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Effect of propionate on fatty acid and cholesterol synthesis and on acetate metabolism in isolated rat hepatocytes

Published online by Cambridge University Press:  09 March 2007

Christian Demigné
Affiliation:
Laboratoire des Maladies Métaboliques, INRA de Clermont Ferrand/Theix, F-63122 St-Genès Champanelle, France
Christine Morand
Affiliation:
Laboratoire des Maladies Métaboliques, INRA de Clermont Ferrand/Theix, F-63122 St-Genès Champanelle, France
Marie-Anne Levrat
Affiliation:
Laboratoire des Maladies Métaboliques, INRA de Clermont Ferrand/Theix, F-63122 St-Genès Champanelle, France
Catherine Besson
Affiliation:
Laboratoire des Maladies Métaboliques, INRA de Clermont Ferrand/Theix, F-63122 St-Genès Champanelle, France
Corinne Moundras
Affiliation:
Laboratoire des Maladies Métaboliques, INRA de Clermont Ferrand/Theix, F-63122 St-Genès Champanelle, France
Christian Rémésy
Affiliation:
Laboratoire des Maladies Métaboliques, INRA de Clermont Ferrand/Theix, F-63122 St-Genès Champanelle, France
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Abstract

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In the present study the actual role of propionic acid in the control of fatty acid and cholesterol synthesis was investigated in isolated liver cells from fed rats maintained in the presence of near-physiological concentrations of glucose, glutamine and acetate. Using 3H2O for lipid labelling, propionate appears as an effective inhibitor of fatty acid synthesis and to a lesser extent of cholesterol synthesis, even at the lowest concentration used (0·6 mmol/l). Butyrate is a potent activator of both synthetic pathways, and the activating effect was not counteracted by propionate. Using 1-[14C]acetate, it was observed that propionate at a moderate concentration, or 1 mmol oleate/l, are both very effective inhibitors of 14C incorporation into fatty acid and cholesterol. This incorporation was drastically inhibited when propionate and oleate were present together in the incubation medium. The net utilization of acetate by rat hepatocytes was impaired by propionate, in contrast to oleate. 1-[14C]butyrate was utilized at a high rate for fatty acid synthesis, but to a lesser extent for cholesterol synthesis; both processes were unaffected by propionate. Intracellular citrate concentration was not markedly depressed by propionate, whereas it was strongly elevated by butyrate. In conclusion, propionate may represent an effective inhibitor of lipid synthesis when acetate is a major source of acetyl-CoA, a situation which is encountered with diets rich in readily-fermentable fibres. The present findings also suggest that propionate may be effective at concentrations close to values measured in vivo in the portal vein.

Type
Effects of propionate in isolated hepatocytes
Copyright
Copyright © The Nutrition Society 1995

References

REFERENCES

Arjmandi, B. H., Craig, J., Nathani, S. & Reeves, R. D. (1992) Soluble dietary fiber and cholesterol influence on in vivo hepatic and intestinal cholesterol synthesis in rats. Journal of Nutrition 122, 15591565.CrossRefGoogle ScholarPubMed
Beaulieu, K. E. & McBurney, M. I. (1992) Changes in pig serum lipids, nutrient digestibility and sterol excretion during cecal infusion of propionate. Journal of Nutrition 122, 241245.CrossRefGoogle ScholarPubMed
Bergman, E. N. (1990) Energy contribution of volatile fatty acids in the gastrointestinal tract in various species. Physiological Reviews 70, 567590.CrossRefGoogle ScholarPubMed
Bergstrom, J. D., Wong, G. A., Edwards, P. A. & Edmond, J. (1984) The regulation of acetoacetyl-CoA synthetase activity by modulators of cholesterol synthesis in vivo and the utilization of acetoacetate for cholesterogenesis. Journal of Biological Chemistry 259, 1454814553.CrossRefGoogle ScholarPubMed
Berry, M. N., Edwards, A. M. & Barrit, G. J. (1991) Isolated hepatocytes, preparation, properties and applications. In Laboratory Techniques in Biochemistry and Molecular Biology, Vol. 21, pp. 1458 [Burdon, R.H. and Van Kuippenberg, P. H., editors]. Amsterdam: Elsevier.Google Scholar
Buckley, B. M. & Williamson, D. H. (1977) Origin of blood acetate in the rat. Biochemical Journal 166, 539545.CrossRefGoogle ScholarPubMed
Cameron-Smith, D., Collier, G. R. & O'Dea, K. (1994) Effect of propionate on in vivo carbohydrate metabolism in streptozotocin-induced diabetic rats. Metabolism 43, 728734.CrossRefGoogle Scholar
Chen, W. J. L., Anderson, J. W. & Jennings, D. (1984) Propionate may mediate the hypocholesterolemic effects of certain soluble fibers in cholesterol-fed rats. Proceedings of the Society for Experimental Biology and Medicine 175, 215218.CrossRefGoogle ScholarPubMed
Corkey, B. E., Martin-Roquero, A., Walajtys-Rode, E., Williams, R. J. & Williamson, J. R. (1982) Regulation of branched-chain α-ketoacid pathway in the liver. Journal of Biological Chemistry 257, 96689676.CrossRefGoogle Scholar
Crabtree, B., Gordon, M.-J. & Christie, S. L. (1990) Measurement of the rates of acetyl-CoA hydrolysis and synthesis from acetate in rat hepatocytes and the role of these fluxes in substrate cycling. Biochemical Journal 270, 219225.CrossRefGoogle ScholarPubMed
Crabtree, B., Souter, M.-J. & Anderson, S. E. (1989) Evidence that the production of acetate in rat hepatocytes is a predominantly cytoplasmic process. Biochemical Journal 257, 673678.CrossRefGoogle ScholarPubMed
Demigné, C. & Rémésy, C. (1994) Short chain fatty acids and hepatic metabolism. In Short Chain Fatty Acids, pp. 272282 [Binder, H.J., Cummings, J. and Soergel, K. H., editors]. Lancaster: Kluwer.Google Scholar
Demigné, C., Yacoub, C, Rémésy, C. & Fafournoux, P. (1986) Propionate and butyrate metabolism in rat or sheep hepatocytes. Biochimica et Biophysica Acta 874, 535542.CrossRefGoogle Scholar
Favier, M.-L., Rékmésy, C., Moundras, C. & Demigné, C. (1995) Effectiveness of low levels of cyclodextrin for lowering plasma lipids in rats. Metabolism 44, 200207.CrossRefGoogle Scholar
Gibbons, G. F., Attwell Thomas, C. P. & Pullinger, C. R. (1986) The metabolic route by which oleate is converted into cholesterol in rat hepatocytes. Biochemical Journal 235, 1924.CrossRefGoogle ScholarPubMed
Gordon, M. J. & Crabtree, B. (1992) The effects of propionate and butyrate on acetate metabolism in rat hepatocytes. International Journal of Biochemistry 24, 10291031.CrossRefGoogle ScholarPubMed
Illman, R. J., Topping, D. L., McIntosh, G. H., Trimble, R. P., Storer, G. B., Taylor, M. N. & Cheng, B.-Q. (1988) Hypocholesterolaemic effects of dietary propionate studies in whole animals and in perfused rat liver. Annals of Nutrition and Metabolism 32, 97107.CrossRefGoogle ScholarPubMed
Levrat, M.-A., Favier, M.-L., Moundras, C, Rémésy, C., Demigné, C. & Morand, C. (1994) Role of dietary propionic acid and bile acid excretion in the hypocholesterolemic effects of oligosaccharides in rats. Journal of Nutrition 124, 531538.CrossRefGoogle ScholarPubMed
Levrat, M.-A., Rémésy, C. & Demigné, C. (1991) High propionic acid fermentations and mineral accumulation in the cecum of rats adapted to different levels of inulin. Journal of Nutrition 121, 17301737.Google ScholarPubMed
Lowe, D. M. & Tubbs, P. K. (1985) Succinylation and inactivation of 3-hydroxy-3-methylglutaryl CoA synthase by succinyl CoA and its possible relevance in the control of ketogenesis. Biochemical Journal 232, 3742·1.CrossRefGoogle ScholarPubMed
Mellanby, J. & Williamson, D. H. (1974) Acetoacetate. In Methods of Enzymatic Analysis, Vol. 4, pp. 18401843 [Bergmeyer, H. U., editor]. New York: Academic Press.CrossRefGoogle Scholar
Möllering, H. (1989) Citrate determination. In Methods of Enzymatic Analysis, Vol. 7, pp. 212, [Bergmeyer, H. U. editor]. Weinheim: VCH.Google Scholar
Morand, C., Besson, C., Demigné, C. & Rémésy, C. (1994 a) Importance of the modulation of glycolysis in the control of lactate metabolism by fatty acids in the isolated hepatocytes from fed rats. Archives of Biochemistry and Biophysics 309, 254260.CrossRefGoogle ScholarPubMed
Morand, C., Levat, M.-A., Besson, C., Demigné, C. & Rémésy, C. (1994 b) Effects of a diet rich in resistant starch on hepatic lipid metabolism in the rat. Journal of Nutritional Biochemistry 5, 138144.CrossRefGoogle Scholar
Moundras, C., Behr, S. R., Demigné, C., Mazur, A. & Rémésy, C. (1994) Fermentable carbohydrates which enhance bile acid excretion exert a cholesterol lowering effect in rats together with depressed apolipoprotein E-rich HDL. Journal of Nutrition 124, 21792188.CrossRefGoogle Scholar
Nishina, P. M. & Freedland, P. M. (1990) Effects of propionate on lipid biosynthesis in isolated rat hepatocytes. Journal of Nutrition 120, 668673.CrossRefGoogle ScholarPubMed
Rémésy, C. & Demigné, C. (1974) Determination of volatile fatty acids in plasma after ethanolic extraction. Biochemical Journal 141, 8591.CrossRefGoogle ScholarPubMed
Rémésy, C., Demigné, C. & Morand, C. (1992) Metabolism and utilisation of short chain fatty acids produced by colonic fermentations. In Dietary Fibre - A Component of Food, pp. 137165 [Schweizer, T.F. and Edwards, C. A., editors]. London: Springer.CrossRefGoogle Scholar
Roitelman, J. & Shechter, I. (1989) Studies on the catalytic site of rat liver HMG-CoA reductase: interaction with CoA-thioesters and inactivation with iodoacetamide. Journal of Lipid Research 30, 97107.CrossRefGoogle ScholarPubMed
Sendl, A, Schliack, M., Löser, R., Stanislaus, F. & Wagner, H. (1992) Inhibition of cholesterol synthesis in vitro by extracts and isolated compounds prepared from garlic and wild garlic. Atherosclerosis 94, 7595.CrossRefGoogle ScholarPubMed
Soboll, S., Elbers, R., Scholz, R. & Heldt, H.-W. (1980) Subcellular distribution of di- and tricarboxylates and pH gradients in perfused rat liver. Hoppe-Seyler's Zeitschrift für Physiologische Chemie 361, 6976.CrossRefGoogle ScholarPubMed
Stark, A. H. & Madar, Z. (1993) In vitro production of short-chain fatty acids by bacterial fermentation of dietary fibre compared with effects of those fibers on hepatic sterol synthesis in rats. Journal of Nutrition 123, 21662173.Google ScholarPubMed
Truswell, A. S. & Beynen, A. C. (1992) Dietary fibre and plasma lipids: potential for prevention and treatment of hyperlipidaemias. In Dietary Fibre - A Component of Food, pp. 295332 [Schweizer, T.F. and Edwards, C. A., editors]. London: Springer.CrossRefGoogle Scholar
Venter, C. S., Vorster, H. H. & Van der Nest, D. G. (1990) Comparison between physiological effects of konjac-glucomannan and propionate in baboons fed ‘western’ diets. Journal of Nutrition 120, 10461053.CrossRefGoogle ScholarPubMed
Williamson, D. H. & Mellanby, J. (1974) D-3-Hydroxybutyrate. In Methods of Enzymatic Analysis, Vol. 4, pp. 18361839 [Bergmeyer, H. U., editor]. New York: Academic Press.CrossRefGoogle Scholar
Wright, R. S., Anderson, J. W. & Bridges, S. R. (1990) Propionate inhibits hepatocyte lipid synthesis. Proceedings of the Society for Experimenial Biology and Medicine 195, 2629.CrossRefGoogle ScholarPubMed
Zhang, Y., Argarwal, K. C., Beylot, M., Soloviev, M., David, F., Reider, M. W., Anderson, V. E., Tserng, K.-Y. & Brunengraber, H. (1994) Nonhomogeneous labelling of liver extra-mitochondria1 acetyl-CoA. Journal of Biological Chemistry 269, 1102511029.CrossRefGoogle ScholarPubMed