bims-ciryme 2020-11-15 papers

on Circadian rhythms and metabolism

Issue of 2020–11–15
two papers selected by
Gabriela Da Silva Xavier, University of Birmingham

Reshaping circadian metabolism in the suprachiasmatic nucleus and prefrontal cortex by nutritional challenge.
The core clock transcription factor BMAL1 drives circadian β-cell proliferation during compensatory regeneration of the endocrine pancreas.

Proc Natl Acad Sci U S A. 2020 Nov 10. pii: 202016589. [Epub ahead of print]

Reshaping circadian metabolism in the suprachiasmatic nucleus and prefrontal cortex by nutritional challenge.

Paola Tognini, Muntaha Samad, Kenichiro Kinouchi, Yu Liu, Jean-Christophe Helbling, Marie-Pierre Moisan, Kristin L Eckel-Mahan, Pierre Baldi, Paolo Sassone-Corsi.

  Food is a powerful entrainment cue for circadian clocks in peripheral tissues, and changes in the composition of nutrients have been demonstrated to metabolically reprogram peripheral clocks. However, how food challenges may influence circadian metabolism of the master clock in the suprachiasmatic nucleus (SCN) or in other brain areas is poorly understood. Using high-throughput metabolomics, we studied the circadian metabolome profiles of the SCN and medial prefrontal cortex (mPFC) in lean mice compared with mice challenged with a high-fat diet (HFD). Both the mPFC and the SCN displayed a robust cyclic metabolism, with a strikingly high sensitivity to HFD perturbation in an area-specific manner. The phase and amplitude of oscillations were drastically different between the SCN and mPFC, and the metabolic pathways impacted by HFD were remarkably region-dependent. Furthermore, HFD induced a significant increase in the number of cycling metabolites exclusively in the SCN, revealing an unsuspected susceptibility of the master clock to food stress.

Keywords:  circadian clock; high-fat diet; metabolome reorganization; prefrontal cortex; suprachiasmatic nucleus

DOI:  https://doi.org/10.1073/pnas.2016589117
Genes Dev. 2020 Nov 12.

The core clock transcription factor BMAL1 drives circadian β-cell proliferation during compensatory regeneration of the endocrine pancreas.

Volodymyr Petrenko, Miri Stolovich-Rain, Bart Vandereycken, Laurianne Giovannoni, Kai-Florian Storch, Yuval Dor, Simona Chera, Charna Dibner.

  Circadian clocks in pancreatic islets participate in the regulation of glucose homeostasis. Here we examined the role of these timekeepers in β-cell regeneration after the massive ablation of β cells by doxycycline-induced expression of diphtheria toxin A (DTA) in Insulin-rtTA/TET-DTA mice. Since we crossed reporter genes expressing α- and β-cell-specific fluorescent proteins into these mice, we could follow the fate of α- and β cells separately. As expected, DTA induction resulted in an acute hyperglycemia, which was accompanied by dramatic changes in gene expression in residual β cells. In contrast, only temporal alterations of gene expression were observed in α cells. Interestingly, β cells entered S phase preferentially during the nocturnal activity phase, indicating that the diurnal rhythm also plays a role in the orchestration of β-cell regeneration. Indeed, in arrhythmic Bmal1-deficient mice, which lack circadian clocks, no compensatory β-cell proliferation was observed, and the β-cell ablation led to aggravated hyperglycemia, hyperglucagonemia, and fatal diabetes.

Keywords:  Insulin-rtTA/TET-DTA mouse model; circadian clockwork; diabetes; glucose metabolism; pancreatic α and β cells; β-cell proliferation; β-cell regeneration

DOI:  https://doi.org/10.1101/gad.343137.120