This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Brown, A.-M. Articles by Gibbons, G. F. Search for Related Content PubMed PubMed Citation Articles by Brown, A.-M. Articles by Gibbons, G. F. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Dietary Fats Related Collections Animal models of human disease Lipid and lipoprotein metabolism

(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:106-114.)
© 1999 American Heart Association, Inc.

Original Contributions

Administration of n-3 Fatty Acids in the Diets of Rats or Directly to Hepatocyte Cultures Results in Different Effects on Hepatocellular ApoB Metabolism and Secretion

Anna-Marie Brown; Jenni Castle; Abdel-Malek Hebbachi; Geoffrey F. Gibbons

From the Metabolic Research Laboratory, Radcliffe Infirmary, Oxford, England.

Correspondence to Dr G.F. Gibbons, Metabolic Research Laboratory, Radcliffe Infirmary, Woodstock Road, Oxford OX2 6HE, England. E-mail geoff.gibbons{at}mrl.ox.ac.uk

Abstract—Hepatocytes derived either from rats fed a diet enriched in n-3 fatty acids or from rats fed a low-fat diet and cultured with an n-3 fatty acid (eicosapentaenoic acid, EPA) in vitro were used to distinguish between the dietary effects and the direct effects of n-3 fatty acids on hepatocellular apolipoprotein (apo) B metabolism and secretion. ApoB-48 and apoB-100 synthesis, degradation, and secretion as large (d<1.006) and small (d>1.006) particles were determined after a pulse label with [³⁵S]methionine. These effects were compared with changes in triacylglycerol (TAG) synthesis and secretion and with changes in de novo fatty acid synthesis (using ³H₂O incorporation) under identical conditions. When n-3 fatty acid was given via the dietary route, apoB-48 very low density lipoprotein (VLDL) secretion was inhibited, but there was no effect on the secretion of apoB-100 VLDL. There was no effect on the secretion of either apoB-48 or apoB-100 as small, dense particles (d>1.006). Cellular TAG synthesis was significantly inhibited under these conditions, and fatty acid synthesis de novo was inhibited by 80%. By contrast, after direct addition of EPA to hepatocytes from normal rats, the secretion of both apoB-48 and apoB-100 VLDL was suppressed. The secretion of apoB-48, but not of apoB-100, as dense particles was also inhibited. However, there was little or no effect on TAG synthesis nor on fatty acid synthesis de novo. In addition, whereas dietary administration of n-3 fatty acid gave rise to decreased net synthesis and degradation of apoB-48, direct administration in vitro resulted in increased degradation with no effect on net synthesis. We conclude that the effects of n-3 fatty acids on hepatic lipid and apoB metabolism differ according to whether they are administered in vivo, via the dietary route, or in vitro, via direct addition to hepatocyte cultures.

Key Words: apolipoprotein B • hepatocytes • VLDL • dietary fish oil • fatty acid synthesis

This article has been cited by other articles:

				R. B. Heath, F. Karpe, R. W. Milne, G. C. Burdge, S. A. Wootton, and K. N. Frayn Dietary fatty acids make a rapid and substantial contribution to VLDL-triacylglycerol in the fed state Am J Physiol Endocrinol Metab, March 1, 2007; 292(3): E732 - E739. [Abstract] [Full Text] [PDF]

				P. Aspichueta, S. Perez, B. Ochoa, and O. Fresnedo Endotoxin promotes preferential periportal upregulation of VLDL secretion in the rat liver J. Lipid Res., May 1, 2005; 46(5): 1017 - 1026. [Abstract] [Full Text] [PDF]

				K. M. Botham, X. Zheng, M. Napolitano, M. Avella, C. Cavallari, R. Rivabene, and E. Bravo The Effects of Dietary n-3 Polyunsaturated Fatty Acids Delivered in Chylomicron Remnants on the Transcription of Genes Regulating Synthesis and Secretion of Very-Low-Density Lipoprotein by the Liver: Modulation by Cellular Oxidative State Experimental Biology and Medicine, February 1, 2003; 228(2): 143 - 151. [Abstract] [Full Text] [PDF]

				C. Vasandani, A. I. Kafrouni, A. Caronna, Y. Bashmakov, M. Gotthardt, J. D. Horton, and D. K. Spady Upregulation of hepatic LDL transport by n-3 fatty acids in LDL receptor knockout mice J. Lipid Res., May 1, 2002; 43(5): 772 - 784. [Abstract] [Full Text] [PDF]

				G. Asset, E. Bauge, J. C. Fruchart, and J. Dallongeville Lack of Triglyceride-Lowering Properties of Fish Oil in Apolipoprotein E-Deficient Mice Arterioscler Thromb Vasc Biol, March 1, 2001; 21(3): 401 - 406. [Abstract] [Full Text] [PDF]