bims-ciryme 2020-09-20 papers

Nat Commun. 2020 09 16. 11(1): 4643

Time-restricted feeding alters lipid and amino acid metabolite rhythmicity without perturbing clock gene expression.

Leonidas S Lundell, Evelyn B Parr, Brooke L Devlin, Lars R Ingerslev, Ali Altıntaş, Shogo Sato, Paolo Sassone-Corsi, Romain Barrès, Juleen R Zierath, John A Hawley.

Time-restricted feeding (TRF) improves metabolism independent of dietary macronutrient composition or energy restriction. To elucidate mechanisms underpinning the effects of short-term TRF, we investigated skeletal muscle and serum metabolic and transcriptomic profiles from 11 men with overweight/obesity after TRF (8 h day-1) and extended feeding (EXF, 15 h day-1) in a randomised cross-over design (trial registration: ACTRN12617000165381). Here we show that muscle core clock gene expression was similar after both interventions. TRF increases the amplitude of oscillating muscle transcripts, but not muscle or serum metabolites. In muscle, TRF induces rhythmicity of several amino acid transporter genes and metabolites. In serum, lipids are the largest class of periodic metabolites, while the majority of phase-shifted metabolites are amino acid related. In conclusion, short-term TRF in overweight men affects the rhythmicity of serum and muscle metabolites and regulates the rhythmicity of genes controlling amino acid transport, without perturbing core clock gene expression.

DOI: https://doi.org/10.1038/s41467-020-18412-w

Nat Commun. 2020 09 14. 11(1): 4614

TRESK is a key regulator of nocturnal suprachiasmatic nucleus dynamics and light adaptive responses.

Tatjana Lalic, Aiste Steponenaite, Liting Wei, Sridhar R Vasudevan, Alistair Mathie, Stuart N Peirson, Gurprit S Lall, M Zameel Cader.

The suprachiasmatic nucleus (SCN) is a complex structure dependent upon multiple mechanisms to ensure rhythmic electrical activity that varies between day and night, to determine circadian adaptation and behaviours. SCN neurons are exposed to glutamate from multiple sources including from the retino-hypothalamic tract and from astrocytes. However, the mechanism preventing inappropriate post-synaptic glutamatergic effects is unexplored and unknown. Unexpectedly we discovered that TRESK, a calcium regulated two-pore potassium channel, plays a crucial role in this system. We propose that glutamate activates TRESK through NMDA and AMPA mediated calcium influx and calcineurin activation to then oppose further membrane depolarisation and rising intracellular calcium. Hence, in the absence of TRESK, glutamatergic activity is unregulated leading to membrane depolarisation, increased nocturnal SCN firing, inverted basal calcium levels and impaired sensitivity in light induced phase delays. Our data reveals TRESK plays an essential part in SCN regulatory mechanisms and light induced adaptive behaviours.

DOI: https://doi.org/10.1038/s41467-020-17978-9

Science. 2020 Sep 18. 369(6510): 1450-1455

Species-specific segmentation clock periods are due to differential biochemical reaction speeds.

Mitsuhiro Matsuda, Hanako Hayashi, Jordi Garcia-Ojalvo, Kumiko Yoshioka-Kobayashi, Ryoichiro Kageyama, Yoshihiro Yamanaka, Makoto Ikeya, Junya Toguchida, Cantas Alev, Miki Ebisuya.

Although mechanisms of embryonic development are similar between mice and humans, the time scale is generally slower in humans. To investigate these interspecies differences in development, we recapitulate murine and human segmentation clocks that display 2- to 3-hour and 5- to 6-hour oscillation periods, respectively. Our interspecies genome-swapping analyses indicate that the period difference is not due to sequence differences in the HES7 locus, the core gene of the segmentation clock. Instead, we demonstrate that multiple biochemical reactions of HES7, including the degradation and expression delays, are slower in human cells than they are in mouse cells. With the measured biochemical parameters, our mathematical model accounts for the two- to threefold period difference between the species. We propose that cell-autonomous differences in biochemical reaction speeds underlie temporal differences in development between species.

DOI: https://doi.org/10.1126/science.aba7668