bims-ciryme Biomed News
on Circadian rhythms and metabolism
Issue of 2024–11–17
five papers selected by
Gabriela Da Silva Xavier, University of Birmingham



  1. Science. 2024 Nov 08. 386(6722): 673-677
      Circadian desynchrony induced by shiftwork or jet lag is detrimental to metabolic health, but how synchronous or desynchronous signals are transmitted among tissues is unknown. We report that liver molecular clock dysfunction is signaled to the brain through the hepatic vagal afferent nerve (HVAN), leading to altered food intake patterns that are corrected by ablation of the HVAN. Hepatic branch vagotomy also prevents food intake disruptions induced by high-fat diet feeding and reduces body weight gain. Our findings reveal a homeostatic feedback signal that relies on communication between the liver and the brain to control circadian food intake patterns. This identifies the hepatic vagus nerve as a potential therapeutic target for obesity in the setting of chronodisruption.
    DOI:  https://doi.org/10.1126/science.adn2786
  2. Diabetologia. 2024 Nov 12.
       AIMS/HYPOTHESIS: Gestational diabetes mellitus (GDM) affects 14% of all pregnancies worldwide and is associated with cardiometabolic risk. We aimed to exploit high-resolution wearable device time-series data to create a fine-grained physiological characterisation of the postpartum GDM state in free-living conditions, including clinical variables, daily glucose dynamics, food and drink consumption, physical activity, sleep patterns and heart rate.
    METHODS: In a prospective observational study, we employed continuous glucose monitors (CGMs), a smartphone food diary, triaxial accelerometers and heart rate and heart rate variability monitors over a 2 week period to compare women who had GDM in the previous pregnancy (GDM group) and women who had a pregnancy with normal glucose metabolism (non-GDM group) at 1-2 months after delivery (baseline) and 6 months later (follow-up). We integrated CGM data with ingestion events recorded with the smartphone app MyFoodRepo to quantify the rapidity of returning to preprandial glucose levels after meal consumption. We inferred the properties of the underlying 24 h rhythm in the baseline glucose. Aggregating the baseline and follow-up data in a linear mixed model, we quantified the relationships between glycaemic variables and wearable device-derived markers of circadian timing.
    RESULTS: Compared with the non-GDM group (n=15), the GDM group (n=22, including five with prediabetes defined based on fasting plasma glucose [5.6-6.9 mmol/l (100-125 mg/dl)] and/or HbA1c [39-47 mmol/mol (5.7-6.4%)]) had a higher BMI, HbA1c and mean amplitude of glycaemic excursion at baseline (all p≤0.05). Integrating CGM data and ingestion events showed that the GDM group had a slower postprandial glucose decrease (p=0.01) despite having a lower proportion of carbohydrate intake, similar mean glucose levels and a reduced amplitude of the underlying glucose 24 h rhythm (p=0.005). Differences in CGM-derived variables persisted when the five women with prediabetes were removed from the comparison. Longitudinal analysis from baseline to follow-up showed a significant increase in fasting plasma glucose across both groups. The CGM-derived metrics showed no differences from baseline to follow-up. Late circadian timing (i.e. sleep midpoint, eating midpoint and peak time of heart rate) was correlated with higher fasting plasma glucose and reduced amplitudes of the underlying glucose 24 h rhythm (all p≤0.05).
    CONCLUSIONS/INTERPRETATION: We reveal GDM-related postpartum differences in glucose variability and 24 h rhythms, even among women clinically considered to be normoglycaemic. Our results provide a rationale for future interventions aimed at improving glucose variability and encouraging earlier daily behavioural patterns to mitigate the long-term cardiometabolic risk of GDM.
    TRIAL REGISTRATION: ClinicalTrials.gov no. NCT04642534.
    Keywords:  Circadian rhythms; Continuous glucose monitoring; Gestational diabetes mellitus; Mean amplitude of glycaemic excursion; Postpartum period; Smartphone food diary app; Wearable devices
    DOI:  https://doi.org/10.1007/s00125-024-06318-x
  3. PLoS One. 2024 ;19(11): e0312911
      An organism's biological processes are adapted to and driven by rhythmicity in the natural environment and periodicity of light is one of the most influential factors. In a developing organism, the onset of circadian rhythmicity might indicate the time point of functional necessity for aligning processes to the environment. Here, the circadian clock mechanism has been studied in the developing brain of Atlantic salmon (Salmo salar), by comparing the endogenous feeding alevin, independent on the environment for nutritional supply, to the exogenous feeding fry, dependent on the light period for detecting and catching prey. The results showed that while only a few clock genes were cyclic in the yolk sac alevins, many of the clock genes and genes of the circadian rhythm pathway cycled significantly in the feeding fry. Few genes were differentially expressed between time points in the circadian sampling series during the yolk sac stage, but several hundred genes were found differentially expressed in the first feeding stage. Genes important for cell cycle progression were cyclic or differentially expressed between time points after exogenous feeding, indicating a clock-controlled cell cycle at this stage. The expression of important genes in the melatonin synthesis were also cyclic in the feeding fry with an acrophase in the transition between light and dark or in darkness. Analyzing the impact of exogenous feeding on the developing brain supported a shift from utilization of proteins and lipids in the yolk to utilization and allocation of dietary energy and nutrients. Taken together, the life history transition related to onset of exogenous feeding is linked to the establishment of a persistent circadian rhythmicity in the salmon brain, which needs to be synchronized to light-dark cycles to enable the fry to search and capture feed.
    DOI:  https://doi.org/10.1371/journal.pone.0312911
  4. Int J Mol Sci. 2024 Oct 26. pii: 11491. [Epub ahead of print]25(21):
      A cluster of metabolic changes occur to provide energy for fetal growth and development during pregnancy. There is a burgeoning body of research highlighting the pivotal role of circadian rhythms in the pathogenesis of metabolic disorders and lipid homeostasis in mammals. Perturbations of the circadian system and lipid metabolism during gestation might be responsible for a variety of adverse reproductive outcomes comprising miscarriage, gestational diabetes mellitus, and preeclampsia. Growing studies have confirmed that resynchronizing circadian rhythms might alleviate metabolic disturbance. However, there is no clear evidence regarding the specific mechanisms by which the diurnal rhythm regulates lipid metabolism during pregnancy. In this review, we summarize previous knowledge on the strong interaction among the circadian clock, lipid metabolism, and pregnancy. Analyzing the circadian clock genes will improve our understanding of how circadian rhythms are implicated in complex lipid metabolic disorders during pregnancy. Exploring the potential of resynchronizing these circadian rhythms to disrupt abnormal lipid metabolism could also result in a breakthrough in reducing adverse pregnancy outcomes.
    Keywords:  circadian rhythm; lipid metabolism; pregnancy; pregnancy-related diseases; sleep
    DOI:  https://doi.org/10.3390/ijms252111491
  5. PNAS Nexus. 2024 Nov;3(11): pgae497
      Circadian clocks exist in all types of organisms and coordinate key biological processes, e.g. photosynthesis in phytoplankton (microalgae) and land plants. We asked whether a circadian rhythm sustains in phytoplankton when living under constant illumination without environmental cues. Here, we report the first transcriptomic architecture of persistent oscillatory gene expression in the model marine diatom, Phaeodactylum tricornutum living under constant illumination and temperature without environmental cues. We show that cyclic expression of a considerable number of genes involved in light harvesting and carbon fixation sustained after 24 h of constant illumination (free-running), which could pose additional constraints on cell growth under constant light conditions. Over long-term adaptation to constant illumination, the majority of the rhythmic genes identified under diel light conditions lose their oscillatory expression in the absence of external entrainers, and the genes potentially controlled by persistent circadian clocks are primarily involved in transcriptional regulation and cell division. We find constant illumination leads to an increased average expression of transcription factors and cell division genes, while genes involved in the Calvin-Benson cycle and pigment biosynthesis are kept at low expression levels, which plays a role in the down-regulation of photosynthetic efficiency. By manipulation of the dark rest period, we confirm a fine-tuned light/dark cycle could dramatically improve photosynthetic efficiency in microalgae. Our results unveil a novel persistent circadian rhythm on photosynthetic regulation in marine phytoplankton and provide critical insights into the interaction between environmental signals and inheritable internal circadian clocks in diatoms.
    Keywords:  Phaeodactylum tricornutum; circadian clocks; intrinsic circadian rhythm; photosynthesis; phytoplankton
    DOI:  https://doi.org/10.1093/pnasnexus/pgae497