Aqp5^−/− mice exhibit reduced maximal body O₂ consumption under cold exposure, normal pulmonary gas exchange, and impaired formation of brown adipose tissue

The fundamental body functions that determine maximal O 2 uptake (V̇o 2max ) have not been studied in Aqp5 −/− mice (aquaporin 5, AQP5). We measured V̇o 2max to globally assess these functions and then investigated why it was found altered in Aqp5 −/− mice. V̇o 2max was measured by the Helox technique, which elicits maximal metabolic rate by intense cold exposure of the animals. We found V̇o 2max 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 2 saturation were normal and identical between Aqp5 −/− and WT mice, indicating that AQP5 does not contribute to pulmonary O 2 exchange. The cause for the decreased V̇o 2max thus might be found in decreased O 2 consumption of an intensely O 2 -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 2 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 2max under this condition.