bims-ciryme Biomed News
on Circadian rhythms and metabolism
Issue of 2025–05–11
six papers selected by
Gabriela Da Silva Xavier, University of Birmingham



  1. Sci Rep. 2025 May 09. 15(1): 16156
      The circadian clock has evolved to synchronize animal behaviour and physiology with the external environment. Present in almost all cells, the clock is made up of a transcription-translation feedback loop that is responsive to cues such as light/dark cycles (photoperiod) and the time of feeding. Chinook salmon (Oncorhynchus tshawytscha) is a fish species whose clock is thought to be adapted in natural populations according to their latitude, where photoperiod variation can be extreme in northern spring/summer conditions. Here, we probed for the expression of circadian clock genes in four tissues of juvenile Chinook salmon under different environmental conditions. We find that the circadian clock is optimal when photoperiod is coupled with regular feeding during daylight hours. We further tested the effects of constant light and time-restricted feeding, environmental factors that are known to affect daily gene expression rhythms, on the expression of clock genes, appetite-regulating hormones, and metabolic regulators in the intestine of juvenile Chinook. We find that overall constant light is chrono-disruptive irrespective of the timing of food. The resulting disruption in gene expression produces aberrant rhythms, and affects glucose homeostasis, despite an increase in growth. Our data suggests photoperiod and time-restricted feeding could be optimized in Chinook aquaculture and raise the question of whether and how photoperiod changes are compensated in northern-adapted populations.
    Keywords:  Circadian entrainment; Circadian rhythms; Photoperiod; Salmon
    DOI:  https://doi.org/10.1038/s41598-025-01069-0
  2. Proc Natl Acad Sci U S A. 2025 May 13. 122(19): e2422446122
      How central and peripheral circadian clocks regulate protein metabolism and affect tissue mass homeostasis has been unclear. Circadian shifts in the balance between anabolism and catabolism control muscle growth rate in young zebrafish independent of behavioral cycles. Here, we show that the ubiquitin-proteasome system (UPS) and autophagy, which mediate muscle protein degradation, are each upregulated at night under the control of the muscle peripheral clock. Perturbation of the muscle transcriptional molecular clock disrupts nocturnal proteolysis, increases muscle growth measured over 12 h, and compromises muscle function. Mechanistically, the shifting circadian balance of Ror and Rev-erb regulates nocturnal UPS, autophagy, and muscle growth through altered TORC1 activity. Although environmental zeitgebers initially mitigate defects, lifelong muscle clock inhibition reduces muscle size and growth rate, accelerating aging-related loss of muscle mass and function. Circadian misalignment such as shift work, sleep deprivation, or dementia may thus unsettle muscle proteostasis, contributing to muscle wasting and sarcopenia.
    Keywords:  autophagy; circadian clock; mTOR; muscle; proteasome
    DOI:  https://doi.org/10.1073/pnas.2422446122
  3. PNAS Nexus. 2025 May;4(5): pgaf120
      Circadian clocks regulate biological activities, providing organisms with a fitness advantage under diurnal conditions by enabling anticipation and adaptation to recurring external changes. Three proteins, KaiA, KaiB, and KaiC, constitute the circadian clock in the cyanobacterial model Synechococcus elongatus PCC 7942. Several techniques established to measure circadian output in Synechococcus yielded comparably weak signals in Synechocystis sp. PCC 6803, a strain important for biotechnological applications. We applied an approach that does not require genetic modifications to monitor the circadian rhythms in Synechococcus and Synechocystis. We placed batch cultures in shake flasks on a sensor detecting backscattered light via noninvasive online measurements. Backscattering oscillated with a period of ∼24 h around the average growth. Wavelet and Fourier transformations are applied to determine the period's significance and length. In Synechocystis, oscillations fulfilled the circadian criteria of temperature compensation and entrainment by external stimuli. Remarkably, dilution alone synchronized oscillations. Western blotting revealed that the backscatter was ∼6.5 h phase-delayed in comparison to KaiC3 phosphorylation.
    Keywords:  KaiC3; Synechocystis sp. PCC 6803; backscatter; circadian clock; cyanobacteria
    DOI:  https://doi.org/10.1093/pnasnexus/pgaf120
  4. Curr Biol. 2025 May 08. pii: S0960-9822(25)00511-1. [Epub ahead of print]
      Intertidal organisms, such as the crustaceans Eurydice pulchra and Parhyale hawaiensis, express daily and tidal rhythms of physiology and behavior to adapt to their temporally complex environments. Although the molecular-genetic basis of the circadian clocks driving daily rhythms in terrestrial animals is well understood, the nature of the circatidal clocks driving tidal rhythms remains a mystery. Using in situ hybridization, we identified discrete clusters of ∼60 putative "clock" cells co-expressing canonical circadian clock genes across the protocerebrum of E. pulchra and P. hawaiensis brains. In field-collected, tidally rhythmic E. pulchra sampled under a light:dark (LD) cycle, the expression of period (per) and cryptochrome 2 (cry2) exhibited daily rhythms in particular cell groups, whereas timeless (tim) showed 12-h rhythms in others. In tidally rhythmic laboratory-reared P. hawaiensis, previously entrained to 12.4-h cycles of agitation under LD and sampled under continuous darkness, several cell groups (e.g., medioposterior cells) exhibited circadian expression of per and cry2. In contrast, dorsal-lateral cells in the protocerebrum exhibited robust ∼12-h, i.e., circatidal, rhythms of per and cry2, phased to the prior tidal agitation but not the prior LD. In P. hawaiensis exhibiting daily behavior under LD without tidal agitation, robust daily rhythms of per and cry2 expression were evident in medioposterior and other cells, whereas expression in dorsal-lateral cells was not rhythmic, underlining their essentially tidal periodicity. These results implicate canonical circadian molecules in circatidal timekeeping and reveal conserved brain networks as potential neural substrates for the generation of daily and tidal rhythms appropriate to intertidal habitats.
    Keywords:  Bmal1; Clock; amphipod; circadian; circatidal; cryptochrome2; isopod; period; protocerebrum; timeless
    DOI:  https://doi.org/10.1016/j.cub.2025.04.047
  5. FASEB Bioadv. 2025 May;7(5): e70006
      Physiology is closely synchronized to daily and seasonal light/dark cycles. Humans artificially extend daylight and experience irregular light schedules, resulting in dysregulation of metabolism and body mass. In rodents, winter-like conditions (cold and short photoperiod) can alter energy balance and adipose tissue mass. To determine if photoperiod alone, independent of temperature, is a strong enough signal to regulate adiposity, we compared the effects of long and short photoperiod at thermoneutrality on adiposity and WAT gene expression in photoperiod-sensitive, F1 generation wild-derived adult male white-footed mice (Peromyscus leucopus). Mice were housed in long-day (16:8 light:dark) or short-day (8:16 light:dark) photoperiod conditions at thermoneutrality (27°C) for 4 weeks with the extended light being provided through artificial lighting. Photoperiod did not impact body weight or calorie consumption. However, mice housed in long photoperiod with extended artificial light selectively developed greater visceral WAT mass without changing subcutaneous WAT or interscapular BAT mass. This was accompanied by a decrease in Adrβ3 and Ucp1 mRNA expression in visceral WAT with no change in Pgc1a, Lpl, or Hsl. Expression of Per1, Per2, and Nr1d1 mRNA in visceral WAT differed between long and short photoperiods over time when aligned to circadian time but not onset of darkness, indicating alterations in clock gene expression with photoperiod. These findings suggest that extended photoperiod through artificial light can promote visceral fat accumulation alone, independent of temperature, supporting that artificial light may play a role in obesity.
    Keywords:  Peromyscus; adiposity; circadian rhythm; clock genes; photoperiod
    DOI:  https://doi.org/10.1096/fba.2024-00115
  6. Nat Commun. 2025 May 08. 16(1): 4270
      24-hour biological rhythms are essential to maintain physiological homeostasis. Disruption of these rhythms increases the risks of multiple diseases. Biological rhythms are known to have a genetic basis formed by core clock genes, but how individual genetic variation shapes the oscillating transcriptome and contributes to human chronophysiology and disease risk is largely unknown. Here, we mapped interactions between temporal gene expression and genotype to identify quantitative trait loci (QTLs) contributing to rhythmic gene expression. These newly identified QTLs were termed as rhythmic QTLs (rhyQTLs), which determine previously unappreciated rhythmic genes in human subpopulations with specific genotypes. Functionally, rhyQTLs and their associated rhythmic genes contribute extensively to essential chronophysiological processes, including bile acid and lipid metabolism. The identification of rhyQTLs sheds light on the genetic mechanisms of gene rhythmicity, offers mechanistic insights into variations in human disease risk, and enables precision chronotherapeutic approaches for patients.
    DOI:  https://doi.org/10.1038/s41467-025-59524-5