bims-ciryme Biomed News
on Circadian rhythms and metabolism
Issue of 2022‒05‒01
three papers selected by
Gabriela Da Silva Xavier
University of Birmingham

  1. Trends Neurosci. 2022 Apr 21. pii: S0166-2236(22)00061-3. [Epub ahead of print]
      The circadian clock provides cue-independent anticipatory signals for diurnal rhythms of baseline glucose levels and glucose tolerance. The central circadian clock is located in the hypothalamic suprachiasmatic nucleus (SCN), which comprises primarily GABAergic neurons. The SCN clock regulates physiological diurnal rhythms of endogenous glucose production (EGP) and hepatic insulin sensitivity through neurohumoral mechanisms. Disruption of the molecular circadian clock is associated with the extended dawn phenomenon (DP) in type 2 diabetes (T2D), referring to hyperglycemia in the early morning without nocturnal hypoglycemia. The DP affects nearly half of patients with diabetes, with poorly defined etiology and a lack of targeted therapy. Here we review neural and secreted factors in physiological diurnal rhythms of glucose metabolism and their pathological implications for the DP.
    Keywords:  GABA; SCN; circadian rhythm; diabetes; metabolism; neuron
  2. Biol Psychiatry. 2022 Feb 18. pii: S0006-3223(22)00094-4. [Epub ahead of print]
      BACKGROUND: Substance use disorders are associated with disruptions in circadian rhythms. Both human and animal work have shown the integral role for circadian clocks in the modulation of reward behaviors. Astrocytes have emerged as key regulators of circadian rhythmicity. However, no studies to date have identified the role of circadian astrocyte function in the nucleus accumbens (NAc), a hub for reward regulation, or determined the importance of these rhythms for reward-related behavior.METHODS: Using astrocyte-specific RNA sequencing across time of day, we first characterized diurnal variation of the NAc astrocyte transcriptome. We then investigated the functional significance of this circadian regulation through viral-mediated disruption of molecular clock function in NAc astrocytes, followed by assessment of reward-related behaviors, metabolic-related molecular assays, and whole-cell electrophysiology in the NAc.
    RESULTS: Strikingly, approximately 43% of the astrocyte transcriptome has a diurnal rhythm, and key metabolic pathways were enriched among the top rhythmic genes. Moreover, mice with a viral-mediated loss of molecular clock function in NAc astrocytes show a significant increase in locomotor response to novelty, exploratory drive, operant food self-administration, and motivation. At the molecular level, these animals also show disrupted metabolic gene expression, along with significant downregulation of both lactate and glutathione levels in the NAc. Loss of NAc astrocyte clock function also significantly altered glutamatergic signaling onto neighboring medium spiny neurons, alongside upregulated glutamate-related gene expression.
    CONCLUSIONS: Taken together, these findings demonstrate a novel role for astrocyte circadian molecular clock function in the regulation of the NAc and reward-related behaviors.
    Keywords:  Astrocytes; BMAL1; Circadian rhythms; Metabolic state; Nucleus accumbens; Reward
  3. Sci Rep. 2022 Apr 29. 12(1): 7064
      We assessed the effects of feeding regimen (ad libitum vs. time-restricted food access) and type of food (normal chow (NC: 12% fat) vs. moderately high calorie diet (mHCD: 31% fat)) on fertility competence of female mice. Mice fed mHCD had higher number of oocytes than mice fed NC. On the other hand, when mice were fed NC under time-restricted access to food (NT), the developmental rate to the blastocyst per number of normally fertilized ova was significantly decreased compared to others. The reactive oxygen species (ROS) level in oocytes increased in time-restricted food access and NC group. Transcriptome analysis of whole ovarian tissues from these mice showed a change in the cholesterol metabolism among the four groups. Time-restricted food access decreased serum LDL cholesterol level in both NC and mHCD groups. Moreover, the number of atretic follicles increased in NT mice compared to ad libitum food access mice. The present study shows that mHCD feeding increases the number of ovulated oocytes and that time-restricted feeding of NC impairs the developmental competence of oocytes after fertilization, probably due to the changes in serum cholesterol levels and an increase in the ROS content in oocytes.