bims-ciryme 2023-03-19 papers

Issue of 2023‒03‒19
two papers selected by
Gabriela Da Silva Xavier
University of Birmingham

Glia. 2023 Mar 15.

Astrocytic circadian clock control of energy expenditure by transcriptional stress responses in the ventromedial hypothalamus.

Lucia Mendoza-Viveros, Clarisa Marmolejo-Gutierrez, Carolina Cid-Castro, Quetzalcóatl Escalante-Covarrubias, Emilie Montellier, Erick Carreño-Vázquez, Lilia G Noriega, Laura A Velázquez-Villegas, Armando R Tovar, Paolo Sassone-Corsi, Lorena Aguilar-Arnal, Ricardo Orozco-Solis.

Hypothalamic circuits compute systemic information to control metabolism. Astrocytes residing within the hypothalamus directly sense nutrients and hormones, integrating metabolic information, and modulating neuronal responses. Nevertheless, the role of the astrocytic circadian clock on the control of energy balance remains unclear. We used mice with a targeted ablation of the core-clock gene Bmal1 within Gfap-expressing astrocytes to gain insight on the role played by this transcription factor in astrocytes. While this mutation does not substantially affect the phenotype in mice fed normo-caloric diet, under high-fat diet we unmasked a thermogenic phenotype consisting of increased energy expenditure, and catabolism in brown adipose and overall metabolic improvement consisting of better glycemia control, and body composition. Transcriptomic analysis in the ventromedial hypothalamus revealed an enhanced response to moderate cellular stress, including ER-stress response, unfolded protein response and autophagy. We identified Xbp1 and Atf1 as two key transcription factors enhancing cellular stress responses. Therefore, we unveiled a previously unknown role of the astrocytic circadian clock modulating energy balance through the regulation of cellular stress responses within the VMH.

Keywords: astrocytes; brown adipose tissue; circadian rhythms; energy expenditure; ventromedial hypothalamus

DOI: https://doi.org/10.1002/glia.24360

Front Netw Physiol. 2021 ;1 803011

Synergies of Multiple Zeitgebers Tune Entrainment.

Saskia Grabe, Elmir Mahammadov, Marta Del Olmo, Hanspeter Herzel.

Circadian rhythms are biological rhythms with a period close to 24 h. They become entrained to the Earth's solar day via different periodic cues, so-called zeitgebers. The entrainment of circadian rhythms to a single zeitgeber was investigated in many mathematical clock models of different levels of complexity, ranging from the Poincaré oscillator and the Goodwin model to biologically more detailed models of multiple transcriptional translational feedback loops. However, circadian rhythms are exposed to multiple coexisting zeitgebers in nature. Therefore, we study synergistic effects of two coexisting zeitgebers on different components of the circadian clock. We investigate the induction of period genes by light together with modulations of nuclear receptor activities by drugs and metabolism. Our results show that the entrainment of a circadian rhythm to two coexisting zeitgebers depends strongly on the phase difference between the two zeitgebers. Synergistic interactions of zeitgebers can strengthen diurnal rhythms to reduce detrimental effects of shift-work and jet lag. Medical treatment strategies which aim for stable circadian rhythms should consider interactions of multiple zeitgebers.

Keywords: circadian clock; mathematical model; resonance; synchronisation; zeitgeber synergy

DOI: https://doi.org/10.3389/fnetp.2021.803011