, and LRH-1 Represses Bile Acid Biosynthesis,” Molecular Cell, Vol. 6, No. 3, 2000, pp. 517-526. doi:10.1016/S1097-2765(00)00051-4.