Endogenous circadian regulation and phase resetting of clinical metabolic biomarkers

Jun 12, 2021Journal of pineal research

Natural body clock control and daily timing changes of key metabolic health markers

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Abstract

Endogenous circadian rhythms in cholesterol and other metabolic biomarkers were observed in a study involving 41 participants.

Circadian rhythms in cholesterol, HDL, LDL, albumin, total protein, VLDL, and triglycerides were identified under constant routine conditions.
These rhythms were largely obscured under typical daily conditions, with the exception of cholesterol, which maintained similar phases in both settings.
Simulated shiftwork resulted in a significant delay of the cholesterol rhythm by approximately -3.7 to -4.2 hours and a notable advance by +5.1 hours in abrupt shift protocols.
Dim Light Melatonin Onset (DLMO) also showed similar phase shifts during shiftwork simulations, with changes of -6.6 hours and +3.1 hours depending on the protocol.
Exploratory analysis indicated that metabolic biomarkers may experience phase shifts due to the effects of simulated shiftwork.

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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 40 hours constant routine protocol (CR; constant environmental and behavioral conditions) and evaluated the impact of typical daily conditions with periodic sleep and meals (baseline; 8 hours sleep at night, four meals during a 16 hour 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 ± 2.3 years), 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 ± 8.9 years) across four protocols; two with abrupt 8 hour delay shifts and exposure to either blue-enriched or standard white light; and either an abrupt or gradual 8 hour advance (1.6 hours/day over 5 days) both with exposure to blue-enriched white light. In the delay protocols, the cholesterol rhythm shifted later by -3.7 hours and -4.2 hours, respectively, compared to -6.6 hours and -4.7 hours, for DLMO. There was a significant advance in cholesterol in the abrupt (+5.1 hours) but not the gradual (+2.1 hours) protocol, compared to +3.1 hours and +2.8 hours 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.

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Endogenous circadian regulation and phase resetting of clinical metabolic biomarkers

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