bims-ciryme Biomed News
on Circadian rhythms and metabolism
Issue of 2026–09–13
two papers selected by
Gabriela Da Silva Xavier, University of Birmingham
  1. Cell-type-specific circadian and light-responsive transcriptional dynamics in adult Drosophila neurons.
  2. Time-restricted feeding improved metabolic hormone levels and energy metabolism in high-fat diet-fed Leap2-/- Mice.
  1. Proc Natl Acad Sci U S A. 2026 Sep 15. 123(37): e2619143123
    Cell-type-specific circadian and light-responsive transcriptional dynamics in adult Drosophila neurons.
    Gillian Berglund, Pranav Ojha, Maria Ivanova, Melina Pérez Torres, Michael Rosbash.
      The Drosophila adult central brain contains 240 circadian neurons, of which there are more than 25 different neuron subtypes based on connectomic data. Recent single-cell RNA-seq characterization of these neurons "around the clock" also indicates a similar number of molecular subtypes of circadian neurons, but other conclusions from these transcriptomic studies warranted verifying and extending with other approaches. To address these limitations, we used three complementary approaches: 1) We used a genetic multiplexing strategy to profile the transcriptomes of circadian neurons from multiple time points in a single experiment, reducing confounding technical variation between timepoints; 2) Large numbers of single nuclei were sequenced (snRNA-seq), which was enabled because the method El-INTACT purifies nuclei from frozen heads; 3) We assayed 12 time points under both light-dark and constant darkness conditions. These approaches showed dramatic transcriptional differences between time points in many circadian neuron types and enhanced time-of-day gene expression analysis. The data indicate that most of this regulation is transcriptional and circadian. There were however a small number of light-dependent transcripts, including some that correspond to mammalian immediate-early genes. They probably play a role in the light-regulation of gene expression and behavior in specific neurons, perhaps circadian entrainment or phase-shifting. The results taken together provide a more comprehensive picture of gene expression heterogeneity within adult Drosophila circadian neurons including how intrinsic clock mechanisms and light cues are integrated across circadian neuron subtypes.
    Keywords:  circadian neurons; immediate-early genes; snRNA-Seq
    DOI:  https://doi.org/10.1073/pnas.2619143123
  2. J Endocrinol. 2026 Sep 08. pii: JOE-25-0416. [Epub ahead of print]
    Time-restricted feeding improved metabolic hormone levels and energy metabolism in high-fat diet-fed Leap2-/- Mice.
    Jianmei Yang, Ying Zhao, Yueli Pu, Yang Chen, Yinfang Chen, Lisha Yi, Peter Y Liu, Chen Chen.
      Time-restricted feeding combats obesity by restoring the insulin/growth hormone ratio. Growth hormone and appetite are stimulated by ghrelin but inhibited by Leap2. Whether time-restricted feeding reduces weight gain through Leap2 inhibition is unknown. Ten-week-old male Leap2+/+ and Leap2-/- mice were divided randomly into four groups: Leap2+/+ normal diet (n=6), Leap2+/+ high-fat diet (n=6), Leap2-/- normal diet (n=8), and Leap2-/- high-fat diet (n=8). Body weight was measured weekly. In further experiments, the Leap2-/- high-fat diet mice were randomly assigned to time-restricted feeding or control for 10 weeks. Metabolic parameters were monitored; growth hormone profiles in 6 hours were obtained at week 5, and insulin and glucose tolerance tests were performed at week 8 or 9. Expression of metabolism-related genes was assessed in the liver, white adipose, and brown adipose after 10 weeks. Body weight was significantly increased in Leap2-/- mice with normal diet and further increased in both Leap2-/- and wild-type mice by high-fat diet, with more weight gain in Leap2-/- mice. Time-restricted feeding decreased body weight, fat, and liver weight; improved growth hormone pulsatility, insulin sensitivity, and glucose tolerance; and enhanced lipid metabolism, oxygen consumption, and physical activity during the dark phase, while altering gene expression related to glucose and lipid utilization. It decreased adipocyte size and prevented liver fat accumulation. Although Leap2-/- mice gained more weight during high-fat diet, time-restricted feeding improved growth hormone, insulin, glucose, and lipid metabolism without changing total caloric intake over the 10-week protocol, similar to that observed in wild-type mice.
    Keywords:   Leap2; High fat diet; Insulin; Time-restricted feeding; growth hormone
    DOI:  https://doi.org/10.1530/JOE-25-0416
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