Higher central circadian temperature amplitude is associated with greater metabolite rhythmicity in humans

Abstract

Robust circadian rhythms are essential for optimal health. The central circadian clock controls temperature rhythms, which are known to organize the timing of peripheral circadian rhythms in rodents. In humans, however, it is unknown whether temperature rhythms relate to the organization of circadian rhythms throughout the body. We assessed core body temperature amplitude and the rhythmicity of 929 blood plasma metabolites across a 40-h constant routine protocol, controlling for behavioral and environmental factors that mask endogenous temperature rhythms, in 23 healthy individuals (mean [± SD] age = 25.4 ± 5.7 years, 5 women). Valid core body temperature data were available in 17/23 (mean [± SD] age = 25.6 ± 6.3 years, 1 woman). Individuals with higher core body temperature amplitude had a greater number of metabolites exhibiting circadian rhythms (R² = 0.37, p = .009). Higher core body temperature amplitude was also associated with less variability in the free-fitted periods of metabolite rhythms within an individual (R² = 0.47, p = .002). These findings indicate that a more robust central circadian clock is associated with greater organization of circadian metabolite rhythms in humans. Metabolite rhythms may therefore provide a window into the strength of the central circadian clock.

Keywords: Biological rhythms; Circadian clock; Circadian organization; Core body temperature; Peripheral oscillators.

Figure 1

(A) Circadian metabolites that were significantly rhythmic for each participant. Rows represent the 17 participants, ordered by core body temperature amplitude, and columns represent the 46 circadian metabolites, ordered by number of significantly rhythmic instances across participants. (B) Core body temperature, split by tertiles into low (red; N = 6), moderate (purple; N = 5), and high (blue; N = 6) circadian amplitude. Color groupings map to rows indicated by the colored brackets in panel A. Points and error bars represent mean and standard deviation of core body temperature within 2-h bins relative to core body temperature minima. (C) Higher core body temperature amplitude was associated with a greater number of rhythmic circadian metabolites. (D) Higher core body temperature amplitude was associated with lower within-individual variability in metabolite periods. Linear models (black line) and corresponding 95% confidence intervals (gray shading) are shown for both associations. Variability in the metabolite period distribution is shown for the participants with the lowest (E) and highest (F) core body temperature amplitudes, plotted as the difference in period for each rhythmic metabolite from each participant’s mean metabolite period.