COORDINATE DIURNAL REGULATION OF HEPATIC ACYL-COENZYME-A - CHOLESTEROL ACYLTRANSFERASE AND CELLULAR-LEVELS OF ESTERIFIED CHOLESTEROL

Hepatic ACAT, HMG-CoA reductase and both cellular free and esterified cholesterol were measured at 3 h intervals over a 24 h period in the r at. ACAT exhibited a characteristic low amplitude diurnal rhythm with maximum activity at the mid-light phase that was significantly higher than the minimum activity observed at the mid-dark phase. The cellular esterified cholesterol concentration showed a diurnal rhythm that clo sely paralleled the rhythm of ACAT activity. The cellular free cholest erol concentration was not significantly altered during the 24 h cycle . In rats fed cholesterol, the diurnal rhythm of ACAT was still mainta ined despite the increase in ACAT activity during the entire 24 h cycl e suggesting that the ACAT rhythm is the result of changes in the leve l of ACAT protein expression. The results also indicate that the diurn al rhythms of ACAT and HMG-CoA reductase are generated by a process in dependent of the LDL receptor rhythm. All three rhythms are also indep endent of changes in the level of free cholesterol in the cell.