Desynchrony between brain and peripheral clocks caused by CK1δ/ε disruption in GABA neurons does not lead to adverse metabolic outcomes

Proceedings of the National Academy of Sciences of the United States of America
Vincent van der VinneDavid R Weaver

Abstract

Circadian disruption as a result of shift work is associated with adverse metabolic consequences. Internal desynchrony between the phase of the suprachiasmatic nuclei (SCN) and peripheral clocks is widely believed to be a major factor contributing to these adverse consequences, but this hypothesis has never been tested directly. A GABAergic Cre driver combined with conditional casein kinase mutations (Vgat-Cre + CK1δ fl/fl ε fl/+ ) was used to lengthen the endogenous circadian period in GABAergic neurons, including the SCN, but not in peripheral tissues, to create a Discordant mouse model. These mice had a long (27.4 h) behavioral period to which peripheral clocks entrained in vivo, albeit with an advanced phase (∼6 h). Thus, in the absence of environmental timing cues, these mice had internal desynchrony between the SCN and peripheral clocks. Surprisingly, internal desynchrony did not result in obesity in this model. Instead, Discordant mice had reduced body mass compared with Cre-negative controls on regular chow and even when challenged with a high-fat diet. Similarly, internal desynchrony failed to induce glucose intolerance or disrupt body temperature and energy expenditure rhythms. Subsequently, a lighting cycle of 2-h l...Continue Reading

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Citations

Nov 12, 2018·Journal of Neuroendocrinology·Isa KolbeHenrik Oster
Oct 1, 2018·The European Journal of Neuroscience·Aliza K De Nobrega, Lisa C Lyons
Jun 17, 2020·The Journal of Physiology·Denise KemlerKaryn A Esser
Jul 14, 2020·Journal of Pineal Research·Yuying LiJie Yin
Jun 16, 2018·The Journal of Experimental Biology·Vincent van der VinneSteven J Swoap
Feb 13, 2021·Science·Kevin B Koronowski, Paolo Sassone-Corsi
Dec 8, 2021·Journal of Biological Rhythms·Blanca Martin-BurgosMary E Harrington
Jan 14, 2022·Journal of Biological Rhythms·Ciearra B SmithDavid R Weaver

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