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.