bims-ciryme 2019-12-01 papers

Mol Metab. 2019 Dec;pii: S2212-8778(19)30915-9. [Epub ahead of print]30 140-151

Circadian clock network desynchrony promotes weight gain and alters glucose homeostasis in mice.

Isa Kolbe, Brinja Leinweber, Matthias Brandenburger, Henrik Oster.

OBJECTIVE: A network of endogenous circadian clocks adapts physiology and behavior to recurring changes in environmental demands across the 24-hour day cycle. Circadian disruption promotes weight gain and type 2 diabetes development. In this study, we aim to dissect the roles of different tissue clocks in the regulation of energy metabolism.
METHODS: We used mice with genetically ablated clock function in the circadian pacemaker of the suprachiasmatic nucleus (SCN) under different light and feeding conditions to study peripheral clock resetting and the role of the peripheral clock network in the regulation of glucose handling and metabolic homeostasis.
RESULTS: In SCN clock-deficient mice, behavioral and non-SCN tissue clock rhythms are sustained under rhythmic lighting conditions but deteriorate quickly in constant darkness. In parallel to the loss of behavioral and molecular rhythms, the animals develop adiposity and impaired glucose utilization in constant darkness. Restoring peripheral clock rhythmicity and synchrony by time-restricted feeding normalizes body weight and glucose metabolism.
CONCLUSIONS: These data reveal the importance of an overall synchronized circadian clockwork for the maintenance of metabolic homeostasis.

Keywords: Body weight; Circadian clock; Constant darkness; Glucose metabolism; Light-dark cycle; Suprachiasmatic nucleus

DOI: https://doi.org/10.1016/j.molmet.2019.09.012

Proc Natl Acad Sci U S A. 2019 Nov 27. pii: 201910590. [Epub ahead of print]

Sleep-wake-driven and circadian contributions to daily rhythms in gene expression and chromatin accessibility in the murine cortex.

Charlotte N Hor, Jake Yeung, Maxime Jan, Yann Emmenegger, Jeffrey Hubbard, Ioannis Xenarios, Felix Naef, Paul Franken.

The timing and duration of sleep results from the interaction between a homeostatic sleep-wake-driven process and a periodic circadian process, and involves changes in gene regulation and expression. Unraveling the contributions of both processes and their interaction to transcriptional and epigenomic regulatory dynamics requires sampling over time under conditions of unperturbed and perturbed sleep. We profiled mRNA expression and chromatin accessibility in the cerebral cortex of mice over a 3-d period, including a 6-h sleep deprivation (SD) on day 2. We used mathematical modeling to integrate time series of mRNA expression data with sleep-wake history, which established that a large proportion of rhythmic genes are governed by the homeostatic process with varying degrees of interaction with the circadian process, sometimes working in opposition. Remarkably, SD caused long-term effects on gene-expression dynamics, outlasting phenotypic recovery, most strikingly illustrated by a damped oscillation of most core clock genes, including Arntl/Bmal1, suggesting that enforced wakefulness directly impacts the molecular clock machinery. Chromatin accessibility proved highly plastic and dynamically affected by SD. Dynamics in distal regions, rather than promoters, correlated with mRNA expression, implying that changes in expression result from constitutively accessible promoters under the influence of enhancers or repressors. Serum response factor (SRF) was predicted as a transcriptional regulator driving immediate response, suggesting that SRF activity mirrors the build-up and release of sleep pressure. Our results demonstrate that a single, short SD has long-term aftereffects at the genomic regulatory level and highlights the importance of the sleep-wake distribution to diurnal rhythmicity and circadian processes.

Keywords: circadian; epigenetics; gene expression; long-term effects; sleep

DOI: https://doi.org/10.1073/pnas.1910590116

Nat Cell Biol. 2019 Nov 25.

Diurnal oscillations of endogenous H2O2 sustained by p66Shc regulate circadian clocks.

Jian-Fei Pei, Xun-Kai Li, Wen-Qi Li, Qian Gao, Yang Zhang, Xiao-Man Wang, Jia-Qi Fu, Shen-Shen Cui, Jia-Hua Qu, Xiang Zhao, De-Long Hao, Dapeng Ju, Na Liu, Kate S Carroll, Jing Yang, Eric Erquan Zhang, Ji-Min Cao, Hou-Zao Chen, De-Pei Liu.

Redox balance, an essential feature of healthy physiological steady states, is regulated by circadian clocks, but whether or how endogenous redox signalling conversely regulates clockworks in mammals remains unknown. Here, we report circadian rhythms in the levels of endogenous H2O2 in mammalian cells and mouse livers. Using an unbiased method to screen for H2O2-sensitive transcription factors, we discovered that rhythmic redox control of CLOCK directly by endogenous H2O2 oscillations is required for proper intracellular clock function. Importantly, perturbations in the rhythm of H2O2 levels induced by the loss of p66Shc, which oscillates rhythmically in the liver and suprachiasmatic nucleus (SCN) of mice, disturb the rhythmic redox control of CLOCK function, reprogram hepatic transcriptome oscillations, lengthen the circadian period in mice and modulate light-induced clock resetting. Our findings suggest that redox signalling rhythms are intrinsically coupled to the circadian system through reversible oxidative modification of CLOCK and constitute essential mechanistic timekeeping components in mammals.

DOI: https://doi.org/10.1038/s41556-019-0420-4

Br J Nutr. 2019 Nov 27. 1-24

Circadian misalignment imposed by nocturnal feeding tends to increase fat deposition in pigs.

Rik J J van Erp, Sonja de Vries, Theo A T G van Kempen, Leo A Den Hartog, Walter J J Gerrits.

Misalignment of day/night and feeding rhythms have been shown to increase fat deposition and the risk for metabolic disorders in humans and rodents. In most studies, however, food intake and intake patterns are not controlled. We studied the effects of circadian misalignment on energy expenditure in pigs in a setting in which we controlled food intake as well as intake patterns. Twelve groups of five male pigs were housed in respiration chambers and fed either during the day (10.00 - 18.00 hours; diurnal feeding: DF) or night (22.00 - 06.00 hours; nocturnal feeding: NF), bihourly the same sequential meals, representing 15, 10, 25, 30 and 20% of the daily allowance. Paired feeding was applied to ensure equal gross energy intake between treatments. Apparent total tract digestibility, energy balances, and heat partitioning were measured, and analysed using a mixed linear model. Apparent total tract energy and dry matter digestibility tended to be lower for NF-pigs than DF-pigs (P < 0·10). Heat production was 3% lower for NF-pigs than DF-pigs (P < 0·026) increasing fat retention by 7% in NF-pigs (P = 0·050). Nocturnal-fed pigs were less active than DF-pigs during the feeding period, but more active during the fasting period. Resting metabolic rate was greater for DF-pigs than NF-pigs during the fasting period. Methane production was 30% greater in NF-pigs than in DF-pigs (P < 0·001). In conclusion, circadian misalignment has little effect on nutrient digestion, but alters nutrient partitioning, ultimately increasing fat deposition. The causality of the association between circadian misalignment and methane production rates remains to be investigated.

Keywords: Circadian clock; Energy metabolism; Feed intake pattern; Heat production; Methane production

DOI: https://doi.org/10.1017/S0007114519003052