Norepinephrine Controls Both Torpor Initiation and Emergence via Distinct Mechanisms in the Mouse

Some mammals, including laboratory mice, enter torpor in response to food deprivation, and leptin can attenuate these bouts of torpor. We previously showed that dopamine β-hydroxylase knockout (Dbh −/−) mice, which lack norepinephrine (NE), do not reduce circulating leptin upon fasting nor do they enter torpor. To test whether the onset of torpor in mice during a fast requires a NE-mediated reduction in circulating leptin, double mutant mice deficient in both leptin (ob/ob) and DBH (DBL MUT) were generated. Upon fasting, control and ob/ob mice entered torpor as assessed by telemetric core Tb acquisition. While fasting failed to induce torpor in Dbh −/− mice, leptin deficiency bypassed the requirement for NE, as DBL MUT mice readily entered torpor upon fasting. These data indicate that sympathetic activation of white fat and suppression of leptin is required for the onset of torpor in the mouse. Emergence from torpor was severely retarded in DBL MUT mice, revealing a novel, leptin-independent role for NE in torpor recovery. This phenotype was mimicked by administration of a β3 adrenergic receptor antagonist to control mice during a torpor bout. Hence, NE signaling via β3 adrenergic receptors presumably in brown fat is the first neurotransmitter-receptor system identified that is required for normal recovery from torpor

Mitochondrial metabolism in hibernation and daily torpor: a review.

Hibernation and daily torpor involve substantial decreases in body temperature and metabolic rate, allowing birds and mammals to cope with cold environments and/or limited food. Regulated suppression of mitochondrial metabolism probably contributes to energy savings: state 3 (phosphorylating) respiration is lower in liver mitochondria isolated from mammals in hibernation or daily torpor compared to normothermic controls, although data on state 4 (non-phosphorylating) respiration are equivocal. However, no suppression is seen in skeletal muscle, and there is little reliable data from other tissues. In both daily torpor and hibernation, liver state 3 substrate oxidation is suppressed, especially upstream of electron transport chain complex IV. In hibernation respiratory suppression is reversed quickly in arousal even when body temperature is very low, implying acute regulatory mechanisms, such as oxaloacetate inhibition of succinate dehydrogenase. Respiratory suppression depends on in vitro assay temperature (no suppression is evident below approximately 30 degrees C) and (at least in hibernation) dietary polyunsaturated fats, suggesting effects on inner mitochondrial membrane phospholipids. Proton leakiness of the inner mitochondrial membrane does not change in hibernation, but this also depends on dietary polyunsaturates. In contrast proton leak increases in daily torpor, perhaps limiting reactive oxygen species production