Exercise mitigates sleep-loss-induced changes in glucose tolerance, mitochondrial function, sarcoplasmic protein synthesis, and diurnal rhythms

Abstract

Objective: Sleep loss has emerged as a risk factor for the development of impaired glucose tolerance. The mechanisms underpinning this observation are unknown; however, both mitochondrial dysfunction and circadian misalignment have been proposed. Because exercise improves glucose tolerance and mitochondrial function, and alters circadian rhythms, we investigated whether exercise may counteract the effects induced by inadequate sleep.

Methods: To minimize between-group differences of baseline characteristics, 24 healthy young males were allocated into one of the three experimental groups: a Normal Sleep (NS) group (8 h time in bed (TIB) per night, for five nights), a Sleep Restriction (SR) group (4 h TIB per night, for five nights), and a Sleep Restriction and Exercise group (SR+EX) (4 h TIB per night, for five nights and three high-intensity interval exercise (HIIE) sessions). Glucose tolerance, mitochondrial respiratory function, sarcoplasmic protein synthesis (SarcPS), and diurnal measures of peripheral skin temperature were assessed pre- and post-intervention.

Results: We report that the SR group had reduced glucose tolerance post-intervention (mean change ± SD, P value, SR glucose AUC: 149 ± 115 A.U., P = 0.002), which was also associated with reductions in mitochondrial respiratory function (SR: -15.9 ± 12.4 pmol O₂.s^-1.mg^-1, P = 0.001), a lower rate of SarcPS (FSR%/day SR: 1.11 ± 0.25%, P < 0.001), and reduced amplitude of diurnal rhythms. These effects were not observed when incorporating three sessions of HIIE during this period (SR+EX: glucose AUC 67 ± 57, P = 0.239, mitochondrial respiratory function: 0.6 ± 11.8 pmol O₂.s^-1.mg^-1, P = 0.997, and SarcPS (FSR%/day): 1.77 ± 0.22%, P = 0.971).

Conclusions: A five-night period of sleep restriction leads to reductions in mitochondrial respiratory function, SarcPS, and amplitude of skin temperature diurnal rhythms, with a concurrent reduction in glucose tolerance. We provide novel data demonstrating that these same detrimental effects are not observed when HIIE is performed during the period of sleep restriction. These data therefore provide evidence in support of the use of HIIE as an intervention to mitigate the detrimental physiological effects of sleep loss.

Keywords: Circadian rhythms; Exercise; Glucose tolerance; Mitochondria; Sleep.

Graphical abstract

Figure 1

Schematic representation of the study protocol. OGTT – oral glucose tolerance test, GXT – graded exercise test, D₂O – deuterium oxide ingestion, HIIE – high-intensity interval exercise, R – ad libitum recovery sleep, PSG – polysomnography sleep monitoring, participant screening refers to medical questionnaires, exclusion criteria, and habitual sleep and physical activity monitoring.

Figure 2

Measures of diurnal peripheral skin temperature A) basal skin temperature, B) amplitude, and C) coefficient of fit (R²) pre- and post-intervention. Pre-intervention measurements are Day 2 and 3 (until 23:00 h) and the post-intervention measurements are Day 6 and Day 7. Normal Sleep (NS, n = 8), Sleep Restriction (SR, n = 8), and Sleep Restriction and Exercise (SR+EX, n = 8). ∗ Denotes significant within-group differences from pre- to post-intervention (P < 0.05).

Figure 3

Plasma glucose and insulin concentrations for pre- and post-intervention oral glucose tolerance tests (OGTT). Plasma glucose and insulin concentrations throughout the 120-minute OGTT in the (A, B) Normal Sleep (NS), (C, D) Sleep Restriction (SR), and (E, F) Sleep Restriction and Exercise (SR+EX) groups. G) glucose and H) insulin total area under the curve (AUC) during the OGTT. Values are mean$\pm$ SD, individual data points are shown, ∗ Denotes significant within-group differences from pre- to post-intervention (P < 0.05). # Denotes significant between group difference for the change from pre- to post-intervention compared to the NS group (P < 0.05). n = 8 per group.

Figure 4

Mitochondrial respiratory function and markers of mitochondrial content from pre-intervention compared to post-intervention. A) Mitochondrial respiratory function in the Normal Sleep (NS), Sleep Restriction (SR), and Sleep Restriction and Exercise (SR+EX) groups. (B) Citrate synthase activity and (C) fold-change of protein content for subunits of mitochondrial complexes (I–V) from pre- to post-intervention. Mitochondrial complex 1 (CI) - NDUFB8, Complex 2 (CII) - SDHB, Complex 3 (CIII) - Core protein 2 (UQCCRC2), Complex 4 (CIV) – MTCO, and Complex 5 (CV) – ATP5A. (D) Representative image of protein content for mitochondrial complexes. (ETF+CI+CII)_P- maximal coupled mitochondrial respiration through ETF, CI and CII; Pre – pre-intervention, Post – post-intervention. n = 8 per group. ∗ Denotes significant difference within group from pre- to post-intervention (P < 0.05). δ Denotes significant between group difference, for the change from pre- to post-intervention compared to the SR+EX group (P < 0.05).

Figure 5

Citrate synthase (CS) activity from fractionated skeletal muscle samples and sarcoplasmic protein synthesis (SarcPS) – A) CS activity of whole-muscle lysate (Total), myofibrillar (Myo), and sarcoplasmic (Sarc) fractions were assessed from the same muscle samples (n = 5). B) Fractional synthetic rate (FSR) of SarcPS during the sleep intervention. Data are mean ± SD. Normal Sleep (NS), Sleep Restriction (SR), and Sleep Restriction + Exercise (SR+EX), n = 8 per group. ∗ Denotes significantly different from other groups (P < 0.05).

Figure 6

Skeletal muscle mitochondrial-, circadian-, and glucose-related protein content A) PGC-1α, B) DRP1, C) MFN2, D) p53, E) BMAL1, F) GLUT4, and G) representative western blot images. Data are mean values ± SD, normalized to pre-intervention values. Normal Sleep (NS), Sleep Restriction (SR) and Sleep Restriction and Exercise (SR+EX), n = 8 per group. ∗ Denotes significant change from pre-intervention (P < 0.05).