Endogenous circadian regulation and phase resetting of clinical metabolic biomarkers.

Abstract

Shiftwork and circadian disruption are associated with adverse metabolic effects. Therefore, we examined whether clinical biomarkers of metabolic health are under endogenous circadian regulation using a 40hours constant routine protocol (CR; constant environmental and behavioral conditions) and evaluated the impact of typical daily conditions with periodic sleep and meals (baseline; 8hours sleep at night, four meals during a 16hour wake episode) on the phase and amplitude of these rhythms. Additionally, we tested whether these circadian rhythms are reset during simulated shiftwork. Under CR (n=16 males, mean age±SD=23.4±2.3years), we found endogenous circadian rhythms in cholesterol, HDL and LDL, albumin and total protein, and VLDL and triglyceride. The rhythms were masked under baseline conditions except for cholesterol, which had near-identical phases under both conditions. Resetting of the cholesterol rhythm and Dim Light Melatonin Onset (DLMO) was then tested in a study of simulated shiftwork (n=25, 14 females, 36.3±8.9years) across four protocols; two with abrupt 8hour delay shifts and exposure to either blue-enriched or standard white light; and either an abrupt or gradual 8hour advance (1.6hours/day over 5days) both with exposure to blue-enriched white light. In the delay protocols, the cholesterol rhythm shifted later by -3.7hours and -4.2hours, respectively, compared to -6.6hours and -4.7hours, for DLMO. There was a significant advance in cholesterol in the abrupt (+5.1hours) but not the gradual (+2.1hours) protocol, compared to +3.1hours and +2.8hours in DLMO, respectively. Exploratory group analysis comparing the phases of all metabolic biomarkers under both studies showed evidence of phase shifts due to simulated shiftwork. These results show that clinical biomarkers of metabolic health are under endogenous circadian regulation but that the expression of these rhythms is substantially influenced by environmental factors. These rhythms can also be reset, which has implications for understanding how both behavioral changes and circadian shifts due to shiftwork may disrupt metabolic function.