Abstract
The development of fatty acid metabolism was studied in isolated hepatocytes from newborn rats. Ketone-body production from oleate is increased 6-fold between 0 and 16 h after birth. This increase is related to an enhanced beta-oxidation rather than to a channeling of acetyl-CoA from the tricarboxylic acid cycle to ketone-body synthesis. The increase in oleate oxidation is not related to a decreased esterification rate, as the latter is already low at birth and does not decrease further. At birth, lipogenic rate is 2-3-fold lower than in fed adult rats and it decreases to undetectable values in 16 h-old rats. A 90% inhibition of lipogenesis in hepatocytes of newborn rats (0 h) by glucagon and 5-(tetradecyloxy)-2-furoic acid does not lead to an increased oxidation of non-esterified fatty acids. This suggests that the inverse relationship between lipogenesis and ketogenesis in the starved newborn rat is not responsible for the switch-on of fatty acid oxidation at birth. Moreover, ketogenesis from octanoate, a medium-chain fatty acid the oxidation of which is independent of carnitine acyltransferase, follows the same developmental pattern at birth as that from oleate.
Full text
PDF





Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Augenfeld J., Fritz I. B. Carnitine palmitolyltransferase activity and fatty acid oxidation by livers from fetal and neonatal rats. Can J Biochem. 1970 Mar;48(3):288–294. doi: 10.1139/o70-050. [DOI] [PubMed] [Google Scholar]
- Bailey E. Regulation of hepatic lipid metabolism during development of the rat. Biochem Soc Trans. 1981 Oct;9(5):371–372. doi: 10.1042/bst0090371. [DOI] [PubMed] [Google Scholar]
- Benito M., Williamson D. H. Evidence for a reciprocal relationship between lipogenesis and ketogenesis in hepatocytes from fed virgin and lactating rats. Biochem J. 1978 Oct 15;176(1):331–334. doi: 10.1042/bj1760331. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berry M. N., Friend D. S. High-yield preparation of isolated rat liver parenchymal cells: a biochemical and fine structural study. J Cell Biol. 1969 Dec;43(3):506–520. doi: 10.1083/jcb.43.3.506. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bremer J. The effect of fasting on the activity of liver carnitine palmitoyltransferase and its inhibition by malonyl-CoA. Biochim Biophys Acta. 1981 Sep 24;665(3):628–631. doi: 10.1016/0005-2760(81)90282-4. [DOI] [PubMed] [Google Scholar]
- Christiansen R. Z., Bremer J. Active transport of butyrobetaine and carnitine into isolated liver cells. Biochim Biophys Acta. 1976 Nov 2;448(4):562–577. doi: 10.1016/0005-2736(76)90110-3. [DOI] [PubMed] [Google Scholar]
- Cook G. A., Otto D. A., Cornell N. W. Differential inhibition of ketogenesis by malonyl-CoA in mitochondria from fed and starved rats. Biochem J. 1980 Dec 15;192(3):955–958. doi: 10.1042/bj1920955. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Drahota Z., Hahn P., Kleinzeller A., Kostolánská A. Acetoacetate formation by liver slices from adult and infant rats. Biochem J. 1964 Oct;93(1):61–65. doi: 10.1042/bj0930061. [DOI] [PMC free article] [PubMed] [Google Scholar]
- FOLCH J., LEES M., SLOANE STANLEY G. H. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957 May;226(1):497–509. [PubMed] [Google Scholar]
- Ferre P., Pegorier J. P., Assan R., Marliss E. B., Girard J. Influence of exogenous cortisol and triglyceride feeding on glucose homeostasis in the fasted newborn rat. Pediatr Res. 1978 Jul;12(7):751–756. doi: 10.1203/00006450-197807000-00002. [DOI] [PubMed] [Google Scholar]
- Ferré P., Pégorier J. P., Williamson D. H., Girard J. R. The development of ketogenesis at birth in the rat. Biochem J. 1978 Dec 15;176(3):759–765. doi: 10.1042/bj1760759. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ferré P., Satabin P., El Manoubi L., Callikan S., Girard J. Relationship between ketogenesis and gluconeogenesis in isolated hepatocytes from newborn rats. Biochem J. 1981 Nov 15;200(2):429–433. doi: 10.1042/bj2000429. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Foster P. C., Bailey E. Changes in hepatic fatty acid degradation and blood lipid and ketone body content during development of the rat. Enzyme. 1976;21(5):397–407. doi: 10.1159/000458889. [DOI] [PubMed] [Google Scholar]
- KOREN Z., SHAFRIR E. PLACENTAL TRANSFER OF FREE FATTY ACIDS IN THE PREGNANT RAT. Proc Soc Exp Biol Med. 1964 Jun;116:411–414. doi: 10.3181/00379727-116-29263. [DOI] [PubMed] [Google Scholar]
- Lorenzo M., Caldés T., Benito M., Medina J. M. Lipogenesis in vivo in maternal and foetal tissues during late gestation in the rat. Biochem J. 1981 Aug 15;198(2):425–428. doi: 10.1042/bj1980425. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mayes P. A., Felts J. M. Regulation of fat metabolism of the liver. Nature. 1967 Aug 12;215(5102):716–718. doi: 10.1038/215716a0. [DOI] [PubMed] [Google Scholar]
- McCune S. A., Harris R. A. Mechanism responsible for 5-(tetradecyloxy)-2-furoic acid inhibition of hepatic lipogenesis. J Biol Chem. 1979 Oct 25;254(20):10095–10101. [PubMed] [Google Scholar]
- McGarry J. D., Foster D. W. In support of the roles of malonyl-CoA and carnitine acyltransferase I in the regulation of hepatic fatty acid oxidation and ketogenesis. J Biol Chem. 1979 Sep 10;254(17):8163–8168. [PubMed] [Google Scholar]
- McGarry J. D., Leatherman G. F., Foster D. W. Carnitine palmitoyltransferase I. The site of inhibition of hepatic fatty acid oxidation by malonyl-CoA. J Biol Chem. 1978 Jun 25;253(12):4128–4136. [PubMed] [Google Scholar]
- McGarry J. D., Mannaerts G. P., Foster D. W. A possible role for malonyl-CoA in the regulation of hepatic fatty acid oxidation and ketogenesis. J Clin Invest. 1977 Jul;60(1):265–270. doi: 10.1172/JCI108764. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McGarry J. D., Takabayashi Y., Foster D. W. The role of malonyl-coa in the coordination of fatty acid synthesis and oxidation in isolated rat hepatocytes. J Biol Chem. 1978 Nov 25;253(22):8294–8300. [PubMed] [Google Scholar]
- Ontko J. A., Johns M. L. Evaluation of malonyl-CoA in the regulation of long-chain fatty acid oxidation in the liver. Evidence for an unidentified regulatory component of the system. Biochem J. 1980 Dec 15;192(3):959–962. doi: 10.1042/bj1920959. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Panek E., Cook G. A., Cornell N. W. Inhibition by 5-(tetradecyloxy)-2-furoic acid of fatty acid and cholesterol synthesis in isolated rat hepatocytes. Lipids. 1977 Oct;12(10):814–818. doi: 10.1007/BF02533270. [DOI] [PubMed] [Google Scholar]
- Pillay D., Bailey E. Perinatal lipogenesis in the liver and brown adipose tissue of the rat. Int J Biochem. 1982;14(6):511–517. doi: 10.1016/0020-711x(82)90119-7. [DOI] [PubMed] [Google Scholar]
- Robles-Valdes C., McGarry J. D., Foster D. W. Maternal-fetal carnitine relationship and neonatal ketosis in the rat. J Biol Chem. 1976 Oct 10;251(19):6007–6012. [PubMed] [Google Scholar]
- Saggerson E. D., Carpenter C. A. Effects of fasting, adrenalectomy and streptozotocin-diabetes on sensitivity of hepatic carnitine acyltransferase to malonyl CoA. FEBS Lett. 1981 Jul 6;129(2):225–228. doi: 10.1016/0014-5793(81)80170-6. [DOI] [PubMed] [Google Scholar]
- Saggerson E. D., Carpenter C. A. Regulation of hepatic carnitine palmitoyltransferase activity during the foetal-neonatal transition. FEBS Lett. 1982 Dec 13;150(1):177–180. doi: 10.1016/0014-5793(82)81329-x. [DOI] [PubMed] [Google Scholar]
- Snell K., Walker D. G. Glucose metabolism in the newborn rat. Temporal studies in vivo. Biochem J. 1973 Apr;132(4):739–752. doi: 10.1042/bj1320739. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stansbie D., Brownsey R. W., Crettaz M., Denton R. M. Acute effects in vivo of anti-insulin serum on rates of fatty acid synthesis and activities of acetyl-coenzyme A carboxylase and pyruvate dehydrogenase in liver and epididymal adipose tissue of fed rats. Biochem J. 1976 Nov 15;160(2):413–416. doi: 10.1042/bj1600413. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Turlan P., Ferre P., Girard J. R. Evidence that medium-chain fatty acid oxidation can support an active gluconeogenesis in the suckling newborn rat. Biol Neonate. 1983;43(1-2):103–108. doi: 10.1159/000241644. [DOI] [PubMed] [Google Scholar]
- Tutwiler G. F., Ryzlak M. T. Inhibition of mitochondrial carnitine palmitoyl transferase by 2-tetradecylglycidic acid (McN-3802) (preliminary communication). Life Sci. 1980 Feb 4;26(5):393–397. doi: 10.1016/0024-3205(80)90156-3. [DOI] [PubMed] [Google Scholar]
- WILLIAMSON D. H., MELLANBY J., KREBS H. A. Enzymic determination of D(-)-beta-hydroxybutyric acid and acetoacetic acid in blood. Biochem J. 1962 Jan;82:90–96. doi: 10.1042/bj0820090. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wapnir R. A., Tildon J. T., Cornblath M. Metabolic differences in offspring of rats fed high-fat and control diets. Am J Physiol. 1973 Mar;224(3):596–599. doi: 10.1152/ajplegacy.1973.224.3.596. [DOI] [PubMed] [Google Scholar]
- Whitelaw E., Williamson D. H. Effects of lactation of ketogenesis from oleate or butyrate in rat hepatocytes. Biochem J. 1977 Jun 15;164(3):521–528. doi: 10.1042/bj1640521. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yeh Y. Y., Zee P. Insulin, a possible regulator of ketosis in newborn and suckling rats. Pediatr Res. 1976 Mar;10(3):192–197. doi: 10.1203/00006450-197603000-00010. [DOI] [PubMed] [Google Scholar]
