bims-ciryme Biomed News
on Circadian rhythms and metabolism
Issue of 2020‒03‒01
three papers selected by
Gabriela Da Silva Xavier
University of Birmingham

  1. Cells. 2020 Feb 20. pii: E489. [Epub ahead of print]9(2):
      Misalignment between natural light rhythm and modern life activities induces disruption of the circadian rhythm. It is mainly evident that light at night (LAN) interferes with the human endocrine system and contributes to the increasing rates of obesity and lipid metabolic disease. Maintaining hepatointestinal circadian homeostasis is vital for improving lipid homeostasis. Melatonin is a chronobiotic substance that plays a main role in stabilizing bodily rhythm and has shown beneficial effects in protecting against obesity. Based on the dual effect of circadian rhythm regulation and antiobesity, we tested the effect of melatonin in mice under constant light exposure. Exposure to 24-h constant light (LL) increased weight and insulin resistance compared with those of the control group (12-h light-12-h dark cycle, LD), and simultaneous supplementation in the melatonin group (LLM) ameliorated this phenotype. Constant light exposure disturbed the expression pattern of a series of transcripts, including lipid metabolism, circadian regulation and nuclear receptors in the liver. Melatonin also showed beneficial effects in improving lipid metabolism and circadian rhythm homeostasis. Furthermore, the LL group had increased absorption and digestion of lipids in the intestine as evidenced by the elevated influx of lipids in the duodenum and decrease in the efflux of lipids in the jejunum. More interestingly, melatonin ameliorated the gut microbiota dysbiosis and improved lipid efflux from the intestine. Thus, these findings offer a novel clue regarding the obesity-promoting effect attributed to LAN and suggest a possibility for obesity therapy by melatonin in which melatonin could ameliorate rhythm disorder and intestinal dysbiosis.
    Keywords:  LAN; hepatointestinal; lipid homeostasis; melatonin; microbiota
  2. Elife. 2020 Feb 26. pii: e55275. [Epub ahead of print]9
      Mammalian circadian rhythms are generated by a transcription-based feedback loop in which CLOCK:BMAL1 drives transcription of its repressors (PER1/2, CRY1/2), which ultimately interact with CLOCK:BMAL1 to close the feedback loop with ~24-hour periodicity. Here we pinpoint a key difference between CRY1 and CRY2 that underlies their differential strengths as transcriptional repressors. Both cryptochromes bind the BMAL1 transactivation domain similarly to sequester it from coactivators and repress CLOCK:BMAL1 activity. However, we find that CRY1 is recruited with much higher affinity to the PAS domain core of CLOCK:BMAL1, allowing it to serve as a stronger repressor that lengthens circadian period. We discovered a dynamic serine-rich loop adjacent to the secondary pocket in the photolyase homology region (PHR) domain that regulates differential binding of cryptochromes to the PAS domain core of CLOCK:BMAL1. Notably, binding of the co-repressor PER2 remodels the serine loop of CRY2, making it more CRY1-like and enhancing its affinity for CLOCK:BMAL1.
    Keywords:  biochemistry; chemical biology; mouse
  3. Endocrinology. 2020 Feb 26. pii: bqaa028. [Epub ahead of print]
      In female mammals, cycles in reproductive function depend both on the biological clock synchronized to the light/dark cycle, and a balance between the negative and positive feedbacks of estradiol whose concentration varies during oocyte maturation. In women, studies report that chronodisruptive environments such as shiftwork, may impair fertility and gestational success. The objective of this study was to explore the effects of shifted light/dark cycles on both the robustness of the estrous cycles and the timing of the preovulatory luteinizing hormone (LH) surge in female mice. When mice were exposed to a single 10 h-phase advance or 10 h-phase delay, the occurrence and timing of the LH surge and estrous cyclicity were recovered at the third estrous cycle. By contrast, when mice were exposed to chronic shifts (successive rotations of 10 h-phase advances for 3 days followed by 10 h-phase delays for 4 days), they exhibited a severely impaired reproductive activity. Most mice had no preovulatory LH surge already at the beginning of the chronic shifts. Furthermore, the gestational success of mice exposed to chronic shifts was reduced since the number of pups was two times lower in shifted as compared to control mice. In conclusion, this study reports that exposure of female mice to a single-phase shift has minor reproductive effects, whereas exposure to chronically disrupted light/dark cycles markedly impairs the occurrence of the preovulatory LH surge, leading to reduced fertility.
    Keywords:  Circadian disruptionShiftwork; Estrous cycle; Luteinizing Hormone surge