Negative Feedback in Sterol Biosynthesis and Lipoprotein Release by the Perfused Rat Liver 1

Abstract

Summary

A high cholesterol diet (5%) given to rats over a 3- to 4-wk period markedly suppressed incorporation of acetate-2-¹⁴C in the perfused liver into both stored hepatic cholesterol and into sterol released into the perfusion medium. Perfused livers from low cholesterol-fed rats incorporated radioacetate into sterols at rates at least 50 times those observed in livers of high cholesterol-fed rats. In all animals, during the 3-hr perfusion period, only a small fraction of newly synthesized sterol was released from liver, the remainder being stored within it. Newly synthesized sterol was not detectable in the circulating perfusate until 45–55 min had elapsed. The data demonstrate the cholesterol feedback phenomenon in the perfusion fluid of the perfused rat liver, the quantitative relationship between stored and released new sterols, and the minimal appearance time required for newly synthesized lipoprotein to appear in the circulation of this perfused system.