Aqp5 -/- mice exhibit reduced maximal body O 2 consumption under cold exposure, normal pulmonary gas exchange, and impaired formation of brown adipose tissue.

The fundamental body functions that determine maximal O uptake (V̇o) have not been studied in Aqp5 mice (aquaporin 5, AQP5). We measured V̇o to globally assess these functions and then investigated why it was found altered in Aqp5 mice. V̇o was measured by the Helox technique, which elicits maximal metabolic rate by intense cold exposure of the animals. We found V̇o reduced in Aqp5 mice by 20%-30% compared with wild-type (WT) mice. As AQP5 has been implicated to act as a membrane channel for respiratory gases, we studied whether this is caused by the known lack of AQP5 in the alveolar epithelial membranes of Aqp5 mice. Lung function parameters as well as arterial O saturation were normal and identical between Aqp5 and WT mice, indicating that AQP5 does not contribute to pulmonary O exchange. The cause for the decreased V̇o thus might be found in decreased O consumption of an intensely O-consuming peripheral organ such as activated brown adipose tissue (BAT). We found indeed that absence of AQP5 greatly reduces the amount of interscapular BAT formed in response to 4 wk of cold exposure, from 63% in WT to 25% in Aqp5 animals. We conclude that lack of AQP5 does not affect pulmonary O exchange, but greatly inhibits transformation of white to brown adipose tissue. As under cold exposure, BAT is a major source of the animals' heat production, reduction of BAT likely causes the decrease in V̇o under this condition.