Diurnal rhythmicity of human cholesterol synthesis: normal pattern and adaptation to simulated "jet lag"

The diurnal rhythm of cholesterol synthesis was determined by deuterium incorporation from body water in five normolipemic men studied during a 24-h baseline period and on the 1st, 2nd, and 4th days of a simulated 12-h time zone shift achieved by delaying sleep times and, starting on the 2nd day, meal-times. Profiles of plasma cortisol and thyrotropin (TSH) were obtained simultaneously. Under baseline conditions, cholesterol 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 pattern of cholesterol synthesis, however, was shifted 5 h on the 2nd shifted day and approximately 12 h on the 4th. The diurnal variation of synthetic rate cholesterol fractional synthesis and plasma cortisol levels was negatively correlated on both the baseline day and the 1st shifted day. A positive correlation with the TSH rhythm was found on the 1st day only. During the 2nd and 4th days, the rhythm of cholesterol synthesis adapted faster than the rhythms of cortisol and TSH. These findings indicate that cholesterol synthesis is not acutely entrained by the sleep-wake cycle nor is it primarily entrained by the circadian clock.