PT  - JOURNAL ARTICLE
AU  - Sarah M. Mohr
AU  - Rafael Dai Pra
AU  - Maryann P. Platt
AU  - Viktor V. Feketa
AU  - Marya Shanabrough
AU  - Luis Varela
AU  - Ashley Kristant
AU  - Haoran Cao
AU  - Dana K. Merriman
AU  - Tamas L. Horvath
AU  - Sviatoslav N. Bagriantsev
AU  - Elena O. Gracheva
TI  - Hypothalamic thyroid hormone deficiency underlies reversible anorexia in a mammalian hibernator
AID  - 10.1101/2023.03.15.532843
DP  - 2023 Jan 01
TA  - bioRxiv
PG  - 2023.03.15.532843
4099  - http://biorxiv.org/content/early/2023/03/16/2023.03.15.532843.short
4100  - http://biorxiv.org/content/early/2023/03/16/2023.03.15.532843.full
AB  - 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 StatementThe authors have declared no competing interest.