Abstract

The effects of feeding cholestyramine to pregnant rats, which has been shown to increase the fetal hepatic rate-limiting enzyme in cholesterol synthesis, HMG CoA reductase, on the plasma cholesterol density distribution was studied in the young adult male rat offspring before and after feeding a diet high in fat and cholesterol. As in previous studies, offspring of rats fed cholestyramine during pregnancy had a plasma total cholesterol level similar to controls when fed a low fat and cholesterol diet, but higher than controls when fed a 20% (wt/wt) fat plus 5% (wt/wt) cholesterol diet. Analyses of the plasma cholesterol density distribution by continuous gradient ultracentrifugation showed that, compared to control rats, rats born to dams fed cholestyramine had more cholesterol in the higher density regions of plasma before and after a 7-d high fat and cholesterol diet challenge. After a 4- or 7-d diet challenge, rats fed cholestyramine had 2-3 times more cholesterol in the d less than or equal to 1.006 g/ml range of plasma compared to the control offspring. The results suggest that long term changes in cholesterol metabolism due to early nutrition in the rat may include altered plasma or intestinal lipoprotein metabolism, rather than an effect specific to hepatic cholesterol synthesis.

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