Czech J. Anim. Sci., 2014, 59(9):391-398 | DOI: 10.17221/7650-CJAS
Effect of dietary eicosapentaenoic and docosahexaenoic acid on expression of rat liver genes controlling cholesterol homeostasis and on plasma cholesterol levelOriginal Paper
- 1 Department of Food Technology, Mendel University in Brno, Brno, Czech Republic
- 2 Department of Animal Morphology, Physiology and Genetics, Mendel University in Brno, Brno, Czech Republic
- 3 CEITEC MENDELU, Mendel University in Brno, Brno, Czech Republic
- 4 Department of Animal Nutrition and Forage Production, Mendel University in Brno, Brno, Czech Republic
A hypothesis that eicosapentaenoic acid + docosahexaenoic acid (EPA+DHA) lower plasma cholesterol via increased expression of the Insig-1 gene with ensuing decrease of expression of genes coding for 3-hydroxy-3-methyl-glutaryl-CoA reductase (Hmgcr) and low density lipoprotein receptor (Ldlr) was tested in rats fed a diet with 3% of fish oil (FO). Expression of the Insig-1 gene in the liver of the FO-fed rats was 730% (P < 0.05) of the control. However, contrary to the hypothesis, expression of the Hmgcr gene and Ldlr gene was 165% and 210% of the control (P > 0.05). Nevertheless, FO in the diet decreased (P < 0.05) plasma cholesterol of rats by 10% (from 1.19 to 1.07 mmol/l); it was therefore concluded that the cholesterol-lowering effect of EPA+DHA is at least partly based on mechanisms other than tested in the present experiment.
Keywords: PPARα; SREBP-2; Insig-1; cholesterol; PUFAn-3; rats
Published: September 30, 2014 Show citation
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References
- Arai T., Kim H.J., Chiba H., Matsumoto A. (2009a): Antiobesity effect of fish oil and fish oil-fenofibrate combination in female KK mice. Journal of Atherosclerosis and Thrombosis, 16, 674-683.
Go to original source...
Go to PubMed...
- Arai T., Kim H.J., Chiba H., Matsumoto A. (2009b): Interaction of fenofibrate and fish oil in relation to lipid metabolism in mice. Journal of Atherosclerosis and Thrombosis, 16, 283-291.
Go to original source...
Go to PubMed...
- Botolin D., Wang Y., Christian B., Jump D.B. (2006): Docosahexaenoic acid (22:6, n-3) regulates rat hepatocyte SREBP-1 nuclear abundance by Erk- and 26S proteasome-dependent pathways. Journal of Lipid Research, 47, 181-192.
Go to original source...
Go to PubMed...
- Campioli E., Rustichelli C., Avallone R. (2012): N-3 dietary supplementation and lipid metabolism: differences between vegetable- and fish-derived oils. Journal of Functional Foods, 4, 207-212.
Go to original source...
- Caputo M., Zirpoli H., Torino G., Tecce M. (2010): Selective regulation of UGT1A1 and SREBP-1c mRNA expression by docosahexaenoic, eicosapentaenoic, and arachidonic acids. Journal of Cellular Physiology, 226, 187-193.
Go to original source...
Go to PubMed...
- Densupsoontorn N., Worgall T.S., Seo T., Hamai H., Deckelbaum J. (2007): Fatty acid supplied as triglyceride regulates SRE-mediated gene expression as efficiently as free fatty acids. Lipids, 42, 885-891.
Go to original source...
Go to PubMed...
- Eslick G.D., Howe P.R.C., Smith C., Priest R., Bensoussan A. (2009): Benefits of fish oil supplementation in hyperlipidemia: a systematic review and meta-analysis. International Journal of Cardiology, 136, 4-16.
Go to original source...
Go to PubMed...
- Fernandez-Alvarez A., Alvarez M.S., Gonzalez R., Cucarella C., Muntane J., Casado M. (2011): Human SREBP1c expression in liver is directly regulated by peroxisome proliferator-activated receptor α (PPAR&alpha). Journal of Biological Chemistry, 286, 21466-21477.
Go to original source...
Go to PubMed...
- Ferramosca A., Conte L., Zara V. (2012): A krill oil supplemented diet reduces the activities of the mitochondrial tricarboxylate carrier and of the cytosolic lipogenic enzymes in rats. Journal of Animal Physiology and Animal Nutrition, 96, 295-306.
Go to original source...
Go to PubMed...
- Givens D.I., Gibbs R.A. (2008): Current intakes of EPA and DHA in European populations and the potential of animalderived foods to increase them. Proceedings of the Nutrition Society, 67, 273-280.
Go to original source...
Go to PubMed...
- Hirako S., Kim H.J., Arai T., Chiba H., Matsumoto A. (2010): Effect of concomitantly used fish oil and cholesterol on lipid metabolism. Journal of Nutritional Biochemistry, 21, 573-579.
Go to original source...
Go to PubMed...
- Jacobson T.A., Glickstein S.B., Rowe J.D., Soni P.N. (2012): Effects of eicosapentaenoic acid and docosahexaenoic acid on low-density lipoprotein cholesterol and other lipids: a review. Journal of Clinical Lipidology, 6, 5-18.
Go to original source...
Go to PubMed...
- Jump D.B. (2008): N-3 polyunsaturated fatty acid regulation of hepatic gene transcription. Current Opinion in Lipidology, 19, 242-247.
Go to original source...
Go to PubMed...
- Kamisako T., Tanaka Y., Ikeda T., Yamamoto K., Ogawa H. (2012): Dietary fish oil regulates gene expression of cholesterol and bile acid transporters in mice. Hepatology Research, 42, 321-326.
Go to original source...
Go to PubMed...
- Komprda T. (2012): Eicosapentaenoic and docosahexaenoic acids as inflammation-modulating and lipid homeostasis influencing nutraceuticals: a review. Journal of Functional Foods, 4, 25-38.
Go to original source...
- Komprda T., Zornikova G., Rozikova V., Borkovcova M., Przywarova A. (2013): The effect of dietary Salvia hispanica seed on the content of n-3 long-chain polyunsaturated fatty acids in tissues of selected animal species, including edible insects. Journal of Food Composition and Analysis, 32, 36-43.
Go to original source...
- Konig B., Koch A., Spielmann J., Hilgenfeld C., Stangl G.I., Eder K. (2007): Activation of PPARα lowers synthesis and concentration of cholesterol by reduction of nuclear SREBP-2. Biochemical Pharmacology, 73, 574-585.
Go to original source...
Go to PubMed...
- Lecker J., Matthan N.R., Billheimer J.T., Rader D.J., Lichtenstein A.H. (2011): Changes in cholesterol homeostasis modify the response of F1B hamsters to dietary very long chain n-3 and n-6 polyunsaturated fatty acids. Lipids in Health and Disease, 10:186.
Go to original source...
Go to PubMed...
- Lopez-Huertas E. (2009): Health effects of oleic acid and long chain omega-3 fatty acids (EPA and DHA) enriched milks. A review of intervention studies. Pharmacological Research, 61, 200-207.
Go to original source...
Go to PubMed...
- Lu J., Borthwick F., Hassanali Z., Wang Y., Mangat R., Ruth M., Shi D., Jaeschke A., Russel J.C., Field C.J., Proctor S.D., Vine D.F. (2011): Chronic dietary n-3 PUFA intervention improves dislipidaemia and subsequent cardiovascular complications in the JSR:LA-cp rat model of the metabolic syndrome. British Journal of Nutrition, 105, 1572-1582.
Go to original source...
Go to PubMed...
- Luci S., Konig B., Giemsa B., Huber S., Hause G., Kluge H., Stangl G.I., Eder K. (2007): Feeding of a deep-fried fat causes PPARα activation in the liver of pigs as a non-proliferating species. British Journal of Nutrition, 97, 872-882.
Go to original source...
Go to PubMed...
- Maki K.C., Van Elswyk M.E., McCarthy D., Seeley M.A., Veith P.E., Hess S.P., Ingram K.A., Halvorson J.J., Calaguas E.M., Davidson M.H. (2003): Lipid responses in mildly hypertriglyceridemic men and women to consumption of docosahexaenoic acid-enriched eggs. International Journal for Vitamin and Nutrition Research, 73, 357-368.
Go to original source...
Go to PubMed...
- Nakamura M.T., Cheon Y., Li Y., Nara T.Y. (2004): Mechanisms of regulation of gene expression by fatty acids. Lipids, 39, 1077-1083.
Go to original source...
Go to PubMed...
- Popovic T., Borozan S., Arsic A., Debeljak-Martacic J., Vucic V., de Luka S., Milovanovic I., Trbovic A., Glibetic M. (2011): Effects of n-3 supplementation on plasma and liver phospholipid fatty acids profile in aged Wistar rats. Croatica Chemica Acta, 84, 73-79.
Go to original source...
- Ramprasath V.R., Jones P.J.H., Buckley D.D., Woollett L.A., Heubi J.E. (2012): Decreased plasma cholesterol concentrations after PUFA-rich diets are not due to reduced cholesterol absorption/synthesis. Lipids, 47, 1063-1071.
Go to original source...
Go to PubMed...
- Sato R. (2010): Sterol metabolism and SREBP activation. Archives of Biochemistry and Biophysics, 501, 177-181.
Go to original source...
Go to PubMed...
- Sugiyama E., Ishikawa Y., Li Y., Kagai T., Nobayashi M., Tanaka N., Kamijo Y., Yokoyama S., Hara A., Aoyama T. (2008): Eicosapentaenoic acid lowers plasma and liver cholesterol levels in the presence of peroxisome proliferators-activated receptor alpha. Life Sciences, 83, 19-28.
Go to original source...
Go to PubMed...
- Takahashi Y. (2011): Soy protein and fish oil independently decrease serum lipid concentrations but interactively reduce hepatic enzymatic activity and gene expression involved in fatty acid synthesis in rats. Journal of Nutritional Science and Vitaminology, 57, 56-64.
Go to original source...
Go to PubMed...
- Xiao Y., Qianchun G., Jiqu X., Fenghong G., Qingde H., Zhihua Y., Jine Y. (2012): Effects of cold-pressed and vitamin Eenriched flaxseed oils on lipid profile and antioxidant status in high-fat fed rats. European Journal of Lipid Science and Technology, 114, 461-468.
Go to original source...
- Yamazaki R.K., Brito G.A.P., Coelho I., Pequitto D.C.T., Yamaguchi A.A., Borghetti G., Schiessel D.L., Kryczyk M., Machado J., Rocha R.E.R., Aikawa J., Iagher F., Naliwako K., Tanhoffer R.A., Nunes N.A., Fernandes L.C. (2011): Low fish oil intake improves insulin sensitivity, lipid profile and muscle metabolism on insulin resistant MSG-obese rats. Lipids in Health and Disease, 10, 66.
Go to original source...
Go to PubMed...
- Zhang Z., Wang H., Jiao R., Peng C., Wong Y.M., Yeung V.S.Y., Huang Y., Chen Z.-Y. (2009): Choosing hamsters but not rats as a model for studying plasma cholesterol-lowering activity of functional foods. Molecular Nutrition and Food Research, 53, 921-930.
Go to original source...
Go to PubMed...
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