Nutr Res Pract.  2010 Dec;4(6):462-469.

Effect of dietary protamine on lipid metabolism in rats

Affiliations
  • 1Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita, Osaka, 564-8680, Japan. fukunagk@kansai-u.ac.jp
  • 2Department of Biotechnology and Environmental Chemistry, Kitami Institute of Technology, Kitami, Hokkaido 090-8507, Japan.
  • 3Department of Public Health, Kansai Medical University, Moriguchi, Osaka, 570-8506, Japan.

Abstract

Protamine has been widely used as a pharmaceutical product and natural food preservative. However, few studies have been conducted to assess the beneficial function of dietary protamine. This study examined the effects of dietary salmon protamine on serum and liver lipid levels and the expression levels of genes encoding proteins involved in lipid homeostasis in the liver of rats. Groups of male Wistar rats were fed AIN93G diet containing 2% or 5% protamine. After 4 weeks of feeding these diets, markedly decreased serum and liver cholesterol (CHOL) and triacylglycerol levels were noted. Increased activity of liver carnitine palmitoyltransferase-2 and acyl-CoA oxidase, which are key enzymes of fatty acid beta-oxidation in the mitochondria and peroxisomes, was found in rats fed on protamine. Furthermore, rats fed protamine showed enhanced fecal excretion of CHOL and bile acid and increased liver mRNA expression levels of ATP-binding cassette (ABC) G5 and ABCG8, which form heterodimers and play a major role in the secretion of CHOL into bile. The decrease in triacylglycerol levels in protamine-fed rats was due to the enhancement of liver beta-oxidation. Furthermore, rats fed protamine exhibited decreased CHOL levels through the suppression of CHOL and bile acid absorption and the enhancement of CHOL secretion into bile. These results suggest that dietary protamine has beneficial effects that may aid in the prevention of lifestyle-related diseases such as hyperlipidemia and atherosclerosis.

Keyword

Protamine; lipid metabolism; beta-oxidation; cholesterol; triacylglycerol

MeSH Terms

Absorption
Acyl-CoA Oxidase
Animals
Atherosclerosis
Bile
Carnitine
Cholesterol
Diet
Homeostasis
Humans
Hyperlipidemias
Lipid Metabolism
Liver
Male
Mitochondria
Peroxisomes
Proteins
Rats
Rats, Wistar
RNA, Messenger
Salmon
Triglycerides
Acyl-CoA Oxidase
Carnitine
Cholesterol
Proteins
RNA, Messenger
Triglycerides

Figure

  • Fig. 1 The expression levels of enzymes related to cholesterol metabolism in the liver of Wistar rat fed diets of the control (□), ProtL (▒), and ProtH (■) diets. Data are means ± SD (n = 7). Relative values are presented as the ratio of each mRNA to GAPDH mRNA. Values not sharing a common letter are significantly different at P < 0.05. Data were analyzed by Tukey-Kramer test. The expression levels of enzymes related to cholesterol metabolism were analyzed by the real-time quantitative polymerase chain reaction method. CYP7A1, cholesterol 7α-hydroxylase; HMGR, 3-hydroxy-3methylglutaryl-CoA reductase; LDL-R, low density lipoprotein receptor; SR-B1, scavenger receptor class B type 1; ABCA1, ATP-binding cassette A1; ABCG5, ATP-binding cassette G5; ABCG8, ATP-binding cassette G8; GAPDH, glyceraldehyde-3-phosphate dehydrogenase


Reference

1. Formiguera X, Cantón A. Obesity: epidemiology and clinical aspects. Best Pract Res Clin Gastroenterol. 2004. 18:1125–1146.
Article
2. Dyerberg J, Bang HO, Hjorne N. Fatty acid composition of the plasma lipids in Greenland Eskimos. Am J Clin Nutr. 1975. 28:958–966.
Article
3. Iso H, Kobayashi M, Ishihara J, Sasaki S, Okada K, Kita Y, Kokubo Y, Tsugane S. JPHC Study Group. Intake of fish and n3 fatty acids and risk of coronary heart disease among Japanese: the Japan Public Health Center-Based (JPHC) Study Cohort I. Circulation. 2006. 113:195–202.
Article
4. He K, Song Y, Daviglus ML, Liu K, Van Horn L, Dyer AR, Greenland P. Accumulated evidence on fish consumption and coronary heart disease mortality: a meta-analysis of cohort studies. Circulation. 2004. 109:2705–2711.
Article
5. Simopoulos AP. Omega-3 fatty acids in inflammation and autoimmune diseases. J Am Coll Nutr. 2002. 21:495–505.
Article
6. Simopoulos AP. Omega-3 fatty acids in health and disease and in growth and development. Am J Clin Nutr. 1991. 54:438–463.
Article
7. Dahl L, Bjørkkjaer T, Graff IE, Malde MK, Klementsen B. Fish--more than just omega 3. Tidsskr Nor Laegeforen. 2006. 126:309–311.
8. Zhang X, Beynen AC. Influence of dietary fish proteins on plasma and liver cholesterol concentrations in rats. Br J Nutr. 1993. 69:767–777.
Article
9. Murata M, Sano Y, Bannai S, Ishihara K, Matsushima R, Uchida M. Fish protein stimulated the fibrinolysis in rats. Ann Nutr Metab. 2004. 48:348–356.
Article
10. Hosomi R, Fukunaga K, Arai H, Nishiyama T, Yoshida M. Effects of dietary fish protein on serum and liver lipid concentrations in rats and the expression of hepatic genes involved in lipid metabolism. J Agric Food Chem. 2009. 57:9256–9262.
Article
11. Jaques LB. Protamine--antagonist to heparin. Can Med Assoc J. 1973. 108:1291–1293. 1295–1297.
12. Aspedon A, Groisman EA. The antibacterial action of protamine: evidence for disruption of cytoplasmic membrane energization in Salmonella typhimurium. Microbiology. 1996. 142:3389–3397.
Article
13. Tsujita T, Matsuura Y, Okuda H. Studies on the inhibition of pancreatic and carboxylester lipases by protamine. J Lipid Res. 1996. 37:1481–1487.
Article
14. Duarte-Vázquez MA, García-Padilla S, Olvera-Ochoa L, González-Romero KE, Acosta-Iñiguez J, De la Cruz-Cordero R, Rosado JL. Effect of protamine in obesity induced by high-fat diets in rats. Int J Obes (Lond). 2009. 33:687–692.
Article
15. Reeves PG, Nielsen FH, Fahey GC Jr. 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. J Nutr. 1993. 123:1939–1951.
Article
16. Horton JD, Bashmakov Y, Shimomura I, Shimano H. Regulation of sterol regulatory element binding proteins in livers of fasted and refed mice. Proc Natl Acad Sci U S A. 1998. 95:5987–5992.
Article
17. Hatch FT. Practical methods for plasma lipoprotein analysis. Adv Lipid Res. 1968. 6:1–68.
18. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951. 193:265–275.
Article
19. Ide T, Watanabe M, Sugano M, Yamamoto I. Activities of liver mitochondrial and peroxisomal fatty acid oxidation enzymes in rats fed trans fat. Lipids. 1987. 22:6–10.
Article
20. Markwell MA, McGroarty EJ, Bieber LL, Tolbert NE. The subcellular distribution of carnitine acyltransferases in mammalian liver and kidney. A new peroxisomal enzyme. J Biol Chem. 1973. 248:3426–3432.
Article
21. Kelley DS, Nelson GJ, Hunt JE. Effect of prior nutritional status on the activity of lipogenic enzymes in primary monolayer cultures of rat hepatocytes. Biochem J. 1986. 235:87–90.
Article
22. Tanabe T, Nakanishi S, Hashimoto T, Ogiwara H, Nikawa J, Numa S. Acetyl-CoA carboxylase from rat liver : EC 6.4.1.2 Acetyl-CoA: carbon-dioxide ligase (ADP-forming). Lipids Part C. Methods Enzymol. 1981. New York: Academic Press;5–16.
23. Kelley DS, Kletzien RF. Ethanol modulation of the hormonal and nutritional regulation of glucose 6-phosphate dehydrogenase activity in primary cultures of rat hepatocytes. Biochem J. 1984. 217:543–549.
Article
24. Ichihara K, Norikura S, Fujii S. Microsomal phosphatidate phosphatase in maturing safflower seeds. Plant Physiol. 1989. 90:413–419.
Article
25. van de Kamer JH, ten Bokkel Huinink H, Weyers HA. Rapid method for the determination of fat in feces. J Biol Chem. 1949. 177:347–355.
Article
26. Moriyama T, Kishimoto K, Ngai K, Urade R, Ogawa T, Uthumi S, Maruyama N, Maebuchi M. Soybean beta-conglycinin diet suppresses serum triglyceride levels in normal and genetically obese mice by induction of beta-oxidation, downregulation of fatty acid synthase, and inhibition of triglyceride absorption. Biosci Biotechnol Biochem. 2004. 68:352–359.
Article
27. Higaki N, Sato K, Suda H, Suzuka T, Komori T, Saeki T, Nakamura Y, Ohtsuki K, Iwami K, Kanamoto R. Evidence for the existence of a soybean resistant protein that captures bile acid and stimulates its fecal excretion. Biosci Biotechnol Biochem. 2006. 70:2844–2852.
Article
28. Nagata Y, Tanaka K, Sugano M. Serum and liver cholesterol levels of rats and mice fed soy-bean protein or casein. J Nutr Sci Vitaminol (Tokyo). 1981. 27:583–593.
Article
29. Tsujita T, Sumiyoshi M, Takaku T, Momsen WE, Lowe ME, Brockman HL. Inhibition of lipases by epsilon-polylysine. J Lipid Res. 2003. 44:2278–2286.
30. Fielding BA, Frayn KN. Lipoprotein lipase and the disposition of dietary fatty acids. Br J Nutr. 1998. 80:495–502.
Article
31. Iwami K, Kitagawa M, Ibuki F. Effect of dietary proteins and/or their digestive products on intestinal taurocholate absorption. J Nutr Sci Vitaminol (Tokyo). 1990. 36:S141–S146.
Article
32. Kayashita J, Shimaoka I, Nakajoh M, Yamazaki M, Kato N. Consumption of buckwheat protein lowers plasma cholesterol and raises fecal neutral sterols in cholesterol-Fed rats because of its low digestibility. J Nutr. 1997. 127:1395–1400.
Article
33. Tamehiro N, Shigemoto-Mogami Y, Kakeya T, Okuhira K, Suzuki K, Sato R, Nagao T, Nishimaki-Mogami T. Sterol regulatory element-binding protein-2- and liver X receptor-driven dual promoter regulation of hepatic ABC transporter A1 gene expression: mechanism underlying the unique response to cellular cholesterol status. J Biol Chem. 2007. 282:21090–21099.
Article
34. García-Villafranca J, Guillén A, Castro J. Involvement of nitric oxide/cyclic GMP signaling pathway in the regulation of fatty acid metabolism in rat hepatocytes. Biochem Pharmacol. 2003. 65:807–812.
Article
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