Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1993 Oct 1;295(Pt 1):217–220. doi: 10.1042/bj2950217

Induction of peroxisomal beta-oxidation by a microbial catabolite of cholic acid in rat liver and cultured rat hepatocytes.

T Nishimaki-Mogami 1, A Takahashi 1, K Toyoda 1, Y Hayashi 1
PMCID: PMC1134841  PMID: 8216219

Abstract

The capability of (4R)-4-(2,3,4,6,6a beta,7,8,9,9a alpha,9b beta-decahydro-6a beta-methyl-3-oxo-1H-cyclopental[f]quinolin-7 beta-yl)valeric acid (DCQVA), a catabolite of cholic acid produced by enterobacteria, to induce peroxisome proliferation in vivo and in vitro was studied. Rats given 0.3% DCQVA in the diet for 2 weeks showed marked increases in peroxisomal beta-oxidation, mitochondrial 2,4-dienoyl-CoA reductase and microsomal laurate omega-oxidation activities in the liver compared with control rats given the diet without DCQVA. Cultured rat hepatocytes treated with DCQVA for 72 h also exhibited greatly enhanced beta-oxidation activity. The increased activity was concentration-dependent and the effective concentrations were comparable with those of clofibric acid that produced the same degree of induction in the assay. The results demonstrate that DCQVA is a potent peroxisome proliferator that occurs naturally in rat intestine.

Full text

PDF
217

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berge R. K., Aarsland A., Kryvi H., Bremer J., Aarsaether N. Alkylthioacetic acid (3-thia fatty acids)--a new group of non-beta-oxidizable, peroxisome-inducing fatty acid analogues. I. A study on the structural requirements for proliferation of peroxisomes and mitochondria in rat liver. Biochim Biophys Acta. 1989 Aug 22;1004(3):345–356. doi: 10.1016/0005-2760(89)90083-0. [DOI] [PubMed] [Google Scholar]
  2. Borrebaek B., Osmundsen H., Christiansen E. N., Bremer J. Increased 4-enoyl-CoA reductase activity in liver mitochondria of rats fed high-fed diets and its effect on fatty acid oxidation and the inhibitory action of pent-4-enoate. FEBS Lett. 1980 Nov 17;121(1):23–24. doi: 10.1016/0014-5793(80)81257-9. [DOI] [PubMed] [Google Scholar]
  3. Casteels M., Schepers L., Van Eldere J., Eyssen H. J., Mannaerts G. P. Inhibition of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid oxidation and of bile acid secretion in rat liver by fatty acids. J Biol Chem. 1988 Apr 5;263(10):4654–4661. [PubMed] [Google Scholar]
  4. DE DUVE C., PRESSMAN B. C., GIANETTO R., WATTIAUX R., APPELMANS F. Tissue fractionation studies. 6. Intracellular distribution patterns of enzymes in rat-liver tissue. Biochem J. 1955 Aug;60(4):604–617. doi: 10.1042/bj0600604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dommes V., Baumgart C., Kunau W. H. Degradation of unsaturated fatty acids in peroxisomes. Existence of a 2,4-dienoyl-CoA reductase pathway. J Biol Chem. 1981 Aug 25;256(16):8259–8262. [PubMed] [Google Scholar]
  6. Gibson G. G., Orton T. C., Tamburini P. P. Cytochrome P-450 induction by clofibrate. Purification and properties of a hepatic cytochrome P-450 relatively specific for the 12- and 11-hydroxylation of dodecanoic acid (lauric acid). Biochem J. 1982 Apr 1;203(1):161–168. doi: 10.1042/bj2030161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hayakawa S., Fujiwara T. Microbiological degradation of bile acids, further degradation of a cholic acid metabolite containing the hexahydroindane nucleus by Corynebacterium equi. Biochem J. 1977 Feb 15;162(2):387–397. doi: 10.1042/bj1620387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hayakawa S., Hashimoto S., Onaka T. Microbiological degradation of bile acids. Nitrogenous hexahydroindane derivatives formed from cholic acid by Streptomyces rubescens. Biochem J. 1976 Dec 15;160(3):745–755. doi: 10.1042/bj1600745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hayakawa S. Microbiological transformation of bile acids. Adv Lipid Res. 1973;11:143–192. doi: 10.1016/b978-0-12-024911-4.50011-8. [DOI] [PubMed] [Google Scholar]
  10. Hayashi H., Fukui K., Yamasaki F. Association of the liver peroxisomal fatty acyl-CoA beta-oxidation system with the synthesis of bile acids. J Biochem. 1984 Dec;96(6):1713–1719. [PubMed] [Google Scholar]
  11. Hayashi H., Miwa A. The role of peroxisomal fatty acyl-CoA beta-oxidation in bile acid biosynthesis. Arch Biochem Biophys. 1989 Nov 1;274(2):582–589. doi: 10.1016/0003-9861(89)90473-6. [DOI] [PubMed] [Google Scholar]
  12. Horie S., Ishii H., Suga T. Changes in peroxisomal fatty acid oxidation in the diabetic rat liver. J Biochem. 1981 Dec;90(6):1691–1696. doi: 10.1093/oxfordjournals.jbchem.a133645. [DOI] [PubMed] [Google Scholar]
  13. Ishii H., Fukumori N., Horie S., Suga T. Effects of fat content in the diet on hepatic peroxisomes of the rat. Biochim Biophys Acta. 1980 Jan 18;617(1):1–11. doi: 10.1016/0005-2760(80)90218-0. [DOI] [PubMed] [Google Scholar]
  14. Kawashima Y., Horii S., Matsunaga T., Hirose A., Adachi T., Kozuka H. Co-induction by peroxisome proliferators of microsomal 1-acylglycerophosphocholine acyltransferase with peroxisomal beta-oxidation in rat liver. Biochim Biophys Acta. 1989 Sep 25;1005(2):123–129. doi: 10.1016/0005-2760(89)90177-x. [DOI] [PubMed] [Google Scholar]
  15. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  16. Lock E. A., Mitchell A. M., Elcombe C. R. Biochemical mechanisms of induction of hepatic peroxisome proliferation. Annu Rev Pharmacol Toxicol. 1989;29:145–163. doi: 10.1146/annurev.pa.29.040189.001045. [DOI] [PubMed] [Google Scholar]
  17. Mizugaki M., Nishimaki T., Yamamoto H., Sagi M., Yamanaka H. Studies on the metabolism of unsaturated fatty acids. XI. Alterations in the activities of enoyl-CoA hydratase, 3-hydroxyacyl-CoA epimerase and 2,4-dienyl-CoA reductase in rat liver mitochondria and peroxisomes by clofibrate. J Biochem. 1982 Dec;92(6):2051–2054. doi: 10.1093/oxfordjournals.jbchem.a134140. [DOI] [PubMed] [Google Scholar]
  18. Neat C. E., Thomassen M. S., Osmundsen H. Effects of high-fat diets on hepatic fatty acid oxidation in the rat. Isolation of rat liver peroxisomes by vertical-rotor centrifugation by using a self-generated, iso-osmotic, Percoll gradient. Biochem J. 1981 Apr 15;196(1):149–159. doi: 10.1042/bj1960149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Nishimaki-Mogami T., Tanaka A., Minegishi K., Takahashi A. Effect of sorbic acid feeding on peroxisomes and sorboyl-CoA metabolizing enzymes in mouse liver. Selective induction of 2,4-dienoyl-CoA hydratase. Biochem Pharmacol. 1991 Jul 5;42(2):239–246. doi: 10.1016/0006-2952(91)90709-e. [DOI] [PubMed] [Google Scholar]
  20. Ortiz de Montellano P. R., Reich N. O. Specific inactivation of hepatic fatty acid hydroxylases by acetylenic fatty acids. J Biol Chem. 1984 Apr 10;259(7):4136–4141. [PubMed] [Google Scholar]
  21. Osmundsen H., Bremer J., Pedersen J. I. Metabolic aspects of peroxisomal beta-oxidation. Biochim Biophys Acta. 1991 Sep 11;1085(2):141–158. doi: 10.1016/0005-2760(91)90089-z. [DOI] [PubMed] [Google Scholar]
  22. Ostlund Farrants A. K., Björkhem I., Pedersen J. I. Differential induction of peroxisomal oxidation of palmitic acid and 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid in rat liver. Biochim Biophys Acta. 1990 Sep 18;1046(2):173–177. [PubMed] [Google Scholar]
  23. Osumi T., Hashimoto T. Peroxisomal beta oxidation system of rat liver. Copurification of enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase. Biochem Biophys Res Commun. 1979 Jul 27;89(2):580–584. doi: 10.1016/0006-291x(79)90669-7. [DOI] [PubMed] [Google Scholar]
  24. Russell D. W., Setchell K. D. Bile acid biosynthesis. Biochemistry. 1992 May 26;31(20):4737–4749. doi: 10.1021/bi00135a001. [DOI] [PubMed] [Google Scholar]
  25. Schepers L., Van Veldhoven P. P., Casteels M., Eyssen H. J., Mannaerts G. P. Presence of three acyl-CoA oxidases in rat liver peroxisomes. An inducible fatty acyl-CoA oxidase, a noninducible fatty acyl-CoA oxidase, and a noninducible trihydroxycoprostanoyl-CoA oxidase. J Biol Chem. 1990 Mar 25;265(9):5242–5246. [PubMed] [Google Scholar]
  26. Schram A. W., Goldfischer S., van Roermund C. W., Brouwer-Kelder E. M., Collins J., Hashimoto T., Heymans H. S., van den Bosch H., Schutgens R. B., Tager J. M. Human peroxisomal 3-oxoacyl-coenzyme A thiolase deficiency. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2494–2496. doi: 10.1073/pnas.84.8.2494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Smeland T. E., Nada M., Cuebas D., Schulz H. NADPH-dependent beta-oxidation of unsaturated fatty acids with double bonds extending from odd-numbered carbon atoms. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6673–6677. doi: 10.1073/pnas.89.15.6673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Thompson S. L., Burrows R., Laub R. J., Krisans S. K. Cholesterol synthesis in rat liver peroxisomes. Conversion of mevalonic acid to cholesterol. J Biol Chem. 1987 Dec 25;262(36):17420–17425. [PubMed] [Google Scholar]
  29. Thompson S. L., Krisans S. K. Rat liver peroxisomes catalyze the initial step in cholesterol synthesis. The condensation of acetyl-CoA units into acetoacetyl-CoA. J Biol Chem. 1990 Apr 5;265(10):5731–5735. [PubMed] [Google Scholar]
  30. Watkins P. A., Chen W. W., Harris C. J., Hoefler G., Hoefler S., Blake D. C., Jr, Balfe A., Kelley R. I., Moser A. B., Beard M. E. Peroxisomal bifunctional enzyme deficiency. J Clin Invest. 1989 Mar;83(3):771–777. doi: 10.1172/JCI113956. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Weeks G., Wakil S. J. Studies on the mechanism of fatty acid synthesis. 18. Preparation and general properties of the enoyl acyl carrier protein reductases from Escherichia coli. J Biol Chem. 1968 Mar 25;243(6):1180–1189. [PubMed] [Google Scholar]
  32. Yao Z. M., Vance D. E. The active synthesis of phosphatidylcholine is required for very low density lipoprotein secretion from rat hepatocytes. J Biol Chem. 1988 Feb 25;263(6):2998–3004. [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES