bims-ciryme Biomed News
on Circadian rhythms and metabolism
Issue of 2019‒11‒24
eight papers selected by
Gabriela Da Silva Xavier
University of Birmingham


  1. Proc Natl Acad Sci U S A. 2019 Nov 22. pii: 201911189. [Epub ahead of print]
    Gaucher J, Kinouchi K, Ceglia N, Montellier E, Peleg S, Greco CM, Schmidt A, Forne I, Masri S, Baldi P, Imhof A, Sassone-Corsi P.
      Binge drinking and chronic exposure to ethanol contribute to alcoholic liver diseases (ALDs). A potential link between ALDs and circadian disruption has been observed, though how different patterns of alcohol consumption differentially impact hepatic circadian metabolism remains virtually unexplored. Using acute versus chronic ethanol feeding, we reveal differential reprogramming of the circadian transcriptome in the liver. Specifically, rewiring of diurnal SREBP transcriptional pathway leads to distinct hepatic signatures in acetyl-CoA metabolism that are translated into the subcellular patterns of protein acetylation. Thus, distinct drinking patterns of alcohol dictate differential adaptation of hepatic circadian metabolism.
    Keywords:  acetylation; alcohol; circadian; liver; metabolism
    DOI:  https://doi.org/10.1073/pnas.1911189116
  2. Mol Cell Endocrinol. 2019 Nov 19. pii: S0303-7207(19)30357-0. [Epub ahead of print] 110655
    Sen A, Hoffmann HM.
      Precise timing in hormone release from the hypothalamus, the pituitary and ovary is critical for fertility. Hormonal release patterns of the reproductive axis are regulated by a feedback loop within the hypothalamic-pituitary-gonadal (HPG) axis. The timing and rhythmicity of hormone release and tissue sensitivity in the HPG axis is regulated by circadian clocks located in the hypothalamus (suprachiasmatic nucleus, kisspeptin and GnRH neurons), the pituitary (gonadotrophs), the ovary (theca and granulosa cells), the testis (Leydig cells), as well as the uterus (endometrium and myometrium). The circadian clocks integrate environmental and physiological signals to produce cell endogenous rhythms generated by a transcriptional-translational feedback loop of transcription factors that are collectively called the "molecular clock". This review specifically focuses on the contribution of molecular clock transcription factors in regulating hormone release patterns in the reproductive axis, with an emphasis on the female reproductive system. Specifically, we discuss the contributions of circadian rhythms in distinct neuronal populations of the female hypothalamus, the molecular clock in the pituitary and its overall impact on female and male fertility.
    Keywords:  Circadian rhythms; Clock genes; Estrogen; Gene transcription; Gonadotropin-releasing hormone; Hormone release; Hypothalamic-pituitary-gonadal axis; Kisspeptin; Ovary; Suprachiasmatic nucleus
    DOI:  https://doi.org/10.1016/j.mce.2019.110655
  3. Mol Cell Endocrinol. 2019 Nov 15. pii: S0303-7207(19)30354-5. [Epub ahead of print] 110652
    Focke CMB, Iremonger KJ.
      Oscillations are a fundamental feature of neural and endocrine systems. The hypothalamic-pituitary-adrenal (HPA) axis dynamically controls corticosteroid secretion in basal conditions and in response to stress. Across the 24-h day, HPA axis activity oscillates with both an ultradian and circadian rhythm. These rhythms have been shown to be important for regulating metabolism, inflammation, mood, cognition and stress responsiveness. Here we will discuss the neural and endocrine mechanisms driving these rhythms, the physiological importance of these rhythms and health consequences when they are disrupted.
    Keywords:  Adrenal; Circadian; Corticotropin-releasing hormone; Glucocorticoid receptor; Paraventricular nucleus; Pituitary; Rhythm; Ultradian
    DOI:  https://doi.org/10.1016/j.mce.2019.110652
  4. Elife. 2019 11 20. pii: e49578. [Epub ahead of print]8
    Rohr KE, Pancholi H, Haider S, Karow C, Modert D, Raddatz NJ, Evans J.
      Annual changes in the environment threaten survival, and numerous biological processes in mammals adjust to this challenge via seasonal encoding by the suprachiasmatic nucleus (SCN). To tune behavior according to day length, SCN neurons display unified rhythms with synchronous phasing when days are short, but will divide into two sub-clusters when days are long. The transition between SCN states is critical for maintaining behavioral responses to seasonal change, but the mechanisms regulating this form of neuroplasticity remain unclear. Here we identify that a switch in chloride transport and GABAA signaling is critical for maintaining state plasticity in the SCN network. Further, we reveal that blocking excitatory GABAA signaling locks the SCN into its long day state. Collectively, these data demonstrate that plasticity in GABAA signaling dictates how clock neurons interact to maintain environmental encoding. Further, this work highlights factors that may influence susceptibility to seasonal disorders in humans.
    Keywords:  GABA; chloride; circadian clock network; coupling; mouse; neuroscience; suprachiasmatic nucleus; synchronization
    DOI:  https://doi.org/10.7554/eLife.49578
  5. ACM BCB. 2019 Sep;2019 5-14
    De Los Santos H, Bennett KP, Hurley JM.
      Circadian rhythms are 24-hour biological cycles that control daily molecular rhythms in many organisms. The cellular elements that fall under the regulation of the clock are often studied through the use of omics-scale data sets gathered over time to determine how circadian regulation impacts cellular physiology. Previously, we created the ECHO (Extended Circadian Harmonic Oscillator) tool to identify rhythms in these data sets. Using ECHO, we found that circadian oscillations widely undergo a change in amplitude over time and that these amplitude changes have a biological function in the cell. However, ECHO does not align gene ontologies with the identified oscillating genes to give functional context. Thus, we created ENCORE (ECHO Native Circadian Ontological Rhythmicity Explorer), a novel visualization tool which combines the disparate databases of Gene Ontologies, protein-protein interactions, and auxiliary information to uncover the meaning of circadianly-regulated genes. This freely-available tool performs automatic enrichment and creates publication-worthy visualizations which we used to extend previously-gathered data on circadian regulation of physiology from published omics-scale studies in three circadian model organisms: mouse, fruit fly, and Neurospora crassa.
    Keywords:  circadian rhythms; gene enrichment; gene expression; protein-protein interaction networks; proteomics; transcriptomics; visualizations
    DOI:  https://doi.org/10.1145/3307339.3342137
  6. Curr Biol. 2019 Nov 18. pii: S0960-9822(19)31252-7. [Epub ahead of print]29(22): R1176-R1178
    Doležel D.
      Circadian clocks are time-measuring devices found in a majority of organisms synchronizing their behavior and metabolism with the day-light cycle. What happens in extreme latitudes, where the environmental conditions can be harsh at any time of day?
    DOI:  https://doi.org/10.1016/j.cub.2019.09.061
  7. Nat Metab. 2019 Nov;1(11): 1059-1073
    Hahn O, Drews LF, Nguyen A, Tatsuta T, Gkioni L, Hendrich O, Zhang Q, Langer T, Pletcher S, Wakelam MJO, Beyer A, Grönke S, Partridge L.
      Dietary restriction (DR) during adulthood can greatly extend lifespan and improve metabolic health in diverse species. However, whether DR in mammals is still effective when applied for the first time at old age remains elusive. Here, we report results of a late-life DR switch experiment employing 800 mice, in which 24 months old female mice were switched from ad libitum (AL) to DR or vice versa. Strikingly, the switch from DR-to-AL acutely increases mortality, whereas the switch from AL-to-DR causes only a weak and gradual increase in survival, suggesting a memory of earlier nutrition. RNA-seq profiling in liver, brown (BAT) and white adipose tissue (WAT) demonstrate a largely refractory transcriptional and metabolic response to DR after AL feeding in fat tissue, particularly in WAT, and a proinflammatory signature in aged preadipocytes, which is prevented by chronic DR feeding. Our results provide evidence for a nutritional memory as a limiting factor for DR-induced longevity and metabolic remodeling of WAT in mammals.
    DOI:  https://doi.org/10.1038/s42255-019-0121-0
  8. Diabetes. 2019 Nov 22. pii: db190606. [Epub ahead of print]
    Dashti HS, Vetter C, Lane JM, Smith MC, Wood AR, Weedon MN, Rutter MK, Garaulet M, Scheer FA, Saxena R.
      Night shift work, behavioral rhythms, and the common MTNR1B risk single nucleotide polymorphism (SNP), rs10830963, associate with type 2 diabetes, however, whether they exert joint effects to exacerbate type 2 diabetes risk is unknown. Among employed participants of European ancestry in the UK Biobank (N=189,488), we aimed to test the cross-sectional independent associations and joint interactions of these risk factors on odds of type 2 diabetes (n=5,042 cases) and HbA1c levels (n=175,156). Current shift work, definite morning or evening preference, and MTNR1B rs10830963 risk-allele associate with type 2 diabetes and HbA1c levels. The effect of rs10830963 was not modified by shift work schedules. While marginal evidence of interaction between self-reported morningness-eveningness preference and rs10830963 was seen on risk of type 2 diabetes, this interaction did not persist when analysis was expanded to include all participants regardless of employment status and when using accelerometer-derived sleep-midpoint as an objective measure of morningness-eveningness preference. Our findings suggest that the MTNR1B risk-allele carriers may not have greater vulnerability to shift work or morningness-eveningness preference.
    DOI:  https://doi.org/10.2337/db19-0606