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Journal of Lipid Research, Vol. 44, 1946-1955, October 2003
Copyright © 2003 by American Society for Biochemistry and Molecular Biology
A fish oil diet produces different degrees of suppression of apoB and triglyceride secretion in human apoB transgenic mouse strains
Department of Medicine, Columbia University, College of Physicians & Surgeons, New York, NY 10032
1 To whom correspondence should be addressed. e-mail: lh99{at}columbia.edu
Human apolipoprotein B (apoB) transgenic (HuBTg) mouse strains were used to assess genetic effects on the response to fish oil (FO), a source of n-3 fatty acids. A congenic HuBTg strain of the C57BL/6 (B6) background and six F1 HuBTg strains were fed a FO for 2 weeks. Different responses of plasma lipid levels to FO were observed among these strains. In particular, plasma apoB levels changed minimally in FO-fed male B6 HuBTg mice, but increased markedly (
40%) in FO-fed male FVB/NJ (FVB) x B6 F1 HuBTg mice. These strain differences were determined mainly by hepatic apoB secretion rates and were likely regulated by posttranscriptional mechanisms. In addition, plasma triglyceride (TG) levels were reduced (14%) in FO-fed B6 mice, but not in FVB x B6 mice. These strain differences were determined mainly by TG secretion rates, but were not due to differences in hepatic lipogenesis. Hepatic mRNA levels of acyl-CoA oxidase, reflective of peroxisomal ß-oxidation rate, were increased in FO-fed B6 but not in FVB x B6 mice, which could account for the difference in TG secretion rates.
In summary, differential effects of FO on plasma apoB and TG levels in B6 and FVB x B6 HuBTg mice were associated with strain differences in hepatic apoB and TG secretion and in peroxisomal ß-oxidation.
Abbreviations: AOX, acyl-CoA oxidase; B6, C57BL/6; CPTI, carnitine palmitoyltransferase; FAS, fatty acid synthase; FVB, FVB/NJ; FO, fish oil; HuBTg, human apoB transgenic mouse; LDLR, LDL receptor; MTP, microsomal triglyceride transfer protein; PPAR, peroxisome proliferator-activated receptor; SREBP, sterol responsive element binding protein; TG, triglyceride; WTD, Western-type diet
Supplementary key words apolipoprotein B secretion • low density lipoprotein receptor • hepatic lipogenesis • peroxisomal ß-oxidation • acyl-CoA oxidase
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