TY - JOUR T1 - Hypothalamic thyroid hormone deficiency underlies reversible anorexia in a mammalian hibernator JF - bioRxiv DO - 10.1101/2023.03.15.532843 SP - 2023.03.15.532843 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 Y1 - 2023/01/01 UR - http://biorxiv.org/content/early/2023/03/16/2023.03.15.532843.abstract N2 - 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. ER -