DIURNAL RHYTHMICITY OF HUMAN CHOLESTEROL-SYNTHESIS - NORMAL PATTERN AND ADAPTATION TO SIMULATED JET-LAG

The diurnal rhythm of cholesterol synthesis was determined by deuteriu m incorporation from body water in five normolipemic men studied durin g a 24-h baseline period and on the 1st, 2nd, and 4th days of a simula ted 12-h time zone shift achieved by delaying sleep times and, startin g on the 2nd day, mealtimes. Profiles of plasma cortisol and thyrotrop in (TSH) were obtained simultaneously. Under baseline conditions, chol esterol synthetic rates varied from essentially zero in the morning to maximal values around midnight. On the 1st shifted day, this diurnal variation was unaltered despite sleep-wake reversal. The diurnal patte rn of cholesterol synthesis, however, was shifted 5 h on the 2nd shift ed day and similar to 12 h on the 4th. The diurnal variation of synthe tic rate cholesterol fractional synthesis and plasma cortisol levels w as negatively correlated on both the baseline day and the 1st shifted day. A positive correlation with the TSH rhythm was found on the 1st d ay only. During the 2nd and 4th days, the rhythm of cholesterol synthe sis adapted faster than the rhythms of cortisol and TSH. These finding s indicate that cholesterol synthesis is not acutely entrained by the sleep-wake cycle nor is it primarily entrained by the circadian clock.