Short-term changes in hepatic HMG-CoA reductase in rats fed diets containing cholesterol or oat bran

In vivo regulation of hepatic HMG-CoA reductase (HMGR) (mevalonate:NADP+ oxidoreductase [acylating CoA]; EC 1.1.1.34] by phosphorylation/dephosphorylation has not been demonstrated. Rats were meal-fed semipurified diets; effects of inclusion of cholesterol (2%) or oat bran (15%) in a single meal on expressed (phosphorylated) and total (dephosphorylated) activities of HMGR were measured from 15 min to 4 hr after presentation of the meal. Expressed activity was not significantly altered in response to the control diet during the time periods examined, while total HMGR activity declined by 15 min and increased through 4 hr to an activity about 1.5 times control levels. Addition of cholesterol resulted in little change in expressed activity but a greater and more sustained reduction in total activity. Oat bran caused reductions in both total and expressed activities, which were maintained through 4 hr. Total HMGR activity was best correlated with apparent demand for cholesterol synthesis.