bims-ciryme 2020-11-08 papers

Endocrinology. 2020 Dec 01. pii: bqaa180. [Epub ahead of print]161(12):

The Circadian Clock, Shift Work, and Tissue-Specific Insulin Resistance.

Johanneke E Oosterman, Suzan Wopereis, Andries Kalsbeek.

Obesity and type 2 diabetes (T2D) have become a global health concern. The prevalence of obesity and T2D is significantly higher in shift workers compared to people working regular hours. An accepted hypothesis is that the increased risk for metabolic health problems arises from aberrantly timed eating behavior, that is, eating out of synchrony with the biological clock. The biological clock is part of the internal circadian timing system, which controls not only the sleep/wake and feeding/fasting cycle, but also many metabolic processes in the body, including the timing of our eating behavior, and processes involved in glucose homeostasis. Rodent studies have shown that eating out of phase with the endogenous clock results in desynchronization between rhythms of the central and peripheral clock systems and between rhythms of different tissue clocks (eg, liver and muscle clock). Glucose homeostasis is a complex process that involves multiple organs. In the healthiest situation, functional rhythms of these organs are synchronized. We hypothesize that desynchronization between different metabolically active organs contributes to alterations in glucose homeostasis. Here we summarize the most recent information on desynchronization between organs due to shift work and shifted food intake patterns and introduce the concept of phenotypic flexibility, a validated test to assess the contribution of each organ to insulin resistance (IR) in humans. We propose this test as a way to provide further insight into the possible desynchronization between tissue clocks. Because different types of IR benefit from different therapeutic approaches, we also describe different chronotherapeutic strategies to promote synchrony within and between metabolically active organs.

Keywords: circadian timing system; eating pattern; glucose; insulin resistance; shift work

DOI: https://doi.org/10.1210/endocr/bqaa180

Mol Metab. 2020 Oct 30. pii: S2212-8778(20)30184-8. [Epub ahead of print] 101110

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

Nicholas J Saner, Matthew J-C Lee, Jujiao Kuang, Nathan W Pitchford, Gregory D Roach, Andrew Garnham, Amanda J Genders, Tanner Stokes, Elizabeth A Schroder, Zhiguang Huo, Karyn A Esser, Stuart M Phillips, David J Bishop, Jonathan D Bartlett.

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. Given that exercise improves glucose tolerance, mitochondrial function, and alters circadian rhythms, we investigated whether exercise may counteract the effects induced by inadequate sleep.
METHODS: 24 healthy young males were allocated, so as to minimise between-group differences of baseline characteristics, 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 concurrent reductions 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

DOI: https://doi.org/10.1016/j.molmet.2020.101110

Sci Adv. 2020 Nov;pii: eabd0384. [Epub ahead of print]6(45):

The mammalian circadian pacemaker regulates wakefulness via CRF neurons in the paraventricular nucleus of the hypothalamus.

Daisuke Ono, Yasutaka Mukai, Chi Jung Hung, Srikanta Chowdhury, Takashi Sugiyama, Akihiro Yamanaka.

In mammals, the daily rhythms of physiological functions are timed by the central circadian clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Although the importance of the SCN for the regulation of sleep/wakefulness has been suggested, little is known about the neuronal projections from the SCN, which regulate sleep/wakefulness. Here, we show that corticotropin-releasing factor (CRF) neurons in the hypothalamic paraventricular nucleus mediate circadian rhythms in the SCN and regulate wakefulness. Optogenetic activation of CRF neurons promoted wakefulness through orexin/hypocretin neurons in the lateral hypothalamus. In vivo Ca2+ recording showed that CRF neurons were active at the initiation of wakefulness. Furthermore, chemogenetic suppression and ablation of CRF neurons decreased locomotor activity and time in wakefulness. Last, a combination of optical manipulation and Ca2+ imaging revealed that neuronal activity of CRF neurons was negatively regulated by GABAergic neurons in the SCN. Our findings provide notable insights into circadian regulation of sleep/wakefulness in mammals.

DOI: https://doi.org/10.1126/sciadv.abd0384

Front Cell Infect Microbiol. 2020 ;10 525097

Sleeping Sickness: A Tale of Two Clocks.

Filipa Rijo-Ferreira, Joseph S Takahashi.

Sleeping sickness is caused by a eukaryotic unicellular parasite known to infect wild animals, cattle, and humans. It causes a fatal disease that disrupts many rhythmic physiological processes, including daily rhythms of hormonal secretion, temperature regulation, and sleep, all of which are under circadian (24-h) control. In this review, we summarize research on sleeping sickness parasite biology and the impact it has on host health. We also consider the possible evolutionary advantages of sleep and circadian deregulation for the parasite.

Keywords: circadial rhythm disorders; circadian; infectious disease; parasite; sleep

DOI: https://doi.org/10.3389/fcimb.2020.525097

Neuroendocrinology. 2020 Oct 30.

CORTISOL CIRCADIAN RHYTHM AND INSULIN RESISTANCE IN MUSCLE: EFFECT OF DOSING AND TIMING OF HYDROCORTISONE EXPOSURE ON INSULIN SENSITIVITY IN SYNCHRONIZED MUSCLE CELLS.

Mariarosaria Negri, Claudia Pivonello, Chiara Simeoli, Gilda Di Gennaro, Mary Anna Venneri, Francesca Sciarra, Rosario Ferrigno, Cristina de Angelis, Emilia Sbardella, Maria Cristina De Martino, Annamaria Colao, Andrea M Isidori, Rosario Pivonello.

INTRODUCTION/AIM: Circadian rhythm disruption is emerging as a risk factor for metabolic disorders and particularly, alterations in clock genes circadian expression have been shown to influence insulin sensitivity. Recently, the reciprocal interplay between the circadian clock machinery and HPA axis has been largely demonstrated: the circadian clock may control the physiological circadian endogenous glucocorticoids secretion and action; glucocorticoids, in turn, are potent regulator of the circadian clock and their inappropriate replacement has been associated with metabolic impairment. The aim of the current study was to investigate in vitro the interaction between the timing-of-the-day exposure to different hydrocortisone (HC) concentrations on muscle insulin sensitivity.
METHODS: Serum-shock synchronized mouse skeletal muscle C2C12 cells were exposed to different HC concentrations recapitulating the circulating daily physiological cortisol profile (standard cortisol profile), the circulating daily cortisol profile that reached in adrenal insufficient (AI) patients treated with once-daily MR-HC (flat cortisol profile) and treated with thrice-daily of conventional IR-HC (steep cortisol profile). The 24 hrs spontaneous oscillation of the clock genes in synchronized C2C12 cells was used to align the timing for in vitro HC exposure (Bmal1 acrophase, midphase and bathyphase) with the reference times of cortisol peaks in AI treated with IR-HC (8 am, 1 pm, 6 pm). A panel of 84 insulin sensitivity related genes and intracellular insulin signaling proteins were analyzed by RT-qPCR and western blot, respectively.
RESULTS: Only the steep profile, characterized by a higher HC exposure during Bmal1 bathyphase, produced significant downregulation in 21 insulin sensitivity-related genes. Among these, Insr, Irs1, Irs2, Pi3kca and Adipor2 were downregulated when compared the flat to the standard or steep profile. Reduced intracellular IRS1 Tyr608, AKT Ser473, AMPK Thr172 and ACC Ser79 phosphorylations were also observed.
CONCLUSIONS: The current study demonstrated that is late-in-the-day cortisol exposure that modulates insulin sensitivity-related genes expression and intracellular insulin signaling in skeletal muscle cells.

DOI: https://doi.org/10.1159/000512685