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Publication : Dietary fatty acids and dietary cholesterol differ in their effect on the in vivo regulation of apolipoprotein A-I and A-II gene expression in inbred strains of mice.

First Author  Srivastava RA Year  1992
Journal  Biochim Biophys Acta Volume  1125
Issue  3 Pages  251-61
PubMed ID  1596514 Mgi Jnum  J:1067
Mgi Id  MGI:49599 Doi  10.1016/0005-2760(92)90053-x
Citation  Srivastava RA, et al. (1992) Dietary fatty acids and dietary cholesterol differ in their effect on the in vivo regulation of apolipoprotein A-I and A-II gene expression in inbred strains of mice. Biochim Biophys Acta 1125(3):251-61
abstractText  Dietary cholesterol and dietary saturated fatty acids affected the plasma concentrations of various HDL components and the hepatic and intestinal expression of the apolipoprotein (apo) A-I gene and the hepatic expression of the A-II gene differently in three inbred strains of female mice. Thus, the HC diet (0.5% cholesterol, no added fatty acids) decreased HDL-cholesterol in C57BL and SWR strains but not in the C3H strain; plasma apo A-I and apo A-II concentrations decreased in all three strains. HDL-C/apo A-I and apo A-I/apo A-II mass ratios increased, suggesting that the HC diet altered both the concentrations and the compositions of HDL particles. In contrast, the HF diet (20% hydrogenated coconut oil, no added cholesterol) increased HDL cholesterol and apo A-I concentrations. The combination diet (HF/C, 20% coconut oil plus 0.5% cholesterol) increased HDL cholesterol and decreased triacylglycerols. Apo A-I concentrations were unaltered except for a significant increase in SWR mice. Apo A-II concentrations decreased in all strains. To examine molecular events that could lead to the changes in plasma apo A-I and apo A-II, we measured transcription rates in hepatic nuclei and steady state mRNA concentrations in liver and intestine and apo A-I synthetic rates in liver. Dietary cholesterol and fatty acids produced differing effects at transcriptional as well as post-transcriptional loci and the changes differed according to mouse strain. The most pronounced strain-related differences for both apo A-I and apo A-II occurred at post-transcriptional loci of apoprotein production. These could represent altered rates of translation in, or secretion from liver and/or intestine, or altered rates of clearance from plasma. In conclusion, the regulation of apo A-I and apo A-II gene expression by diet occurs at several steps of their production and perhaps also in catabolic pathways. This study identifies potential loci of regulation and forms the basis for future studies investigating specific genetic and molecular regulatory mechanisms.
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