RT Journal Article
SR Electronic
T1 Hypothalamic thyroid hormone deficiency underlies reversible anorexia in a mammalian hibernator
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2023.03.15.532843
DO 10.1101/2023.03.15.532843
A1 Sarah M. Mohr
A1 Rafael Dai Pra
A1 Maryann P. Platt
A1 Viktor V. Feketa
A1 Marya Shanabrough
A1 Luis Varela
A1 Ashley Kristant
A1 Haoran Cao
A1 Dana K. Merriman
A1 Tamas L. Horvath
A1 Sviatoslav N. Bagriantsev
A1 Elena O. Gracheva
YR 2023
UL http://biorxiv.org/content/early/2023/03/16/2023.03.15.532843.abstract
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.