Abstract
Short-term exposure of isolated rat hepatocytes to short- and medium-chain fatty acids led to an activation of acetyl-CoA carboxylase as measured in digitonin-permeabilized hepatocytes. Up to a certain concentration, typical for each of the fatty acids used, fatty acid-dependent activation of acetyl-CoA carboxylase coincided with an increase in the rate of fatty acid synthesis in intact hepatocytes, as determined by the incorporation of 3H from 3H2O water into fatty acids. At higher concentrations loss of stimulation of fatty acid synthesis occurred, but not the enhancement of carboxylase activity. With the fatty acids tested (C8:0-C14:0), the peak in fatty acid synthesis coincided with a peak in the level of malonyl-CoA. The onset of the stimulation of carboxylase activity coincided with the start of the peak in both fatty acid synthesis and malonyl-CoA. The longer the chain length of the fatty acid added, the lower the concentration at which the rate of fatty acid synthesis and the level of malonyl-CoA reached a peak and carboxylase activity started to become elevated. In cell suspensions incubated with increasing concentrations of fatty acids, accumulation of lactate decreased progressively. The latter observation, in combination with the fact that the activity of acetyl-CoA carboxylase is not always related to the rate of fatty acid biosynthesis, suggests that under these conditions not the activity of the carboxylase but the flux through the glycolytic sequence determines, at least in part, the rate of fatty acid synthesis de novo.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bach A. C., Babayan V. K. Medium-chain triglycerides: an update. Am J Clin Nutr. 1982 Nov;36(5):950–962. doi: 10.1093/ajcn/36.5.950. [DOI] [PubMed] [Google Scholar]
- Baquet A., Maisin L., Hue L. Swelling of rat hepatocytes activates acetyl-CoA carboxylase in parallel to glycogen synthase. Biochem J. 1991 Sep 15;278(Pt 3):887–890. doi: 10.1042/bj2780887. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Beynen A. C., Vaartjes W. J., Geelen M. J. Opposite effects of insulin and glucagon in acute hormonal control of hepatic lipogenesis. Diabetes. 1979 Sep;28(9):828–835. doi: 10.2337/diab.28.9.828. [DOI] [PubMed] [Google Scholar]
- Bijleveld C., Geelen M. J. Measurement of acetyl-CoA carboxylase activity in isolated hepatocytes. Biochim Biophys Acta. 1987 Apr 24;918(3):274–283. doi: 10.1016/0005-2760(87)90231-1. [DOI] [PubMed] [Google Scholar]
- Buechler K. F., Beynen A. C., Geelen M. J. Studies on the assay, activity and sedimentation behaviour of acetyl-CoA carboxylase from isolated hepatocytes incubated with insulin or glucagon. Biochem J. 1984 Aug 1;221(3):869–874. doi: 10.1042/bj2210869. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Davies D. R., Van Schaftingen E., Hers H. G. Interference by pyruvate carboxylase in the measurement of acetyl-CoA carboxylase in crude liver preparations. Biochem J. 1982 Feb 15;202(2):559–560. doi: 10.1042/bj2020559. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Geelen M. J., Beynen A. C., Christiansen R. Z., Lepreau-Jose M. J., Gibson D. M. Short-term effects of insulin and glucagon on lipid synthesis in isolated rat hepatocytes. Covariance of acetyl-CoA carboxylase activity and the rate of 3H2O incorporation into fatty acids. FEBS Lett. 1978 Nov 15;95(2):326–330. doi: 10.1016/0014-5793(78)81022-9. [DOI] [PubMed] [Google Scholar]
- Geelen M. J., Harris R. A., Beynen A. C., McCune S. A. Short-term hormonal control of hepatic lipogenesis. Diabetes. 1980 Dec;29(12):1006–1022. doi: 10.2337/diab.29.12.1006. [DOI] [PubMed] [Google Scholar]
- Gibson D. M., Lyons R. T., Scott D. F., Muto Y. Synthesis and degradation of the lipogenic enzymes of rat liver. Adv Enzyme Regul. 1972;10:187–204. doi: 10.1016/0065-2571(72)90014-3. [DOI] [PubMed] [Google Scholar]
- Groot P. H., Van Loon C. M., Hülsmann W. C. Identification of the palmitoyl-CoA synthetase present in the inner membrane-matrix fraction of rat liver mitochondria. Biochim Biophys Acta. 1974 Jan 23;337(1):1–12. doi: 10.1016/0005-2760(74)90034-4. [DOI] [PubMed] [Google Scholar]
- Hanson R. W., Ballard F. J. Citrate, pyruvate, and lactate contaminants of commercial serum albumin. J Lipid Res. 1968 Sep;9(5):667–668. [PubMed] [Google Scholar]
- Hardie D. G. Regulation of fatty acid and cholesterol metabolism by the AMP-activated protein kinase. Biochim Biophys Acta. 1992 Feb 12;1123(3):231–238. doi: 10.1016/0005-2760(92)90001-c. [DOI] [PubMed] [Google Scholar]
- Harris R. A. Studies on the inhibition of hepatic lipogenesis by N-6,O-2'-dibutyryl adenosine 3',5'-monophosphate. Arch Biochem Biophys. 1975 Jul;169(1):168–180. doi: 10.1016/0003-9861(75)90330-6. [DOI] [PubMed] [Google Scholar]
- Hill J. O., Peters J. C., Swift L. L., Yang D., Sharp T., Abumrad N., Greene H. L. Changes in blood lipids during six days of overfeeding with medium or long chain triglycerides. J Lipid Res. 1990 Mar;31(3):407–416. [PubMed] [Google Scholar]
- Hue L., Maisin L., Rider M. H. Palmitate inhibits liver glycolysis. Involvement of fructose 2,6-bisphosphate in the glucose/fatty acid cycle. Biochem J. 1988 Apr 15;251(2):541–545. doi: 10.1042/bj2510541. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Janski A. M., Cornell N. W. Subcellular distribution of enzymes determined by rapid digitonin fractionation of isolated hepatocytes. Biochem J. 1980 Feb 15;186(2):423–429. doi: 10.1042/bj1860423. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Linn T. C. Purification and crystallization of rat liver fatty acid synthetase. Arch Biochem Biophys. 1981 Jul;209(2):613–619. doi: 10.1016/0003-9861(81)90320-9. [DOI] [PubMed] [Google Scholar]
- Lopes-Cardozo M., van den Bergh S. G. Ketogenesis in isolated rat liver mitochondria. I. Relationships with the citric acid cycle and with the mitochondrial energy state. Biochim Biophys Acta. 1972;283(1):1–15. doi: 10.1016/0005-2728(72)90092-8. [DOI] [PubMed] [Google Scholar]
- McGarry J. D., Foster D. W. Regulation of hepatic fatty acid oxidation and ketone body production. Annu Rev Biochem. 1980;49:395–420. doi: 10.1146/annurev.bi.49.070180.002143. [DOI] [PubMed] [Google Scholar]
- Nilsson A., Sundler R., Akesson B. Effect of different albumin-bound fatty acids on fatty acid and cholesterol biosynthesis in rat hepatocytes. FEBS Lett. 1974 Sep 1;45(1):282–285. doi: 10.1016/0014-5793(74)80862-8. [DOI] [PubMed] [Google Scholar]
- Nomura T., Iguchi A., Sakamoto N., Harris R. A. Effects of octanoate and acetate upon hepatic glycolysis and lipogenesis. Biochim Biophys Acta. 1983 Dec 20;754(3):315–320. [PubMed] [Google Scholar]
- Numa S., Ringelmann E., Lynen F. Zur Hemmung der Acetyl-CoA-Carboxylase durch Fettsäure-Coenzym A-Verbindungen. Biochem Z. 1965 Dec 1;343(3):243–257. [PubMed] [Google Scholar]
- Schönfeld P., Wojtczak A. B., Geelen M. J., Kunz W., Wojtczak L. On the mechanism of the so-called uncoupling effect of medium- and short-chain fatty acids. Biochim Biophys Acta. 1988 Dec 7;936(3):280–288. doi: 10.1016/0005-2728(88)90003-5. [DOI] [PubMed] [Google Scholar]
- Seglen P. O. Preparation of isolated rat liver cells. Methods Cell Biol. 1976;13:29–83. doi: 10.1016/s0091-679x(08)61797-5. [DOI] [PubMed] [Google Scholar]
- Siess E. A., Brocks D. G., Lattke H. K., Wieland O. H. Effect of glucagon on metabolite compartmentation in isolated rat liver cells during gluconeogenesis from lactate. Biochem J. 1977 Aug 15;166(2):225–235. doi: 10.1042/bj1660225. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sundler R., Akesson B., Nilsson A. Effect of different fatty acids on glycerolipid synthesis in isolated rat hepatocytes. J Biol Chem. 1974 Aug 25;249(16):5102–5107. [PubMed] [Google Scholar]
- Tol V. A. Aspects of long-chain acyl-COA metabolism. Mol Cell Biochem. 1975 Apr 30;7(1):19–31. doi: 10.1007/BF01732160. [DOI] [PubMed] [Google Scholar]
- Van Lith H. A., Herman S., Zhang X., Van Der Palen J. G., Van Zutphen L. F., Beynen A. C. Influence of dietary fats on butyrylcholinesterase and esterase-1 (ES-1) activity in plasma of rats. Lipids. 1990 Dec;25(12):779–786. doi: 10.1007/BF02535897. [DOI] [PubMed] [Google Scholar]
- Wiley J. H., Leveille G. A. Metabolic consequences of dietary medium-chain triglycerides in the rat. J Nutr. 1973 Jun;103(6):829–835. doi: 10.1093/jn/103.6.829. [DOI] [PubMed] [Google Scholar]