Two partially inbred strains of laboratory opossums exhibit extremely high or low levels of low-density lipoprotein (LDL) cholesterol concentrations, respectively, when challenged with a high-cholesterol and high-fat (HCHF) diet. The present studies were conducted to determine whether the catabolism or the production of LDL apolipoprotein B (apoB) is responsible for the variability in plasma LDL cholesterol and apoB concentrations. Iodinated LDL prepared from plasma of donor opossums consuming HCHF diet was injected into high- and low-responding recipients maintained on the HCHF diet. Blood was drawn at intervals beginning at 3 minutes and ending at 24 hours. At the end of the study, animals were necropsied, and livers were removed for isolation of RNA. Plasma LDL apoB was separated by sodium dodecyl sulfate-electrophoresis, and the level of radioactivity was determined. Hepatic LDL receptor and apoB mRNA levels were measured by Northern blotting. Radioactivity decay curves were plotted by using the radioactivity at each time point as percentage of the radioactivity recovered at 3 minutes. Fractional catabolic rates (FCRs) were calculated by the curve peeling technique. Steady-state production rates were calculated by multiplying the FCR values with apoB concentrations. LDL apoB FCR was slightly higher (1.63-fold) in low responders than in high responders. On the other hand, LDL apoB production was much higher (5.5-fold) in high responders than in low responders. There was no difference in hepatic mRNA levels for either the LDL receptor or apoB. The differences in LDL apoB FCR may be explained on the basis of differences in pool size between the 2 strains. Therefore, LDL apoB production is the major determinant of diet-induced hyperlipidemia in laboratory opossums. Because LDL apoB production was not associated with hepatic mRNA levels, the production of LDL apoB is regulated posttranscriptionally or posttranslationally.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism