Astrocytic circadian clock control of energy expenditure by transcriptional stress responses in the ventromedial hypothalamus
Por:
Mendoza-Viveros, Lucia, Marmolejo-Gutierrez, Clarisa, Cid-Castro, Carolina, Escalante-Covarrubias, Quetzalcoatl, Montellier, Emilie, Carreno-Vazquez, Erick, Noriega, Lilia G., Velazquez-Villegas, Laura A., Tovar, Armando R., Sassone-Corsi, Paolo, Aguilar-Arnal, Lorena, Orozco-Solis, Ricardo
Publicada:
1 ene 2023
Ahead of Print:
1 mar 2023
Resumen:
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.
Filiaciones:
Inst Nacl Med Genom INMEGEN, Mexico City, DF, Mexico
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Mexico City, DF, Mexico
Univ Calif Irvine, Irvine, CA USA
Univ Grenoble Alpes, Grenoble Alpes, France
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Mexico City, DF, Mexico
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