A fish oil diet produces different degrees of suppression of apoB and triglyceride secretion in human apoB transgenic mouse strains

Abstract

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) × 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 × 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 β-oxidation rate, were increased in FO-fed B6 but not in FVB × 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 × B6 HuBTg mice were associated with strain differences in hepatic apoB and TG secretion and in peroxisomal β-oxidation.