pH and Metabolic Depression in Mammalian Hibernation. The Example of Brown Adipose Tissue

The extent of reduction of metabolic rate in mammalian hibernation suggests that metabolic depression is taking place, beyond the Arrhenius effect of temperature on enzymatic reaction rates.

Intermittent breathing frequently occurs in deep hibernation, with long apneas accompanied with bradycardia and depletion of oxygen stores. This is somewhat similar to diving, but whether it contributes to metabolic depression is still unproven.

CO₂ accumulates in blood and tissues during the entry into hibernation, giving rise to a respiratory acidosis. Correlative evidence in vivo supports the involvement of hypercapnia in metabolic depression. In brown adipose tissue (a major source of regulatory thermogenesis in cold-adapted small mammals), intracellular alkalinization normally contributes to the thermogenic response to the physiological stimulus norepinephrine. This involves the interaction of H⁺ ions with the binding of regulatory nucleotides to the uncoupling protein, which controls heat production in the mitochondria. In isolated cells, hypercapnia overrides this effect and reduces the thermogenic response. Depression by hypercapnia thus occurs via the reversal of a preexisting activating mechanism.

Although hibernation is a popular example of metabolic depression in mammals, many questions are still unresolved. For instance, is metabolism depressed beyond the simple effect of temperature? If so, does the accumulation of CO₂ in the tissues of the torpid animal exert an inhibitory role, and which? As we will see, studies on a tissue specialized in heat production in small mammals, the brown adipose tissue, provide direct answers to such questions, and show how a preexisting activating mechanism could be turned by hibernators into a means of downregulating energy consumption.