Dietary cholate increases plasma levels of apolipoprotein B in mice by posttranscriptional mechanisms

To induce atherogenesis in mice, a high fat (HF) diet is supplemented with cholic acid (CA), which increases apoB-containing particles and lower apoA- I-containing particles. HF diet without CA increases levels of both HDL and LDL, suggesting that CA may be responsible for the elevation of LDL and lo wering of HDL. The mechanism of dietary CA-induced lowering of apoA-I-conta ining particles has recently been reported. In this study, we examined the mechanism of CA- and HF-induced elevation of apoB-containing lipoproteins i n mice. Mice were fed the following four diets: control chow (C), high fat high cholesterol, (HF), control and 0.5% cholate (CA), and HF + CA. Dietary CA increased the plasma levels of apoB-containing particles by similar to 2-fold when compared to control; VLDL levels increased 2-fold, and LDL leve ls increased 1.3-fold. On HF diet, VLDL increased by 1.4-fold, and LDL by 2 -fold, suggesting that CA and HF-induced increases of apoB-containing parti cles occurred by different mechanisms. We investigated the potential mechan isms regulating plasma levels of apoB in CA- and HF-fed mice. Although hepa tic apoB mRNA levels did not change on CA diet, apoB-100 mRNA increased rel ative to B-48 as a result or decreased editing of apoB mRNA. Measurements o f hepatic LDL receptor mRNA suggested that CA diet down-regulated LDL recep tor mRNA, possibly by increasing the levels of hepatic cholesterol. Since p lasma and hepatic vitamin E levels did not show significant changes on CA-c ontaining diets, it suggests that dietary CA did not act by increasing the absorption of dietary fat. Hepatic lipase, known to modulate plasma levels of apoB-containing particles, did not show changes in CA- or HF-fed mice. T aken together, these results suggest that dietary CA increased apoB-contain ing particles both in chow-fed and fat-fed mice by enhancing the relative p roduction of