bims-ciryme Biomed News
on Circadian rhythms and metabolism
Issue of 2023–01–22
four papers selected by
Gabriela Da Silva Xavier, University of Birmingham



  1. Acta Physiol (Oxf). 2023 Jan 16. e13936
      The circadian clock is a hierarchical timing system regulating most physiological and behavioral functions with a period of approximately 24 hours in humans and other mammalian species. The circadian clock drives daily eating rhythms that, in turn, reinforce the circadian clock network itself to anticipate and orchestrate metabolic responses to food intake. Eating is tightly interconnected with the circadian clock and recent evidence shows that the timing of meals is crucial for the control of appetite and metabolic regulation. Obesity results from combined long-term dysregulation in food intake (homeostatic and hedonic circuits), energy expenditure, and energy storage. Increasing evidence supports that the loss of synchrony of daily rhythms significantly impairs metabolic homeostasis and is associated with obesity. This review presents an overview of mechanisms regulating food intake (homeostatic/hedonic) and focuses on the crucial role of the circadian clock on the metabolic response to eating, thus providing a fundamental research axis to maintain a healthy eating behavior.
    Keywords:  circadian misalignment; homeostatic/hedonic food intake; mammalian circadian clock; metabolism; obesity
    DOI:  https://doi.org/10.1111/apha.13936
  2. FASEB J. 2023 Feb;37(2): e22772
      Circadian disruption (CD) is the consequence of a mismatch between endogenous circadian rhythms and behavior, and frequently occurs in shift workers. CD has often been linked to impairment of glucose and lipid homeostasis. It is, however, unknown if these effects are sex dependent. Here, we subjected male and female C57BL/6J mice to 6-h light phase advancements every 3 days to induce CD and assessed glucose and lipid homeostasis. Within this model, we studied the involvement of gonadal sex hormones by injecting mice with gonadotropin-releasing hormone-antagonist degarelix. We demonstrate that CD has sex-specific effects on glucose homeostasis, as CD elevated fasting insulin levels in male mice while increasing fasting glucose levels in female mice, which appeared to be independent of behavior, food intake, and energy expenditure. Absence of gonadal sex hormones lowered plasma insulin levels in male mice subjected to CD while it delayed glucose clearance in female mice subjected to CD. CD elevated plasma triglyceride (TG) levels and delayed plasma clearance of TG-rich lipoproteins in both sexes, coinciding with reduced TG-derived FA uptake by adipose tissues. Absence of gonadal sex hormones did not notably alter the effects of CD on lipid metabolism. We conclude that CD causes sex-dependent effects on glucose metabolism, as aggravated by male gonadal sex hormones and partly rescued by female gonadal sex hormones. Future studies on CD should consider the inclusion of both sexes, which may eventually contribute to personalized advice for shift workers.
    Keywords:  circadian disruption; glucose homeostasis; gonadal hormones; lipid homeostasis; sex
    DOI:  https://doi.org/10.1096/fj.202201586R
  3. Curr Opin Plant Biol. 2023 Jan 12. pii: S1369-5266(22)00162-5. [Epub ahead of print]73 102333
      Plants must match their metabolism to daily and seasonal fluctuations in their environment to maximise performance in natural conditions. Circadian clocks enable organisms to anticipate and adapt to these predictable and unpredictable environmental challenges. Metabolism is increasingly recognised as an integrated feature of the plant circadian system. Metabolism is an important circadian-regulated output but also provides input to this dynamic timekeeping mechanism. The spatial organisation of metabolism within cells and between tissues, and the temporal features of metabolism across days, seasons and development, raise interesting questions about how metabolism influences circadian timekeeping. The various mechanisms by which metabolic signals influence the transcription-translation feedback loops of the circadian oscillator are emerging. These include roles for major metabolic signalling pathways, various retrograde signals, and direct metabolic modifications of clock genes or proteins. Such metabolic feedback loops enable intra- and intercellular coordination of rhythmic metabolism, and recent discoveries indicate these contribute to diverse aspects of daily, developmental and seasonal timekeeping.
    Keywords:  Circadian; Development; Environment; Metabolism; Plants; Signalling
    DOI:  https://doi.org/10.1016/j.pbi.2022.102333
  4. Proc Natl Acad Sci U S A. 2023 Jan 24. 120(4): e2209329120
      The suprachiasmatic nucleus (SCN) is composed of functionally distinct subpopulations of GABAergic neurons which form a neural network responsible for synchronizing most physiological and behavioral circadian rhythms in mammals. To date, little is known regarding which aspects of SCN rhythmicity are generated by individual SCN neurons, and which aspects result from neuronal interaction within a network. Here, we utilize in vivo miniaturized microscopy to measure fluorescent GCaMP-reported calcium dynamics in arginine vasopressin (AVP)-expressing neurons in the intact SCN of awake, behaving mice. We report that SCN AVP neurons exhibit periodic, slow calcium waves which we demonstrate, using in vivo electrical recordings, likely reflect burst firing. Further, we observe substantial heterogeneity of function in that AVP neurons exhibit unstable rhythms, and relatively weak rhythmicity at the population level. Network analysis reveals that correlated cellular behavior, or coherence, among neuron pairs also exhibited stochastic rhythms with about 33% of pairs rhythmic at any time. Unlike single-cell variables, coherence exhibited a strong rhythm at the population level with time of maximal coherence among AVP neuronal pairs at CT/ZT 6 and 9, coinciding with the timing of maximal neuronal activity for the SCN as a whole. These results demonstrate robust circadian variation in the coordination between stochastically rhythmic neurons and that interactions between AVP neurons in the SCN may be more influential than single-cell activity in the regulation of circadian rhythms. Furthermore, they demonstrate that cells in this circuit, like those in many other circuits, exhibit profound heterogenicity of function over time and space.
    Keywords:  AVP; SCN; in vivo calcium imaging
    DOI:  https://doi.org/10.1073/pnas.2209329120