The Bioenergetic Network of Adenosine in Hibernation, Sleep, and Thermoregulation

Abstract

Adenosine is a homeostatic bioenergetic network regulator that plays a fundamental role in energy homeostasis through biochemical, bioenergetic, and receptor dependent processes. Hibernation, torpor, and sleep are integral to energy homeostasis. Here we review evidence that adenosine receptor dependent signaling as well as biochemical and bioenergetic influences of adenosine are essential to all three of these processes placing adenosine at the core of mammalian energy homeostasis. Central A1 adenosine receptor (A1R) dependent signaling is necessary for onset of hibernation and fasting-induced torpor in ground squirrels, hamsters, and mice. Activation of A1R within the central nervous system is sufficient to induce hibernation. A seasonally mediated change in sensitivity to central A1R stimulation is necessary for A1R agonist-induced hibernation in ground squirrels and may underlie the distinction between sleep and hibernation. One function of sleep is to restore brain energy homeostasis, while the primary function of hibernation and torpor is to restore or protect somatic energy homeostasis. Where in the brain A1R agonists act to induce torpor and how central A1R dependent signaling reduces metabolic rate to 1–2 % of resting metabolic rate in hibernating animals is a topic for further research. Understanding mechanisms of energy homeostasis may have implications for treatment of stroke, cardiac arrest, and other conditions where delivery of blood fails to meet demand.