bims-ciryme 2026-04-19 papers

PLoS Biol. 2026 Apr 15. 24(4): e3003475

Circadian rhythms remain temperature compensated during a Q neuron-induced hibernation-like state in mice.

Arisa Hirano, Tohru M Takahashi, Hiroto Ashitomi, Kazumasa Z Tanaka, Takeshi Sakurai.

The circadian clock is an internal timekeeping system that enables organisms to adapt to daily environmental changes. A defining property of this clock is temperature compensation, whereby the circadian period remains relatively constant despite fluctuations in temperature. Although this phenomenon has been extensively studied in cultured cells and tissues, how the mammalian circadian clock responds to hypothermia in vivo remains largely unknown. Here, we examined circadian dynamics in a hibernation-like state in mice, termed Q neuron-induced hypometabolic and hypothermic state (QIH), which lowers core and brain temperatures to approximately 25 °C for extended periods. We found that free-running behavioral and body temperature rhythms were preserved after QIH, exhibiting only minor phase changes. In vivo recordings further revealed that neuronal firing rhythms in the suprachiasmatic nucleus (SCN) and molecular rhythms of PER2::Luc bioluminescence in peripheral tissues persisted during QIH with dampened amplitudes but largely unaltered circadian periods. In contrast, SCN and kidney slice cultures maintained at the same temperature displayed strongly attenuated or reset PER2::Luc oscillations. Together, these findings demonstrate that the circadian period is robustly temperature compensated in vivo, likely supported by systemic regulatory mechanisms beyond cell-autonomous clockwork. Our results provide new insight into the fundamental biology of circadian robustness and establish a framework for understanding clock function during hibernation and potential medical hypothermia.

DOI: https://doi.org/10.1371/journal.pbio.3003475

Endocr Connect. 2026 Apr 14. pii: EC-26-0016. [Epub ahead of print]

Adiponectin Modulates the Diurnal Hepatic Transcriptome and Energy Metabolism in Male Mice.

Misa Hirose, Enrique Calvo, Violetta Pilorz, Meike Kaehler, Ingolf Cascorbi, Inga Nagel, Leonardo Vinicius Monteiro de Assis, Henrik Oster.

Adiponectin is an adipocyte-derived hormone with insulin-sensitizing and lipid-lowering effects. Its expression and circulating levels show pronounced variation across the day, which opens the possibility that adiponectin influences metabolic programs in target tissues, such as the liver in a time-of-day dependent manner. To test this, we compared liver circadian transcriptome profiles (with sampling at 4-hour intervals) between adiponectin-deficient (ADQ-KO) and wild-type (ADQ-WT) mice. Adiponectin loss led to tonic (i.e., time independent) transcriptional changes in the liver with 1,393 differentially expressed genes (518 up- and 875 downregulated). These included upregulation of chromatin and RNA processing pathways and downregulation of immune and mitochondrial metabolic genes. At the same time, circadian analysis identified a marked reprogramming of transcriptome rhythms in ADQ-KO livers with changes in MESOR (n = 3,369 transcripts), amplitude (n = 386), and phase of gene expression (n = 603). Genes associated with mitochondrial respiration and fatty acid metabolism showed reduced rhythm amplitude and MESOR, whereas glycolytic genes exhibited increased MESOR. One of the identified adiponectin candidate targets and a regulator of hepatic metabolism, Hif1a, was further studied by functional assays in murine hepatocytes. Pharmacological adiponectin receptor activation promoted glycolysis and mitochondrial respiration under normoxia, but these effects were attenuated under hypoxia mimicry, consistent with HIF1a-dependent interference. These findings suggest adiponectin as a regulator of liver circadian metabolism, modulating both the timing and magnitude of energy-related gene expression programs, potentially in part through a HIF1a-mediated mechanism.

Keywords: Adiponectin; Circadian metabolism; Hypoxia-Inducible Factor 1-alpha; Liver; Transcription

DOI: https://doi.org/10.1530/EC-26-0016

PLoS Biol. 2026 Apr;24(4): e3003717

Glucose is dynamically regulated by time of day in humans and Drosophila.

Dania M Malik, Pinky Kain, Seth D Rhoades, Arjun Sengupta, Shirley L Zhang, Annika Barber, Paula Haynes, Erna Sif Arnardottir, Allan Pack, Richard G Kibbey, Amita Sehgal, Aalim M Weljie.

Biological clocks shape metabolism, but how circadian programs govern nutrient processing is unclear. Here, using human metabolomics and 13C6-glucose tracing in Drosophila, we delineate previously under characterized daily oscillations in glucose-derived metabolic networks, providing a mechanistic framework for a purpose-built isotope-tracing approach. In flies, we reveal a pronounced "rush hour" of glucose utilization early in the light phase, with carbons directed to biosynthetic and energetic pathways. By contrast, a dopamine reuptake-deficient hyperactive mutant (fumin) with elevated metabolic rate shows phase-shifted and amplified metabolic peaks, indicating that altered neural signaling reshapes temporal glucose flux. Neither altered feeding schedules nor short-term fasting disrupt these intrinsic metabolic rhythms, strongly suggesting that circadian timing, rather than nutrient availability, orchestrates temporal homeostasis. By integrating human metabolite profiling with isotope-tracing in flies, we define a conserved temporal architecture of glucose utilization and demonstrate that metabolic flux is dynamically gated across the day. Our findings establish a framework for understanding how circadian misalignment contributes to metabolic dysfunction and disease.

DOI: https://doi.org/10.1371/journal.pbio.3003717

NAR Genom Bioinform. 2026 Jun;8(2): lqag041

The circadian isoform landscape of mouse livers.

Alexander Zee, Dori Z Q Deng, Luciano DiTacchio, Christopher Vollmers.

The mammalian circadian clock is an autoregulatory feedback process that is responsible for homeostasis in mouse livers. These circadian processes are well understood at the gene level; however, they are not well understood at the isoform level. To investigate circadian oscillations at the isoform level, we used the nanopore-based R2C2 method to create over 78 million highly accurate, full-length complementary DNA reads for 12 RNA samples extracted from mouse livers collected at 2 h intervals. To generate a circadian mouse liver isoform-level transcriptome, we processed these reads using the Mandalorion tool, which identified and quantified 58 612 isoforms, 1806 of which showed circadian oscillations. We performed detailed analysis on the circadian oscillation of these isoforms, their coding sequences, and transcription start sites and compiled easy-to-access resources for other researchers. This study and its results add a new layer of detail to the quantitative analysis of transcriptomes.

DOI: https://doi.org/10.1093/nargab/lqag041