Translational Regulation of Hepatic HMG-CoA Reductase by Dietary Cholesterol

The question of whether dietary cholesterol exerts feedback regulation on hepatic HMG-CoA reductase at the level of translation was examined by performing polysome profile analysis. Liver polysomes from rats fed 2% cholesterol in their diets for 3 days were compared with those isolated from rats fed a normal chow diet. Northern blotting analysis of the individual fractions revealed that cholesterol feeding reduced the portion of HMG-CoA reductase mRNA associated with translationally active polysomes by over 50% and progressively increased the percentage of reductase mRNA present in the monosomal fractions. In the lightest monosomal fraction over 10 times as much reductase mRNA was present in samples from cholesterol animals as compared to controls. These findings indicate that dietary cholesterol exerts significant feedback regulation on hepatic HMG-CoA reductase at the translational level.