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Hypothalamic thyroid hormone deficiency underlies reversible anorexia in a mammalian hibernator

Sarah M. Mohr, Rafael Dai Pra, Maryann P. Platt, Viktor V. Feketa, Marya Shanabrough, Luis Varela, Ashley Kristant, Haoran Cao, Dana K. Merriman, Tamas L. Horvath, View ORCID ProfileSviatoslav N. Bagriantsev, View ORCID ProfileElena O. Gracheva
doi: https://doi.org/10.1101/2023.03.15.532843
Sarah M. Mohr
1Department of Cellular and Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA
2Department of Neuroscience, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA
3Kavli Institute for Neuroscience, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA
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Rafael Dai Pra
1Department of Cellular and Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA
2Department of Neuroscience, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA
3Kavli Institute for Neuroscience, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA
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Maryann P. Platt
1Department of Cellular and Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA
2Department of Neuroscience, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA
3Kavli Institute for Neuroscience, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA
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Viktor V. Feketa
1Department of Cellular and Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA
2Department of Neuroscience, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA
3Kavli Institute for Neuroscience, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA
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Marya Shanabrough
4Department of Comparative Medicine, Yale University School of Medicine, 310 Cedar Street, New Haven, CT 06510, USA
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Luis Varela
4Department of Comparative Medicine, Yale University School of Medicine, 310 Cedar Street, New Haven, CT 06510, USA
5Achucarro Basque Center for Neuroscience, Leioa, Spain 48940
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Ashley Kristant
4Department of Comparative Medicine, Yale University School of Medicine, 310 Cedar Street, New Haven, CT 06510, USA
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Haoran Cao
1Department of Cellular and Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA
2Department of Neuroscience, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA
3Kavli Institute for Neuroscience, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA
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Dana K. Merriman
6Department of Biology, University of Wisconsin-Oshkosh, 800 Algoma Boulevard, Oshkosh, WI 54901, USA
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Tamas L. Horvath
4Department of Comparative Medicine, Yale University School of Medicine, 310 Cedar Street, New Haven, CT 06510, USA
5Achucarro Basque Center for Neuroscience, Leioa, Spain 48940
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Sviatoslav N. Bagriantsev
1Department of Cellular and Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA
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  • ORCID record for Sviatoslav N. Bagriantsev
  • For correspondence: slav.bagriantsev@yale.edu elena.gracheva@yale.edu
Elena O. Gracheva
1Department of Cellular and Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA
2Department of Neuroscience, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA
3Kavli Institute for Neuroscience, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA
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  • ORCID record for Elena O. Gracheva
  • For correspondence: slav.bagriantsev@yale.edu elena.gracheva@yale.edu
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Abstract

Mammalian hibernators survive prolonged periods of cold and resource scarcity by temporarily modulating normal physiological functions, but the mechanisms underlying these adaptations are poorly understood. The hibernation cycle of thirteen-lined ground squirrels lasts for 5–7 months and comprises weeks of hypometabolic, hypothermic torpor interspersed with 24–48-hour periods of an active-like interbout arousal (IBA) state. We show that ground squirrels, who endure the entire hibernation season without food, have negligible hunger drive during IBAs. These squirrels exhibit reversible inhibition of the hypothalamic feeding center, such that hypothalamic arcuate nucleus neurons exhibit reduced sensitivity to the orexigenic and anorexigenic effects of ghrelin and leptin, respectively. However, hypothalamic infusion of thyroid hormone during an IBA is sufficient to rescue hibernation anorexia. Our results reveal that thyroid hormone deficiency underlies hibernation anorexia and demonstrate the functional flexibility of the hypothalamic feeding center.

Competing Interest Statement

The authors have declared no competing interest.

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Posted March 16, 2023.
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Hypothalamic thyroid hormone deficiency underlies reversible anorexia in a mammalian hibernator
Sarah M. Mohr, Rafael Dai Pra, Maryann P. Platt, Viktor V. Feketa, Marya Shanabrough, Luis Varela, Ashley Kristant, Haoran Cao, Dana K. Merriman, Tamas L. Horvath, Sviatoslav N. Bagriantsev, Elena O. Gracheva
bioRxiv 2023.03.15.532843; doi: https://doi.org/10.1101/2023.03.15.532843
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Hypothalamic thyroid hormone deficiency underlies reversible anorexia in a mammalian hibernator
Sarah M. Mohr, Rafael Dai Pra, Maryann P. Platt, Viktor V. Feketa, Marya Shanabrough, Luis Varela, Ashley Kristant, Haoran Cao, Dana K. Merriman, Tamas L. Horvath, Sviatoslav N. Bagriantsev, Elena O. Gracheva
bioRxiv 2023.03.15.532843; doi: https://doi.org/10.1101/2023.03.15.532843

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