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. 2015 Nov 1;38(11):1683-91.
doi: 10.5665/sleep.5142.

Changes in Plasma Lipids During Exposure to Total Sleep Deprivation

Free PMC article

Changes in Plasma Lipids During Exposure to Total Sleep Deprivation

Eric Chern-Pin Chua et al. Sleep. .
Free PMC article


Study objectives: The effects of sleep loss on plasma lipids, which play an important role in energy homeostasis and signaling, have not been systematically examined. Our aim was to identify lipid species in plasma that increase or decrease reliably during exposure to total sleep deprivation.

Design: Twenty individuals underwent sleep deprivation in a laboratory setting. Blood was drawn every 4 h and mass spectrometry techniques were used to analyze concentrations of 263 lipid species in plasma, including glycerolipids, glycerophospholipids, sphingolipids, and sterols.

Setting: Chronobiology and Sleep Laboratory, Duke-NUS Graduate Medical School.

Participants: Healthy ethnic-Chinese males aged 21-28 y (n = 20).

Interventions: Subjects were kept awake for 40 consecutive hours.

Measurements and results: Each metabolite time series was modeled as a sum of sinusoidal (circadian) and linear components, and we assessed whether the slope of the linear component differed from zero. More than a third of all individually analyzed lipid profiles exhibited a circadian rhythm and/or a linear change in concentration during sleep deprivation. Twenty-five lipid species showed a linear and predominantly unidirectional trend in concentration levels that was consistent across participants. Choline plasmalogen levels decreased, whereas several phosphatidylcholine (PC) species and triacylglycerides (TAG) carrying polyunsaturated fatty acids increased.

Conclusions: The decrease in choline plasmalogen levels during sleep deprivation is consistent with prior work demonstrating that these lipids are susceptible to degradation by oxidative stress. The increase in phosphatidylcholines and triacylglycerides suggests that sleep loss might modulate lipid metabolism, which has potential implications for metabolic health in individuals who do not achieve adequate sleep.

Keywords: circadian; lipids; metabolism; sleep deprivation.


Figure 1
Figure 1
Circadian and linear trends in lipid metabolite concentrations during prolonged wakefulness. Representative lipids are shown that exhibited circadian variation and either a linear increase (TAG 54:4, Subject F) or decrease (PC 40:4p, Subject I) in plasma concentrations during total sleep deprivation. For each subject and metabolite, the time course of concentrations was modeled as a sum of sinusoidal and linear components (top), which allowed for separate analysis of circadian (middle) and linear trends (bottom) in the time series. Black circles show z-scored concentration values for replicate samples at each time point, and the traces indicate the best-fit regression line. Vertical gray bars show the usual hours of sleep. Results are shown using relative clock time with relative bedtime defined as midnight, as study events were timed according to each person's prestudy sleep-wake schedule. The total number of acyl carbons and double bonds is indicated for each metabolite (carbons:double bonds).
Figure 2
Figure 2
Plasma lipid concentrations show substantial variation during total sleep deprivation. (A) The heat map shows circadian-regulated lipid metabolites across a group of 20 subjects. Colors show z-scored concentration levels. Individual metabolite traces are organized from top to bottom by lipid categories including glycerolipids (GL), glycerophospholipids (GP), and sphingolipids (SP). Within each lipid category, metabolites are arranged from top to bottom by the timing of their peak concentration levels. (B) The heat map shows lipids that exhibited a decreasing or increasing linear trend during prolonged wakefulness, after taking into account underlying circadian variation in the metabolite time-series. Data are displayed as in A, with hotter colors corresponding to higher concentrations, and cooler colors showing lower concentration levels in plasma. (C) The Venn diagram shows the number and overlap of individual lipid profiles that exhibited circadian (cycling) behavior and either a linear decrease or increase during the sleep deprivation protocol. The sizes of the rings correspond to the number of metabolites, and percentages are shown relative to all individual metabolite traces examined (i.e., of 5,260 lipid profiles). (D) Pie charts show the proportions of lipid metabolites that exhibited cycling and/or linear trends in each of the major lipid categories examined. The size of each pie corresponds to the number of lipids analyzed within each category.
Figure 3
Figure 3
Linear decrease in choline plasmalogen levels during total sleep deprivation. The linear trend is shown for a representative plasmalogen species (PC 34:2p), after taking into account the circadian component. The concentration of PC 34:2p decreased over time in 15 of 20 subjects. Subject codes are shown at the top of each plot and vertical gray bars highlight the usual hours of sleep. One participant showed a linear increase in PC 34:2p (Subject Q), whereas the slope in the other four subjects was not significant (Subjects J, L, O, and T; not shown). Black circles show z-scored concentration values in replicate samples at each time point with the best-fit linear regression.
Figure 4
Figure 4
Lipid species that increased or decreased reliably across subjects during total sleep deprivation. The heat map shows lipid species that exhibited a significant linear trend in at least half of study participants. In each subject (labeled A to T), metabolites that decreased are shown in dark blue, and metabolites that increased are shown in red. Lipids that did not show a significant increasing or decreasing trend over time are shown in light blue. The horizontal bar graph on the right summarizes the number of subjects who showed an increasing or decreasing trend in plasma concentration levels for each lipid species labeled on the left of the heat map. The suffix “p” indicates the plasmalogen form of PC. The total number of acyl carbons and double bonds is indicated for each metabolite (carbons:double bonds). DAG, diacylglyceride; PC, phosphatidylcholine; PI, phosphatidylinositol; SM, sphingomyelin; TAG, triacylglyceride.
Figure 5
Figure 5
Time course of phosphatidylcholine (PC) and triacylglyceride (TAG) levels in human plasma during sleep deprivation. Changes in total molar concentration of the plasmalogen form of PC (PCp, 20 species), diacyl PC (21 species), and TAG (64 species) are shown for 20 subjects who were kept awake for 40 consecutive hours using constant routine procedures. In addition to circadian variation in the time series, there was a decrease in choline plasmalogen over time (top). As shown by the gray trace, a decreasing trend in total ethanolamine plasmalogen (PEp, 18 species) was also observed. In contrast, the total concentration of diacyl PC (middle) and TAG (bottom) increased in plasma. Vertical gray bars highlight the usual hours of sleep. Each trace shows the average of z-scored concentrations across subjects. Error bars show the standard error of the mean.

Comment in

  • In Pursuit of Sleep-Circadian Biomarkers.
    Mullington J, Pack AI, Ginsburg GS. Mullington J, et al. Sleep. 2015 Nov 1;38(11):1665-6. doi: 10.5665/sleep.5132. Sleep. 2015. PMID: 26446123 Free PMC article. No abstract available.

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