Torpor in mice is induced by both leptin-dependent and -independent mechanisms.
We tested the effect of chronic leptin treatment on fasting-induced torpor in leptin-deficient A-ZIP/F-1 and ob/ob mice. A-ZIP/F-1 mice have virtually no white adipose tissue and low leptin levels, whereas ob/ob mice have an abundance of fat but no leptin. These two models allowed us to examine the roles of adipose tissue and leptin in the regulation of entry into torpor. Torpor is a short-term hibernation-like state that allows conservation of metabolic fuels. We first characterized the A-ZIP/F-1 animals, which have a 10-fold reduction in total body triglyceride stores. Upon fasting, A-ZIP/F-1 mice develop a lower metabolic rate and decreased plasma glucose, insulin, and triglyceride levels, with no increase in free fatty acids or beta-hydroxybutyrate. Unlike control mice, by 24 hr of fasting, they have nearly exhausted their triglycerides and are catabolizing protein. To conserve energy supplies during fasting, A-ZIP/F-1 (but not control) mice entered deep torpor, with a minimum core body temperature of 24 degrees C, 2 degrees C above ambient. In ob/ob mice, fasting-induced torpor was completely reversed by leptin treatment. In contrast, neither leptin nor thyroid hormone prevented torpor in A-ZIP/F-1 mice. These data suggest that there are at least two signals for entry into torpor in mice, a low leptin level and another signal that is independent of leptin and thyroid hormone levels. Studying rodent torpor provides insight into human torpor-like states such as near drowning in cold water and induced hypothermia for surgery.
Gavrilova
O
O
Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Leon
L R
LR
Marcus-Samuels
B
B
Mason
M M
MM
Castle
A L
AL
Refetoff
S
S
Vinson
C
C
Reitman
M L
ML
D000222:Adaptation, Physiological; D000818:Animals; D004734:Energy Metabolism; D005215:Fasting / Q000502:physiology*; D020738:Leptin / Q000172:deficiency / Q000502:physiology*; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D013739:Testosterone / Q000097:blood; D013963:Thyroid Hormones / Q000097:blood; D014280:Triglycerides / Q000378:metabolism
D020738:Leptin; D008112:Liver Glycogen; D013963:Thyroid Hormones; D014280:Triglycerides; D013739:Testosterone