Regulation of rabbit intestinal acyl coenzyme A-cholesterol acyltransferase in vivo and in vitro.

The rate of intestinal cholesterol esterification may be an important determinant of the rates of entry and exit of cholesterol from the body. Acyl coenzyme A-cholesterol acyltransferase, the intracellular cholesterol esterifying enzyme, may play a role in this process. To assess this, the response of rabbit intestinal acyl coenzyme A-cholesterol acyltransferase in vivo was studied. Animals were fed a diet containing cholesterol and corn oil, and they responded with an increase in acyl coenzyme A-cholesterol acyltransferase activity. The increase was apparent in all segments of the intestine proximal to the distal ileum, and it occurred specifically in the villus cells where the bulk of lipid absorption is believed to take place. In cultured intestinal explants, the activity responded rapidly to sterols (increased) and to fatty acids (decreased) when control intestine was used. If intestine from cholesterol-corn oil-fed animals was cultured, sterols still induced an increase, but fatty acids did not affect the enzyme activity. The acutely induced increases in acyl coenzyme A-cholesterol acyltransferase activity were not prevented by cycloheximide. The results show that acyl coenzyme A-cholesterol acyltransferase in the absorptive cells of intestine responds both acutely and chronically to dietary factors, supporting the hypothesis that acyl coenzyme A-cholesterol acyltransferase plays a role in cholesterol absorption.